emtricitabine--tenofovir-disoproxil-fumarate-drug-combination and HIV-Infections

At Bristol-Myers (BM) (1985-1990), John C. Martin started his HIV career with directing the clinical development of didanosine (ddI) and stavudine (d4T). During this period, he became aware of the acyclic nucleoside phosphonates (ANPs), such as (

Topics: Alanine; Anti-HIV Agents; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Hepatitis B; History, 20th Century; History, 21st Century; HIV; HIV Infections; Humans; Pre-Exposure Prophylaxis; Reverse Transcriptase Inhibitors; Tenofovir

Pre-exposure prophylaxis (PrEP) has proven to be a highly effective and safe way to prevent HIV infection. Seroconversion and primary HIV infection are exceptional if adherence to PrEP is good. However, primary HIV infection while using PrEP can occur, albeit rarely, and HIV drug resistance might develop. Furthermore, the scope of PrEP is expected to expand, and clinicians might face potential seroconversions and primary HIV infection in patients starting or taking PrEP. The characteristics of primary HIV infection in users of PrEP are poorly described. PrEP users present a lower viral load peak during primary HIV infection and, frequently, fewer symptoms than individuals not exposed to PrEP. Additionally, PrEP prolongs the stages of seroconversion, thus potentially complicating diagnosis of primary HIV infection. Drug resistance is rare, occurring mostly when PrEP is initiated in undiagnosed patients who are at an extremely early stage of infection, in whom detection of HIV-RNA was not used to rule out HIV infection. Therefore, careful exclusion of primary HIV infection before starting PrEP is crucial. In patients presenting with primary HIV infection while on PrEP, a drug with a high genetic barrier (or even two) should be added to tenofovir disoproxil fumarate-emtricitabine until test results for resistance are available.

Topics: Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV Seropositivity; HIV-1; Humans; Pre-Exposure Prophylaxis; Tenofovir; Viral Load

Topics: Administration, Oral; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Pre-Exposure Prophylaxis; Pregnancy; Pregnancy Outcome

women in sub-Saharan Africa (SSA) are disproportionately affected by the HIV epidemic. In 2019, they constituted 59% of new infections; thus, they remain a key population for control. Public health interventions to prevent acquisition of HIV in this high-risk population are urgently needed. Tenofovir-based pre-exposure prophylaxis (TFV-PrEP) has been shown to reduce HIV infections in other key populations. However, comprehensive evidence regarding TFV-PrEP effectiveness in women living in SSA has not been determined. Therefore, we undertook a systematic review to determine the effectiveness of tenofovir-1% (TFV-1%) vaginal gel, oral tenofovir (TFV) and tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis for primary acquisition of HIV in at-risk women living in SSA.. OVID Medline, Embase, CENTRAL, Web of Science and Clinical Trials.gov were searched for eligible studies from 1. from 2002 non-duplicate articles, four RCTs evaluating the effectiveness of one or more of the interventions against placebos were included. TFV-1% vaginal gel, oral TDF or TDF-FTC were not effective in preventing the acquisition of HIV infection in women living in SSA. However, poor adherence by study participants could have confounded the true effectiveness of TFV-PrEP in this high risk population. Meta-analysis was not conducted given the limited number of eligible studies identified from the search.. the current evidence does not support the effectiveness of TFV-PrEP for HIV in SSA women. More studies aimed at addressing factors driving low adherence to HIV interventions in this high risk population are urgently needed in order to improve the design of future RCTs leading to the determination of more reliable estimates of TFV-1% vaginal gel or oral TDF or TDF-FTC effectiveness. Protocol registration: this systematic review was not registered in PROSPERO.

Topics: Africa South of the Sahara; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Medication Adherence; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Tenofovir

Transgender persons are at increased risk of HIV infection and would benefit from pre-exposure prophylaxis (PrEP) use. However, barriers to healthcare and a lack of data regarding PrEP efficacy among transgender persons limits use. A related issue is whether a drug-drug interaction (DDI) exists between gender affirming hormone therapy (GAHT) and PrEP. Recently, small pharmacokinetic studies were conducted to assess this interaction.. This review will assess the pharmacology of PrEP agents, existing data regarding potential DDIs between GAHT and PrEP, and hypothetical mechanisms for these DDIs. A summary will be provided on implications for PrEP use among transgender persons.. Theoretically, DDIs are not expected between GAHT and PrEP. However, among transgender women (TGW) on GAHT, small studies identified a minor DDI between GAHT and tenofovir/emtricitabine (TFV/FTC), with TFV/FTC exposures ~12-27% lower among TGW vs. cisgender men. The mechanism of DDIs is unclear and requires further study. For perspective, median TFV/FTC concentrations were still within the range of median concentrations reported across controlled pharmacokinetic studies. TFV-disphosphate/FTC-triphosphate concentrations were similar between TGW and cisgender men. In summary, TDF/FTC likely reaches protective concentrations and should continue to be offered as PrEP for transgender persons.

Topics: Animals; Anti-HIV Agents; Drug Interactions; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Hormones; Humans; Male; Pre-Exposure Prophylaxis; Transgender Persons

The antiretroviral combination of emtricitabine-tenofovir disoproxil fumarate (FTC/TDF) was approved by the U.S. Food and Drug Administration for use as pre-exposure prophylaxis (PrEP) in individuals at high risk for acquiring human immunodeficiency virus (HIV) in July 2012. Since then, Centers for Disease Control and Prevention guidelines for the use of PrEP have been published and implemented into clinical practice throughout the United States. A number of published open-label and PrEP demonstration projects have evaluated the real-world use of PrEP including analysis of the barriers to its use and addressing major concerns. Despite the approval of FTC/TDF for PrEP, its use for this indication relies on patient and provider acceptance, and its effectiveness requires patient adherence and retention in care during periods of high-risk behaviors. Concerns regarding the use of PrEP in healthy individuals persist and include medication adverse effects including renal dysfunction and bone mineral density loss; risk compensation leading to HIV infections, sexually transmitted infections, and unintended pregnancies; and the development of drug resistance in the event of seroconversion. The cost-effectiveness of PrEP continues to be assessed with the greatest cost-effectiveness remaining in those at highest risk of acquiring HIV. Additionally, cases of HIV acquisition in individuals who are adherent to PrEP highlight scenarios in which PrEP is not 100% effective including against the transmission of drug-resistant HIV strains. This review examines data on the implementation of PrEP outside the setting of clinical trials with the aim of providing clinicians with a summary of the current barriers and opportunities for PrEP use with a specific focus on the role of pharmacists in the optimization of PrEP implementation.

Topics: Anti-HIV Agents; Cost-Benefit Analysis; Drug Prescriptions; Drug Resistance, Multiple, Viral; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Patient Compliance; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic

Women in the United States and especially women of color continue to acquire human immunodeficiency virus (HIV) infection. During reproductive health visits, health care providers are ideally positioned to assess HIV risk and offer HIV prevention strategies, including preexposure prophylaxis (also known as "PrEP"), a once-daily fixed-dose combination of emtricitabine with tenofovir disoproxil fumarate approved by the U.S. Food and Drug Administration for use to prevent HIV acquisition in persons at risk. Family planning, pregnancy, and postpartum visits provide an opportunity to ask sensitive questions about sexual and reproductive health and to help women navigate preference-sensitive decisions, including an individualized plan for HIV prevention. Exposure to a fixed-dose combination of emtricitabine with tenofovir disoproxil fumarate during pregnancy and breastfeeding appears to be safe with respect to maternal and infant outcomes. This article reviews the critical issues, challenges, and opportunities when implementing preexposure prophylaxis for women at risk for HIV who are seeking family planning services or pregnancy or postpartum care.

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Family Planning Services; Female; HIV Infections; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; Reproductive Health

The review describes the evidence for HIV preexposure prophylaxis (PrEP) with daily combined tenofovir disoproxil fumarate and emtricitabine for adolescents and young adults. Current recommendations are described, as are the unique medical, socioeconomic, and legal considerations regarding the use of PrEP for youth.. PrEP with daily oral tenofovir disoproxil fumarate-emtricitabine has been shown to help prevent new HIV infection among adults at substantial risk. Evidence suggests a protective benefit of PrEP for youth at risk for HIV, although low adherence is emerging as a barrier to effective use.. Effective use of antiretrovirals for PrEP represents a seminal development in HIV prevention efforts. Improving access and adherence to PrEP for youth has the potential to substantially reduce the incidence of HIV in this population.

Topics: Adolescent; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Pre-Exposure Prophylaxis; Treatment Outcome; Young Adult

Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety.. To compare the efficacy and safety of these three combinations.. Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC).. Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC.. The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.. El tratamiento inicial de la infección por VIH se basa en el uso de tres medicamentos, dos de ellos inhibidores de transcriptasa reversa análogos de nucleósido. Existen tres combinaciones de estos medicamentos aprobadas por diferentes guías, con resultados divergentes en cuanto a eficacia y seguridad.. Comparar la eficacia y seguridad de las 3 combinaciones.. Revisión sistemática y metanálisis en red de ensayos clínicos con asignación aleatoria comparando dosis fijas de Tenofovir Disoproxil Fumarato/Emtricitabina (TDF/FTC), Abacavir/Lamivudina (ABC/3TC) y Zidovudina/Lamivudina (ZDV/3TC).. Siete ensayos clínicos cumplieron los criterios de elegibilidad. Los resultados sugirieron mayor eficacia con TDF/FTC vs ABC/3TC a 96 semanas y vs. ZDV/3TC a 48 semanas. Sin embargo, existe heterogeneidad clínica y estadística. Se realizó análisis de subgrupos por tercer medicamento y por nivel de carga viral previa al tratamiento, sin encontrar diferencias en control virológico. Se pudo realizar metanálisis en red con TDF/FTC vs ZDV/3TC y proporción de pacientes con respuesta virológica, sin diferencias a las 48 semanas ni 96 semanas. Las comparaciones directas evidenciaron mayor riesgo de supresión de médula ósea de ZDV/3TC vs TDF/FTC y de reacciones de hipersensibilidad de ABC/3TC vs ZDV/3TC.. Los resultados no demostraron diferencias en efectividad entre las intervenciones; sin embargo, debido a heterogeneidad en cuanto al tercer medicamento y el tiempo de seguimiento entre los estudios incluidos, dicho resultado no es definitivo. Los resultados plantean la necesidad de realizar nuevos estudios que ayuden a mejorar las recomendaciones de tratamiento en los pacientes infectados por el VIH.

Topics: Anti-HIV Agents; Dideoxynucleosides; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Lamivudine; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome; Zidovudine

Although pre-exposure prophylaxis (PrEP)-the use of antiretroviral drugs by non-infected people to prevent the acquisition of HIV-is a promising preventive option, important public health questions remain. Daily oral emtricitabine (FTC)-tenofovir disoproxil fumarate (TDF) is highly efficacious in preventing the acquisition of HIV in people at risk as a result of a range of different types of sexual exposure. There is good evidence of efficacy in women and men, and when men who have sex with men use event based dosing. Studies have been conducted in several countries and epidemics. Because adherence to this treatment varies greatly there are questions about its public health benefit. Oral FTC-TDF is extremely safe, with minimal impact on kidney, bone, or pregnancy outcomes, and there is no evidence that its effectiveness has been reduced by risk compensation during open label and programmatic follow-up. It is too early to assess the impact of this treatment on the incidence of sexually transmitted infections (STIs) at a population level. Many challenges remain. Access to pre-exposure prophylaxis is limited and disparities exist, including those governed by race and sex. Different pricing and access models need to be explored to avoid further widening inequalities. The optimal combination prevention program needs to be defined, and this will depend on local epidemiology, service provision, and cost effectiveness. This review updates the evidence base for pre-exposure prophylaxis regarding its effectiveness, safety, and risk compensation.

Topics: Adolescent; Adult; Anti-Retroviral Agents; Cost-Benefit Analysis; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Healthcare Disparities; HIV; HIV Infections; Homosexuality, Male; Humans; Incidence; Male; Middle Aged; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Risk-Taking; Sexually Transmitted Diseases; Treatment Adherence and Compliance; Treatment Outcome; Young Adult

Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present challenges in the implementation and use of PrEP. The aim of this review is to discuss safety concerns observed in completed clinical trials on the use of PrEP. We performed a literature search on PrEP in PubMed, global advocacy for HIV prevention (Aids Vaccine Advocacy Coalition) database, clinical trials registry " http://www.clinicaltrials.gov " and scholar.google, using combination search terms 'pre-exposure prophylaxis', 'safety concerns in the use of pre-exposure prophylaxis', 'truvada use as PrEP', 'guidelines for PrEP use', 'HIV pre-exposure prophylaxis' and 'tenofovir' to identify clinical trials and literature on PrEP. We present findings associated with safety issues on the use of PrEP based on a review of 11 clinical trials on PrEP with results on safety and efficacy as at April 2016. We also reviewed findings from routine real-life practice reports. The pharmacological intervention for PrEP was tenofovir disoproxil fumarate/emtricitabine in a combined form as Truvada

Topics: Animals; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Pre-Exposure Prophylaxis; Tenofovir

This article describes the use of tenofovir/emtricitabine (Truvada) as prevention for exposure to HIV [preexposure prophylaxis (PrEP)] infection in the USA. The use of PrEP and the challenges of implementation are very instructive as other countries adopt this intervention and it becomes a fundamental part of worldwide efforts for HIV prevention and much can be learned from the first 3 years in the USA.. Randomized trials and demonstration projects have shown the benefits of PrEP for men and women who are at risk for HIV. Numerous studies have showed that the level of prevention is excellent when the drug is taken at least four times weekly, once adequate levels are obtained. However, adherence remains a critical issue as well as tailoring delivery models for specific populations. Six recent studies are discussed, that support excellent efficacy and significantly support PrEP as a means of prevention. These projects have shown high acceptance of PrEP with excellent adherence by individuals demonstrated by those at risk remaining free of HIV over extended periods of time.. The USA faces three significant challenges in scaling up PrEP. The first challenge in implementation in the USA is to get individuals to recognize the actual risks that their behaviors represent and to engage with providers to address these issues. The second challenge is getting a population of providers to recognize the exact same issues and offer PrEP in a compassionate, nonjudgmental fashion. The third challenge is identifying the set of providers and locations to scale-up the response in a timely, cost-effective fashion.

Topics: Anti-HIV Agents; Chemoprevention; Clinical Trials as Topic; Delivery of Health Care; Disease Transmission, Infectious; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; United States

According to the Americans with Disabilities Act (1990), couples with blood-borne viruses that lead to infectious disease cannot be denied fertility treatment as long as the direct threat to the health and safety of others can be reduced or eliminated by a modification of policies or procedures. Three types of infectious patients are commonly discussed in the context of fertility treatment: those with human immunodeficiency virus (HIV), hepatitis C or hepatitis B. Seventy-five per cent of hepatitis C or HIV positive men and women are in their reproductive years, and these couples look to assisted reproductive techniques for risk reduction in conceiving a pregnancy. In many cases, only one partner is infected. Legal and ethical questions about treatment of infectious patients aside, the question most asked by clinical embryologists and andrologists is: "What are the laboratory protocols for working with gametes and embryos from patients with infectious disease?" The serostatus of each patient is the key that informs appropriate treatments. This guidance document describes protocols for handling gametes from seroconcordant and serodiscordant couples with infectious disease. With minor modifications, infectious patients with stable disease status and undetectable or low viral load can be accommodated in the IVF laboratory.

Topics: Cryopreservation; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Fertilization in Vitro; Germ Cells; Hemorrhagic Fever, Ebola; Hepatitis B; Hepatitis C; HIV Infections; HIV Seropositivity; Humans; Infectious Disease Transmission, Vertical; Male; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Infectious; Reproductive Techniques, Assisted; Risk; Risk Reduction Behavior; Semen; Spermatozoa; Viral Load; Zika Virus Infection

Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are nucleoside reverse transcriptase inhibitors approved as pre-exposure prophylaxis (PrEP) against human immunodeficiency virus (HIV). Prophylactic TDF-based regimens have been shown to reduce the risk of HIV infection by 74 to 92% among participants with detectable drug levels. Adverse events observed in clinical trials include nausea, elevated creatinine and liver enzymes, and decreased bone mineral density.. This article reviews the pharmacology, pharmacokinetics, and the safety profile of TDF and FTC used as PrEP for HIV infection.. TDF-FTC can have a large impact in preventing HIV infections among high risk individuals when taken daily. Although TDF-FTC is associated with adverse events, they can be minimized with clinician-guided monitoring.

Topics: Animals; Anti-HIV Agents; Creatinine; Drug Monitoring; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Liver; Pre-Exposure Prophylaxis; Reverse Transcriptase Inhibitors

HIV pre-exposure prophylaxis (PrEP) is a prevention technology that involves prescribing antiretroviral drugs to HIV-negative people to protect them from infection. This paper considers how the development of the technology has necessitated the parallel configuration of its users, and how this process has affected the perception and uptake of the technology. In designing a technology, potential users are typically defined, enabled and constrained, partly to create a target population (or market) for the technology, but also to reassure people that it can be used safely and effectively. This process may or may not be helpful for the uptake and use of the technology. Published research on PrEP indicates that while the technology was under trial, the primary focus was on the 'at-risk' subject in need of PrEP, with little or no consideration of the other qualities necessary for successful use. Post-trial accounts of PrEP have begun to outline desirable qualities of successful PrEP use, such as caution, compliance and being organised. It appears that the PrEP user was only partially configured during the technology's development, and the initial focus on risk has done little to counter fears of the technology, which may partially account for its slow uptake.

Topics: Anti-HIV Agents; Bisexuality; Diffusion of Innovation; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Pre-Exposure Prophylaxis; Risk Assessment

Antiretroviral preexposure prophylaxis (PrEP; emtricitabine and tenofovir disoproxil fumarate [Truvada]) prevents HIV without penalizing sexual pleasure, and may even enhance pleasure (e.g., by reducing HIV-related anxiety). However, concern about sexual risk behavior increasing with PrEP use (risk compensation) and corresponding stereotypes of promiscuity may undermine PrEP's preventive potential. In this commentary, we review literature on sexual behavior change accompanying PrEP use, discuss risk compensation concerns and the "Truvada whore" stereotype as PrEP barriers, question the appropriateness of restricting PrEP access because of risk compensation, and consider sexual pleasure as a benefit of PrEP, an acceptable motive for seeking PrEP, and a core element of health. It is essential for science to trump stereotypes and sex-negative messaging in guiding decision-making affecting PrEP access and uptake.

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Pleasure; Pre-Exposure Prophylaxis; Sexual Behavior; Social Stigma; Stereotyping

The HIV antiretroviral drug emtricitabine/tenofovir disoproxil fumarate (Truvada) was recently approved as preexposure prophylaxis (PrEP) therapy for adults at high risk for sexually acquired HIV infection. This article reviews the data supporting the efficacy of PrEP, and provides other relevant data regarding the implementation of PrEP.

Topics: Adult; Anti-HIV Agents; Antibiotic Prophylaxis; Deoxycytidine; Drug Approval; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds; Risk Assessment; Treatment Outcome; United States; United States Food and Drug Administration

Treatment as prevention is expected to have a major role in reducing HIV incidence, but other prevention interventions will also be required to bring the epidemic under control, particularly among key populations. One or more forms of pre-exposure prophylaxis (PrEP) will likely play a critical role. Oral PrEP with emtricitabine-tenofovir (Truvada®) is currently available in the US and some other countries, but uptake has been slow. We review the concerns that have contributed to this slow uptake and discuss current and future research in this critical area of HIV prevention research.

Topics: Administration, Oral; Anti-Retroviral Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Organophosphorus Compounds; Pre-Exposure Prophylaxis

Topics: Anti-HIV Agents; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Drug Costs; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Organophosphorus Compounds; Treatment Outcome; United States

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Insurance Coverage; Insurance, Health; Organophosphorus Compounds; Primary Prevention

Topics: Adverse Drug Reaction Reporting Systems; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Organophosphorus Compounds; Outcome Assessment, Health Care; Pregnancy; Primary Prevention; Registries; Risk Management

Twenty years after its original discovery, tenofovir has acquired a crucial position in the fight against human immunodeficiency virus (HIV). First, tenofovir disoproxil fumarate (TDF) is not only efficacious against, and has been licensed for the treatment of HIV (AIDS), but also HBV (hepatitis B). Second, for the treatment of HIV infections, TDF can be used in combination with other anti-HIV drugs, such as emtricitabine (combination termed Truvada(®)) and Truvada can be further combined with efavirenz, rilpivirine, elvitegravir, atazanavir, or darunavir, as a single once-daily oral pill. Third, Truvada can be used prophylactically to prevent transmission of HIV infection. And fourth, to prevent sexual HIV transmission, tenofovir could also be used topically (i.e., as a vaginal gel).

Topics: Adenine; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV; HIV Infections; Humans; Organophosphonates; Organophosphorus Compounds; Tenofovir

The pre-exposure chemoprophylaxis (PrEP) is an experimental approach to HIV prevention. The use of antiretroviral drugs has been shown to be effective in prevention HSIV infection in animals. The results from ongoing clinical PrEP trials have demonstrated that antiretrovirals were able to reduce HIV incidence in women and men. The CAPRISA-004 study demonstrated that 1% TDF gel applied intravaginally decreased the risk of HIV infection among heterosexual women in South Africa. The largest global trial iPr Ex conducted in men who have sex with men (MSM), has demonstrated that chemoprophylaxis with daily oral TDF/FTC was 44% effective in protecting against HIV transmission. Following the results of the iPrEx study, the US CDC issued the interim guidance regarding the use of oral PrEP among MSM. Currently more then 20.000 people will be enrolled in studies with oral or topical antiretroviral agents as pre-exposure chemoprophylaxis.

