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

The current recommended antiretroviral treatment is a highly active antiretroviral therapy (HAART). Although HAART has been associated with improved clinical response to treatment, issues of adherence and viral resistance are major challenges limiting its success. There is a need for an effective and safe first-line regimen, to cope with the ever-increasing incidence of non-adherence and primary resistance. A more recent first-line treatment regimen consists of Tenofovir (TDF, 300 mg) + Emtricitabine (FTC, 200 mg) + Efavirenz (EFV, 600 mg).. To evaluate the effects and safety of TDF + FTC + EFV as first-line treatment for patients with HIV.. We searched the Cochrane Central Register of Controlled Trials, EMBASE, GATEWAY, LILACS, PubMed, AEGIS, and the WHO prospective clinical trials registry in November 2011.. Randomized controlled trials evaluating the effects of TDF + FTC + EFV compared with other HAART regimens.. Two reviewers independently assessed trial eligibility and risk of bias, and extracted data from the included study.. Only one study involving 517 antiretroviral-naive HIV infected adults was included in this review. Participants were randomly assigned to receive either a regimen of TDF (300 mg), FTC (200mg), and EFV (600mg ) once daily; or a regimen of fixed-dose zidovudine (AZT) (300 mg) and lamivudine (3TC) (150 mg) twice daily plus EFV (600mg) once daily. Significantly more patients in the TDF-FTC group reached and maintained HIV RNA levels of less than 50 copies per milliliter compared to the AZT- 3TC group (RR 1.13; 95% CI 1.02 to 1.25). Also, more participants in the TDF-FTC group had greater increase from baseline CD4 cell counts compared to the AZT-3TC group (190 vs. 158 cells per mm(3)). More patients in the AZT-3TC group than in the TDF-FTC group had adverse events resulting in discontinuation of the study drugs (9% vs. 4%, respectively; P = 0.02). There was no statistically significant difference in all cause mortality (RR 0.50; 95% CI 0.05 to 5.46).. Only one trial has shown beneficial effects and safety of TDF+ FTC + EFV as first-line treatment for patients with HIV. The effects and safety of TDF + FTC + EFV as first-line treatment for patients with HIV cannot be assessed on the basis of only one trial. Further studies evaluating the effects and safety of TDF + FTC + EFV as first-line treatment for patients with HIV are needed.

Topics: Adenine; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Oxazines; Reverse Transcriptase Inhibitors

The triple-drug once-daily combination pill containing tenofovir, emtricitabine and rilpivirine for HIV treatment was launched in 2011, both in the USA (Complera) and the E.U. (Eviplera). The active ingredients of Complera or Eviplera are the nucleotide reverse transcriptase inhibitor (NtRTI) tenofovir, the nucleoside reverse transcriptase inhibitor (NRTI) emtricitabine, and the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine. Rilpivirine originated from a collaborative research I had started with Dr. Paul Janssen in 1987, whereas tenofovir emanated from a collaborative research with Dr. Antonin Holý and Gilead Sciences. Exactly twenty-five years later rilpivirine and tenofovir joined each other, together with emtricitabine, in the same "combo" pill, representing a full treatment regimen for AIDS (HIV infection) based on a single once-daily pill.

Topics: Adenine; Animals; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Emtricitabine, Rilpivirine, Tenofovir Drug Combination; HIV Infections; HIV-1; Humans; Nitriles; Organophosphonates; Oxazines; Pyrimidines; Rilpivirine; Tenofovir

The current recommended antiretroviral treatment is a highly active antiretroviral therapy (HAART). Although HAART has been associated with improved clinical response to treatment, issues of adherence and viral resistance are major challenges limiting its success. There is a need for an effective and safe first-line regimen, to cope with the ever-increasing incidence of non-adherence and primary resistance. A more recent first-line treatment regimen consists of Tenofovir (TDF, 300 mg) + Emtricitabine (FTC, 200 mg) + Efavirenz (EFV, 600 mg).. To evaluate the effects and safety of TDF + FTC + EFV as first-line treatment for patients with HIV.. We searched the Cochrane Central Register of Controlled Trials, EMBASE, GATEWAY, LILACS, PubMed, AEGIS, and the WHO prospective clinical trials registry in November 2011.. Randomized controlled trials evaluating the effects of TDF + FTC + EFV compared with other HAART regimens.. Two reviewers independently assessed trial eligibility and risk of bias, and extracted data from the included study.. Only one study involving 517 antiretroviral-naive HIV infected adults was included in this review. Participants were randomly assigned to receive either a regimen of TDF (300 mg), FTC (200mg), and EFV (600mg ) once daily; or a regimen of fixed-dose zidovudine (AZT) (300 mg) and lamivudine (3TC) (150 mg) twice daily plus EFV (600mg) once daily. Significantly more patients in the TDF-FTC group reached and maintained HIV RNA levels of less than 50 copies per milliliter compared to the AZT- 3TC group (RR 1.13; 95% CI 1.02 to 1.25). Also, more participants in the TDF-FTC group had greater increase from baseline CD4 cell counts compared to the AZT-3TC group (190 vs. 158 cells per mm(3)). More patients in the AZT-3TC group than in the TDF-FTC group had adverse events resulting in discontinuation of the study drugs (9% vs. 4%, respectively; P = 0.02). There was no statistically significant difference in all cause mortality (RR 0.50; 95% CI 0.05 to 5.46).. Only one trial has shown beneficial effects and safety of TDF+ FTC + EFV as first-line treatment for patients with HIV. The effects and safety of TDF + FTC + EFV as first-line treatment for patients with HIV cannot be assessed on the basis of only one trial. Further studies evaluating the effects and safety of TDF + FTC + EFV as first-line treatment for patients with HIV are needed.

Topics: Adenine; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Oxazines; Reverse Transcriptase Inhibitors

The non-nucleoside reverse transcriptase inhibitor, efavirenz, and the two nucleoside reverse transcriptase inhibitors, emtricitabine and tenofovir disoproxil fumarate (tenofovir DF) are now available as a single-tablet regimen (efavirenz/emtricitabine/tenofovir DF 600 mg/200 mg/300 mg; Atripla®). The efavirenz/emtricitabine/tenofovir DF single-tablet regimen is the first once-daily, single-tablet, triple antiretroviral therapy (ART) formulation available for the treatment of HIV infection and, in the EU, is indicated for use in adults infected with HIV-1 who have been virologically suppressed for >3 months on their current ART regimen. In treatment-experienced adults with HIV-1 infection already virologically suppressed with ART, switching to once-daily triple combination therapy with efavirenz, emtricitabine and tenofovir DF (including the single-tablet regimen) is effective in maintaining virological suppression and is generally well tolerated, according to several randomized, open-label or noncomparative multicentre trials and an open-label extension study of up to 96 weeks' duration. Moreover, additional data from some of these studies indicate that adherence to treatment was maintained or improved after switching to the once-daily triple combination, with patients generally preferring the efavirenz/emtricitabine/tenofovir DF single-tablet regimen over their previous more complex regimen and (in one of two trials) finding it easier to follow. Thus, the efavirenz/emtricitabine/tenofovir DF single-tablet regimen provides a convenient once-daily regimen for use in treatment-experienced adults that may confer an advantage over more complex or frequently administered regimens for which adherence to treatment is an issue.

Topics: Adenine; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Medication Adherence; Organophosphonates; Oxazines; Patient Satisfaction; Quality of Life; Reverse Transcriptase Inhibitors

The biggest challenge facing highly antiretroviral-experienced patients and their caregivers is the diminishing number of therapeutic options available that sustain activity despite increasing numbers of drug-resistance mutations. New options in antiretroviral treatment have been introduced: two new members of traditional antiretroviral classes (darunavir and etravirine) and two drugs with novel mechanisms of action (raltegravir and maraviroc). Each was approved for use in treatment-experienced patients. A fifth drug-containing efavirenz, tenofovir, and emtricitabine (Atripla; Bristol-Myers Squibb, New York, NY, and Gilead Sciences, Foster City, CA)-is a novel coformulation of existing drugs from two different classes, simplifying administration with the intent of increasing adherence. Because successful management of HIV infection requires the simultaneous use of three or more drugs, understanding the pharmacologic aspects of coadministration is critical. This review summarizes the pharmacokinetic properties affecting the administration of these recently approved drugs in light of highly active antiretroviral treatment guidelines.

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Darunavir; Deoxycytidine; Drug Combinations; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Nitriles; Organophosphonates; Oxazines; Practice Guidelines as Topic; Pyridazines; Pyrimidines; Reverse Transcriptase Inhibitors; Sulfonamides

BIT225 is a first-in-class inhibitor of human immunodeficiency virus (HIV) type 1 Vpu. A phase II trial enrolled 36 HIV-1-infected, treatment-naive participants in Thailand to receive standard-of-care antiretroviral therapy (ART), tenofovir disoproxil fumarate/emtricitabine/efavirenz (Atripla), with 100 or 200 mg of BIT225 or placebo (daily) for 12 weeks. Combined treatment with BIT225 and ART was found to be generally safe and well tolerated, with antiviral efficacy comparable to that of ART alone. The secondary end point-soluble CD163, a marker of monocyte/macrophage inflammation-was noted to be significantly decreased in the BIT225 arm. Plasma-derived activated CD4+ and CD8+ T cells, natural killer cells, and interleukin 21 were increased in those treated with BIT225. These findings are consistent with inhibition of the known effects of HIV Vpu and may reflect clinically important modulation of inflammatory and immune function. Further clinical study is planned to both confirm and extend these important findings in treatment-naive, and treatment-experienced individuals. Clinical Trials Registration. Australian New Zealand Clinical Trials Registry (Universal Trial Number U1111-1191-2194).

Topics: Anti-HIV Agents; Australia; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Guanidines; HIV Infections; HIV-1; Human Immunodeficiency Virus Proteins; Humans; Inflammation; Pyrazoles; Thailand; Viral Regulatory and Accessory Proteins; Viroporin Proteins

Antiretroviral therapy (ART), especially with tenofovir disoproxil fumarate (TDF), has been associated with accelerated bone turnover and leads to significant bone loss.. We aimed to determine the effect of vitamin D2 and calcium on bone mineral density (BMD) in HIV-infected patients receiving TDF/emtricitabine (FTC)/efavirenz (EFV).. A prospective, open-label, randomized controlled study was conducted. Eligible patients were ART naïve HIV individuals who initiated TDF/FTC/EFV. The study group received supplementation with vitamin D2 and calcium carbonate, whereas the control group was administered only ART. The primary outcome was the percentage change in total hip BMD at week 24 compared with baseline.. A total of 18 patients were randomized (9 in each group). The mean (standard deviation; SD) total hip BMD significantly decreased from baseline in both groups, from 0.96 (0.14) g/cm2 to 0.93 (0.13) g/cm2 in the study group (p = 0.006) and from 0.87 (0.11) g/cm2 to 0.84 (0.11) g/cm2 in the control group (p = 0.004). The mean (SD) lumbar spine BMD significantly decreased from baseline in both groups, from 1.00 (0.13) g/cm2 to 0.97 (0.13) g/cm2 (p = 0.004) in the study group and from 0.90 (0.09) g/cm3 to 0.86 (0.08) g/cm2 in the control group (p = 0.006). At week 24, the mean (SD) lumbar spine BMD was significantly greater in the study group than in the control group (p = 0.042). However, there were no significant differences in the percentage change of total hip, lumbar spine, and femoral neck BMD between both groups. No adverse events were reported. In conclusion, as early as 24 weeks after TDF initiation, a significant decline in BMD was detected.. Vitamin D2 and calcium supplements should be considered for HIV-infected patients receiving TDF/FTC/EFV in a resource-limited setting where there are limited ART options (Clinicaltrials. gov NCT0287643).

Topics: Adolescent; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Bone Density Conservation Agents; Bone Resorption; Calcium Carbonate; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Femur Neck; Hip; HIV Infections; HIV-1; Humans; Lumbar Vertebrae; Male; Middle Aged; Prospective Studies; Vitamin D; Young Adult

Antiretroviral drugs contained in single tablet Atripla have pharmacokinetic properties that could allow for longer than once-daily dosing. We hypothesized that simplifying Atripla once daily to 3-day per week would be feasible, able to maintain viral suppression and less toxic.. Virologically suppressed (≥2 years) HIV+ adults on Atripla once daily, CD4 greater than 350 cells/μl at inclusion, and no prior documented virological failure or evidence of resistance mutations to efavirenz, tenofovir, or emtricitabine were randomized to maintain their once-daily (OD) regimen or to reduce it to 3 days (Mondays, Wednesdays, and Fridays) a week (3W) (A-TRI-WEEK pilot trial). Primary end-point was the proportion of patients free of treatment failure (noncompleter = failure) at 24 weeks. CD4 and CD8 cells, ultrasensitive HIV-1 RNA, Pittsburg Sleep Quality Index (PSQI), bone mineral density, plasma efavirenz levels, and fasting blood and urine chemistries were measured at baseline and 24 weeks. The study is registered at ClinicalTrials.gov, NCT01778413.. Sixty-one patients were randomized. All patients in both arms remained free of treatment failure (estimated difference 0%; 95% confidence interval -14.1 to 14.1). Ultrasensitive plasma HIV-1 RNA below detection threshold showed no difference between arms (70% in the 3W arm vs. 71% in the OD arm, P = 0.933) at 24 weeks. Total cholesterol and femur T-score significantly increased, whereas PSQI, plasma efavirenz, albumin/creatinine and beta-2-microglobulin in urine significantly decreased in the 3W arm relative to OD arm.. The A-TRI-WEEK study represents a proof of concept for the feasibility of three-day per week Atripla maintenance that should be further confirmed in a larger, well powered clinical trial.