Topics: Adenine; Administration, Oral; Animals; Anti-HIV Agents; Chemoprevention; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Organophosphonates; Organophosphorus Compounds; Reverse Transcriptase Inhibitors; Tenofovir

Topics: Animals; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Organophosphorus Compounds; Randomized Controlled Trials as Topic

The nucleoside analogue reverse transcriptase inhibitor (RTI) emtricitabine and the nucleotide analogue RTI tenofovir disoproxil fumarate (tenofovir DF) have each shown antiviral activity against a number of HIV clinical isolates and cell lines. HIV variants with reduced susceptibility to emtricitabine and tenofovir have been selected for in vitro and have also been isolated from patients receiving the agents. Low rates of these variants have been observed in patients experiencing virological failure in large studies of emtricitabine- or tenofovir DF-containing therapy. Co-formulated oral emtricitabine/tenofovir DF was bioequivalent to the two agents as separate formulations in a pharmacokinetic trial in healthy volunteers. There are no published data on the clinical antiviral efficacy of co-formulated oral emtricitabine/tenofovir DF. However, each agent is effective in combination regimens with other drugs. Ongoing studies in antiretroviral-naive patients are evaluating the efficacy of the individual formulations given together in combination with efavirenz or lopinavir/ritonavir. In the latter trial, HIV RNA levels were reduced and CD4+ cell counts were increased at 24 and 48 weeks. Emtricitabine and tenofovir DF are generally well tolerated. Diarrhoea, nausea and vomiting were the most common adverse events reported with coadministered emtricitabine and tenofovir DF as separate formulations as part of combination therapy.

Topics: Anti-HIV Agents; Deoxycytidine; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds; Reverse Transcriptase Inhibitors

Tenofovir alafenamide shows high antiviral efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate when used for HIV treatment. Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir alafenamide versus emtricitabine and tenofovir disoproxil fumarate for HIV prevention.. This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both. We enrolled adult cisgender men who have sex with men and transgender women who have sex with men, both with a high risk of acquiring HIV on the basis of their self-reported sexual behaviour in the past 12 weeks or their recent history (within 24 weeks of enrolment) of bacterial sexually transmitted infections. Participants with current or previous use of PrEP with emtricitabine and tenofovir disoproxil fumarate were not excluded. We used a computer-generated random allocation sequence to randomly assign (1:1) participants to receive either emtricitabine (200 mg) and tenofovir alafenamide (25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). As such, all participants were given two tablets. The trial sponsor, investigators, participants, and the study staff who provided the study drugs, assessed the outcomes, and collected the data were masked to group assignment. The primary efficacy outcome was incident HIV infection, which was assessed when all participants had completed 48 weeks of follow-up and half of all participants had completed 96 weeks of follow-up. This full analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug and had at least one post-baseline HIV test. Non-inferiority of emtricitabine and tenofovir alafenamide to emtricitabine and tenofovir disoproxil fumarate was established if the upper bound of the 95·003% CI of the HIV incidence rate ratio (IRR) was less than the prespecified non-inferiority margin of 1·62. We prespecified six secondary bone mineral density and renal biomarker safety endpoints to evaluate using the safety analysis set. This analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02842086, and is no longer recruiting.. Between Sept 13, 2016, and June 30, 2017, 5387 (92%) of 5857 participants were randomly assigned and received emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693). At the time of the primary efficacy analysis (ie, when all participants had completed 48 weeks and 50% had completed 96 weeks) emtricitabine and tenofovir alafenamide was non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the IRR, was less than the prespecified non-inferiority margin of 1·62 (IRR 0·47 [95% CI 0·19-1·15]). After 8756 person-years of follow-up, 22 participants were diagnosed with HIV, seven participants in the emtricitabine and tenofovir alafenamide group (0·16 infections per 100 person-years [95% CI 0·06-0·33]), and 15 participants in the emtricitabine and tenofovir disoproxil fumarate group (0·34 infections per 100 person-years [0·19-0·56]). Both regimens were well tolerated, with a low number of participants reporting adverse events that led to discontinuation of the study drug (36 [1%] of 2694 participants in the emtricitabine and tenofovir alafenamide group vs 49 [2%] of 2693 participants in the emtricitabine and tenofovir disoproxil fumarate group). Emtricitabine and tenofovir alafenamide was superior to emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarker safety endpoints.. Daily emtricitabine and tenofovir alafenamide shows non-inferior efficacy to daily emtricitabine and tenofovir disoproxil fumarate for HIV prevention, and the number of adverse events for both regimens was low. Emtricitabine and tenofovir alafenamide had more favourable effects on bone mineral density and biomarkers of renal safety than emtricitabine and tenofovir disoproxil fumarate.. Gilead Sciences.

Topics: Adenine; Adult; Anti-HIV Agents; Double-Blind Method; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Europe; Female; HIV Infections; HIV-1; Homosexuality, Male; Humans; Male; North America; Placebos; Pre-Exposure Prophylaxis; Prevalence; Safety; Sexual and Gender Minorities; Tenofovir; Treatment Outcome

Efficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for PrEP is strongly dependent on the adherence. We examined the concordance between indirect adherence measures and protective drug levels among participants retained through 48 weeks in the PrEP Brasil Study.. PrEP Brasil was a prospective, multicenter, open-label demonstration project evaluating PrEP provision for men who have sex with men (MSM) and transgender women (TGW) at higher risk for HIV infection within the setting of Brazilian Public Health System. Three indirect adherence measures were obtained at week 48: medication possession ratio (MPR), pill count and self-report (30-days recall). Tenofovir diphosphate (TFV-DP) concentration in Dried Blood Spot (DBS) was measured at week 48. Areas under (AUC) the receiver operating characteristics (ROC) curve were used to evaluate the concordance between achieving protective drug levels (TFV-DP≥700fmol/punch) and the indirect adherence measures. Youden's index and distance to corner were used to determine the optimal cutoff points for each indirect adherence measure. We calculated sensitivity, specificity, negative (NPV) and positive (PPV) predictive values for the found cutoff points. Finally, Delong test was used to compare AUCs.. From April, 2014 to July, 2016, 450 participants initiated PrEP, 375(83.3%) were retained through 48 weeks. Of these, 74% (277/375) had TFV-DP ≥700fmol/punch. All adherence measures discriminated between participants with and without protective drug levels (AUC>0.5). High indirect adherence measure was predictive of protective drug levels (PPV>0.8) while low indirect adherence measure was not predictive of lack of protective drug levels (NPV<0.5). No significant differences were found between the adherence methods (p = 0.44).. Low-burden measurements such as MPR and self-report can be used to predict PrEP adherence in a public health context in Brazil for MSM and TGW retained through 48 weeks. Clinical Trial Number: NCT01989611.

Topics: Adolescent; Adult; Anti-HIV Agents; Brazil; Dried Blood Spot Testing; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Feasibility Studies; Female; HIV Infections; Humans; Male; Medication Adherence; Pre-Exposure Prophylaxis; Prospective Studies; Self Report; Sexual and Gender Minorities; Transgender Persons; Treatment Outcome; Young Adult

Pre-exposure prophylaxis (PrEP) is a novel HIV prevention method whereby HIV-negative individuals take the drugs tenofovir and emtricitabine to prevent HIV acquisition. Optimal adherence is critical for PrEP efficacy. Chemsex describes sexual activity under the influence of psychoactive drugs, in the UK typically; crystal methamphetamine, gamma-hydroxybutyrate(GHB) and/or mephedrone. Chemsex drug use has been associated with increased HIV transmission risk among gay, bisexual and other men who have sex with men (GBM) and poor ART adherence among people living with HIV. This study assessed whether self-reported chemsex events affected self-reported daily PrEP adherence among PROUD study participants.. 1479 follow-up visit forms and 2260 monthly adherence forms from 388 participants were included in the analyses, with 38.5% visit forms reporting chemsex since last visit and 29.9% follow-up periods reporting <7/7ID. No statistically significant associations were observed between reporting <7/7ID and chemsex (aOR=1.29 [95% CI 0.90-1.87], p = 0.168). Statistically significant associations were seen between reporting <7/7ID and participants perceiving that they would miss PrEP doses during the trial, Asian ethnicity, and reporting unemployment at baseline.. These analyses suggest PrEP remains a feasible and effective HIV prevention method for GBM engaging in chemsex, a practise which is prevalent in this group and has been associated with increased HIV transmission risk.

Topics: Adolescent; Adult; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Follow-Up Studies; HIV Infections; Humans; Male; Medication Adherence; Middle Aged; Pre-Exposure Prophylaxis; Self Report; Sexual and Gender Minorities; Sexual Behavior; Substance-Related Disorders; Young Adult

Daily emtricitabine/tenofovor is effective at preventing HIV acquisition and is approved for HIV pre-exposure prophylaxis (PrEP). Blacks in the United States have a disproportionately high rate of HIV, and uptake of PrEP has been very low in this population. We conducted a pilot study in a high-prevalence city to test whether a culturally-tailored counseling center for young Black men who have sex with men (BMSM) positively impacted their access and uptake of PrEP. 50 young BMSM were randomized to either a PrEP counseling center group or a control group, and were then encouraged to obtain PrEP from a PrEP provider. At the end of 3 month study, six participants in the intervention group compared with none in the control group had initiated PrEP (p = 0.02). This pilot study demonstrates that a culturally-tailored counseling center might be an effective at increasing the uptake of PrEP in young BMSM.

Topics: Adolescent; Adult; Anti-HIV Agents; Black or African American; Counseling; Culturally Competent Care; District of Columbia; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Behavior; HIV Infections; Homosexuality, Male; Humans; Male; Pilot Projects; Pre-Exposure Prophylaxis; Sexual and Gender Minorities; Sexual Behavior; United States; Young Adult

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.

Topics: Adenine; Adult; Aged; Alanine; Anti-HIV Agents; Cobicistat; Darunavir; Drug Combinations; Drug Substitution; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Protease Inhibitors; Sustained Virologic Response; Tablets; Tenofovir; Treatment Outcome; Viral Load

Studies have shown that women diagnosed with herpes simplex virus-2 (HSV-2) have a higher risk for bacterial vaginosis (BV) infection. We investigated the presence of HSV-2 infections as a risk factor for incident BV infections in high risk, Human immunodeficiency virus (HIV) uninfected women enrolled in a HIV prevention trial in Durban, South Africa. The Vaginal and Oral Interventions to Control the Epidemic trial was a multicentre, double blinded, randomized controlled trial which was designed to estimate the effectiveness of daily treatment with vaginal tenofovir gel, oral tenofovir disoproxil fumarate and oral Truvada in preventing HIV-1 infection in women. Women provided samples for the diagnosis of HSV-2 and BV. The presence of HSV-2 antibodies was detected using HerpeSelect™ ELISA IgG. Bacterial vaginosis was diagnosed using the Nugent scoring system. To assess the risk of BV incidence, modelled as a time-dependent variable, we used the Andersen-Gill model with robust variance estimation and Efron methods for ties. Overall, 2750 women were enrolled in the VOICE trial at our study sites. Women who had a HSV-2 infection at enrolment were shown to be at increased risk for incident BV infections (adjusted hazard ratio 1.17, 95% CI 1.08, 1.27, p ≤ 0.001). In addition, being of a young age, being unmarried and having a partner that has other partners were significantly associated with subsequent BV infection. Our findings therefore advocate the need for strengthening STI prevention efforts among women in high burden STI settings.

Topics: Administration, Intravaginal; Administration, Oral; Adult; Cross-Sectional Studies; Developing Countries; Double-Blind Method; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Gels; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV Seronegativity; Humans; Incidence; Risk Factors; South Africa; Tenofovir; Unsafe Sex; Vaginosis, Bacterial; Young Adult

The success of longitudinal trials depends greatly on using effective strategies to retain participants and ensure internal validity, maintain sufficient statistical power, and provide for the generalizability of study results.. This paper describes the challenges and specific strategies used to retain participants in a Phase 2B safety and effectiveness study of daily oral and vaginal tenofovir formulations for the prevention of HIV-1 infection in the MTN-003 (VOICE) trial in Kampala, Uganda.. Once enrolled, participants were seen every 28 days at the research site and their study product was re-filled. Challenges to retention included a mobile population, non-disclosure of study participation to spouse/family, and economic constraints. Strategies used to maintain high participation rates included the use of detailed locator information, a participant tracking database, regular HIV/STI testing, and the formation of close bonds between staff and subjects.. We enrolled 322 women out of the 637 screened. The overall retention rate was 95% over a 3 year follow up period. Only 179 (3%) out of the 6124 expected visits were missed throughout study implementation. Reasons for missed visits included: participants thinking that they did not need frequent visits due to their HIV negative status, time constraints due to commercial sex work, and migration for better employment.. With the implementation of multi-faceted comprehensive follow-up and retention strategies, we achieved very high retention rates in the MTN-003 study. This paper provides a blueprint for effective participant retention strategies for other longitudinal HIV prevention studies in resource-limited settings in Sub-Saharan Africa.

Topics: Administration, Intravaginal; Administration, Oral; Adult; Albuterol, Ipratropium Drug Combination; Anti-HIV Agents; Clinical Trials as Topic; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Gels; HIV Infections; Humans; Longitudinal Studies; Patient Participation; Tenofovir; Uganda

Post-exposure prophylaxis (PEP) for HIV is often poorly tolerated and not completed. Alternative PEP regimens may improve adherence and completion, aiding HIV prevention. We conducted a randomized controlled trial of a maraviroc-based PEP regimen compared with a standard-of-care regimen using ritonavir-boosted lopinavir.. Patients meeting criteria for PEP were randomized to tenofovir disoproxil/emtricitabine (200/245 mg) once daily plus ritonavir-boosted lopinavir (Kaletra ® 400/100 mg) or maraviroc 300 mg twice daily. The composite primary endpoint was completion of 28 days of the allocated PEP regimen without grade 3 or 4 clinical or laboratory adverse events (AEs) related to the PEP medication.. Two hundred and thirteen individuals were randomized (107 to maraviroc; 106 to Kaletra ® arm). Follow-up rates were high in both groups. There was no difference in the primary endpoint; 70 (71%) in the maraviroc and 64 (65%) in the Kaletra ® arm ( P  =   0.36) completed PEP without grade 3 or 4 AEs. Discontinuation of PEP was the same (18%) in both groups. There were no grade 3 or 4 clinical AEs in either arm, but more grade 1 or 2 clinical AEs in the Kaletra ® arm (91% versus 70%; P  < 0.001). Antidiarrhoeal medication use was higher in the Kaletra ® arm (67% versus 25%; P  < 0.001). There were no HIV seroconversions in the study period.. The completion rate in the absence of grade 3 or 4 AEs was similar with both regimens. Maraviroc-based PEP was better tolerated, supporting its use as an option for non-occupational PEP.

Topics: Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Cyclohexanes; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Male; Maraviroc; Medication Adherence; Post-Exposure Prophylaxis; Ritonavir; Triazoles; Young Adult

Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV-uninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection.

Topics: Anti-HIV Agents; Drug Resistance, Multiple, Viral; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Medication Adherence; Pre-Exposure Prophylaxis; Tenofovir

Adolescents represent a key population for implementing preexposure prophylaxis (PrEP) interventions worldwide, yet tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for PrEP is only licensed for adults.. To examine the safety of and adherence to PrEP along with changes in sexual risk behavior among adolescent men who have sex with men (MSM).. Adolescent Medicine Trials Network for HIV/AIDS Interventions 113 (Project PrEPare) was a PrEP demonstration project that evaluated the safety, tolerability, and acceptability of TDF/FTC and patterns of use, rates of adherence, and patterns of sexual risk behavior among healthy young MSM aged 15 to 17 years. Participants were recruited from adolescent medicine clinics and their community partners in 6 US cities, had negative test results for human immunodeficiency virus (HIV) but were at high risk for acquiring an infection, and were willing to participate in a behavioral intervention and accept TDF/FTC as PrEP.. All participants completed an individualized evidence-based behavioral intervention and were provided with daily TDF/FTC as PrEP for 48 weeks.. The main objectives were to: (1) provide additional safety data regarding TDF/FTC use among young MSM who had negative test results for HIV; (2) examine the acceptability, patterns of use, rates of adherence, and measured levels of tenofovir diphosphate in dried blood spots; and (3) examine patterns of risk behavior when young MSM were provided with a behavioral intervention in conjunction with open-label TDF/FTC.. Among 2864 individuals screened (from August 2013 to September 2014), 260 were eligible and 78 were enrolled (mean [SD] age, 16.5 [0.73] years), of whom 2 (3%) were Asian/Pacific Islander, 23 (29%) were black/African American, 11 (14%) were white, 16 (21%) were white Hispanic, and 26 (33%) were other/mixed race/ethnicity. Over 48 weeks of PrEP use, 23 sexually transmitted infections were diagnosed in 12 participants. The HIV seroconversion rate was 6.4 (95% CI: 1.3-18.7) per 100 person-years. Tenofovir diphosphate levels consistent with a high degree of anti-HIV protection (>700 fmol/punch) were found in 42 (54%), 37 (47%), 38 (49%), 22 (28%), 13 (17%), and 17 (22%) participants at weeks 4, 8, 12, 24, 36, and 48, respectively.. Adolescent Medicine Trials Network for HIV/AIDS Interventions 113 enrolled a diverse sample of adolescent MSM at risk for HIV who consented to study participation. Approximately half achieved protective drug levels during the monthly visits, but adherence decreased with quarterly visits. Youth may need additional contact with clinical staff members to maintain high adherence.. clinicaltrials.gov Identifier: NCT01769456.

Topics: Adolescent; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Feasibility Studies; Follow-Up Studies; HIV Infections; Homosexuality, Male; Humans; Male; Medication Adherence; Pre-Exposure Prophylaxis; Risk-Taking; Treatment Outcome; United States

Topics: Adult; CD4-Positive T-Lymphocytes; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV Reverse Transcriptase; Humans; Lymphocyte Activation; Male; Phosphorylation; Pre-Exposure Prophylaxis; Reverse Transcriptase Inhibitors; Substrate Specificity; Viral Load

Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect.. PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986).. We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients.. In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection.. MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.

Topics: Adult; Anti-HIV Agents; Bisexuality; Condoms; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; England; HIV Infections; HIV-1; Homosexuality, Male; Humans; Male; Pilot Projects; Pre-Exposure Prophylaxis; Treatment Outcome; Unsafe Sex

Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated.. The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection.. Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series.. PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.

Topics: Adult; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Hepatitis B, Chronic; HIV Infections; Homosexuality, Male; Humans; Liver Function Tests; Male; Middle Aged; Pre-Exposure Prophylaxis; Transgender Persons; Young Adult

FEM-PrEP-a clinical trial of daily, oral emtricitabine/tenofovir disoproxil fumarate for HIV prevention among women in sub-Saharan Africa-did not show a reduction in HIV acquisition because of low adherence to the study pill. We conducted a follow-up study to identify reasons for nonadherence.. Qualitative, semistructured interviews (n = 88) and quantitative, audio computer-assisted self-interviews (n = 224) were conducted with former FEM-PrEP participants in Bondo, Kenya, and Pretoria, South Africa. Thematic analysis was used to analyze the qualitative data, and descriptive statistics were used to describe audio computer-assisted self-interviews responses. Data are presented within the 5 categories of Ickovics' and Meisler's conceptual framework on adherence: (1) the individual, (2) trial characteristics and study pill regimen, (3) patient-provider relationship, (4) clinical setting, and (5) the disease.. Participants' explanations for nonadherence were primarily situated within 3 of the framework's 5 categories: (1) the individual, (2) trial characteristics and study pill regimen, and (3) the disease. Concerns about the investigational nature of the drug being tested and side effects were the prominent reasons reported for nonadherence. Participants also described being discouraged from taking the study pill by members of the community, their sexual partners, and other participants, primarily because of these same concerns. Limited acceptability of the pill's attributes influenced nonadherence for some participants as did concerns about HIV-related stigma. In addition, many participants reported that others continued in FEM-PrEP while not taking the study pill because of the trial's ancillary benefits and visit reimbursement-factors related to the clinical setting. Negative patient-provider relationships were infrequently reported as a factor that influenced nonadherence.. Despite substantial study staff engagement with participants and communities, concerns about the study pill and discouragement from others seemed to have influenced nonadherence considerably. Alternative study designs or procedures and enhanced community engagement paradigms may be needed in future studies.

Topics: Administration, Oral; Adult; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Kenya; Medication Adherence; Pre-Exposure Prophylaxis; Risk Factors; Social Support; South Africa; Tanzania

ENCORE1 demonstrated non-inferiority of daily efavirenz 400 mg (EFV400) versus 600 mg (EFV600) to 96 weeks in treatment-naïve, HIV-infected adults but concerns regarding lower EFV400 concentrations remained. Therefore, relationships between EFV pharmacokinetics (PK) and key genetic polymorphisms with 96-week efficacy and safety were investigated.. Relationships between EFV PK parameters and single nucleotide polymorphisms (SNP; CYP2B6, CYP2A6, CYP3A4, NR1I3, NR1I2, ABCB1) with plasma HIV-RNA (pVL) <200 copies/mL and EFV discontinuation and adverse events at 96 weeks were explored. Receiver operating characteristic curve analysis evaluated the predictability of mid-dose interval (C12) cutoffs and 96-week pVL.. A total of 606 patients (32 % female; 37 % African, 33 % Asian; n = 311 EFV400, n = 295 EFV600) were included. EFV PK parameters, including C12, were not associated with pVL <200 copies/mL at 96 weeks (odds ratio [OR] 5.25, 95 % confidence interval [CI] 0.41-67.90, p = 0.204). Lower risk of CNS-related adverse events was associated with CYP2B6 983TC/CC (OR 0.35, 95 % CI 0.15-0.81, p = 0.015) and higher risk was associated with CYP2B6 15582CT/TT and ABCB1 3435TT (OR 1.46, 95 % CI 1.02-2.09, p = 0.040; OR 2.31, 95 % CI 1.33-4.02, p = 0.003, respectively). Discontinuation due to adverse events (clinician decision) was independently associated with dose (OR 2.54, 95 % CI 1.19-5.43, p = 0.016). C12 between 0.47 and 0.76 mg/L provided sensitivity/specificity >90 % (100 %/92.3 to 98.9 %/92.3 %) for achieving pVL <200 copies/mL at 96 weeks.. A higher rate of EFV-related adverse events and discontinuations due to these events for EFV600 were not driven by polymorphisms assessed. Although a single threshold concentration associated with HIV suppression may be clinically useful, it was not viable for ENCORE1. Implementation of EFV400 would improve toxicity management whilst still maintaining good efficacy.

Topics: Adolescent; Adult; Alkynes; Anti-HIV Agents; Area Under Curve; Benzoxazines; Constitutive Androstane Receptor; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Genotype; HIV Infections; Humans; Male; Metabolic Clearance Rate; Middle Aged; Pharmacogenetics; Polymorphism, Single Nucleotide; RNA, Viral; Young Adult

Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease inflammatory markers and impact on HIV persistence by cell-dependent mechanisms, and show unique effects of MVC in duodenal immunity driven by higher drug tissue penetration and possibly by class-dependent effects.

Topics: Adult; Alkynes; Anti-HIV Agents; Benzoxazines; CCR5 Receptor Antagonists; Chromatography, High Pressure Liquid; Cyclohexanes; Cyclopropanes; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; HIV Infections; HIV Integrase Inhibitors; Humans; Immunity, Mucosal; Lymphocyte Activation; Male; Maraviroc; Pilot Projects; Raltegravir Potassium; T-Lymphocyte Subsets; Triazoles

VOICE-a phase 2B, placebo-controlled, randomized trial testing daily use of an antiretroviral tablet (tenofovir or Truvada) or daily use of tenofovir gel in 5029 women from South Africa, Uganda, and Zimbabwe-found none of the drug regimens effective in reducing HIV-1 acquisition in the intent-to-treat analysis. More than half of women assigned to active products in a case cohort sample had no drug detected in any plasma specimens tested during the trial. Yet, in response to questions asked of participants during the trial, ≥90 % of doses were reportedly taken. To explore factors associated with low adherence, a behavioral termination visit questionnaire was developed after early closure of the oral tenofovir and vaginal gel arms. We hypothesized that participants would be more forthcoming about nonuse after they exited the trial than during monthly/quarterly follow-up visits. Comparison of adherence reporting at routine follow-up visits with reporting at trial termination, however, indicates that disclosure of product nonadherence did not increase at the termination visit as anticipated. In resource-limited settings where women value the ancillary benefits provided by trial participation and are concerned that disclosure of nonuse may jeopardize trial participation, objective measures of adherence may yield more meaningful data regarding the inability or reluctance to use than measures of product use derived from self-report.

Topics: Administration, Oral; Adult; Anti-HIV Agents; Deception; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Gels; HIV Infections; Humans; Medication Adherence; Middle Aged; Pre-Exposure Prophylaxis; Self Disclosure; South Africa; Tenofovir; Uganda; Young Adult; Zimbabwe

Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis (PrEP) use is associated with a small but statistically significant decline in estimated glomerular filtration rate (eGFR). We investigated the reversibility of eGFR decline among HIV-uninfected adults discontinuing PrEP.. Data were from the Partners PrEP Study, a randomized trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among African HIV-uninfected men and women with baseline creatinine clearance ≥60 mL/min. Serum creatinine was measured quarterly while on-study medication and at month 1 and 2 after discontinuation. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration Equation.. A total of 3924 individuals had a poststudy drug serum creatinine measurement after the scheduled drug discontinuation (1271 for TDF, 1308 for FTC-TDF, and 1345 for placebo); 65% were men, median age was 35 (range 18-64) years. Median time on study drug was 33 (interquartile range 25-36) months overall, and 36 months (interquartile range 30-36) for TDF and FTC-TDF. Mean eGFR at the last on-treatment visit was 129 mL·min·1.73 m for TDF and 128 mL·min·1.73 m for FTC-TDF versus 131 mL·min·1.73 m for placebo (2-3 mL·min·1.73 m mean decline for PrEP versus placebo, P ≤ 0.01), and this difference reversed by 4 weeks after drug discontinuation (mean eGFR at the first postdrug visit: 130 mL·min 1.73 m in all groups). More than 96% of participants had a confirmed >75% eGFR rebound to baseline level by 8 weeks after drug discontinuation, with similar proportions across treatment groups.. In this large, placebo-controlled study of TDF-based PrEP, the small reduction in mean eGFR associated with PrEP reversed within weeks after discontinuation.

Topics: Adolescent; Adult; Anti-HIV Agents; Creatinine; Drug Administration Schedule; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Glomerular Filtration Rate; HIV; HIV Infections; Humans; Kidney Diseases; Male; Middle Aged; Pre-Exposure Prophylaxis; Young Adult

Pre-exposure prophylaxis (PrEP) has proven biological efficacy to reduce the sexual acquisition of the human immunodeficiency virus (HIV). The PROUD study found that PrEP conferred higher protection than in placebo-controlled trials, reducing HIV incidence by 86 % in a population with seven-fold higher HIV incidence than expected. We present the baseline characteristics of the PROUD study population and place the findings in the context of national sexual health clinic data.. The PROUD study was designed to explore the real-world effectiveness of PrEP (tenofovir-emtricitabine) by randomising HIV-negative gay and other men who have sex with men (GMSM) to receive open-label PrEP immediately or after a deferral period of 12 months. At enrolment, participants self-completed two baseline questionnaires collecting information on demographics, sexual behaviour and lifestyle in the last 30 and 90 days. These data were compared to data from HIV-negative GMSM attending sexual health clinics in 2013, collated by Public Health England using the genitourinary medicine clinic activity database (GUMCAD).. The median age of participants was 35 (IQR: 29-43). Typically participants were white (81 %), educated at a university level (61 %) and in full-time employment (72 %). Of all participants, 217 (40 %) were born outside the UK. A sexually transmitted infection (STI) was reported to have been diagnosed in the previous 12 months in 330/515 (64 %) and 473/544 (87 %) participants reported ever having being diagnosed with an STI. At enrolment, 47/280 (17 %) participants were diagnosed with an STI. Participants reported a median (IQR) of 10 (5-20) partners in the last 90 days, a median (IQR) of 2 (1-5) were condomless sex acts where the participant was receptive and 2 (1-6) were condomless where the participant was insertive. Post-exposure prophylaxis had been prescribed to 184 (34 %) participants in the past 12 months. The number of STI diagnoses was high compared to those reported in GUMCAD attendees.. The PROUD study population are at substantially higher risk of acquiring HIV infection sexually than the overall population of GMSM attending sexual health clinics in England. These findings contribute to explaining the extraordinary HIV incidence rate during follow-up and demonstrate that, despite broad eligibility criteria, the population interested in PrEP was highly selective.. Current Controlled Trials ISRCTN94465371 . Date of registration: 28 February 2013.

Topics: Adolescent; Adult; Anti-HIV Agents; Drug Administration Schedule; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; England; HIV Infections; Homosexuality, Male; Humans; Incidence; Male; Middle Aged; Pilot Projects; Primary Prevention; Reverse Transcriptase Inhibitors; Risk Assessment; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires; Time Factors; Treatment Outcome; Unsafe Sex; Young Adult

Cognitive function is reported to improve after the initiation of combination antiretroviral therapy (cART). Data on the evolution of such changes are limited. We assessed the dynamics of changes in cognitive parameters, in HIV-positive subjects initiating cART.. Cognitive function in seven domains was evaluated for HIV-infected patients without clinically significant cognitive impairment prior to the initiation of cART, and 24 and 48 weeks after. Cognitive scores were transformed using standardised z-scores according to the pooled baseline standard deviation. Global, speed, and accuracy composite z-scores were calculated with changes calculated using a paired t test.. In 14 subjects, change in global cognitive z-scores from baseline was by 0.08 at week 24 (p = 0.59) and 0.15 at week 48 (p = 0.43). Change in composite speed and accuracy z-scores from baseline at weeks 24/48 were 0.07/0.05 (p = 0.45/0.82) and 0.13/0.23 (p = 0.47/0.45), respectively. In two of the cognitive domains assessing speed (learning and monitoring time), a continued improvement from baseline to weeks 24 and 48 was observed (changes of 0.06-0.08 and 0.10-0.19, respectively), whereas in two domains (detection and identification) an initial improvement at week 24 (changes of -0.10 and 0.04 from baseline, respectively) was followed by a deterioration in score at week 48 (changes of -0.12 and -0.08 from baseline, respectively). None of these changes were statistically significant.. A trend for improvement in cognitive function was observed in naïve HIV-positive patients starting cART. The dynamics of this improvement differed both between cognitive domains and the time-points assessed.

Topics: Adult; Anti-HIV Agents; Atazanavir Sulfate; Cognition; Cognition Disorders; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Middle Aged; Neuropsychological Tests; Nevirapine; Ritonavir; Young Adult

Product sharing among participants can impact on adherence and compromise the outcome in clinical trials. We describe incidents of product sharing at the Durban clinical research sites conducting the VOICE trial. The Durban sites enrolled 2750 women with 1103 and 1647 participants randomized to the vaginal gel and oral tablet arms respectively. Monthly pill and applicator counts including product assessments were conducted by pharmacists. Discrepancies with product counts prompted discussions with participants. Thirty-two cases of product sharing were identified. Vaginal gels were more commonly shared than oral tablets. Product sharing between study participants and their female friends or relatives living in the same household was identified as the most common source of product sharing in this analysis. Study product counts and pharmacist-driven discussions with participants may help to identify reasons for product sharing and inform the development of strategies for PrEP implementation outside of the research setting. ClinicalTrials.gov number: NCT00705679.

Topics: Administration, Oral; Adult; Anti-HIV Agents; Double-Blind Method; Drugs, Investigational; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Medication Adherence; Pre-Exposure Prophylaxis; South Africa; Substance-Related Disorders; Tenofovir; Vaginal Creams, Foams, and Jellies; Young Adult

The initiation of antiretroviral therapy (ART) during primary infection may offer clinical benefits for HIV-infected individuals by reducing HIV DNA reservoir size and chronic T-cell activation. Current evidence for the advantages of early ART, however, are mostly derived from cross-sectional studies, with the long-term benefits yet to be ascertained.. We conducted an open-label, nonrandomized study, monitoring for 3 years: plasma viral load (pVL), T-cell phenotypes, and peripheral CD4(+) T-cell associated total, integrated and 2-long terminal repeat HIV DNA species. The study included 16 treatment-naive individuals initiating ART with raltegravir and Truvada during either primary (PHI, n = 8) or chronic (CHI, n = 8) HIV infection.. ART initiated during PHI compared with CHI generated significant reductions of peripheral CD4(+) T-cell HIV DNA reservoirs that were sustained for 3 years of therapy. Median log10 HIV DNA copies/10(6) CD4(+) T cells at the final visit: total; CHI = 3.23 > PHI = 2.72, P < 0.01; integrated; CHI = 2.64 > PHI = 1.77, P < 0.01. Similar trends were observed for pVL, however, did not reach significance: log10 HIV RNA copies/ml plasma at the final visit: CHI = 1.3 ≥ PHI = 0.39, P = 0.08. Both cohorts displayed similar and elevated levels of CD38/HLA-DR coexpression on CD4(+) and CD8(+) T cells relative to uninfected healthy controls.. The reduction in HIV DNA reservoirs generated by the early initiation of ART was sustained for 3 years of therapy. Although the PHI cohort trended to lower levels of pVL, and pVL was associated with CD8(+) T-cell activation, no differences in T-cell activation were observed between the PHI and CHI groups.

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cohort Studies; Cross-Sectional Studies; DNA, Viral; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Immunophenotyping; Lymphocyte Activation; Raltegravir Potassium; RNA, Viral; Viral Load

Antiretroviral preexposure prophylaxis (PrEP) for persons at high risk of human immunodeficiency virus infection is a promising new prevention strategy. Six randomized trials of oral PrEP were recently conducted and demonstrated efficacy estimates ranging from 75% to no effect, with nonadherence likely resulting in attenuated estimates of the protective effect of PrEP. In 1 of these trials, the Partners PrEP Study (Kenya and Uganda, 2008-2011), participants (4,747 serodiscordant heterosexual couples) were randomized to receipt of tenofovir (TDF), coformulated TDF/emtricitabine (FTC), or placebo. Intention-to-treat analyses found efficacy estimates of 67% for TDF and 75% for TDF/FTC. We applied multiple methods to data from that trial to estimate the efficacy of PrEP with high adherence, including principal stratification and inverse-probability-of-censoring (IPC) weights. Results were further from the null when correcting for nonadherence: 1) among the strata with an estimated 100% probability of high adherence (TDF hazard ratio (HR) = 0.19, 95% confidence interval (CI): 0.07, 0.56; TDF/FTC HR = 0.12, 95% CI: 0.03, 0.52); 2) with IPC weights used to approximate a continuously adherent population (TDF HR = 0.18, 95% CI: 0.06, 0.53; TDF/FTC HR = 0.15, 95% CI: 0.04, 0.52); and 3) in per-protocol analysis (TDF HR = 0.18, 95% CI: 0.06, 0.53; TDF/FTC HR = 0.16, 95% CI: 0.05, 0.53). Our results suggest that the efficacy of PrEP with high adherence is over 80%.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Factors; Anti-HIV Agents; Double-Blind Method; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Heterosexuality; HIV Infections; Humans; Incidence; Kenya; Male; Medication Adherence; Models, Statistical; Patient Satisfaction; Pre-Exposure Prophylaxis; Research Design; Sex Factors; Socioeconomic Factors

This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.

Topics: Adolescent; Adult; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Homosexuality, Male; Humans; Kenya; Male; Medication Adherence; Middle Aged; Organophosphorus Compounds; Sex Workers; Stereotyping; Young Adult

The aim of this study was to investigate the effect on fasting lipid parameters of switching to tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) from abacavir (ABC) plus lamivudine (3TC; both fixed-dose combinations), while maintaining ritonavir-boosted lopinavir (LPV/r).. This was an open-label randomized two-arm 12-week controlled study in virologically suppressed HIV-infected patients with elevated cholesterol (≥5.2 mmol/l). Patients stable on ABC/3TC plus LPV/r either continued treatment or switched to TDF/FTC plus LPV/r for 12 weeks. Standard efficacy and safety end points (including fasting lipids) were assessed.. In total, 85 subjects were treated (n=42 ABC/FTC and n=43 TDF/3TC). A statistically significant decrease in total cholesterol was observed in the TDF/FTC group: from median (IQR) 6.22 mmol/l (5.91-6.77) at baseline to 5.75 mmol/l (5.04-6.18) at week 12 (median [IQR] change from baseline -0.73 mmol/l [-1.20- -0.18]; P<0.001). No notable change was observed for the ABC/3TC group. The difference between groups at week 12 was -0.82 mmol/l (P<0.001). For TDF/FTC (but not for ABC/3TC), statistically significant reductions (P<0.05) from baseline were observed in total, low-density lipoprotein, high-density lipoprotein (HDL)- and non-HDL cholesterol (at weeks 4 and 12). Statistically significant decreases were observed in median estimated creatinine clearance (Cockcroft-Gault) from baseline to week 12 for patients who switched to TDF/FTC (-5.47 ml/min) versus the ABC/3TC group (-2.15 ml/min; P=0.016 between groups). Virological suppression was maintained in both groups. No new safety issues were identified.. Switching to TDF/FTC from ABC/3TC was associated with rapid improvements in fasting lipid parameters and continued virological control in patients receiving LPV/r as the third component of antiretroviral therapy. The effect of these changes on clinical end points remains unclear and would need to be evaluated in a longer-term study.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cholesterol; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Drug Substitution; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV; HIV Infections; Humans; Lamivudine; Lipids; Lopinavir; Male; Medication Adherence; Middle Aged; Organophosphorus Compounds; Ritonavir; Treatment Outcome

We report data from NEWART, a randomised phase 4 clinical trial comparing virologic efficacy and safety of nevirapine (NVP) vs. ritonavir-boosted atazanavir (ATV/r) on a background of tenofovir/emtricitabine (TDF/FTC) in HIV-1-infected treatment-naïve patients. This study enrolled patients according to CD4-based initiation criteria for NVP (<250 cells/mm(3) for women and <400 cells/mm(3) for men), to reduce the likelihood of symptomatic hepatic events. NEWART was designed to support and confirm results from ARTEN, an international trial with similar design and study endpoints.. A total of 152 patients were randomised 1 : 1 to open-label NVP 200 mg twice daily or ATV/r (300/100 mg) once daily, plus once daily TDF/FTC (300/200 mg). All participants met CD4(+) guidelines at entry. The primary endpoint for non-inferiority was virologic response prior to and at week 48 (confirmed HIV plasma viral load <50 copies/ml, without rebound or change in ARVs). Safety data, including plasma lipids, were recorded throughout the study.. The primary endpoint was achieved in 46/75 (61.3%) and 50/77 (64.9%) of patients taking NVP and ATV/r, respectively. Frequency of adverse events (AEs) was similar between arms, with 88.0% of NVP-treated patients and 94.8% of ATV/r-treated patients experiencing at least one AE. Nine patients (12%) in each arm experienced an AE that led to discontinuation. At week 48, a significantly greater increase was seen in mean plasma HDL cholesterol (HDL-C) in the NVP arm (9.6 mg/dl) vs. the ATV/r arm (3.5 mg/dl); p = 0.016. Also, total cholesterol (TC):HDL-C ratio on-treatment was -0.38 and -0.02 for the NVP and ATV/r arms, respectively (p = 0.038).. Efficacy results were consistent with the ARTEN study demonstrating that NVP was non-inferior to ATV/r when taken in combination with TDF/FTC. Rates of AEs were similar between the two arms, whereas HDL-C increased and TC:HDL-C decreased significantly more in patients taking NVP than ATV/r.

Topics: Adult; Anti-HIV Agents; Atazanavir Sulfate; Deoxycytidine; Drug Combinations; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lipid Metabolism; Male; Middle Aged; Nevirapine; Oligopeptides; Organophosphorus Compounds; Pyridines; Ritonavir; Treatment Outcome; Viral Load; Young Adult

Topics: Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Deoxycytidine; Drug Combinations; Drug Resistance, Viral; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Lamivudine; Organophosphorus Compounds; Reverse Transcriptase Inhibitors; Time Factors; Viral Load; Zidovudine

Black and Latinx MSM and transgender POC disproportionately experience new HIV diagnoses. Determining effective HIV prevention methods requires the inclusion of these communities in research and thorough post-trial experience evaluations. This study sought to evaluate the experiences of Black and Latinx MSM and transgender POC in HIV prevention research and identify facilitators and barriers to continued trials participation.. A survey was developed in partnership with the community engagement team based on emerging themes during research participant check-ins with the team. The survey was built in REDCap and distributed to participants via text message. The survey assessed experiences with the research process time commitments, study responsibilities, compensation, experiences with Truvada®, characteristics of the research study team and site, barriers to continued study participation, willingness to participate in future studies, and overall satisfaction. All statistical analysis was completed in Stata.. Forty-four participants were enrolled in the study. Most participants (98%) were satisfied with their experiences in HIV prevention research. Job or school schedules were the most frequently cited barrier to study participation while Truvada® provision and adequate study visit compensation, length, number, and frequency were facilitators. Participants reported that research staff made them feel comfortable when talking about sexual behaviors, alcohol use, mental health, drug use, housing problems, violence in relationships, and legal problems.. Evaluating the experiences of key communities in HIV prevention research can help identify barriers and facilitators to clinical trials engagement and improve the design of future trials.