Topics: Adult; Anti-HIV Agents; Drug-Related Side Effects and Adverse Reactions; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Maintenance Chemotherapy; Male; Middle Aged; Pilot Projects; Tablets; Treatment Outcome

Efavirenz (EFV) has been associated with reductions in vitamin D (25[OH]D) and tenofovir (TDF) with increased bone turnover, reductions in bone mineral density (BMD) and renal tubular dysfunction. We hypothesized that switching from fixed-dose TDF/emtricitabine (FTC)/EFV to darunavir/ritonavir monotherapy (DRV/r) might increase 25(OH)D and BMD, and improve renal tubular function.. Subjects with HIV RNA <50 copies/ml on TDF/FTC/EFV for ≥6 months were randomized 1:1 to ongoing TDF/FTC/EFV or DRV/r (800/100 mg once daily) for 48 weeks. The primary end point was change from baseline in 25(OH)D at week 48. Secondary end points included changes in BMD, bone turnover markers and renal tubular function.. A total of 64 subjects (86% male, 66% white, mean [sd] CD4(+) T-cell count 537.3 [191.5]/mm(3)) were analysed. After adjustment for baseline 25(OH)D and demographics, at week 48 DRV/r monotherapy was associated with a +3.6 (95% CI 0.6, 6.6) ng/ml increase in 25(OH)D compared to TDF/FTC/EFV (P=0.02). DRV/r monotherapy was associated with an increase in BMD (+2.9% versus -0.003% at the neck of femur and +2.6% versus +0.008% at the lumbar spine for DRV/r versus TDF/FTC/EFV; P<0.05 for all) and reductions in bone biomarkers compared with those remaining on TDF/FTC/EFV. No significant difference in renal tubular function was observed. Reasons for discontinuation in the DRV/r arm included side effects (n=4) and viral load rebound (n=3), all of which resolved with DRV/r discontinuation or regimen intensification.. Switching from TDF/FTC/EFV to DRV/r in patients with suppressed HIV RNA resulted in significant improvements in 25(OH)D and bone biomarkers, and a 2-3% increase in BMD.

Topics: Adult; Anti-HIV Agents; Bone and Bones; Bone Density; Calcifediol; Darunavir; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Kidney; Male; Middle Aged; Ritonavir; Vitamin D

This 96-week, randomized, open-label study was designed to assess the efficacy and safety of two single-tablet regimens in treatment naïve HIV-1-infected adults: rilpivirine (RPV) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and efavirenz (EFV) + FTC/TDF. Assessments included patient-reported Medication Adherence Self-Report Inventory, SF-12v2 Quality of Life assessment, HIV Treatment Satisfaction Questionnaire, and HIV Symptom Index Questionnaire through Week 48. Additional evaluations included study drug discontinuations due to treatment-emergent adverse events (TEAEs). A total of 786 participants (n=394 RPV/FTC/TDF, n=392 EFV/FTC/TDF) were included. Fewer RPV/FTC/TDF-treated than EFV/FTC/TDF-treated participants discontinued study drug due to TEAEs (2.5% vs. 8.7%), with 41% (14/34) TEAE-related discontinuations in the EFV/FTC/TDF group occurring within the first four weeks of treatment. Treatment adherence and satisfaction remained high through Week 48 and quality of life improved from baseline in both groups. There were no significant between-group differences in virologic success (HIV-1 RNA <50 copies/mL) regardless of adherence (<95% or ≥95%). Significant between-group differences favouring RPV/FTC/TDF were observed for the HIV SIQ symptoms of difficulty falling or staying asleep (p = .022) and diarrhea or loose bowel movements (p = .002). In conclusion, 48-week treatment with RPV/FTC/TDF or EFV/FTC/TDF was associated with high adherence, high treatment satisfaction, and improved quality of life. TEAE-related discontinuations and patient-reported symptoms indicate that RPV/FTC/TDF may be somewhat better tolerated than EFV/FTC/TDF.

Topics: Adult; Anti-HIV Agents; Drug-Related Side Effects and Adverse Reactions; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Rilpivirine, Tenofovir Drug Combination; Female; HIV Infections; HIV-1; Humans; Male; Medication Adherence; Middle Aged; Patient Outcome Assessment; Quality of Life; RNA, Viral; Self Report; Tablets; Treatment Outcome; Viral Load

Topics: Adult; Anti-HIV Agents; Cognition; Darunavir; Drug Substitution; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Male; Middle Aged; Quality of Life; Ritonavir; Sleep

STARTMRK, a phase III noninferiority trial of raltegravir-based versus efavirenz-based therapy in treatment-naive patients, remained blinded until its conclusion at 5 years. We now report the final study results.. Previously untreated patients without baseline resistance to efavirenz, tenofovir, or emtricitabine were eligible for a randomized study of tenofovir/emtricitabine plus either raltegravir or efavirenz. Yearly analyses were planned, with primary and secondary end points stipulated at weeks 48 and 96, respectively. The primary efficacy outcome was the percentage of patients with viral RNA (vRNA) levels <50 copies per milliliter counting noncompleters as failures (NC=F). Changes from baseline CD4 count were computed using an observed-failure approach to missing data. No formal hypotheses were formulated for testing at week 240.. Overall, 71 of 281 raltegravir recipients (25%) and 98 of 282 efavirenz recipients (35%) discontinued the study; discontinuations due to adverse events occurred in 14 (5%) and 28 (10%) patients in the respective groups. In the primary NC=F efficacy analysis at week 240, 198 of 279 (71.0%) raltegravir recipients and 171 of 279 (61.3%) efavirenz recipients had vRNA levels <50 copies per milliliter, yielding a treatment difference {Δ [95% confidence interval (CI)] = 9.5 (1.7 to 17.3)}. Generally comparable between-treatment differences were seen in both the protocol-stipulated sensitivity analyses and the prespecified subgroup analyses. The mean (95% CI) increments in baseline CD4 counts at week 240 were 374 and 312 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Δ(95% CI) = 62 (22 to 102)]. Overall, significantly fewer raltegravir than efavirenz recipients experienced neuropsychiatric side effects (39.1% vs 64.2%, P < 0.001) or drug-related clinical adverse events (52.0% vs 80.1%, P < 0.001).. In this exploratory analysis of combination therapy with tenofovir/emtricitabine in treatment-naive patients at week 240, vRNA suppression rates and increases in baseline CD4 counts were significantly higher in raltegravir than efavirenz recipients. Over the entire study, fewer patients experienced neuropsychiatric and drug-related adverse events in the raltegravir group than in the efavirenz group. Based on better virologic and immunologic outcomes after 240 weeks, raltegravir/tenofovir/emtricitabine seemed to have superior efficacy compared with efavirenz/tenofovir/emtricitabine.

Topics: Adenine; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Deoxycytidine; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Female; HIV Infections; HIV-1; Humans; Male; Organophosphonates; Oxazines; Pyrrolidinones; Raltegravir Potassium; Reverse Transcriptase Inhibitors; Tenofovir; Treatment Outcome

We performed a randomized controlled trial in 30 HIV-infected participants to either continue tenofovir/emtricitabine/efavirenz (Continuation Group) or switch to tenofovir/emtricitabine/raltegravir (Switch Group) for 24 weeks. There were no significant differences in the changes in flow-mediated dilation, 25(OH) vitamin D, or parathyroid hormone levels. Total cholesterol, high sensitivity C-reactive protein, serum alkaline phosphatase, sCD14 levels, and renal function significantly declined in the Switch Group compared with the Continuation Group; however, sCD163 levels significantly increased in the Switch Group. These findings suggest that raltegravir is not inherently more beneficial to endothelial function compared with efavirenz but may impact renal function and monocyte activation.

Topics: Adenine; Adult; Alkaline Phosphatase; Anti-HIV Agents; Biomarkers; Bone and Bones; C-Reactive Protein; Cholesterol; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Endothelium, Vascular; Female; HIV Infections; Humans; Indiana; Inflammation; Male; Organophosphonates; Oxazines; Pyrrolidinones; Raltegravir Potassium; Renal Insufficiency; Treatment Outcome; Viral Load

To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients.. This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART).. A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported.. Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

Topics: Adenine; Adult; Alkynes; Anti-HIV Agents; Antitubercular Agents; Benzoxazines; Cyclopropanes; Deoxycytidine; Drug Combinations; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Ethambutol; Female; HIV Infections; Humans; Isoniazid; Male; Organophosphonates; Oxazines; Pyrazinamide; Reverse Transcriptase Inhibitors; Rifampin; Treatment Outcome; Tuberculosis, Pulmonary

We report week 96 results from a phase 3 trial of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF, n = 348) vs efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF, n = 352). At week 48, EVG/COBI/FTC/TDF was noninferior to EFV/FTC/TDF (88% vs 84%, difference +3.6%, 95% confidence interval: -1.6% to 8.8%). Virologic success (HIV-1 RNA <50 copies/mL) was maintained at week 96 (84% vs 82%, difference +2.7%, 95% CI: -2.9% to 8.3%). Discontinuation due to adverse events was low (5% vs 7%). Median changes in serum creatinine (mg/dL) at week 96 were similar to week 48. These results support the durable efficacy and long-term safety of EVG/COBI/FTC/TDF.

Topics: Adenine; Adult; Anti-HIV Agents; Carbamates; Creatinine; Deoxycytidine; Double-Blind Method; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV-1; Humans; Male; Organophosphonates; Oxazines; Quinolones; RNA, Viral; Thiazoles; Treatment Outcome; Young Adult

Evidence on HIV preexposure prophylaxis (PrEP) among Chinese men who have sex with men (MSM) is critical to guide its large-scale implementation in low- and middle-income countries.. To evaluate incident HIV infection, adherence, safety, and changes in sexual behaviors among MSM using daily PrEP (D-PrEP) and event-driven PrEP (ED-PrEP) in 4 cities in China.. This nonrandomized controlled trial was conducted among HIV-seronegative MSM from December 11, 2018, to November 30, 2020, in Beijing, Shenyang, Chongqing, and Shenzhen. Participants self-chose D-PrEP or ED-PrEP regimens at baseline and could switch regimens during the 12-month study period. HIV-negative MSM who declined to initiate PrEP (nonusers) in the same cities joined a separate parallel prospective cohort and served as control individuals.. PrEP consisted of coformulated tenofovir disoproxil fumarate, 300 mg, and emtricitabine, 200 mg.. The main outcome was incident HIV infection. Poisson regression was used to obtain the HIV incidence rate ratio (IRR).. A total of 1530 MSM were included in the analysis (median age, 30 [IQR, 25-37] years). At baseline, 520 MSM chose D-PrEP (median age, 29 [IQR, 25-35] years) and 503 chose ED-PrEP (median age, 29 [IQR, 25-36] years). The median HIV Risk Index score was 18 (IQR, 12-22) among D-PrEP users and 18 (IQR, 11-22) among ED-PrEP users. Among 507 PrEP nonusers, the median age was 33 (IQR, 27-43) years, and the median HIV Risk Index score was 12 (IQR, 7-18). Although PrEP users had more baseline behaviors associated with HIV risk, the HIV incidence was lower among all PrEP users (adjusted IRR, 0.09 [95% CI, 0.04-0.21]), ED-PrEP users (adjusted IRR, 0.05 [95% CI, 0.01-0.22]), and D-PrEP users (adjusted IRR, 0.12 [95% CI, 0.04-0.33]) compared with PrEP nonusers. There was no difference in HIV incidence between D-PrEP users and ED-PrEP users (IRR, 0.33 [95% CI, 0.06-2.04]). Event-driven PrEP users consumed 40% fewer tablets than D-PrEP users during the study period. Adherence, defined as the proportion of self-reported days with sexual intercourse in which PrEP was taken according to prescription of at least 90%, increased over time among ED-PrEP users (from 57.4% to 77.8%; P < .001 for trend) and decreased over time among D-PrEP users (from 75.1% to 72.1%; P = .02 for trend). Daily PrEP users reported fewer adverse events than ED-PrEP users (193 of 520 [37.1%] vs 241 of 503 [47.9%]).. The findings of this study suggest that D-PrEP and ED-PrEP regimens are associated with lower incidence of HIV and a good safety profile among high-risk MSM in China.. Chinese Clinical Trial Registry number: ChiCTR-IIN-17013762.