Topics: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Sexual and Gender Minorities; Transgender Persons

Timely, accurate adherence data may support oral pre-exposure prophylaxis (PrEP) success and inform prophylaxis choice. We evaluated a Food and Drug Administration (FDA)-approved digital health feedback system (DHFS) with ingestible-sensor-enabled (IS) tenofovir-disoproxil-fumarate plus emtricitabine (Truvada®) in persons starting oral PrEP.. Human immunodeficiency virus (HIV)-negative adults were prescribed IS-Truvada® with DHFS for 12 weeks to observe medication taking behavior. Baseline demographics, urine toxicology, and self-report questionnaires were obtained. Positive detection accuracy and adverse events were computed as percentages, with Kaplan Meier Estimate for persistence-of-use. In participants persisting ≥28 days, adherence patterns (taking and timing) were analyzed, and mixed-effects logistic regression modeled characteristics associated with treatment adherence.. Seventy-one participants were enrolled, mean age 37.6 years (range 18-69), 90.1% male, 77.5% White, 33.8% Hispanic, 95.8% housed, and 74.6% employed. Sixty-three participants (88.7%) persisted ≥28 days, generating 4987 observation days, average 79.2 (29-105). Total confirmed doses were 86.2% (95% confidence interval [CI] 82.5, 89.4), decreasing over time, odds ratio (OR) 0.899 (95% CI .876, .923) per week, P < .001; 79.4% (95% CI 66.7%, 87.3%) of participants had ≥80% adherence. Pattern analysis showed days without confirmed doses clustered (P = .003); regular dose timing was higher among participants with ≥80% confirmed doses (0.828, 95% CI .796 to .859) than among those with <80% (0.542, 95% CI95 .405 to .679) P < .001. In multi-predictor models, better adherence was associated with older age, OR 1.060 (95% CI 1.033, 1.091) per year, P < .001; negative vs positive methamphetamine screen, OR 5.051 (95% CI 2.252, 11.494), P < .001.. DHFS with IS-Truvada® distinguished adherent persons from those potentially at risk of prophylactic failure. Ongoing methamphetamine substance use may impact oral PrEP success.

Topics: Adolescent; Adult; Aged; Anti-HIV Agents; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Homosexuality, Male; Humans; Male; Medication Adherence; Methamphetamine; Middle Aged; Pre-Exposure Prophylaxis; Young Adult

In July 2012, tenofovir disoproxil fumarate-emtricitabine (TDF-FTC, brand name Truvada) was approved by the Food and Drug Administration (FDA) to prevent HIV infection. To estimate the extent of the US government's direct financial contribution to the discovery and development of Truvada, we identified National Institutes of Health awards using FDA documents, peer-reviewed literature, patent records, court filings, and other publicly available materials. We classified seventy-three federal government awards to eleven researchers as being directly linked to the development and clinical testing of Truvada for prevention therapy, through which the US government spent an estimated $143 million. The substantial public funding raises questions about the high price charged by the drug's manufacturer, which reduced its affordability and limited its accessibility as HIV preventive therapy.

Topics: Anti-HIV Agents; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Pharmaceutical Preparations; Tenofovir

In 2019, the U.S. Food and Drug Administration (FDA) approved emtricitabine and tenofovir alafenamide (Descovy) as another option for HIV pre-exposure prophylaxis (PrEP) prevention for high-risk adults and adolescents. With the introduction of this new PrEP, millions of current users on emtricitabine and tenofovir disoproxil fumarate (Truvada), another PrEP medication currently used to prevent HIV transmission, have options of whether to continue their current treatment regime or transition to new treatment options. The objective of this study was to conduct a descriptive analysis to characterize user-generated social media conversations on Reddit associated with FDA-approved PrEP prevention treatment options. Key themes identified were associated with perceptions, knowledge, and attitudes associated with the transition of use of different PrEP medications. Data were collected retrospectively and prospectively from the Reddit platform for posts with keywords filtered for HIV, PrEP, and FDA-approved PrEP prevention treatment from October 2020 to December 2020. We chose the Reddit platform based on prior studies that have identified PrEP user conversations and insights on access challenges for specific AIDS communities, such as gays and men who have sex with men (MSM). Reddit posts were then manually annotated using an inductive content coding approach for key themes regarding the transition of use and other emergent themes from user-generated content. Formal coding of text data was conducted with refined codes, and sub-codes created. A total of 3,120 posts were analyzed from Reddit resulting in 315 posts that were coded for PrEP and 105 posts (33.33%) specific to user discussions regarding the transition of PrEP prevention. Overall, users expressed interest in drug switching to Descovy, particularly in the context of poorer adherence or concerns about existing side effects associated with Truvada. Other major themes included discussions about the cost of Descovy, apprehension about side effects in comparison to Truvada, insurance coverage changes, and discussions about the donation of Truvada to other users after transitioning. Among these discussions, topics related to sexual minorities, including MSM, reported concerns when considering a switch in their HIV prevention regime. Understanding the changing public perception associated with the introduction of new HIV prevention is important in the context of market access, patient safety, pharmacovigilance,

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Anti-HIV Agents; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Retrospective Studies; Sexual and Gender Minorities

This study evaluated the efficacy, safety and durability of a switch to co-formulated RPV/TDF-TAF/FTC (RPV-STR) or DTG/ABC/3TC (DTG-STR) in virologically-suppressed HIV-positive patients in a single Italian centre. All HIV-infected ART-experienced patients switching to RPV-STR or DTG-STR with HIV-RNA <50 copies/mL were included. Outcomes were incidence rate and rate ratios for discontinuation due to all causes (DAC), to adverse events (DAE) and to virological failure (VF) after 4 years of follow-up. We included 402 patients (244 on RPV-STR, 158 on DTG-STR). At Year 4 of follow-up, 124 patients (30.8%) discontinued for any cause (71 on RPV-STR, 53 on DTG-STR). Fifteen patients experienced VF [13 (5.3%) on RPV-STR and 2 (1.3%) on DTG-STR; log-rank, P = 0.4413]. Overall, 46 patients (11.4%) had AEs (23 on RPV-STR, 23 on DTG-STR). Nausea/diarrhoea was more frequent with DTG-STR (4.4% vs. 0%) and neurological toxicity with RPV-STR (4.5% vs. 2.5%). The rate of DAC within the first 3 months was significantly higher with DTG-STR (aRR = 5.88, 95% CI 3.20-10.81; P < 0.001); similarly, the discontinuation rate due to AEs was significantly higher with DTG-STR compared with RPV-STR (aRR = 12.89, 95% CI 5.48-30.32; P < 0.001). No difference in VF was observed between the two groups (RR = 0.47, 95% CI 0.10-2.14; P = 0.335). Patients with undetectable viral load who switched to DTG-STR or RPV-STR maintained virological suppression with a low risk of VF. A higher discontinuation rate was observed with DTG-STR compared with RPV-STR, particularly within 3 months from switch.

Topics: Adult; Anti-HIV Agents; Cohort Studies; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV-1; Humans; Immunocompromised Host; Italy; Lamivudine; Male; Middle Aged; Rilpivirine; Treatment Outcome

Topics: Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Esophagitis; Fumarates; HIV Infections; Humans; Pre-Exposure Prophylaxis; Tenofovir

My collaboration with Prof. Antonín Holý, that spans a period of 3-4 decades (1976-2012), led to the discovery of several acyclic nucleoside phosphonates (ANPs) which were clinically developed by Gilead Sciences: cidofovir, adefovir, and tenofovir. The latter was further converted to two orally bioavailable prodrug forms, TDF and TAF, and both TDF and TAF were further combined with other antiviral drugs, thus giving rise to a broad array of antiviral drug combinations for the treatment of HIV infections. TDF and TAF are both available for the treatment of hepatitis B virus (HBV) infections, and, in combination with emtricitabine, also applicable as Truvada

Topics: Anniversaries and Special Events; Anti-HIV Agents; Antiviral Agents; Cidofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Hepatitis B; Hepatitis B virus; HIV Infections; Humans; Nucleosides; Organophosphonates; Prodrugs; Tenofovir

We estimated list and net prices for tenofovir disoproxil fumarate (TDF) products Truvada, Complera, and Stribild, and their tenofovir alafenamide (TAF) versions Descovy, Odefsey, and Genvoya. Gilead offered discounts for Descovy that resulted into lower net prices compared to Truvada. This strategy encouraged patients switching from Truvada to Descovy before the availability of generic Truvada. Conversely, Gilead offered lower discounts for Odefsey and Genvoya, which resulted into higher net prices compared to Complera and Stribild.

Topics: Anti-HIV Agents; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Rilpivirine, Tenofovir Drug Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Tenofovir

In 2019, US advocates reported misleading language regarding the safety of TDF/FTC (Truvada) used by lawsuit advertisements against Gilead Sciences. We sought to ascertain the reach and effects of the advertisements on preexposure prophylaxis (PrEP) opinions and decisions in a cohort of youth and young adults at-risk for HIV.. An online survey was administered to participants enrolled in Keeping it LITE, a prospective US cohort study of ethnically diverse, sexually active, cisgender and transgender persons ages 13-37.. Quantitative data were analyzed using descriptive and inferential analysis in SAS, and qualitative data via thematic analysis.. Survey response rate was 51.3% (n = 1485). Mean age at baseline was 24. Previous PrEP use was reported by 43% of respondents and 32.7% reported PrEP use in the past 6 months. Almost half (48.7%) were aware of the lawsuit. Most of these participants (81.3%) reported the advertisements did not impact their PrEP use, but 13.2% decided to not to begin a Truvada-based PrEP regimen and 5.5% decided to stop taking Truvada due to the advertisements claims. Predictors of changing PrEP behavior were lower education and no previous PrEP use. The qualitative analysis revealed the advertisements increased skepticism about safety and benefit of Truvada PrEP and led to greater distrust of the pharmaceutical industry.. The advertisements reached a large, diverse US audience. Disturbingly, 18.7% of PrEP candidates who were aware of the lawsuit attributed not initiating or cessation of a Truvada-based PrEP regimen to exposure to the Truvada lawsuit advertisements.

Topics: Adolescent; Adult; Advertising; Anti-HIV Agents; Attitude; Cohort Studies; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Gender Identity; HIV Infections; Homosexuality, Male; Humans; Male; Pre-Exposure Prophylaxis; Prospective Studies; Sexual Behavior; Young Adult

Topics: Drug Resistance, Viral; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV; HIV Infections; Humans; Injections; Male; Pyridones

Tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) is the backbone for both human immunodeficiency virus (HIV) treatment and pre-exposure prophylaxis (PrEP) worldwide. Tenofovir alafenamide (TAF) with FTC is increasingly used in HIV treatment and was recently approved for PrEP among men-who-have-sex-with-men. TDF and TAF are both metabolized into tenofovir (TFV). Antiretrovirals in plasma are taken up into hair over time, with hair levels providing a long-term measure of adherence. Here, we report a simple, robust, highly sensitive, and validated high-performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS)-based analytical method for analyzing TFV and FTC from individuals on either TDF/FTC or TAF/FTC in small hair samples. TFV/FTC are extracted from ~5 mg hair and separated on a column using a gradient elution. The lower quantification limits are 0.00200 (TFV) and 0.0200 (FTC) ng/mg hair; the assay is linear up to 0.400 (TFV) and 4.00 (FTC) ng/mg hair. The intra-day and inter-day coefficients of variance (CVs) are 5.39-12.6% and 6.40-13.5% for TFV and 0.571-2.45% and 2.45-5.16% for FTC. TFV concentrations from participants on TDF/FTC-based regimens with undetectable plasma HIV RNA were 0.0525 ± 0.0295 ng/mg, whereas those from individuals on TAF/FTC-based regimens were 0.0426 ± 0.0246 ng/mg. Despite the dose of TFV in TDF being 10 times that of TAF, hair concentrations of TFV were not significantly different for those on TDF versus TAF regimens. Pharmacological enhancers (ritonavir and cobicistat) did not boost TFV concentrations in hair. In summary, we developed and validated a sensitive analytical method to analyze TFV and FTC in hair and found that hair concentrations of TFV were essentially equivalent among those on TDF and TAF.

Topics: Adenine; Anti-HIV Agents; Chromatography, High Pressure Liquid; Cobicistat; Dose-Response Relationship, Drug; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Hair; Hair Analysis; HIV Infections; Humans; Ritonavir; Tandem Mass Spectrometry; Tenofovir; Tissue Distribution

Topics: Adenine; Alanine; Anti-HIV Agents; Cohort Studies; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Tenofovir

Multiple doses of tenofovir disoproxil fumarate (TDF) together with emtricitabine is effective for HIV preexposure prophylaxis (PrEP). TDF is converted to tenofovir (TFV) in circulation, which is subsequently cleared via tubular secretion by organic ion transporters (OATs; OAT1 and OAT3). Using in vitro kinetic parameters for TFV and the OAT1 and OAT3 inhibitor probenecid, a bottom-up physiologically-based pharmacokinetic model was successfully developed for the first time that accurately describes the probenecid-TFV interaction. This model predicted an increase in TFV plasma exposure by 60%, which was within 15% of the observed clinical pharmacokinetic data, and a threefold decrease in renal cells exposure following coadministration of a 600 mg TDF dose with 2 g probenecid. When compared with multiple-dose regimens, a single-dose probenecid-boosted TDF regimen may be effective for HIV PrEP and improve adherence and safety by minimizing TFV-induced nephrotoxicity by reducing TFV accumulation in renal cells.

Topics: Anti-HIV Agents; Drug Interactions; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Models, Biological; Organic Anion Transport Protein 1; Organic Anion Transporters, Sodium-Independent; Pre-Exposure Prophylaxis; Probenecid; Tenofovir

Clinics providing sexual health care pose unique opportunities to implement HIV pre-exposure prophylaxis (PrEP) programs. The PrEP program at New York City's Sexual Health Clinics provides intensive on-site navigation for linkage to PrEP care. We assessed uptake of this intervention.. We categorized men who have sex with men (MSM) without HIV hierarchically as having had (1) HIV post-exposure prophylaxis (PEP) use (past year); or (2) selected sexually transmitted infections (STI) (past year); or (3) HIV-diagnosed sex/needle-sharing partners (past 6 months); or (4) expressed interest in PrEP (day of clinic visit). We constructed PrEP cascades and used multivariable regression to examine acceptance of PrEP navigation, referral to a PrEP provider, linkage (<60 days), and PrEP prescription.. One thousand three hundred one of 2106 PrEP (62%) patients accepted navigation. Of those, 55% (718/1301) were black or Hispanic MSM. STI and PEP patients had lowest navigation acceptance levels (35%-46%). Of navigated patients, 56% (628/1114) accepted referrals, 46% (288/628) linked to PrEP providers, and 82% (235/288) were prescribed PrEP; overall, 11% of those offered navigation (235/2106) received prescriptions. Navigated MSM with PEP history [adjusted prevalence ratio (aPR) 1.34, 95% confidence interval (CI): 1.16 to 1.56)], previous STI (aPR 1.28, 95% CI: 1.12 to 1.45), or HIV-diagnosed partners (aPR 1.18, 95% CI: 1.01 to 1.37) were more likely than those with PrEP interest to accept referrals. Probability of linkage varied by insurance status; prescription did not vary by patient factors.. Although MSM in key priority groups (eg, previous STI) showed low navigation uptake, those who accepted navigation were likely to be referred for PrEP, suggesting a need for expanded up-front engagement.

Topics: Adult; Ambulatory Care Facilities; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; New York City; Pre-Exposure Prophylaxis; Sexual Health; Young Adult

Topics: Adenine; Alanine; Anti-HIV Agents; Cost-Benefit Analysis; Decision Making, Shared; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Services Accessibility; HIV Infections; Humans; Pre-Exposure Prophylaxis; Tenofovir; United States

When considering PreExposure Prophylaxis (PrEP) as a HIV prevention method, many rely on information available online. Limited research has examined the quality, including readability, of PrEP information on the Internet. The current study evaluates the readability of PrEP information online employing six commonly used readability tests.. This is a cross-sectional study.. Using the Google Chrome browser, a search for articles was conducted using two terms: "pre-exposure prophylaxis" and "Truvada." The URLs of the first 50 English language websites for each term were recorded to create the overall study sample of 100 unique websites. Using six established readability scales, we determined the readability scores for each examined website. Websites were stratified by .com, .org, and .gov URL extensions to compare readability metrics.. Mean Flesch-Kincaid Grade Level (FKGL) was 9.5 (SD = 2.2), mean Gunning Fog Index (GFI) was 11.1 (SD = 2.7), mean Coleman-Liau Index (CLI) was 11.3 (SD = 2.0), while mean Simple Measure of Gobbledygook (SMOG) Grade Level was 12.1 (SD = 1.8). Using Flesch-Kincaid Reading Ease (FRE), one article was found easy to read, while 23 were found of average difficulty to read. Mean New Dale-Chall (NDS) score was 7.3 (SD = 1.3), or grade 9-10. Mean reading levels were significantly different among the commercial, organization, and government sites, however, no category was at the recommended sixth-grade level.. PrEP information online surpasses the reading ability of most U.S. adults. Improving the readability of PrEP information online may help to increase uptake of PrEP among populations at risk for HIV.

Topics: Adult; Comprehension; Consumer Health Information; Cross-Sectional Studies; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Literacy; HIV; HIV Infections; Humans; Internet; Pre-Exposure Prophylaxis; Reading

The use of tenofovir disoproxil fumarate (TDF) in combination with emtricitabine, prescribed for pre-exposure prophylaxis (PrEP), is highly effective at reducing incident sexually transmissible HIV infection among those at risk. TDF is associated with proteinuria, Fanconi syndrome and chronic kidney disease, and is not recommended for use in patients with an estimated creatinine clearance <60 mL min-1. There are currently no Pharmaceutical Benefits Scheme (PBS)-funded PrEP options for patients at risk of HIV infection with moderate renal impairment in Australia. This report describes the case of a patient who acquired HIV soon after PrEP was suspended due to moderate renal impairment. The various clinical and regulatory issues this case raises are discussed.

Topics: Adult; Australia; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Glomerular Filtration Rate; HIV Infections; Humans; Insurance, Pharmaceutical Services; Male; Pre-Exposure Prophylaxis; Renal Insufficiency

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg is a proven strategy for preventing human immunodeficiency virus (HIV) transmission in men who have sex with men (MSM). This study aimed to test the feasibility and acceptability of PrEP delivered at a pilot clinic for MSM in Hong Kong, where PrEP service is currently unavailable.. Partially self-financed PrEP was provided to HIV-negative adult MSM with high behavioural risk of HIV transmission after excluding hepatitis B infection and renal insufficiency. Participants received daily TDF/FTC for 30 weeks at 13.3% of the drug cost. Adherence and behaviours were monitored through questionnaires while creatinine and HIV/STI (sexually transmitted infection) incidence were monitored with point-of-care and laboratory tests. Preference for continuing with PrEP was evaluated at the end of the prescription period.. Seventy-one PrEP-naïve MSM were included in the study, of whom 57 (80%) were retained at the end of 28 weeks. Satisfactory adherence and self-limiting adverse events were reported, while none of the participants contracted HIV. Risk compensation was observed, with an STI incidence of 3.17 per 100 person-years. At the end of the prescription period, a majority (89%) indicated interest in continuing with PrEP. Preference for PrEP was associated with age ≥28 years and peer influence (P=0.04), while stigma was a concern. Price was a deterrent to self-financed PrEP, and only half (51%) considered a monthly cost of ≤HK$500 (US$1=HK$7.8) as reasonable.. A partially self-financed mode of PrEP delivery is feasible with good retention in MSM in Hong Kong.

Topics: Adult; Anti-HIV Agents; Economics, Medical; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Hong Kong; Humans; Incidence; Male; Medication Adherence; Pilot Projects; Pre-Exposure Prophylaxis; Surveys and Questionnaires

Untreated syphilis may lead to severe complications. This infection has recently re-emerged in developed countries with a high number of cases coinfected with human immunodeficiency virus. In these patients, the skin lesions of secondary syphilis can be very atypical.. We report the case of a 38-year-old Bulgarian homosexual man who was coinfected with human immunodeficiency virus and syphilis. His skin contained multiple extensive necrotic lesions with abundant purulent secretion that covered his face, lips, scalp, and torso. Initial clinical diagnoses included varicella pustulosa and staphylococcal dermatitis. Human immunodeficiency virus infection in our patient had been established 2 years earlier in prophylactic studies, but had not been treated. Due to lack of penicillin, he was successfully treated with ceftriaxone, and the skin lesions underwent complete reversal. He also began antiretroviral therapy, which resulted in a significant effect on his immune status. Three months after the onset of antiretroviral therapy, he also achieved optimal viral suppression.. This case emphasizes the importance of considering cutaneous secondary syphilis in the differential diagnosis of any inflammatory cutaneous disorder in individuals infected with human immunodeficiency virus.

Topics: Adult; Anti-Bacterial Agents; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Ceftriaxone; Coinfection; Diagnosis, Differential; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Syphilis; Syphilis, Cutaneous

Risk of HIV infection is high in Chinese MSM, with an annual HIV incidence ranging from 3.41 to 13.7/100 person-years. Tenofovir-based PrEP is effective in preventing HIV transmission in MSM. This study evaluates the epidemiological impact and cost-effectiveness of implementing PrEP in Chinese MSM over the next two decades. A compartmental model for HIV was used to forecast the impact of PrEP on number of infections, deaths, and disability-adjusted life years (DALY) averted. We also provide an estimate of the incremental cost-effectiveness ratio (ICER) and the cost per DALY averted of the intervention. Without PrEP, there will be 1.1-3.0 million new infections and 0.7-2.3 million HIV-related deaths in the next two decades. Moderate PrEP coverage (50%) would prevent 0.17-0.32 million new HIV infections. At Truvada's current price in China, daily oral PrEP costs $46,813-52,008 per DALY averted and is not cost-effective; on-demand Truvada reduces ICER to $25,057-27,838 per DALY averted, marginally cost-effective; daily generic tenofovir-based regimens further reduce ICER to $3675-8963, wholly cost-effective. The cost of daily oral Truvada PrEP regimen would need to be reduced by half to achieve cost-effectiveness and realize the public health good of preventing hundreds of thousands of HIV infections among MSM in China.