Topics: Adult; Anti-HIV Agents; Asian People; China; Cohort Studies; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Homosexuality, Male; Humans; Incidence; Male; Pre-Exposure Prophylaxis; Prospective Studies

Combination antiretroviral therapy (cART) dramatically changed the face of the HIV/AIDS pandemic, making it one of the most prominent medical breakthroughs of the past 3 decades. However, as the life span of persons living with HIV (PLWH) continues to approach that of the general population, the same cannot be said regarding their quality of life. PLWH are affected by comorbid conditions such as high blood pressure, diabetes, and neurocognitive impairment at a higher rate and increased severity than their age-matched counterparts. PLWH also have higher levels of inflammation, the drivers of which are not entirely clear. As cART treatment is lifelong, we assessed here the effects of cART, independent of HIV, on primary human monocyte-derived macrophages (MDMs). MDMs were unskewed or skewed to an alternative phenotype and treated with Atripla or Triumeq, two first-line cART treatments. We report that Triumeq skewed alternative MDMs toward an inflammatory nonsenescent phenotype. Both Atripla and Triumeq caused mitochondrial dysfunction, specifically efavirenz and abacavir. Additionally, transcriptome sequencing (RNA-seq) demonstrated that both Atripla and Triumeq caused differential regulation of genes involved in immune regulation and cell cycle and DNA repair. Collectively, our data demonstrate that cART, independent of HIV, alters the MDM phenotype. This suggests that cART may contribute to cell dysregulation in PLWH that subsequently results in increased susceptibility to comorbidities.

Topics: Anti-HIV Agents; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Macrophages; Mitochondria; Quality of Life

A concept of "all or nothing" inspired the innovation of a one-pill-once-daily HIV treatment. Atripla® was the one pill that combined efavirenz, emtricitabine, and tenofovir disoproxil fumarate to become the first daily single tablet regimen that forever simplified HIV treatment to enhance patient compliance and thus, sustained viral suppression. The making of Atripla incorporated dry granulation and bilayer compression technologies to achieve stability and bioequivalence in an optimal pill size. In 2011, there lacked a standard of care for chronic hepatitis C infections that was safe, simple, short, free of interferon and ribavirin, and with high cure rates. A fixed-dose combination of ledipasvir and sofosbuvir was developed and approved in 2014 to be the first complete daily single tablet regimen for CHC genotype 1 infection. A spray-drying process for particle morphology engineering in a polymer matrix was used for improving bioavailability.

Topics: Adenine; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Hepatitis C; HIV Infections; Humans; Organophosphonates; Tablets

In British Columbia, antiretrovirals are distributed at no cost to patients via a publicly funded program, using generic formulations if available. A generic efavirenz-emtricitabine-tenofovir DF (EFV-FTC-TDF) combination pill became available in April 2018. The authors compared EFV untimed drug levels in subjects switching from brand to generic EFV-FTC-TDF.. Archived plasma HIV viral load samples were identified for consenting participants who switched from brand to generic EFV-FTC-TDF; 3 preswitch and 2-3 postswitch samples, collected ≥1 month apart were assessed for each subject. "Untimed" EFV concentrations with unknown dosing and collection time were assessed using a validated liquid chromatography-tandem mass spectrometry method. Participants' mean, minimum, and maximum EFV levels were compared using the Wilcoxon signed rank test. Participants with EFV levels in the range associated with lower risks of virologic failure and central nervous system toxicity (1000-4000 ng/mL), preswitch and postswitch, were enumerated.. EFV levels were assessed in 297 preswitch and 249 postswitch samples from 99 participants, having exposure to brand and generic EFV for a median of 103 (Q1-Q3: 87-116) and 10.3 (Q1-Q3: 8.9-11.7) months, respectively. The final brand sample was collected at a median of 98 days preswitch; the first generic sample was collected at a median of 133 days postswitch. No significant differences were observed in participant mean EFV levels before (median 1968 ng/mL; Q1-Q3: 1534-2878 ng/mL) and after (median 1987 ng/mL; Q1-Q3: 1521-2834 ng/mL) switch (P = 0.85). Eighty participants had mean EFV levels within the 1000-4000 ng/mL range on the brand drug, of which 74 remained within this range postswitch.. There were no statistically significant differences between untimed EFV levels in patients switching from the brand to generic EFV combination pill. Given the long elimination half-life of EFV, untimed drug levels may be a convenient way to estimate product bioequivalence.

Topics: Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Drugs, Generic; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Treatment Outcome

Sensitive and reproducible diagnostics are fundamental to containing the spread of existing and emerging pathogens. Despite the reliance of clinical virology on qPCR, technical challenges persist that compromise their reliability for sustainable epidemic containment as sequence instability in probe-binding regions produces false-negative results. We systematically violated canonical qPCR design principles to develop a Pan-Degenerate Amplification and Adaptation (PANDAA), a point mutation assay that mitigates the impact of sequence variation on probe-based qPCR performance. Using HIV-1 as a model system, we optimized and validated PANDAA to detect HIV drug resistance mutations (DRMs). Ultra-degenerate primers with 3' termini overlapping the probe-binding site adapt the target through site-directed mutagenesis during qPCR to replace DRM-proximal sequence variation. PANDAA-quantified DRMs present at frequency ≥5% (2 h from nucleic acid to result) with a sensitivity and specificity of 96.9% and 97.5%, respectively. PANDAA is an innovative advancement with applicability to any pathogen where target-proximal genetic variability hinders diagnostic development.

Topics: Anti-HIV Agents; DNA Primers; DNA, Viral; Drug Resistance, Viral; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Genotype; High-Throughput Nucleotide Sequencing; HIV Infections; HIV-1; Humans; Point Mutation; Polymerase Chain Reaction; Reproducibility of Results; Virology

A 38-year-old male presented to the hospital with headache, fever, and meningeal signs. He had undergone a surgical review of a ventriculoperitoneal shunt system one month earlier. A head computed tomography scan showed hydrocephalus. His medical history included a human immunodeficiency virus infection identified four years before and resolved cryptococcal meningitis, which had necessitated the implantation of the shunt system. Ventricular cerebrospinal fluid (CSF) was obtained, which showed inflammation and, in culture, grew a Gram-negative bacillus identified as multidrug-resistant Klebsiella oxytoca. The shunt was removed and a ventricular drain was installed. Treatment with meropenem and amikacin was established without a response; the CSF white blood cell count continued to increase, with cultures remaining positive. The patient's clinical condition deteriorated to stupor. With informed consent, intraventricular (ITV) treatment with tigecycline was initiated at a dose of 5 mg every 24 h and, three days later, the CSF cultures were negativized. Tigecycline levels in the CSF were quantified by liquid chromatography with ultraviolet detection and showed peak concentrations achieved at two hours after the dose of between 178 and 310 μg/mL. After 11 days of treatment with ITV tigecycline and eight negative CSF cultures, a new CSF shunt was installed. During follow-up review 10 months later, the patient reported he was working. The dose of tigecycline used in this study produced levels 15 to 20 times the minimum inhibitory concentration of the bacteria for up to six hours with adequate tolerance.

Topics: Adult; Anti-Bacterial Agents; Anti-HIV Agents; Cerebral Ventriculitis; Drug Resistance, Multiple, Bacterial; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Injections, Intraventricular; Klebsiella Infections; Klebsiella oxytoca; Male; Microbial Sensitivity Tests; Surgical Wound Infection; Tigecycline; Ventriculoperitoneal Shunt

Atripla dose reduction decreases subclinical toxicity and maintains viral suppression in HIV+ individuals but the virological efficacy and immunological safety of this strategy needs to be further confirmed.. Virologically suppressed HIV-infected adults on Atripla once-daily were randomized 1 : 1 to reduce therapy to 3 days a week (3W, n = 30) or to maintain it unchanged (once-daily, n = 31). HIV-1 reservoir (total and integrated HIV-1 DNA in CD4 cells) and immunological cell activation (CD38 and HLA-DR), senescence (CD57 and CD28), apoptosis (annexinV) as well as T-naive, effector memory (TEM) (CCR7, CD45RA) and stem cell memory (TSCM) (CD954 and CD27) populations were measured at baseline, 24 and 48 weeks.. No differences on activation, senescence or apoptosis of both CD4 and CD8 T cells were observed on follow-up. Nave CD4 T-cell proportion showed a significant decrease in the 3W group (mean ± SD): 24.6 ± 13.7 vs. 20.5 ± 12.9 (P = 0.002). No differences in both plasma viral load and HIV reservoir were detected on follow-up. CD4 TSCM levels at 48 weeks correlated with basal integrated HIV-1 DNA in the 3W group but not in the once-daily group. A post hoc analysis of data prior to the study entry revealed a higher viral load zenith and a trend to lower CD4 nadir in 3W vs. once-daily group.. No significant immunological or viral changes were induced in the 3W group confirming the virological efficacy and immunogical safety of this strategy. In-depth virological and immunological analyses are useful in providing additional information in antiretroviral switching studies (Clinical Trials.gov: NCT01778413).

Topics: Adult; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Lymphocyte Activation; Lymphocyte Count; Male; Middle Aged; T-Lymphocyte Subsets; Viral Load

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cognitive Dysfunction; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV; HIV Infections; Humans; Male; Medication Adherence; Mental Status and Dementia Tests; Middle Aged; Prevalence; Risk Factors

We describe a patient with acute renal failure and irreversible kidney damage after an overdose with the fixed dose combination of efavirenz/tenofovir disoproxil fumarate/emtricitabine (Atripla). The acute kidney injury was most probably caused by tenofovir. Efavirenz and emtricitabine seemed relatively safe in overdose. The pharmacokinetics in overdose of all 3 drugs and the effect of hemodialysis on the tenofovir clearance were studied by measuring the plasma concentrations and by the use of clinical pharmacokinetic software.

Topics: Acute Kidney Injury; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; HIV Infections; HIV-1; Humans; Male; Middle Aged; Tenofovir

Universal multi drug antiretroviral treatment in pregnancy is a global priority in our bid to eliminate paediatric HIV infections although few studies have documented the impact of antiretroviral coverage on overall pregnancy outcomes.. We conducted a maternity audit at a large regional hospital in South Africa during July-December 2011 and January-June 2014 with an aim to determine an association between pregnancy outcomes and the ARV treatment guidelines implemented during those specific periods. During 2011, women received either Zidovudine/sd Nevirapine or Stavudine/Lamivudine/Nevirapine if CD4+ count was < 350 cells/ml. During 2014, all HIV positive pregnant women were eligible for a fixed dose combination (FDC) of triple ARVs (Tenofovir/Emtracitabine/Efavirenz).. In 2011, 622 (35.9%) of 1732 HIV positive pregnant women received triple antiretrovirals (D4T/3TC/NVP) and in 2014, 2104 (94.8%) of 2219 HIV positive pregnant women received the fixed dose combination (TDF/FTC/EFV). We observed a reduction in the proportion of unregistered pregnancies, caesarean delivery rate, still birth rate, very low birth weight rate, and very premature delivery rate in 2014. In a bivariate analysis of all 9,847 deliveries, unregistered pregnancies (2.2%) and HIV infection (37.8%) remained significant risk factors for SB(OR 6.36 and 1.43 respectively), PTD(OR 4.23 and 1.26 respectively),LBW (OR 4.07 and 1.26 respectively) and SGA(OR 2.17 and 1.151 respectively). In a multivariable analysis of HIV positive women only, having received AZT/NVP or D4T/3TC/NVP or EFV/TDF/FTC as opposed to not receiving any ARV was significantly associated with reduced odds of a SB (OR 0.08, 0.21 and 0.18 respectively), PTD (OR 0.52, 0.68 and 0.56 respectively) and LBW(0.37, 0.61 and 0.52 respectively).. An improvement in birth outcomes is likely associated with the increased coverage of triple antiretroviral treatment for pregnant women. And untreated HIV infected women and women who do not seek antenatal care should be considered most at risk for poor birth outcomes.