Topics: Anti-HIV Agents; China; Cost-Benefit Analysis; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Incidence; Male; Models, Economic; Models, Statistical; Pre-Exposure Prophylaxis; Quality-Adjusted Life Years; Sexual and Gender Minorities

Background Pre-exposure prophylaxis (PrEP) was introduced in Sexual Health Services of the Welsh National Health Service (NHS Wales) in July 2017 as a 3-year pilot service.. Data were collected through the pre-existing Sexual Health in Wales Surveillance System, to which codes were added to capture PrEP eligibility, outcome of offer of PrEP, reasons for declining and adherence. Eligibility categories were defined based on nationally agreed criteria: men who have sex with men (MSM) and transgender people at high risk of HIV acquisition; partners of HIV-positive individuals not known to be virally suppressed; and heterosexuals reporting condomless intercourse with a HIV-positive individual not known to be virally suppressed.. During the first 6 months, 516 people were eligible, 96% of which were MSM. Overall, 57% of those eligible (296/516) started PrEP. Reasons for declining PrEP were given by 88 (56%) of 157 people; 50 (57%) of whom did not believe themselves to be at risk. Of the available adherence assessments, 89% considered that all risk episodes had been covered. Persistence at 3 months was assessed for 141 people, of which 93 (66%) were still using PrEP. There were no HIV diagnoses in people taking PrEP during the first 6 months. Twenty-nine people were diagnosed with 37 episodes of sexually transmissible infections (STIs) while on PrEP. STI incidence was 105.7 per 100 person-years.. The early trend indicates that implementation of PrEP is progressing as planned, and the service has been utilised by clients. This analysis can help refine implementation, inform planning and research around uptake, use and effect in Wales and internationally.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Health Plan Implementation; HIV Infections; Homosexuality, Male; Humans; Male; Medication Adherence; Middle Aged; National Health Programs; Pilot Projects; Pre-Exposure Prophylaxis; Program Evaluation; Sexual Partners; Transgender Persons; Wales; Young Adult

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Pre-Exposure Prophylaxis; Terminology as Topic

Latino men who have sex with men (MSM) are a group critically affected by HIV. Pre-exposure Prophylaxis (PrEP) is a biomedical prevention strategy that can help reduce new infections in this population. However, PrEP use may expose users to experiences of PrEP-related stigma. In-depth interviews conducted with Latino MSM PrEP users (N = 29) were analyzed using thematic analysis to explore experiences of PrEP stigma. Six themes emerged related to anticipated and enacted PrEP stigma: (1) Perception that PrEP users engage in risky sexual behaviors; (2) PrEP-induced conflict in relationships; (3) Perception that PrEP users are HIV-positive; (4) Generational differences in attitudes toward HIV prevention; (5) Experiences of discomfort, judgment, or homophobia from medical providers; and (6) Gay stigma related to PrEP disclosure to family. Manifestations of stigma included disapproving judgment, negative labeling, rejection, and devaluing individuals. The social consequences associated with using PrEP may deter uptake and persistence among Latino MSM.

Topics: Adult; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Hispanic or Latino; HIV Infections; Homosexuality, Male; Humans; Los Angeles; Male; Middle Aged; Pre-Exposure Prophylaxis; Risk-Taking; Safe Sex; Sexual Behavior; Sexual Partners; Social Stigma; Young Adult

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) significantly reduces the risk of HIV acquisition. TDF is a known nephrotoxin however, renal dysfunction from TDF is mostly reversible following discontinuation.. To describe the renal function, risk factors for renal disease and associated clinical testing practices in a cohort of PrEP patients.. A retrospective review was conducted of all PrEP patients commenced on TDF/FTC at an inner metropolitan sexual health clinic in Sydney, Australia between April 2016 and July 2017, with follow-up data obtained at 3-monthly intervals until 18 months.. 525 patients met inclusion criteria. Patients were almost exclusively male and median age was 34 years (IQR: 28 to 42). At baseline, 1.5% had an estimated glomerular filtration rate (eGFR) <70 mL/min/1.73m2. A small significant drop in eGFR of -2.5 mL/min/1.73m2 (p<0.05) occurred between PrEP commencement and the first follow-up period, followed by a progressive decline in eGFR of -0.38 mL/min/1.73m2 per month (95%CI: -0.57 to -0.20; p<0.001). Renal impairment (eGFR <70 mL/min/1.73m2) occurred in 6.5% of patients and persisted across consecutive follow-up periods in five (1.0%) patients. Patients aged ≥40 years had a greater risk of renal impairment than younger patients (HR 3.9, 95%CI: 1.8 to 8.4; p<0.001), despite similar rates of eGFR decline (p = 0.19). PrEP was discontinued in two patients (0.4%) due to renal function concerns.. PrEP use led to an initial drop in eGFR and a more gradual progressive decline subsequently, but significant renal impairment remained uncommon up to 18 months of follow-up.

Topics: Adult; Age Factors; Anti-HIV Agents; Australia; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Follow-Up Studies; Glomerular Filtration Rate; HIV Infections; Humans; Incidence; Kidney; Male; Middle Aged; Pre-Exposure Prophylaxis; Renal Insufficiency; Retrospective Studies; Risk Factors

Topics: Anti-HIV Agents; Charities; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Services Accessibility; HIV Infections; HIV Seropositivity; Homosexuality, Male; Humans; Male; Pre-Exposure Prophylaxis; United Kingdom

We determined if HIV-1 expression in transgenic (HIV-1-Tg) rats enhanced hepatic genomic changes related to oxidative/nitrosative stress and lipogenesis during cART-treatment, and assessed effects of Mg-supplementation. A clinically used cART (atazanavir-ritonavir+Truvada) was given orally to control and HIV-1-Tg rats (18 weeks) with normal or 6-fold dietary-Mg. Oxidative/nitrosative and lipogenic genes were determined by real-time RT-PCR. cART induced a 4-fold upregulation of sterol regulatory element-binding protein-1 (SREBP-1) in HIV-1-Tg-rats, but not in controls; Tg rats displayed a 2.5-fold higher expression. Both were completely prevented by Mg-supplementation. Nrf2 (Nuclear erythroid-derived factor 2), a master transcription factor controlling redox homeostasis, was down-regulated 50% in HIV-Tg rats, and reduced further to 25% in Tg+cART-rats. Two downstream antioxidant genes, heme oxygenase-1(HmOX1) and Glutathione-S-transferase(GST), were elevated in HIV-Tg alone but were suppressed by cART treatment. Decreased Nrf2 in Tg±cART were normalized by Mg-supplementation along with the reversal of altered HmOX1 and GST expression. Concomitantly, iNOS (inducible nitric oxide synthase) was upregulated 2-fold in Tg+cART rats, which was reversed by Mg-supplementation. In parallel, cART-treatment led to substantial increases in plasma 8-isoprostane, nitrotyrosine, and RBC-GSSG (oxidized glutathione) levels in HIV-1-Tg rats; all indices of oxidative/nitrosative stress were suppressed by Mg-supplementation. Both plasma triglyceride and cholesterol levels were elevated in Tg+cART rats, but were lowered by Mg-supplementation. Thus, the synergistic effects of cART and HIV-1 expression on lipogenic and oxidative/nitrosative effects were revealed at the genomic and biochemical levels. Down-regulation of Nrf2 in the Tg+cART rats suggested their antioxidant response was severely compromised; these abnormal metabolic and oxidative stress effects were effectively attenuated by Mg-supplementation at the genomic level.

Topics: Animals; Anti-Retroviral Agents; Atazanavir Sulfate; Dietary Supplements; Disease Models, Animal; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Gene Expression Regulation; HIV Infections; HIV-1; Humans; Lipogenesis; Liver; Magnesium; Male; NF-E2-Related Factor 2; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Inbred F344; Rats, Transgenic; Ritonavir

Sexual and gender minority (SGM) populations remain at disproportionate risk of HIV infection. Despite the effectiveness of pre-exposure prophylaxis (PrEP) in preventing HIV, PrEP uptake has been slow.. To identify barriers and facilitators of PrEP access by examining SGM patients' experiences with accessing health care systems and engaging with providers about PrEP in a variety of practice settings.. Semi-structured, individual, qualitative interviews.. Twenty-seven sexual and gender minority adults residing in Oregon.. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis.. We identified three main themes. Participants described the centrality of patient-provider relationships to positive experiences around PrEP, the necessity of personally advocating to access PrEP, and the experience of system-level barriers to PrEP access. Participants also made several suggestions to improve PrEP access including improving provider engagement with SGM patients, encouraging providers to initiate conversations about PrEP, and increasing awareness of medication financial support.. In order to reduce HIV disparities, improving PrEP access will require additional efforts by providers and resources across health care settings to reduce barriers. Interventions to improve provider education about PrEP and provider communication skills for discussing sexual health are needed. Additionally, there should be system-level improvements to increase coordination between patients, providers, pharmacies, and payers to facilitate PrEP access and uptake.

Topics: Adult; Aged; Anti-HIV Agents; Attitude of Health Personnel; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Middle Aged; Physician-Patient Relations; Pre-Exposure Prophylaxis; Qualitative Research; Sexual and Gender Minorities; Young Adult

Topics: Anti-HIV Agents; Canada; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Pre-Exposure Prophylaxis; Primary Health Care; Risk Factors

We evaluated the relationship between 2 types of social relationships, ie, (1) external support for use of HIV pre-exposure prophylaxis (PrEP) and related study supplies and (2) participants' disclosure of PrEP use and condom use and HIV PrEP adherence among daily-dosing regimen participants in HIV Prevention Trials Network (HPTN) 067, an open-label trial of oral tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg.. Using HPTN 067 survey data, we developed scales examining (1) Low Perceived External Support for PrEP: low perceived support by others for PrEP use or perceived negative reactions to the pill case (scoring ranges from 0 to 2) and (2) Participant-Staff Disclosure Challenges Scale, which identifies challenges to sharing nonuse of PrEP or condoms to study staff (scoring ranges from 0 to 4); these scales are the primary independent variables. Adherence, the dependent variable, was determined using log-transformed plasma TFV concentrations. generalized estimating equation (GEE) linear regression was used to assess the association between both scales and adherence.. Participants (n = 161) included HIV-uninfected women in South Africa, and men who have sex with men and transgender women, in Thailand and the United States. In multivariable analyses, higher scores in the Participant-Staff Disclosure Challenges Scale were significantly associated with lower PrEP adherence [exp(β) = 0.62, 95% CI: (0.46 to 0.84); P = 0.002] as were increased days since the last PrEP dose [exp(β) = 0.73, 95% CI: (0.65 to 0.83); P ≤ 0.001].. Given the association with adherence, study staff-participant interactions and participants' disclosure of PrEP challenges may be worthwhile intervention targets for improving PrEP adherence in confirmatory studies.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Condoms; Directly Observed Therapy; Disclosure; Drug Therapy, Combination; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Homosexuality, Male; Humans; Male; Medication Adherence; Middle Aged; Pre-Exposure Prophylaxis; Risk-Taking; Sexual and Gender Minorities; Social Networking; South Africa; Surveys and Questionnaires; Tenofovir; Thailand; United States; Young Adult

Topics: Antibodies, Monoclonal, Humanized; Clinical Trials as Topic; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Patient Compliance; Pre-Exposure Prophylaxis

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Homosexuality, Male; Humans; Male; Pre-Exposure Prophylaxis; Sexually Transmitted Diseases, Bacterial; Unsafe Sex

Topics: Anti-HIV Agents; Drug Industry; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Services Accessibility; HIV Infections; Humans; Pre-Exposure Prophylaxis; Risk

Limited data suggest that some gay and other men who have sex with men are using antiretroviral medications informally, without a prescription, for HIV prevention. This qualitative study examined this phenomenon among gay and other men who have sex with men in South Florida. Participants initiated informal antiretroviral medication use as a means of protecting each other and because of the confidence in knowledge of antiretroviral medications shared by their friends and sex partners. The most commonly used medications included Truvada and Stribild. Motivations for use included condom avoidance, risk reduction, and fear of recent HIV exposure. Participants described positive and negative sentiments related to informal use, including concerns about informal antiretroviral medications offering sufficient protection against HIV, and limited knowledge about pre-exposure prophylaxis (PrEP). Because the antiretroviral medications used for PrEP have the potential to prevent HIV infection, future research must consider the informal antiretroviral medication use and related concerns, including adherence, diversion and viral resistance.

Topics: Adolescent; Adult; Anti-HIV Agents; Condoms; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Florida; Health Knowledge, Attitudes, Practice; HIV Infections; Humans; Male; Middle Aged; Motivation; Pre-Exposure Prophylaxis; Qualitative Research; Risk Reduction Behavior; Self Medication; Sexual and Gender Minorities; Young Adult

Initially billed as a game changer, Truvada has faced multiple obstacles to widespread adoption.

Topics: Diffusion of Innovation; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Pre-Exposure Prophylaxis; Reverse Transcriptase Inhibitors

Antiretroviral therapy (ART) has fundamentally altered the natural history of HIV/AIDS, sharply reducing HIV-related morbidity and prolonging longevity. However, there seems to be a resurgence in HIV infection rates in some parts of the world that has prompted consideration of pre-exposure prophylaxis (pre-EP) and vaccination. Despite their good viral suppression profiles, most drugs used as part of ART also have unwanted adverse drug reactions/effects (ADRs). In this article we acknowledge the utility of pre-EP in combating HIV transmission, but we also highlight the need to prepare for management of other unexpected outcomes such as ADRs and viral resistance, to ensure the success of the programme.

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Pre-Exposure Prophylaxis; South Africa; Students; Universities

Transgender women may face a disparate risk for HIV/AIDS compared to other groups. In 2012, Truvada was approved for daily use as HIV pre-exposure prophylaxis (PrEP). However, there is a dearth of research about barriers and facilitators to PrEP in transgender women. This paper will shed light on transgender women living in New York City's perceived and actual challenges to using PrEP and potential strategies to overcome them. After completing an initial screening process, four 90-min focus groups were completed with n = 18 transgender women. Participants were asked what they like and dislike about PrEP. Participants identified the following barriers: uncomfortable side effects, difficulty taking pills, stigma, exclusion of transgender women in advertising, and lack of research on transgender women and PrEP. Facilitators included: reducing pill size, increasing the types of available HIV prevention products, and conducting scientific studies to evaluate PrEP in transgender women.

Topics: Adult; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Focus Groups; HIV Infections; Humans; Male; New York City; Pre-Exposure Prophylaxis; Qualitative Research; Social Stigma; Transgender Persons

Increasing the uptake of pre-exposure prophylaxis (PrEP) to prevent HIV acquisition among at-risk populations, such as young men who have sex with men (YMSM), is of vital importance to slowing the HIV epidemic. Stigma and negative injunctive norms, such as the so called "Truvada Whore" phenomenon, hamper this effort. We examined the prevalence and types of PrEP stigma and injunctive norm beliefs among YMSM and transgender women and associated individual and geospatial factors. A newly created measure of PrEP Stigma and Positive Attitudes was administered to 620 participants in an ongoing longitudinal cohort study. Results indicated lower stigma among White, compared to Black and Latino participants, and among participants not identifying as male. Prior knowledge about PrEP was associated with lower stigma and higher positive attitudes. PrEP stigma had significant geospatial clustering and hotspots were identified in neighborhoods with high HIV incidence and concentration of racial minorities, whereas coldspots were identified in areas with high HIV incidence and low LGBT stigma. These results provide important information about PrEP attitudes and how PrEP stigma differs between individuals and across communities.

Topics: Adolescent; Adult; Chicago; Cohort Studies; Culture; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Health Knowledge, Attitudes, Practice; HIV Infections; Homosexuality, Male; Humans; Longitudinal Studies; Male; Minority Groups; Patient Acceptance of Health Care; Pre-Exposure Prophylaxis; Social Stigma; Social Values; Transgender Persons; Young Adult

Pre-exposure prophylaxis for HIV (PrEP) has been shown to reduce transmission of HIV in a number of trials; however, there is limited evidence regarding the optimal way to deliver PrEP through pre-existing UK services, particularly through fully integrated drop-in sexual health service models. PrEP in the form of Truvada was launched in Wales in July 2017. We set up a PrEP service to be delivered via our drop-in integrated sexual reproductive health service. In the first 5 months of PrEP service provision, we found unforeseen levels of comorbidity, polypharmacy and renal impairment in our cohort of PrEP patients. As a result, we have altered our service model and all patients are now followed up in booked appointment PrEP clinics run by members of the HIV team. Those patients with estimated glomerular filtration rate (eGFR) of 60-70 mL/min or with eGFR of 60-80 mL/min and with comorbidities impacting on renal function are monitored every 4-6 weeks initially, and PrEP has been incorporated into our pre-existing virtual HIV renal clinic for discussion with a renal physician. The PrEP team clinicians report that monitoring and managing the PrEP cohort is now easier in its appointment-only format, although some patients have reported that they would prefer a drop-in system.

Topics: Adolescent; Adult; Aged; Anti-HIV Agents; Appointments and Schedules; Cohort Studies; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Kidney Function Tests; Male; Middle Aged; Pre-Exposure Prophylaxis; Reproductive Health Services; Sexual Behavior; United Kingdom; Young Adult

The number of individuals who have started a regimen for HIV pre-exposure prophylaxis (PrEP) in the United States is not well characterized but has been on the rise since 2012. This analysis assesses the distribution of PrEP use nationally and among subgroups.. A validated algorithm quantifying tenofovir disoproxil fumarate/emtricitabine for PrEP in the United States was applied to a national prescription database to determine the quarterly prevalence of PrEP use. HIV diagnoses from 2016 were used as an epidemiological proxy for PrEP need. The PrEP-to-need ratio (PnR) was defined as the number of PrEP users divided by new HIV diagnoses.. A total of 70,395 individuals used PrEP in the fourth quarter of 2017: 67,166 males and 3229 females. Nationally, prevalence of PrEP use was 26/100,000 (range across states per 100,000 [RAS/100k]: 4-73) and the PnR was 1.8 (RAS: 0.5-6.6). Prevalence of PrEP use among males and females, respectively, was 50/100,000 and 2/100,000 (RAS/100k: 7-143 and 0.3-7) and PnR was 2.1 and 0.4 (RAS: 0.6-7.1 and 0.1-4.0). Prevalence of PrEP use was lowest among individuals aged less than or equal to 24 and more than or equal to 55 years (15/100,000 and 6/100,000, RAS/100k: 1-45 and 0.4-14), with PnR 0.9 and 1.5 (RAS: 0.2-5.6 and 0.3-7.0). The Northeast had the highest PnR (3.3); the South had the lowest (1.0). States with Medicaid expansion had more than double the PnR than states without expansion.. Available data suggest that females, individuals aged less than or equal to 24 years and residents of the South had lower levels of PrEP use relative to epidemic need. These results are ecological, and misclassification may attenuate results. PnR is useful for future assessments of HIV prevention strategy uptake.

Topics: Adolescent; Adult; Age Distribution; Anti-HIV Agents; Cross-Sectional Studies; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Middle Aged; Pre-Exposure Prophylaxis; Prescriptions; Prevalence; United States; Young Adult

Pre-exposure prophylaxis (PrEP) with oral emtricitibine/tenofovir disoproxil fumarate (TDF/FTC) reduces the risk of HIV infection by >90% when taken as prescribed. Trends in prevalence of PrEP use, which account for persons who have stopped PrEP, increased through 2016, but have not been described since.. Annual prevalence estimates of unique, TDF/FTC PrEP users (individuals with ≥1 day of a filled PrEP prescription in a given year) in the United States (US) were generated for 2012-2017 from a national prescription database. A validated algorithm was used to distinguish users of TDF/FTC for HIV or chronic Hepatitis B treatment or postexposure prophylaxis from PrEP users. We calculated annual prevalence of PrEP use overall and by age, sex, and region. We used log-transformation to calculate estimated annual percent change (EAPC) in the prevalence of PrEP use.. Annual prevalence of PrEP use increased from 3.3/100,000 population in 2012 to 36.7 in 2017 -a 56% annual increase from 2012 to 2017 (EAPC: +56%). Annual prevalence of PrEP use increased faster among men than among women (EAPC: +68% and +5%, respectively). By age group, annual prevalence of PrEP use increased fastest among 25- to 34-year olds (EAPC: +61%) and slowest among ≥55-year olds (EAPC: +52%) and ≤24-year olds (EAPC: +51%). In 2017, PrEP use was lowest in the South (29.8/100,000) and highest in the Northeast (62.3/100,000).. Despite overall increases in the annual number of TDF/FTC PrEP users in the US from 2012 to 2017, the growth of PrEP coverage is inconsistent across groups. Efforts to optimize PrEP access are especially needed for women and for those living in the South.

Topics: Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Middle Aged; Pre-Exposure Prophylaxis; United States

Adolescent men who have sex with men (AMSM) account for disproportionately high numbers of new HIV diagnoses. Non-adherence to daily use limiting the effectiveness of oral PrEP (Truvada) has led to current trials with adult MSM testing Cabotegravir, a long-term injectable medication. Once comparative studies with young adult MSM have established relative safety and efficacy of these medications, there will be a need for such comparative trials involving adolescents. Trends in state laws and IRB protocol review indicate that many of these studies will permit youth to provide independent consent for participation. Understanding the motivations of AMSM to participate in HIV biomedical prevention studies is important to ensure their agreement is voluntary without misunderstanding and undue influence. This study examined AMSM attitudes toward participation in oral/injectable PrEP RCTs to inform protections of youth's rights and welfare in future studies.. We administered to 198 ethnically diverse U.S. AMSM, 14-17 years, a web-based survey including demographic and sexual health questions, description of a year-long oral versus injectable PrEP RCT and 26 Likert-type and one open-ended item assessing motivations for and against participation including: perceived benefits and risks of PrEP; free HIV/STI testing and counseling; confidentiality concerns; random assignment; and benefit to others.. Sixty-two percent indicated they were likely to participate in the study. The majority endorsed daily HIV protection, free HIV/STI testing, sexual health counseling, not having to rely on partner's condom use, and altruism as reasons to participate. Reasons against participation included medication side effects, concern taking the pill daily and clinic visits would reveal their sexual orientation and behaviors to parents. Over half erroneously assumed they would be assigned to the condition best for them and 39% indicated free access to services would lead them to participate even if they did not want to. Multiple regression indicated these factors accounted for 55% of the variance in participation choice. Nether age or ethnicity yielded significance.. Results suggest future biomedical HIV prevention research will need to develop procedures to address AMSM's confidentiality concerns, enhance youth's understanding of random assignment, the continued importance of medication adherence and partner condom use during trial participation, and availability of alternative sexual health services to avoid the potentially undue influence of access to free sexual health services.

Topics: Administration, Oral; Adolescent; Anti-HIV Agents; Clinical Trials as Topic; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Knowledge, Attitudes, Practice; HIV Infections; Humans; Injections; Male; Motivation; Patient Participation; Pre-Exposure Prophylaxis; Psychology, Adolescent; Sexual and Gender Minorities; Surveys and Questionnaires

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Services Accessibility; HIV Infections; Humans; Pre-Exposure Prophylaxis; State Medicine; United Kingdom

Topics: Anti-HIV Agents; Biomarkers, Pharmacological; Drug Administration Schedule; Drug Monitoring; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Knowledge, Attitudes, Practice; HIV Infections; Humans; Medication Adherence; Pre-Exposure Prophylaxis; Predictive Value of Tests; Reproducibility of Results

The US Food and Drug Administration (FDA) approved oral daily tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis of human immunodeficiency virus (HIV) infection in 2012 on the basis of two randomized controlled trials (RCTs), one in men who have sex with men (MSM) and another in HIV serodiscordant heterosexual couples. Subsequently, even greater efficacy has been demonstrated in MSM with rapid population-level incidence reductions in some locations. In contrast, studies of antiretroviral pre-exposure prophylaxis (PrEP) in heterosexual women showed only modest or no efficacy, largely attributed to low adherence. The mixed results of antiretroviral-based PrEP bear witness to unique drug development challenges at this complicated intersection of sexual behavior, public health, and drug development. Multiple innovative methods and formulation strategies followed to address unmet medical needs of persons struggling with daily oral PrEP adherence or preference for nonsystemic PrEP options. Clinical pharmacology plays essential roles throughout this PrEP development process, especially in early product development and through pharmacologically informed enhancement and interpretation of clinical trials.

Topics: Administration, Oral; Anti-HIV Agents; Drug Administration Schedule; Drug Development; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV-1; Humans; Male; Medication Adherence; Pre-Exposure Prophylaxis; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Topics: Adult; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Middle Aged; Pre-Exposure Prophylaxis; United States

Tenofovir disoproxil fumarate (TDF), a key component in many human immunodeficiency virus (HIV) treatment regimens, is associated with increased renal and bone toxicities. The contributions of such toxicities to treatment costs, as well as the relative differences in treatment costs for various TDF/emtricitabine (FTC) regimens, remains unexplored.. To estimate and compare mean overall and renal- and bone-specific costs, including total, inpatient, outpatient, and pharmacy costs in patients treated with TDF/FTC+efavirenz (EFV) compared with several non-EFV-containing TDF/FTC regimens.. We conducted a national cohort study of treatment-naive HIV-infected U.S. veterans who initiated treatment from 2003 to 2015 with TDF/FTC in combination with EFV, elvitegravir/cobicistat, rilpivirine, or ritonavir-boosted protease inhibitors (atazanavir, darunavir, or lopinavir). Outcomes of interest were quarterly total, inpatient, outpatient, and pharmacy costs using data from the Veterans Health Administration (VHA) electronic medical record and Managerial Cost Accounting System (an activity-based accounting system that allocates VHA expenditures to patient encounters). We controlled for measured confounders using inverse probability of treatment (IPT) weights and assessed differences using standardized mean differences (SMDs). For comparisons where SMDs exceeded 0.1 after IPT weighting, we used the more conservative matching weights in sensitivity analyses. For hypothesis testing, we compared IPT-adjusted differences in quarterly costs between treatment groups using Mann-Whitney U-tests and generalized estimating equation (GEE) regression models.. Of 33,048 HIV-positive veterans, 7,222 met eligibility criteria, including 4,172 TDF/FTC + EFV recipients; mean (SD) age of the cohort was 50.0 (10.0) years; 96.7% were male; 60.1% were black; and 30.1% were white. Quarterly periods of exposure to EFV-containing regimens were 22,499 and of exposure to non-EFV-containing regimens were 11,633. After IPT weighting, absolute SMDs were < 0.1 except for a few covariates in the rilpivirine comparison. The per-patient adjusted mean total quarterly costs were $7,145 for EFV versus $8,726 for non-EFV (P < 0.001; Mann-Whitney U-test) and the per-patient adjusted mean difference in total quarterly costs was $1,419 lower for EFV versus all non-EFV combined (P < 0.001; GEE model). Corresponding values for outpatient costs ($2,656 vs. $2,942; P < 0.001; difference, -$254; P = 0.001), inpatient costs ($2,009 vs. $2,614; P < 0.001), radiology costs ($213 vs. $276; P < 0.001), and pharmacy costs ($2,480 vs. $3,170; P < 0.001; difference, -$600; P < 0.001) were all lower for EFV versus all non-EFV combined. Findings based on matching weights were qualitatively similar. Contributions of renal and bone costs to the total costs of treatment were very small, ranging between $52 and $94 per patient per quarter for renal outcomes and between $6 and $114 for bone outcomes.. Among 7,222 HIV-treated veterans over an average follow-up of 1.2 years per patient, those patients receiving TDF/FTC + EFV had lower overall health care costs compared with those receiving non-EFV regimens.. This study was funded by Bristol-Myers Squibb. Nelson, Ma, Crook, Knippenberg, Nyman, and LaFleur are employees of the University of Utah, which received a grant from Bristol-Myers Squibb to conduct this study. Nyman also discloses honoraria for consulting from Otsuka and for writing a book chapter from Fresenius. La Fleur reports advisory board and consulting fees from Bristol-Myers Squibb outside of this study. Paul and Esker are employees of, and own stock in, Bristol-Myers Squibb.

Topics: Adult; Ambulatory Care; Anti-HIV Agents; Bone Diseases; Drug Costs; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Hospital Costs; Humans; Kidney Diseases; Male; Middle Aged; Pharmaceutical Services; Risk Factors; Time Factors; Treatment Outcome; United States; United States Department of Veterans Affairs; Veterans Health

HIV pre-exposure prophylaxis (PrEP) is highly effective in men who have sex with men (MSM) at the individual level, but data on population-level impact are lacking. We examined whether rapid, targeted, and high-coverage roll-out of PrEP in an MSM epidemic would reduce HIV incidence in the cohort prescribed PrEP and state-wide in Australia's most populous state, New South Wales.. The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study is an implementation cohort study of daily co-formulated tenofovir disoproxil fumarate and emtricitabine as HIV PrEP. We recruited high-risk gay men in a New South Wales-wide network of 21 clinics. We report protocol-specified co-primary outcomes at 12 months after recruitment of the first 3700 participants: within-cohort HIV incidence; and change in population HIV diagnoses in New South Wales between the 12-month periods before and after PrEP roll-out. The study is registered with ClinicalTrials.gov, number NCT02870790.. We recruited 3700 participants in the 8 months between March 1, 2016, and Oct 31, 2016. 3676 (99%) were men, 3534 (96%) identified as gay, and 149 (4%) as bisexual. Median age was 36 years (IQR 30-45 years). Overall, 3069 (83%) participants attended a visit at 12 months or later. Over 4100 person-years, two men became infected with HIV (incidence 0·048 per 100 person-years, 95% CI 0·012-0·195). Both had been non-adherent to PrEP. HIV diagnoses in MSM in New South Wales declined from 295 in the 12 months before PrEP roll-out to 221 in the 12 months after (relative risk reduction [RRR] 25·1%, 95% CI 10·5-37·4). There was a decline both in recent HIV infections (from 149 to 102, RRR 31·5%, 95% CI 11·3 to 47·3) and in other HIV diagnoses (from 146 to 119, RRR 18·5%, 95% CI -4·5 to 36·6).. PrEP implementation was associated with a rapid decline in HIV diagnoses in the state of New South Wales, which was greatest for recent infections. As part of a combination prevention approach, rapid, targeted, high-coverage PrEP implementation is effective to reduce new HIV infections at the population level.. New South Wales Ministry of Health, Gilead Sciences.

Topics: Adolescent; Adult; Aged; Anti-HIV Agents; Bisexuality; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Incidence; Male; Medication Adherence; Middle Aged; New South Wales; Pre-Exposure Prophylaxis; Prospective Studies; Risk Assessment; Sexual and Gender Minorities; Young Adult

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Pre-Exposure Prophylaxis; Preventive Health Services; Quality Improvement; Scotland; State Medicine

The release of World Health Organisation guidelines recommending the prophylactic use of daily Truvada

Topics: Adult; Anti-HIV Agents; Confidentiality; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Middle Aged; Power, Psychological; Pre-Exposure Prophylaxis; Safe Sex; South Africa; Young Adult

Tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) is effective against HIV acquisition when taken as prescribed. Strategies that identify and intervene with those challenged by adherence to daily medication are needed.. PATH-PrEP was an open-label single-arm interventional cohort study conducted at 2 community-based clinical sites in Los Angeles, CA.. We enrolled self-identified men who have sex with men and transgender women ≥18 years of age at an elevated risk of HIV acquisition. Participants received a postexposure prophylaxis (PEP)-based or PrEP-based HIV prevention package for at least 48 weeks. Plasma tenofovir levels from each PrEP visit assessed as below the limit of quantitation (<10 ng/mL) triggered increased adherence support.. Three hundred one participants enrolled. Forty-eight-week retention in the PrEP cohort was 75.1%. Biomarker evidence of PrEP adherence consistent with ≥4 doses per week at weeks 4, 12, 24, 36, and 48 was found in 83.1%, 83.4%, 75.7%, 71.6%, and 65.5% of participants, respectively; younger and African American participants were less likely to have protective drug levels. Most of those with suboptimal adherence had adherence improvement after brief intervention. One seroconversion occurred in a participant who discontinued PrEP. Nearly half (46.4%) of participants were diagnosed with at least 1 incident sexually transmitted infection during 48 weeks of study follow-up.. PrEP was acceptable and well tolerated in a diverse population of men who have sex with men in Los Angeles. A brief intervention triggered from biomarkers of poor adherence was associated with improved adherence. Drug level monitoring has the potential to allow targeting of additional adherence support to those struggling with daily tablet adherence.

Topics: Adolescent; Adult; Biomarkers; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Los Angeles; Male; Patient Compliance; Pre-Exposure Prophylaxis; Tenofovir; Transgender Persons; Young Adult

Truvada is getting a new lease on life as a preventive agent. It is the only drug approved to prevent HIV infections, and Truvada is the key pharmaceutical component of pre-exposure prophylaxis, which is aimed at preventing, rather than treating, HIV infection and transmission.

Topics: Adenine; Alanine; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Reverse Transcriptase Inhibitors; Tenofovir; Treatment Outcome

On May 14, 2014 the Centers for Disease Control and Prevention (CDC) endorsed the drug Truvada as an HIV preventative, called pre-exposure prophylaxis (PrEP). PrEP has been shown to dramatically reduce the risk of HIV infection, but its rate of adoption has been slow, and discourse surrounding it has been marked by stigma and uncertainty. The purpose of this study was to investigate how PrEP was discussed on Twitter. Our analysis focused on barriers to PrEP adoption and stigmatization of PrEP users. We analyzed a random sample of 1,093 top tweets about PrEP posted to Twitter a year before and a year after the CDC's endorsement. Our results showed that tweets likely reinforced uncertainty about barriers to PrEP adoption and that users employed Twitter's functionality to counter stigmatizing narratives about PrEP. We suggest that our findings illuminate both the limitations and strengths of Twitter as a mechanism for health promotion.

Topics: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Knowledge, Attitudes, Practice; Health Services Accessibility; HIV Infections; Humans; Pre-Exposure Prophylaxis; Social Media; Social Stigma; Treatment Refusal

Consistent over-reporting of product use limits researchers' ability to accurately measure adherence and estimate product efficacy in HIV prevention trials. While lying is a universal characteristic of the human condition, growing evidence of a stark discrepancy between self-reported product use and biologic or pharmacokinetic evidence demands examination of the reasons research participants frequently misrepresent product use in order to mitigate this challenge in future research. This study (VOICE-D) was an ancillary post-trial study of the vaginal and oral interventions to control the epidemic (VOICE) phase IIb trial (MTN 003). It was conducted in three African countries to elicit candid accounts from former VOICE trial participants about why actual product use was lower than reported. In total 171 participants were enrolled between December 2012 and March 2014 in South Africa (n = 47), Uganda (n = 59) and Zimbabwe (n = 65). Data suggested that participants understood the importance of daily product use and honest reporting, yet acknowledged that research participants typically lie. Participants cited multiple reasons for misreporting adherence, including human nature, self-presentation with study staff, fear of repercussions (study termination resulting in loss of benefits and experience of HIV-related stigma), a permissive environment in which it was easy to get away with misreporting, and avoiding inconvenient additional counseling. Some participants also reported mistrust of the staff and reciprocal dishonesty about the study products. Many suggested real-time blood-monitoring during trials would encourage greater fidelity to product use and honesty in reporting. Participants at all sites understood the importance of daily product use and honesty, while also acknowledging widespread misreporting of product use. Narratives of dishonesty may suggest a wider social context of hiding products from partners and distrust about research, influenced by rumors circulating in clinic waiting-rooms and surrounding communities. Prevailing power hierarchies between staff and participants may exacerbate misreporting. Participants recognized and suggested that objective, real-time feedback is needed to encourage honest reporting.

Topics: Administration, Intravaginal; Administration, Oral; Adult; Anti-HIV Agents; Clinical Trials, Phase II as Topic; Deception; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Epidemics; Female; HIV Infections; Humans; Medication Adherence; Qualitative Research; Self Report; Sexual Partners; South Africa; Tenofovir; Uganda; Young Adult; Zimbabwe

The HIV/AIDS epidemic in the US continues to persist, in particular, among race, sexual orientation, and gender minority populations. Pre-exposure prophylaxis (PrEP), or using antiretroviral medications for HIV prevention, is an effective option, but uptake of PrEP has been slow. Sociocultural barriers to using PrEP have been largely underemphasized, yet have the potential to stall uptake and, therefore, warrant further understanding. In order to assess the relationships between potential barriers to PrEP (i.e., PrEP stigma and conspiracy beliefs), and interest in PrEP, Black men and transgender women who have sex with men (BMTW, N = 85) and White MTW (WMTW, N = 179) were surveyed at a gay pride event in 2015 in a large southeastern US city. Bivariate and multivariate logistic regression analyses were completed to examine factors associated with PrEP interest. Among the full sample, moderate levels of PrEP awareness (63%) and low levels of use (9%) were observed. Believing that PrEP is for people who are promiscuous (stigma belief) was strongly associated with lack of interest in using PrEP, and individuals who endorsed this belief were more likely to report sexual risk taking behavior. Conspiracy beliefs related to PrEP were reported among a large minority of the sample (42%) and were more frequently reported among BMTW than WMTW. Given the strong emphasis on the use of biomedical strategies for HIV prevention, addressing sociocultural barriers to PrEP access is urgently needed and failure to do so will weaken the potential benefits of biomedical prevention.

Topics: Adult; Anti-HIV Agents; Black or African American; Culture; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Middle Aged; Pre-Exposure Prophylaxis; Social Stigma; Transgender Persons; United States; Unsafe Sex; White People; Young Adult

Topics: Adult; Anti-HIV Agents; Drug Resistance, Multiple, Viral; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Genes, MDR; HIV Infections; HIV-1; Humans; Male; Mutation; Pre-Exposure Prophylaxis

Topics: Anti-HIV Agents; Chromatography, Liquid; Drug Monitoring; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Tandem Mass Spectrometry; Treatment Outcome; Young Adult

The pre-exposure prophylaxis (PrEP) drug Truvada is a new HIV prevention technology that is predominantly promoted as relevant to HIV-negative gay men. This paper explores what PrEP represents for HIV-positive gay men living in Paris, based upon data collected through interviews and ethnographic research. While HIV-positive gay men do not directly consume Truvada through PrEP, they nonetheless hold opinions and understandings of this drug, specifically as it relates to their own sexuality. This paper expands the representations and meanings of this new technology in a different light through the voices of gay men living with HIV in Paris. The main argument of this article is that PrEP as an additional HIV prevention tool blurs the lines between science, technologies and human sexuality.

Topics: Anthropology, Cultural; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Knowledge, Attitudes, Practice; HIV Infections; Homosexuality, Male; Humans; Interviews as Topic; Male; Paris; Patient Acceptance of Health Care; Pre-Exposure Prophylaxis; Quebec; Sexual Behavior

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Europe; HIV Infections; Humans; Pre-Exposure Prophylaxis

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Unsafe Sex

The antiretroviral regimens including tenofovir and a ritonavir-boosted protease inhibitor (r/PI) have been associated with a reduced bone mineral density (BMD), increased bone turnover markers and renal tubular dysfunction.. An observational, prospective study was performed including HIV-1-infected, virologically suppressed patients treated with tenofovir/emtricitabine plus an r/PI for at least 12 months who switched to raltegravir plus nevirapine. The primary end point was changes after 48 weeks in estimated glomerular filtration rate (eGFR), prevalence of tubular dysfunction, BMD and concentration of two serum markers of bone turnover: collagen type-1 cross-linked C-telopeptide (CTX) and bone-specific alkaline phosphatase (BAP).. A total of 46 patients were enrolled: 78% were male, 96% were Caucasian, the mean age was 45 years and the mean CD4(+) T-lymphocyte count was 681 cells/mm(3). A renal impairment was present in 72% of patients and was the main reason for the switch. After 48 weeks, prevalence of proximal tubular dysfunction decreased significantly (-72%; P<0.001), whereas the mean value of eGFR did not change significantly. At the same time, after 48 weeks a significant increase in both lumbar spine and total hip BMD, T-score and Z-score was reported (+11.5% in lumbar spine T-score; P<0.001), and there was a significant reduction in both CTX and BAP mean serum concentrations (-15% and -13%, respectively; P<0.001). Two (4.3%) patients had virological failure due to suboptimal adherence and one (2.2%) subject discontinued treatment due to a skin rash.. Switching virologically suppressed patients from tenofovir/emtricitabine plus one r/PI to raltegravir plus nevirapine after 48 weeks significantly improved proximal tubular function, increased BMD and reduced serum markers of bone turnover.

Topics: Adult; Anti-HIV Agents; Bone Density; Cohort Studies; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Glomerular Filtration Rate; HIV Infections; Humans; Male; Middle Aged; Nevirapine; Pilot Projects; Raltegravir Potassium; Ritonavir

Genital inflammation associated with sexually transmitted infections increases susceptibility to human immunodeficiency virus (HIV), but it is unclear whether the increased risk can reduce the efficacy of pre-exposure prophylaxis (PrEP). We investigated whether coinfection of macaques with Chlamydia trachomatis and Trichomonas vaginalis decreases the prophylactic efficacy of oral emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). Macaques were exposed to simian/human immunodeficiency virus (SHIV) vaginally each week for up to 16 weeks and received placebo or FTC/TDF pericoitally. All animals in the placebo group were infected with SHIV, while 4 of 6 PrEP recipients remained uninfected (P= .03). Oral FTC/TDF maintains efficacy in a macaque model of sexually transmitted coinfection, although the infection of 2 macaques signals a modest loss of PrEP activity.

Topics: Animals; Anti-HIV Agents; Chlamydia Infections; Chlamydia trachomatis; Coinfection; Disease Models, Animal; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Macaca mulatta; Pre-Exposure Prophylaxis; Simian Acquired Immunodeficiency Syndrome; Trichomonas Vaginitis; Vagina

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Unsafe Sex

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Unsafe Sex

The purpose of this study was to analyze the frequency of incidents of uncertainty in online news articles about Truvada, a drug used to prevent HIV infection. Using a coding scheme that synthesized uncertainty research from health disciplines and communication studies, we analyzed 235 articles from the most-read United States-based news websites. Our results showed that 80.4% of articles contained at least one incident of uncertainty, that articles contained significantly more incidents of uncertainty before the Centers for Disease Control and Prevention (CDC) endorsed Truvada compared to after the CDC endorsed the drug, and that articles mentioning men who have sex with men (MSM) contained significantly more incidents of uncertainty than articles in which they were not mentioned.