Topics: Adolescent; Adult; Anti-Retroviral Agents; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Lamivudine; Nevirapine; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Prenatal Care; South Africa; Stavudine; Young Adult; Zidovudine

Topics: Anti-HIV Agents; CD4 Lymphocyte Count; Dideoxynucleosides; Drug Combinations; Drug Hypersensitivity; Drug Interactions; Drug Resistance, Viral; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine, Rilpivirine, Tenofovir Drug Combination; Heterocyclic Compounds, 3-Ring; HIV Infections; Humans; Lamivudine; Mental Disorders; Oxazines; Piperazines; Pyridones; Viral Load

Data from the SINGLE trial demonstrated that 88% of treatment-naïve HIV-1 patients treated with dolutegravir and abacavir/lamivudine (DTG + ABC/3TC) achieved viral suppression at 48 weeks compared with 81% of patients treated with efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC). It is unclear how this difference in short-term efficacy impacts long-term cost-effectiveness of these regimens. This study sought to evaluate long-term cost-effectiveness of DTG + ABC/3TC vs EFV/TDF/FTC from a US payer perspective.. This study is an individual discrete-event simulation which tracked the disease status and treatment pathway of HIV-1 patients. The model simulated treatment over a lifetime horizon by tracking change in patients' CD4 count, clinical events occurrence (opportunistic infections, cancer, and cardiovascular events), treatment switch, and death. The model included up to four lines of treatment. Baseline patient characteristics, efficacy, and safety of DTG + ABC/3TC and EFV/TDF/FTC were informed by data from the SINGLE trial. The efficacy of subsequent treatment lines, clinical event risks, mortality, cost, and utility inputs were based on literature and expert opinion. Outcomes were lifetime discounted medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER).. Compared with EFV/TDF/FTC, DTG + ABC/3TC increased lifetime costs by $19,153 and per person survival by 0.12 QALYs, resulting in an ICER of $158,890/QALY. ICERs comparing DTG + ABC/3TC to EFV/TDF/FTC remained above the traditional, US willingness-to-pay threshold of $50,000/QALY gained in all scenarios, and above $100,000 or $150,000/QALY gained in most scenarios.. Due to data limitations, the treatment patterns, CD4 count during viral rebound and treatment switch, viral rebound after trial end, and long-term adverse event-related treatment discontinuation were based on assumptions, presented to and approved by clinical experts.. Compared with EFV/TDF/FTC, DTG + ABC/3TC resulted in higher cost and only slightly increased QALYs over a lifetime, with an ICER that exceeded the standard cost-effectiveness threshold. This indicates that the incremental benefit in effectiveness associated with DTG + ABC/3TC may not be worth the incremental increase in costs.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Computer Simulation; Cost-Benefit Analysis; Dideoxynucleosides; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Kaplan-Meier Estimate; Lamivudine; Quality-Adjusted Life Years; United States

ATRIPLA is licensed for use only in HIV-positive persons whose viral loads <50 for ≥ 3 months. We investigated the use of ATRIPLA as first-line antiretroviral therapy (ART) in EuroSIDA using a web-based survey performed in Autumn 2012. 96/112 clinics (85.7 %) completed the survey. Recommendations when initiating first-line ART was TRUVADA plus efavirenz in 36 (37.5 %), ATRIPLA in 35 (36.5 %), a different first-line regimen in 12 clinics (12.5 %), and no recommendation in 7 clinics (7.3 %). ATRIPLA was commonest in Northern (15/21 clinics; 71.4 %), and least common in Eastern Europe (2/31 clinics; 6.5 %; p < 0.0001). Over one-third of the participating clinics in this survey were using ATRIPLA as first-line antiretroviral therapy, despite EMA recommendations.

Topics: Adenine; Adult; Anti-HIV Agents; Cohort Studies; Data Collection; Deoxycytidine; Drug Combinations; Drug Utilization; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Europe; Female; HIV Infections; Humans; Male; Organophosphonates; Oxazines; Prospective Studies

The objective of this study was to evaluate the effectiveness and the clinical tolerance of a combination containing TDF/FTC/EFV in the treatment of HIV infection. This was a retrospective and descriptive study which included 196 adults infected by HIV-1 and treated by a combination containing TDF/FTC/EFV during 29 months in the daily hospital of Bobo Dioulasso. The median duration of follow-up was 7 months IQR [5-14 month]. The median age was 37 years IQR [31-45].With the initiation of treatment ARV, the median of the index of body mass was of 19 IQR [17-22]. The median of the lymphocytes TCD4 was 201/μl IQR [74-298/μl]. During the follow-up, we reported 25 deaths (12.8%). HIV-1 RNA plasma viral load was undetectable in 91.9% of the patients (124/135) at six months of treatment. The majority of the adverse effects of the treatment were of a neurosensory nature (40.5%). The TDF/FTC/EFV combination showed a good effectiveness in the treatment of the infection with HIV-1 in the first intention just as a good clinical tolerance.

Topics: Adenine; Adult; Anti-Retroviral Agents; Burkina Faso; Deoxycytidine; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Organophosphonates; Oxazines; Retrospective Studies; Treatment Outcome

The aim of the study was to assess whether pill burden is associated with self-reported adherence to current combination antiretroviral regimens and health status in a large sample of unselected and chronically treated HIV-infected patients.. An adherence and health status questionnaire was offered to all patients collecting their drugs between March and May 2010 at our clinic; both parameters were primarily evaluated using a visual analogue scale. Linear correlations were evaluated using Spearman's correlation coefficient. Wilcoxon's rank-sum test and the χ(2) test were used to compare quantitative and qualitative variables. The generalized linear model was used in multivariable analyses.. Among 2763 subjects on treatment during the study period, 2114 (78.8% male; mean age 46.9 ± 8.84 years) were tested for adherence; 1803 (85.3%) had viral loads < 50 HIV-1 RNA copies/mL. After adjusting for age, gender, HIV risk factor, current CD4 count, pill burden and dosing interval, adherence was higher in patients with undetectable HIV RNA (P < 0.0001) and directly associated with current CD4 count (P = 0.029). After adjusting for the same variables, health status was better in patients with undetectable viraemia (P = 0.004) and in men who have sex with men (MSM) and heterosexuals compared with injecting drug users and those with other risk factors (P < 0.0001 for MSM and P = 0.008 for heterosexuals); it was also directly associated with current CD4 count (P < 0.0001) and inversely associated with age (P < 0.0001) and pill burden (P = 0.019).. In this highly adherent population, the number of daily pills was related to self-reported health status but not to self-reported adherence, whereas the dosing interval did not influence self-reported adherence or health status.