Topics: Drug Approval; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Mass Media; Uncertainty; United States

Topics: Administration, Oral; Adult; Anti-HIV Agents; Canada; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Feasibility Studies; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Pre-Exposure Prophylaxis; Retrospective Studies; Young Adult

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Pre-Exposure Prophylaxis; Primary Health Care; Wisconsin

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Unsafe Sex

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Unsafe Sex

Topics: Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Routes; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Medication Adherence; Pre-Exposure Prophylaxis

Topics: Drug Approval; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Europe; HIV Infections; HIV-1; Humans; Pre-Exposure Prophylaxis

Topics: Anti-HIV Agents; Drug Approval; Drug Costs; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; England; HIV Infections; Homosexuality, Male; Humans; Male; Pre-Exposure Prophylaxis; State Medicine; Treatment Outcome

Once-daily Truvada (Emtricitabine/Tenofovir) as a method of pre-exposure prophylaxis (PrEP) is one of the most promising biomedical interventions to eliminate new HIV infections; however, uptake among gay, bisexual, and other men who have sex with men has been slow amidst growing concern in popular/social media that PrEP use will result in reduced condom use (i.e., risk compensation). We investigated demographic, behavioral, and psychosocial differences in willingness to use PrEP as well as the perceived impact of PrEP on participants' condom use in a sample of 206 highly sexually active HIV-negative gay and bisexual men. Nearly half (46.1 %) said they would be willing to take PrEP if it were provided at no cost. Although men willing to take PrEP (vs. others) reported similar numbers of recent casual male partners (<6 weeks), they had higher odds of recent receptive condomless anal sex (CAS)-i.e., those already at high risk of contracting HIV were more willing to take PrEP. Neither age, race/ethnicity, nor income were associated with willingness to take PrEP, suggesting equal acceptability among subpopulations that are experiencing disparities in HIV incidence. There was limited evidence to suggest men would risk compensate. Only 10 % of men who had not engaged in recent CAS felt that PrEP would result in them starting to have CAS. Men who had not tested for HIV recently were also significantly more likely than others to indicate willingness to take PrEP. Offering PrEP to men who test infrequently may serve to engage them more in routine HIV/STI testing and create a continued dialogue around sexual health between patient and provider in order to prevent HIV infection.

Topics: Adult; Anti-HIV Agents; Bisexuality; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Pre-Exposure Prophylaxis; Sexual and Gender Minorities; Young Adult

Topics: Anti-Retroviral Agents; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Medication Adherence; Organophosphorus Compounds; Pre-Exposure Prophylaxis

Preexposure prophylaxis (PrEP) for HIV prevention is a novel biomedical prevention method. We have previously modeled PrEP during rectal SHIV exposures in macaques and identified that Simian/Human Immunodeficiency Virus chimera (SHIV)-specific T-cell responses were induced in the presence of antiretroviral drugs, an observation previously termed T-cell chemo-vaccination. This report expands those initial findings by examining a larger group of macaques that were given oral or topical PrEP during repeated vaginal virus exposure.. Thirty-six female pigtail macaques received up to 20 repeat low-dose vaginal inoculations with wild-type (WT) SHIVSF162P3 (n = 24) or a clonal derivative with the tenofovir (TFV) K65R drug-resistant mutation (n = 12). PrEP consisted of oral Truvada (n = 6, WT), TFV vaginal gel (n = 6, K65R), or TFV intravaginal ring (n = 6, WT). The remaining animals were PrEP-inexperienced controls (n = 12, WT; n = 6, K65R). SHIV-specific T cells were identified and characterized using interferon γ Enzyme-Linked ImmunoSpot (ELISPOT) and multiparameter flow cytometry.. Of 9 animals that were on PrEP and remained uninfected during WT SHIV vaginal challenges, 8 (88.9%) developed virus-specific T-cell responses. T cells were in CD4 and CD8 compartments, reached up to 4900 interferon γ-producing cells per million peripheral blood mononuclear cells, and primarily pol directed. In contrast, the replication-impaired K65R virus did not induce detectable T-cell responses, likely reflecting the need for adequate replication.. Virus-specific T-cell responses occur frequently in oral or topical PrEP-protected pigtail macaques after vaginal exposure to WT SHIV virus. The contribution of such immune responses to protection from infection during and after PrEP warrants further investigation.

Topics: Administration, Oral; Administration, Topical; Animals; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Drug Resistance, Viral; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Macaca nemestrina; Organophosphorus Compounds; Pre-Exposure Prophylaxis; Reassortant Viruses; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; T-Lymphocytes

Topics: Anti-Retroviral Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Organophosphorus Compounds; Randomized Controlled Trials as Topic

Topics: Anti-HIV Agents; Centers for Disease Control and Prevention, U.S.; Chemoprevention; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Promotion; HIV Infections; Homosexuality, Male; Humans; Male; Organophosphorus Compounds; Primary Prevention; Transgender Persons; United States

Topics: Anti-HIV Agents; Arrhythmias, Cardiac; Autopsy; Coronary Angiography; Creatine Kinase; Deoxycytidine; Drug Combinations; Electrocardiography; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Fatal Outcome; HIV Infections; Humans; Lopinavir; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Muscular Diseases; Myocarditis; Myocardium; Organophosphorus Compounds; Pulmonary Edema; Ritonavir

The FEM-PrEP trial was a pre-exposure prophylaxis clinical trial to test the safety and efficacy of Truvada (tenofovir disoproxil fumarate and emtricitabine) in the prevention of human immunodeficiency virus infection. Because Truvada can suppress hepatitis B virus replication, and withdrawal of Truvada can cause hepatic flares in patients with chronic hepatitis B, pre-enrollment screening included serological screening for hepatitis B virus markers. Women with chronic infections were not enrolled in the trial. Women found to be unprotected against hepatitis B were enrolled and offered three doses of hepatitis B vaccine. Reinfection and reactivation of previously resolved hepatitis B virus infections have been documented in immunosuppressed individuals but not in healthy individuals. We present the case of a participant enrolled in the FEM-PrEP clinical trial with baseline evidence of immunity against hepatitis B virus who subsequently developed acute hepatitis B.. A 21-year-old Black non-pregnant woman was enrolled in the FEM-PrEP trial. She was human immunodeficiency virus-negative and a serological test for hepatitis B virus was negative. She had evidence of low levels of protection against hepatitis B virus and normal liver function. She had no hepatitis B vaccination history, thus it was concluded that she had post-infection immunity. At week 36 she presented with severely elevated liver enzyme levels that, upon further investigation, were a result of acute hepatitis B virus infection. The infection followed an asymptomatic course until full recovery of her liver enzymes a few weeks later. At study unblinding, the participant was found to be on the Truvada arm. Retrospective plasma drug level testing found low levels of study drugs from week 4. The participant remained human immunodeficiency virus-negative throughout the study.. Hepatitis B virus infection reactivation or reinfection is a rare phenomenon in healthy individuals. However, reactivations have been reported in patients being treated for chronic hepatitis B with the drugs contained in Truvada, after treatment had been withdrawn. This participant may have reactivated after stopping Truvada, or she may have reactivated spontaneously owing to relatively low levels of protective antibodies against hepatitis B. Alternatively, she may have been reinfected. Clinicians should be aware that hepatitis B virus reactivation or reinfection may cause elevated transaminases even in the presence of low baseline immunity.

Topics: Adult; Alanine Transaminase; Anti-HIV Agents; Clinical Trials as Topic; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Hepatitis B; Hepatitis B Antibodies; Hepatitis B virus; Hepatitis B, Chronic; HIV Infections; Humans; Liver; Practice Guidelines as Topic; Pre-Exposure Prophylaxis; Retrospective Studies; Treatment Outcome; Virus Activation

Topics: Biomedical Technology; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Services Research; HIV Infections; Humans

Monocytes are increasingly implicated in the inflammatory consequences of HIV-1 disease, yet their phenotype following antiretroviral therapy (ART) initiation is incompletely defined. Here, we define more completely monocyte phenotype both prior to ART initiation and during 48 weeks of ART.. Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained at baseline (prior to ART initiation) and at weeks 12, 24, and 48 of treatment from 29 patients participating in ACTG clinical trial A5248, an open label study of raltegravir/emtricitibine/tenofovir administration. For comparison, cryopreserved PBMCs were obtained from 15 HIV-1 uninfected donors, each of whom had at least two cardiovascular risk factors. Thawed samples were stained for monocyte subset markers (CD14 and CD16), HLA-DR, CCR2, CX3CR1, CD86, CD83, CD40, CD38, CD36, CD13, and CD163 and examined using flow cytometry.. In untreated HIV-1 infection there were perturbations in monocyte subset phenotypes, chiefly a higher frequency and density (mean fluorescence intensity-MFI) of HLA-DR (%-p = 0.004, MFI-p = .0005) and CD86 (%-p = 0.012, MFI-p = 0.005) expression and lower frequency of CCR2 (p = 0.0002) expression on all monocytes, lower CCR2 density on inflammatory monocytes (p = 0.045) when compared to the expression and density of these markers in controls' monocytes. We also report lower expression of CX3CR1 (p = 0.014) on patrolling monocytes at baseline, compared to levels seen in controls. After ART, these perturbations tended to improve, with decreasing expression and density of HLA-DR and CD86, increasing CCR2 density on inflammatory monocytes, and increasing expression and density of CX3CR1 on patrolling monocytes.. In HIV-1 infected patients, ART appears to attenuate the high levels of activation (HLA-DR, CD86) and to increase expression of the chemokine receptors CCR2 and CX3CR1 on monocyte populations. Circulating monocyte phenotypes are altered in untreated infection and tend to normalize with ART; the role of these cells in the inflammatory environment of HIV-1 infection warrants further study.

Topics: Adult; Anti-HIV Agents; Antigens, CD; Antiretroviral Therapy, Highly Active; Cell Separation; CX3C Chemokine Receptor 1; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Flow Cytometry; HIV Infections; HIV Integrase Inhibitors; HIV-1; HLA-DR Antigens; Humans; Immunophenotyping; Male; Middle Aged; Monocytes; Raltegravir Potassium; Receptors, CCR2; Receptors, Chemokine; Viral Load; Viremia

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Unsafe Sex

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Medication Adherence; Pre-Exposure Prophylaxis; Research Design

Preexposure prophylaxis (PrEP) is a promising approach to prevention of human immunodeficiency virus (HIV) transmission, in which an HIV-negative individual takes a single daily dose of an antiretroviral drug so that, if exposed to HIV, an active antiretroviral drug is already present in his or her system. In this issue of the Journal, Murnane et al. (Am J Epidemiol. 2015;182(10):848-856) use data from the Partners PrEP Study (Kenya and Uganda, 2008-2011) to estimate the efficacy of PrEP under perfect adherence. We discuss Murnane et al.'s work and then examine the larger issues of generalizability or transportability of findings from a randomized trial to a new setting when adherence to an intervention determines its effectiveness. We discuss sufficient conditions for generalizability and use causal directed acyclic graphs to show how these assumptions might play out when trials are used to make inferences about the effect of PrEP in current and future real-world target populations.

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Medication Adherence; Pre-Exposure Prophylaxis; Research Design

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Pre-Exposure Prophylaxis

Topics: Anti-HIV Agents; Drug Costs; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Insurance Coverage; Pre-Exposure Prophylaxis

Topics: Anti-HIV Agents; Automobiles; Coma; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; France; Gyrus Cinguli; HIV Infections; Humans; Neural Pathways; Prefrontal Cortex; Recovery of Function; Smoke-Free Policy; Tobacco Smoke Pollution

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; France; HIV Infections; Humans; Reimbursement Mechanisms

Occupational transmission of HIV among healthcare personnel is rare but has repeatedly been published in the literature. Early initiation of postexposure HIV prophylaxis (HIV-PEP) is crucial to prevent virus transmission. For this reason the need for HIV-PEP has to be evaluated immediately and if necessary, started as soon as possible. This article presents an early intervention program in a university hospital which enables healthcare personnel immediate 24/7/365 access to a HIV-PEP prophylaxis kit following occupational HIV exposure.

Topics: Administration, Oral; Anti-HIV Agents; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Early Medical Intervention; Emergency Treatment; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Germany; HIV Infections; Humans; Infectious Disease Transmission, Patient-to-Professional; Lopinavir; Needlestick Injuries; Organophosphorus Compounds; Post-Exposure Prophylaxis; Pyrrolidinones; Raltegravir Potassium; Ritonavir

 Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (Truvada) has demonstrated efficacy in placebo-controlled clinical trials involving men who have sex with men, high-risk heterosexuals, serodiscordant couples, and intravenous drug users. To assist in the real-world provision of PrEP, the Centers for Disease Control and Prevention (CDC) has released guidance documents for PrEP use..  Adult infectious disease physicians were surveyed about their opinions and current practices of PrEP through the Emerging Infections Network (EIN). Geographic information systems analysis was used to map out provider responses across the United States..  Of 1175 EIN members across the country, 573 (48.8%) responded to the survey. A majority of clinicians supported PrEP but only 9% had actually provided it. Despite CDC guidance, PrEP practices were variable and clinicians reported many barriers to its real-world provision..  The majority of adult infectious disease physicians across the United States and Canada support PrEP but have vast differences of opinion and practice, despite the existence of CDC guidance documents. The success of real-world PrEP will likely require multifaceted programs addressing barriers to its provision and will be assisted with the development of comprehensive guidelines for real-world PrEP.

Topics: Adult; Anti-HIV Agents; Canada; Chemoprevention; Deoxycytidine; Disease Transmission, Infectious; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Organophosphorus Compounds; Pre-Exposure Prophylaxis; United States

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Organophosphorus Compounds; Patient Acceptance of Health Care

Topics: Antiretroviral Therapy, Highly Active; Canada; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds; Pilot Projects; Primary Prevention

Topics: Anti-HIV Agents; Chemoprevention; Deoxycytidine; Disease Transmission, Infectious; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Organophosphorus Compounds; Pre-Exposure Prophylaxis

Topics: Anti-HIV Agents; Chemoprevention; Deoxycytidine; Disease Transmission, Infectious; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Organophosphorus Compounds; Pre-Exposure Prophylaxis

Topics: Anti-HIV Agents; Centers for Disease Control and Prevention, U.S.; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds; United States

The AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) clinical trial examined the efficacy and safety of two ritonavir-boosted protease inhibitors (PI/r), darunavir/r 800/100 mg once daily (QD) and lopinavir/r 800/200 mg daily, both used in combination with tenofovir disoproxil fumarate/emtricitabine. This study aimed to assess the cost effectiveness of the darunavir/r regimen compared with the lopinavir/r regimen in treatment-naive adults with HIV-1 infection in Canada.. A Markov model with a 3-month cycle time and six CD4 cell-count-based health states (>500, 351-500, 201-500, 101-200, 51-100, and 0-50 cells/mm(3)) followed a cohort of treatment-naive adults with HIV-1 infection through initial darunavir/r or lopinavir/r combination therapy and a common set of subsequent regimens over the course of their remaining lifetimes. Population characteristics and transition probabilities were estimated from the ARTEMIS clinical trial and other trials. Costs (in 2014 Canadian dollars), utilities, and mortality were estimated from Canadian sources and published literature. Costs and health outcomes were discounted at 5% per year. One-way and probabilistic sensitivity analyses were performed, including a simple indirect comparison of the darunavir/r initial regimen with an atazanavir/r-based regimen.. In the base-case lifetime analysis, individuals receiving initial therapy with the darunavir/r regimen experienced 0.25 more quality-adjusted life-years (QALYs) with lower antiretroviral drug costs (-$14,246) and total costs (-$18,402) than individuals receiving the lopinavir/r regimen, indicating that darunavir/r dominated lopinavir/r. In an indirect comparison with an atazanavir/r-based regimen, the darunavir/r regimen remained the dominant choice, but with lower cost savings (-$2,303) and QALY gains (0.02). Results were robust to a wide range of other changes in input parameter values, population characteristics, and modeling assumptions. The probabilistic sensitivity analysis demonstrated that the darunavir/r regimen was cost effective compared with the lopinavir/r regimen in over 86% of simulations for willingness-to-pay thresholds between $0 and $100,000 per QALY gained.. Darunavir/r 800/100 mg QD may be a cost-effective PI/r component of initial antiretroviral therapy for treatment-naive adults with HIV-1 infection in Canada.

Topics: Adult; Antiretroviral Therapy, Highly Active; Canada; CD4 Lymphocyte Count; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Darunavir; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Markov Chains; Ritonavir

Topics: Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Hospitals; Humans; Organophosphorus Compounds; Pre-Exposure Prophylaxis; Rhode Island

Topics: Adult; Anti-Retroviral Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Organophosphorus Compounds; Treatment Outcome

Topics: Anti-HIV Agents; Centers for Disease Control and Prevention, U.S.; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV Seronegativity; Humans; Male; Organophosphorus Compounds; Risk-Taking; Sexual Behavior; United States

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Medicalization; Organophosphorus Compounds

Amidst growing global endorsements of new biomedical HIV prevention strategies, ARV-based pre-exposure prophylaxis (ARV PrEP) has garnered considerable attention as a potentially promising prevention strategy. Though it may offer more effective protection for certain at-risk groups than conventional prevention strategies (such as sexual partner reduction, condom use, and prevention of mother-to-child transmission), PrEP is more costly. PrEP requires more ongoing contact between individuals and providers, and a level of surveillance from the health system that is not necessary with other preventive measures. In this sense, it represents a new bio-technology for HIV prevention that poses particular challenges for worldwide implementation, given developing countries' struggling health systems and incomplete HIV treatment programs. Since the emergence of PrEP has stimulated ethical discussions premised on incomplete knowledge of efficacy and implementation, this paper explores the ethical parameters of a likely scenario for PrEP usage in a single, resource-poor country. We first develop a plausible model for PrEP deployment and utilization based on current PrEP research, while carefully considering the reigning institutional values of feasibility and effectiveness in global health approaches. Drawing on ethnographic research of HIV treatment and prevention approaches in Lesotho, we address ethical questions arising from this scenario of PrEP delivery. Lesotho presents a compelling and emblematic case study of PrEP's potential successes and pitfalls in a developing country, given the country's high HIV prevalence, struggles to achieve universal access to HIV treatment regimes, continued existence of stigma around the epidemic, and difficulties in addressing persistent social inequalities that fuel infections.

Topics: Adolescent; Adult; Anti-HIV Agents; Anti-Retroviral Agents; Benzoates; Deoxycytidine; Disease Transmission, Infectious; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Global Health; Health Care Rationing; HIV Infections; HIV Seronegativity; HIV Seropositivity; Humans; Infectious Disease Transmission, Vertical; Lesotho; Male; Medication Adherence; Models, Organizational; Morals; Organophosphorus Compounds; Primary Prevention; Pyrazoles; South Africa; Transients and Migrants; Young Adult

Regular condom use is the standard method for preventing HIV transmission during insertive intercourse. Effective treatment of infected individuals also reduces the risk of transmission. However, even when these preventive measures are used correctly, they are not completely reliable. Emtricitabine (a nucleoside) and tenofovir (a nucleotide) are HIV reverse transcriptase inhibitors. The combination of these 2 drugs has been authorised in the United States for the prevention of HIV-1 infection in adults at high risk, in combination with other preventive measures. Clinical evaluation is based mainly on two double-blind placebo-controlled trials. In a trial involving 2499 men or transgender women (born male) who have sex with men, conducted outside Europe, the incidence of infection was lower among patients treated with emtricitabine + tenofovir than with placebo (2.3 versus 4.3 per 100 person-years, p = 0.005). A subgroup analysis showed no added preventive effect of this treatment among condom users. Another trial including 4758 heterosexual couples in which only one partner was infected, conducted in Uganda and Kenya, showed a lower incidence of HIV infection in the emtricitabine + tenofovir group than in the placebo group after one year of treatment (0.50 versus 1.99 per 100 person-years). No statistically significant difference was found between the emtricitabine + tenofovir combination and tenofovir single-agent prophylaxis. Drug prevention showed no added efficacy in this trial among patients who regularly used condoms. Other trials conducted in Africa among heterosexuals favour the preventive efficacy of emtricitabine + tenofovir, except in one trial in which adherence appeared to be very poor. These trials did not identify any previously unknown adverse effects of emtricitabine + tenofovir. Tenofovir can cause kidney failure. Data from a US registry of pregnancies exposed to emtricitabine or tenofovir rule out any major risk of teratogenicity. In situations in which there is a high risk of HIV transmission, daily intake of emtricitabine + tenofovir appears to roughly halve the risk of sexual transmission, without eliminating it completely. In Western Europe, only persons with infected partners and those who engage in risky sexual practices without condoms are at high risk of infection. Long-term assessment of emtricitabine + tenofovir is justified in these situations, despite the mixed results of previous trials.

Topics: Adult; Anti-HIV Agents; Condoms; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV Reverse Transcriptase; Humans; Male; Organophosphorus Compounds; Reverse Transcriptase Inhibitors; Risk; Risk-Taking; Sexual Behavior

Topics: Anti-HIV Agents; Clinical Trials as Topic; Deoxycytidine; Drug Approval; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Organophosphorus Compounds; Risk Factors; Sexual Partners; Unsafe Sex

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds; Politics

Topics: Anti-HIV Agents; Civil Rights; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Organophosphorus Compounds; United States

Topics: Anti-HIV Agents; Bisexuality; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Services Accessibility; HIV Infections; Homosexuality, Male; Humans; Male; Organophosphorus Compounds; Politics; Risk Factors

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds

The effect of hepatitis C virus (HCV) on antiretroviral therapy (ART) response in patients in sub-Saharan Africa is unknown. We studied 1431 HIV-infected ART initiators in Jos, Nigeria, of whom 6% were HCV coinfected. A similar proportion of HIV/HCV-coinfected and HIV-monoinfected patients achieved HIV RNA <400 copies per milliliter after 24 and 48 weeks of ART (P > 0.05). Hepatotoxicity was uncommon (0.8% and 0.33% at 24 and 48 weeks, respectively) but was more common in the HIV/HCV-coinfected group at 24 (adjusted odds ratio = 19.3; 95% confidence interval: 4.41 to 84.4) and 48 weeks (adjusted odds ratio = 56.7; 95% confidence interval: 5.03 to 636.92). HCV did not significantly impact ART response in this Nigerian cohort.

Topics: Adult; Alanine Transaminase; Alkynes; Anti-Retroviral Agents; Benzoxazines; Chemical and Drug Induced Liver Injury; Coinfection; Cyclopropanes; Deoxycytidine; Drug Combinations; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Hepacivirus; Hepatitis C, Chronic; HIV Infections; Humans; Lamivudine; Logistic Models; Male; Nevirapine; Nigeria; Organophosphorus Compounds; RNA, Viral; Stavudine; Zidovudine

In 2008, the Pre-exposure Prophylaxis Initiative (iPrEx) study expanded to include men who have sex with men (MSM) in Chiang Mai, Thailand. In full, 114 participants from Chiang Mai joined this international double-blinded trial of daily FTC-TDF (Truvada®) or placebo as a pre-exposure prophylaxis (PrEP) HIV prevention strategy. To better understand the characteristics of iPrEx participants specifically from this underserved population in Thailand, and gain insights into their experiences of trying to take a daily tablet as part of this blinded PrEP trial, we conducted a qualitative study. In 2010, 32 MSM iPrEx participants provided in-depth interviews and an additional 14 joined focus group discussions. Results of the qualitative analyzes suggested that participants held generally positive attitudes toward the iPrEx study and study medication and related this to high rates of adherence to the daily regimen. Participants also reflected on the provision of quality health care as part of participation in the trial, as well as support from clinical research staff, family and friends as helpful in supporting high rates of study medication adherence. Discourse concerning challenges to adherence included medication taking behavior, which was contextualized by lifestyle, living arrangement, social life, social stigma in terms of being mistakenly identified as HIV positive or unintentional disclosure of sexual identity to family and friends, and relationship conflicts with partners. The results provide broader perspectives of participant experiences of the study medication and daily adherence in the larger contexts of the MSM community, close relationships, and the study climate, and can be leveraged in constructing PrEP adherence support approaches within these communities.

Topics: Adult; Anti-HIV Agents; Deoxycytidine; Double-Blind Method; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Focus Groups; Health Knowledge, Attitudes, Practice; Health Services Accessibility; HIV Infections; Homosexuality, Male; Humans; Interviews as Topic; Male; Medication Adherence; Organophosphorus Compounds; Preventive Health Services; Thailand; Young Adult

Topics: Anti-HIV Agents; Deoxycytidine; Diffusion of Innovation; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Plan Implementation; HIV Infections; Humans; Organophosphorus Compounds; Primary Prevention

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Plan Implementation; HIV Infections; Humans; Organophosphorus Compounds; Primary Prevention

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Plan Implementation; HIV Infections; Humans; Organophosphorus Compounds; Primary Prevention

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Research

PC-1505 is a C34 peptide derived from the heptad repeat 2 region of HIV-1 gp41 conjugated to human serum albumin for sustained in vivo activity. One single preexposure dose of PC-1505 reduced viral RNA in HIV-1-infected SCID-hu Thy/Liv mice by 3.3 log₁₀ and protected T cells from virus-mediated depletion. In contrast, a single preexposure dose of Truvada reduced viral RNA by only 0.8 log₁₀ and was substantially less effective in preventing T cell depletion.

Topics: Animals; Deoxycytidine; Dose-Response Relationship, Drug; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Genes, MHC Class I; HIV Core Protein p24; HIV Fusion Inhibitors; HIV Infections; Mice; Mice, SCID; Organophosphorus Compounds; Peptides; RNA, Viral; Thymocytes

Topics: Adenine; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Organophosphonates; Organophosphorus Compounds; Tenofovir; United Kingdom

We investigated the dynamics of HIV RNA and HIV DNA levels after the commencement of raltegravir-based antiretroviral therapy (ART) in primary (PHI) and chronically HIV-infected (CHI) individuals (the PINT study).. We recruited 8 PHI and 8 CHI ART-naive individuals who commenced a 1-year combination regimen of Truvada and the integrase inhibitor raltegravir.. Nonlinear mixed effects modelling was used to determine multiphasic decay of plasma HIV RNA levels (pVL), as well as dynamics of total, episomal [2-long terminal repeats (LTR)] and integrated HIV DNA in CD4 T cells from peripheral blood.. Although pVL decreased faster through first and second phase for PHI individuals there was no difference in the final level reaching a mean of 9 copies/ml by week 16 that was maintained thereafter. Total HIV DNA and integrated HIV DNA levels from CHI patients were significantly higher than from PHI patients. However, at no time did 2-LTR levels differ between groups. Of note, 2-LTR circles exhibited an initial increase peaking at week 3 followed by biphasic decay with a half-life of 29 days. Second phase integrated HIV DNA levels were significantly correlated with duration of infection and consistent with this form of infection occurring at approximately 100 000 integration events per day in the absence of ART, achieving its 50% level 2 years after infection.. Integrated HIV DNA levels accumulate with duration of untreated HIV infection. The relatively short half-life and high levels of 2-LTR circles after 1 year support continued HIV transmission during ART.

Topics: Blotting, Western; CD4 Lymphocyte Count; Chronic Disease; Deoxycytidine; DNA, Viral; Drug Combinations; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV Integrase Inhibitors; HIV-1; Humans; Organophosphorus Compounds; Pyrrolidinones; Raltegravir Potassium; Real-Time Polymerase Chain Reaction; RNA, Viral

Topics: Advisory Committees; Anti-HIV Agents; Deoxycytidine; Drug Approval; Drug Combinations; Drug Resistance, Viral; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV; HIV Infections; Humans; Male; Medication Adherence; Organophosphorus Compounds; Risk-Taking; United States; United States Food and Drug Administration

In 2010, randomized controlled trials (RCTs) of two different biomedical strategies to prevent HIV infection had positive findings. However, despite ongoing very high levels of HIV infection in some countries and population groups, it has been made clear by regulatory authorities that the evidence remains insufficient to support either product being made available outside of research contexts in the developing world for at least two years. In addition, prevention trials in endemic areas will continue to test new interventions against placebo. But the judgments of evidentiary standards are never value-neutral. Using the recent trials and their contexts as case studies, we examine the basis for these decisions, which will potentially delay access to scientific innovation to the people who are most urgently in need of it.

Topics: Adenine; Administration, Intravaginal; Administration, Oral; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Ethical Analysis; Ethical Theory; Ethics, Research; Evidence-Based Medicine; Female; Gels; Guidelines as Topic; Health Services Accessibility; Health Services Needs and Demand; HIV Infections; Homosexuality, Male; Humans; Male; Organophosphonates; Organophosphorus Compounds; Primary Prevention; Randomized Controlled Trials as Topic; Research Subjects; Sex Work; Tenofovir; Therapeutic Equipoise; United States; United States Food and Drug Administration

Topics: Anti-HIV Agents; Deoxycytidine; Drug Approval; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds; United States; United States Food and Drug Administration

Topics: Administration, Oral; Anti-Retroviral Agents; Deoxycytidine; Drug Administration Schedule; Drug Approval; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Organophosphorus Compounds; Randomized Controlled Trials as Topic; Risk; Sexually Transmitted Diseases; United States; United States Food and Drug Administration

Topics: Anti-Retroviral Agents; Cost-Benefit Analysis; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Ethics, Medical; Female; HIV Infections; HIV Seronegativity; Humans; Male; Medically Underserved Area; Organophosphorus Compounds; Risk; Sexual Behavior; Social Justice; Unsafe Sex

Topics: Adenine; Anti-HIV Agents; Antiviral Agents; Deoxycytidine; Drug Combinations; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Organophosphorus Compounds; Primary Prevention; Tenofovir; United States; United States Food and Drug Administration

Topics: Anti-HIV Agents; Cost-Benefit Analysis; Deoxycytidine; Drug Approval; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphorus Compounds; United States; United States Food and Drug Administration

In the past few years, the transdisciplinary field of HIV prevention has reached several milestones. Topically applied tenofovir gel provided significant protection from sexual transmission of HIV in a large-scale clinical trial and oral Truvada (emtricitabine/tenofovir disoproxil fumarate) was recently approved for preexposure prophylaxis (PrEP) following two successful clinical trials in men and women. These achievements are tempered by the disappointing results of other clinical trials, which highlight the complexities of prevention research. In this perspective, we discuss scientific and developmental gaps for topical chemoprophylaxis of the sexual transmission of HIV, which depends on the complex interactions between the pharmacokinetics and pharmacodynamics of drugs, formulation and delivery systems, anatomic site of transmission, and host mucosal immune defenses. Despite the considerable time and resources devoted to unraveling the initial steps in sexual transmission of HIV, current knowledge is based on animal models and human explanted tissue, which may not fully recapitulate what happens clinically. Understanding these events, including the role that sex hormones, semen, and mucosal secretions play in transmission, and the interplay between innate immunity, the mucosal environment, and drug efficacy is paramount. This drives some of the most pressing questions in the field.

Topics: Adenine; Administration, Oral; Administration, Topical; Anal Canal; Anti-HIV Agents; Chemoprevention; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Immunity, Innate; Male; Medication Adherence; Mouth Mucosa; Mucous Membrane; Organophosphonates; Organophosphorus Compounds; Sexual Partners; Tenofovir; Vagina; Vaginal Creams, Foams, and Jellies

Topics: Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Heterosexuality; HIV Infections; Humans; Organophosphorus Compounds

Investigate the cost and effects of a single-pill versus two- or three pill first-line antiretroviral combinations in reducing viral load, increasing CD4 counts, and first-line failure rate associated with respective regimens at 6 and 12 months.. Patients on first-line TDF+3TC+EFV, TDF+FTC+EFV, Truvada®+EFV or Atripla® between 1996-2008 were identified and viral load and CD4 counts measured at baseline, six and twelve months respectively. Factors that independently predicted treatment failure at six and twelve months were derived using multivariate Cox's proportional hazard regression analyses. Use and cost of hospital services were calculated at six and twelve months respectively.. All regimens reduced viral load to below the limit of detection and CD4 counts increased to similar levels at six and twelve months for all treatment regimens. No statistically significant differences were observed for rate of treatment failure at six and twelve months. People on Atripla® generated lower healthcare costs for non-AIDS patients at £5,340 (£5,254 to £5,426) per patient-semester and £9,821 (£9,719 to £9,924) per patient-year that was £1,344 (95%CI £1,222 to £1,465) less per patient-semester and £1,954 (95%CI £1,801 to £2,107) less per patient-year compared with Truvada®+EFV; healthcare costs for AIDS patients were similar across all regimens.. The single pill regimen is as effective as the two- and three-pill regimens of the same drugs, but if started as first-line induction therapy there would be a 20% savings on healthcare costs at six and 17% of costs at twelve months compared with Truvada®+EFV, that generated the next lowest costs.

Topics: Adenine; Adult; Anti-Retroviral Agents; CD4 Lymphocyte Count; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Health Care Costs; HIV Infections; Humans; Male; Middle Aged; Organophosphonates; Organophosphorus Compounds; Oxazines; Proportional Hazards Models; United Kingdom; Viral Load

Daily pre-exposure prophylaxis (PrEP) with Truvada (a combination of emtricitabine (FTC) and tenofovir (TFV) disoproxil fumarate (TDF)) is a novel HIV prevention strategy recently found to prevent HIV transmission in men who have sex with men and heterosexual couples. We previously showed that a coitally-dependent Truvada regimen protected macaques against rectal SHIV transmission. Here we examined FTC and tenofovir TFV exposure in vaginal tissues after oral dosing and assessed if peri-coital Truvada also protects macaques against vaginal SHIV infection.. The pharmacokinetic profile of emtricitabine (FTC) and tenofovir (TFV) was evaluated at first dose. FTC and TFV levels were measured in blood plasma, rectal, and vaginal secretions. Intracellular concentrations of FTC-triphosphate (FTC-TP) and TFV-diphosphate (TFV-DP) were measured in PBMCs, rectal tissues, and vaginal tissues. Efficacy of Truvada in preventing vaginal SHIV infection was assessed using a repeat-exposure vaginal SHIV transmission model consisting of weekly exposures to low doses of SHIV162p3. Six pigtail macaques with normal menstrual cycles received Truvada 24 h before and 2 h after each weekly virus exposure and six received placebo. Infection was monitored by serology and PCR amplification of SHIV RNA and DNA.. As in humans, the concentration of FTC was higher than the concentration of TFV in vaginal secretions. Also as in humans, TFV levels in vaginal secretions were lower than in rectal secretions. Intracellular TFV-DP concentrations were also lower in vaginal tissues than in rectal tissues. Despite the low vaginal TFV exposure, all six treated macaques were protected from infection after 18 exposures or 4 full menstrual cycles. In contrast, all 6 control animals were infected.. We modeled a peri-coital regimen with two doses of Truvada and showed that it fully protected macaques from repeated SHIV exposures. Our results open the possibility for simplified PrEP regimens to prevent vaginal HIV transmission in women.

Topics: Animals; Coitus; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Macaca nemestrina; Organophosphorus Compounds; Progesterone; Simian Acquired Immunodeficiency Syndrome; Vagina

Topics: Antiviral Agents; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Organophosphorus Compounds; Risk Factors; United States; United States Food and Drug Administration

Topics: Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Sexual Behavior; Transgender Persons

Topics: Anti-HIV Agents; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Organophosphorus Compounds; Patient Compliance

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Early Termination of Clinical Trials; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Organophosphorus Compounds

Topics: Adenine; Administration, Oral; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Kenya; Organophosphonates; Organophosphorus Compounds; Patient Compliance; Randomized Controlled Trials as Topic; South Africa; Tanzania; Tenofovir

Topics: Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Organophosphorus Compounds; Risk Factors

Topics: Anti-HIV Agents; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Homosexuality, Male; Humans; Male; Organophosphorus Compounds; Post-Exposure Prophylaxis; United States; United States Food and Drug Administration

Topics: Anti-HIV Agents; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Drug Costs; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Medication Adherence; Organophosphorus Compounds

Topics: Chemoprevention; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Health; HIV Infections; Humans; Male; Organophosphorus Compounds; United States; United States Food and Drug Administration; Unsafe Sex

Topics: Adenine; Anti-HIV Agents; Atazanavir Sulfate; CD4 Lymphocyte Count; Clinical Trials, Phase II as Topic; Cytochrome P-450 CYP3A Inhibitors; Deoxycytidine; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Multicenter Studies as Topic; Oligopeptides; Organophosphonates; Organophosphorus Compounds; Oxazines; Pyridines; Quinolones; Randomized Controlled Trials as Topic; Ritonavir; Treatment Outcome; Viral Load

Topics: Adenine; Animals; Anti-HIV Agents; Bone Marrow Transplantation; Clinical Trials as Topic; Deoxycytidine; Disease Models, Animal; Drug Combinations; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV; HIV Antibodies; HIV Infections; Humans; Infection Control; Liver Transplantation; Mice; Occupational Exposure; Organophosphonates; Organophosphorus Compounds; Tenofovir; Thymus Gland; Transplantation Chimera

Topics: Anti-HIV Agents; Clinical Trials, Phase III as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Nitriles; Organophosphorus Compounds; Pyrimidines; Reverse Transcriptase Inhibitors; Rilpivirine; Therapeutic Equivalency

Topics: Adenine; Antiviral Agents; Deoxycytidine; Drug Approval; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Organophosphonates; Organophosphorus Compounds; Technology Transfer; Tenofovir; Vaginal Creams, Foams, and Jellies

Topics: Anti-HIV Agents; Deoxycytidine; Drug Combinations; Drug Costs; Drug Resistance, Viral; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV; HIV Infections; Homosexuality, Male; Humans; Male; Medication Adherence; Organophosphorus Compounds; Randomized Controlled Trials as Topic; Transsexualism

The objective was to evaluate the effectiveness and safety of simplification from tenofovir-lamivudine (TDF-3TC) to Truvada (TVD) in virologically suppressed HIV patients. We carried out an open-label, multicentre, non-controlled study of HIV patients on a stable regimen including TDF-3TC who switched from TDF-3TC to TVD. Viral load responses at 24 and 48 weeks were evaluated. Changes in the calculated glomerular filtration rates (cGFR; Cockcroft-Gault equation) were analysed at baseline and at 24 and 48 weeks. Patients with drug-related nephrotoxicity (cGFR < 60 mL/min at 48 weeks or interruption of TVD because of renal toxicity) were analysed in detail. Two hundred and ninety-five patients with a mean time on TDF-3TC of 19.9 months (range 8.8-29.8) were enrolled. The third drug was a non-nucleoside reverse transcriptase inhibitor, which was administered to 187 patients (76.4% efavirenz) and a protease inhibitor was administered to 108 (43.5% lopinavir/ritonavir). At 48 weeks, 85.7% of the patients were still taking the same regimen, all with an undetectable viral load. The cGFR (mL/min) decreased from baseline (111 [89-130]) to 48 weeks (105 [84-121]); p < 0.0001. The percentage of patients with a cGFR <60 mL/min at 48 weeks was 3.5. Six patients ceased TVD because of drug-related nephrotoxicity. The only factors associated with nephrotoxicity were age, baseline weight and cGFR. Simplification from TDF-3TC to TVD was associated with a decrease in cGFR, with a low prevalence of nephrotoxicity at 48 weeks.

Topics: Adenine; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Central Nervous System; Cohort Studies; Creatinine; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV-1; Humans; Kidney; Lamivudine; Male; Metabolic Clearance Rate; Middle Aged; Organophosphonates; Organophosphorus Compounds; Retrospective Studies; Risk Factors; RNA, Viral; Tenofovir; Viral Load

Topics: Adenine; Anti-HIV Agents; Deoxycytidine; Drug Approval; Drug Combinations; Drugs, Generic; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Organophosphorus Compounds; Reverse Transcriptase Inhibitors; Tenofovir; United States; United States Food and Drug Administration

Topics: Adenine; Anti-Retroviral Agents; Deoxycytidine; Drug Combinations; Drug Industry; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Organophosphorus Compounds; Oxazines

Topics: CD4 Lymphocyte Count; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV; HIV Infections; Humans; Lamivudine; Organophosphorus Compounds; Viral Load

Topics: Anti-HIV Agents; Clinical Trials, Phase III as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV Reverse Transcriptase; Humans; Nitriles; Organophosphorus Compounds; Pyrimidines; Rilpivirine; Tablets

Topics: Animals; Anti-HIV Agents; Congresses as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Haplorhini; HIV Infections; Humans; Mexico; Organophosphorus Compounds

Topics: Anti-HIV Agents; CD4 Lymphocyte Count; Deoxycytidine; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV Integrase Inhibitors; Humans; Multicenter Studies as Topic; Organophosphorus Compounds; Pyrrolidinones; Raltegravir Potassium; Randomized Controlled Trials as Topic; RNA, Viral

Topics: Animals; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Male; Organophosphorus Compounds; South Africa

Topics: Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Lamivudine; Lipids; Lipodystrophy; Organophosphorus Compounds; Viral Load; Zidovudine

Topics: Anti-Retroviral Agents; Clinical Trials as Topic; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Lamivudine; Organophosphorus Compounds; Viral Load

Topics: Adult; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Gastrointestinal Diseases; HIV Infections; Humans; Male; Middle Aged; Organophosphorus Compounds

Topics: Adolescent; Anti-Retroviral Agents; Deoxycytidine; Drug Combinations; Drug Hypersensitivity; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Male; Organophosphorus Compounds

Abacavir/lamivudine (Epzicom) and emtricitabine/tenofovir (Truvada), two new once-daily fixed-dose NRTI combinations, have been approved for use in antiretroviral regimens to treat HIV infection. Epzicom appears to be as effective as its components taken separately and, in one study, Truvada was at least as effective as zidovudine/lamivudine (Combivir). Use of once-daily fixed-dose combinations means less flexibility in dosing, and some patients with hepatic or renal impairment will not be able to take them.

Topics: Anti-HIV Agents; Deoxycytidine; Dideoxynucleosides; Dose-Response Relationship, Drug; Drug Combinations; Drug Hypersensitivity; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Lamivudine; Organophosphorus Compounds

Topics: Anti-HIV Agents; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Organophosphorus Compounds

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Clinical Trials as Topic; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Drug Resistance, Viral; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Organophosphorus Compounds; Patient Compliance; Practice Guidelines as Topic; Survival Rate; Tenofovir