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Carbamates; CD4 Lymphocyte Count; Cross-Sectional Studies; Deoxycytidine; Dideoxynucleosides; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Furans; HIV Infections; Humans; Italy; Lamivudine; Male; Medication Adherence; Middle Aged; Nevirapine; Oligopeptides; Organophosphates; Organophosphonates; Oxazines; Pyridines; Self Report; Sulfonamides; Surveys and Questionnaires; Viral Load

Platelet-activating factor (PAF) is implicated in human immunodeficiency virus (HIV)-related manifestations. Increased PAF synthesis has been recently detected in HIV-infected patients. In this study, we examined in naive HIV-infected patients the in vivo effects of a highly active antiretroviral therapy (HAART) regimen, containing tenofovir-DF/emtricitabine/efavirenz, on PAF metabolism. The specific activities of PAF basic biosynthetic enzymes, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (lyso-PAF-AT), but also the ones of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets, and lipoprotein-associated-phospholipase-A(2) (LpPLA(2)) in plasma, were measured in blood samples of eight asymptomatic naive male HIV-infected patients just before and after 1, 3, and 6 months of treatment. CD4 cell counts, viral load, and several biochemical markers were also measured in the same blood samples of these patients. The repeated measures ANOVA and the Pearson r criterion were used to study statistical differences and correlations-partial correlations, while linear mixed models were conducted in order to estimate association(s) between time-dependent changes in these factors. Before treatment, the activities of PAF-CPT in leukocytes and LpPLA(2) in plasma were found to be inversely correlated with CD4 cell counts and positively correlated with the viral load. After 6 months of treatment, the activities of basic PAF-biosynthetic enzymes, PAF-CPT and lyso-PAF-AT, were both reduced in leukocytes. At 6 months, PAF-AH activity was also reduced in these cells, while LpPLA(2) remained stable. The reduction of PAF-CPT occurred even from the first month, while there is a time-dependent correlation between the increase of CD4 and the decrease of both viral load and PAF-CPT of leukocytes during treatment. Apart from its classical antiretroviral activities the tenofovir-DF/emtricitabine/efavirenz regimen also exhibited favorable effects on PAF metabolism and therefore may also display beneficial effects in some HIV-related conditions, such as cardiovascular disease (CVD), in which PAF is implicated.

Topics: Adenine; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Organophosphonates; Oxazines; Platelet Activating Factor; Viral Load

During pregnancy, the disposition of various drugs is altered due to changes in physiological condition, maternal gastrointestinal absorption, gastric secretion and motility. A fixed dose combination of antiretrovirals is commonly prescribed for the treatment of HIV infection. There is a need to understand the pharmacokinetics and placental transfer of efavirenz-emtricitabine-tenofovir in fixed dose combination during pregnancy. The pharmacokinetics and placental transfer of efavirenz-emtricitabine-tenofovir fixed dose combination was evaluated in timed pregnant and non-pregnant Sprague-Dawley rats at 30, 10, 15 mg/kg p.o., respectively. The plasma, placental tissue, amniotic fluid and fetal tissue concentrations were measured using high performance liquid chromatography combined with tandem mass spectrometric detector (LC-MS/MS). To summarize, the pharmacokinetic profile of efavirenz remained similar in the pregnant and non-pregnant rats. However, a considerable difference in the pharmacokinetics of emtricitabine and tenofovir was observed in pregnant and non-pregnant rats. Efavirenz and emtricitabine showed appreciable placental, amniotic fluid and fetal exposure compared with tenofovir. The present study suggests that a profound impact on antiretroviral pharmacokinetics was observed during pregnancy and there is a need to monitor the exposure levels of each drug when administered as a fixed dose combination during pregnancy. Further studies to explore the pharmacokinetic parameters of fixed dose antiretrovirals during the preclinical stage in a timed-pregnancy rat model are required. Such studies can help in the development of safe and effective medications with a reduced risk of perinatal transmission of HIV-1 infection.

Topics: Adenine; Administration, Oral; Amniotic Fluid; Animals; Anti-HIV Agents; Chromatography, High Pressure Liquid; Deoxycytidine; Dose-Response Relationship, Drug; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Fetus; HIV Infections; Infectious Disease Transmission, Vertical; Maternal-Fetal Exchange; Organophosphonates; Oxazines; Placenta; Pregnancy; Rats, Sprague-Dawley; Tissue Distribution

Topics: Adenine; Adult; Alkynes; Benzoxazines; Cyclopropanes; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Male; Organophosphonates; Oxazines; Psychoses, Substance-Induced; Reverse Transcriptase Inhibitors

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

A single pill daily fixed dose combination of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) provides a potent and convenient treatment option for HIV/AIDS. The components have been shown to be well tolerated and are effective in randomized controlled trials. A literature search revealed no case of hepatic failure reported with this drug combination. We here in describe the 1st case of acute hepatic failure developing after 3 months of treatment with EFV/FTC/TDF in a 41 year old African American male without pre-existing liver disease or risk factors.

Topics: Adenine; Adult; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Liver Failure; Male; Organophosphonates; Oxazines; Reverse Transcriptase Inhibitors

Topics: Adenine; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Deoxycytidine; Drug Approval; Drug Combinations; Drug Labeling; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Oxazines; Randomized Controlled Trials as Topic; United States; United States Food and Drug Administration

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

Rapidly declining visual acuity from neuroretinitis should prompt aggressive diagnostic intervention to preserve eyesight. We present a young adult with human immunodeficiency virus (HIV) infection in whom neuroretinitis was the presenting feature of disseminated bartonellosis. Tissue biopsy was required to establish the diagnosis and directed therapy was associated with restored vision.

Topics: Adenine; Anti-Bacterial Agents; Anti-HIV Agents; Bartonella; Bartonella Infections; Biopsy; Deoxycytidine; Doxycycline; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Lung; Male; Organophosphonates; Oxazines; Retinitis; Rifampin; Treatment Outcome; Young Adult

Topics: Adenine; Anti-HIV Agents; Deoxycytidine; Drug Combinations; Drug Labeling; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Oxazines; Viral Load

Topics: Adenine; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Oxazines; Plasma

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: Adenine; Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; Benzoxazines; Cyclopropanes; Deoxycytidine; Drug Approval; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Europe; HIV Infections; Humans; Organophosphonates; Oxazines; Randomized Controlled Trials as Topic; Reverse Transcriptase Inhibitors; Tenofovir; Viral Load

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Long-Term Care; Lopinavir; Oligopeptides; Organophosphonates; Oxazines; Pyridines; Pyrimidinones; Pyrrolidinones; Raltegravir Potassium; Randomized Controlled Trials as Topic

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Controlled Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Medication Adherence; Organophosphonates; Oxazines; Viral Load

Topics: Adenine; CD4 Lymphocyte Count; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; HIV Infections; Humans; Middle Aged; Organophosphonates; Oxazines; Viral Load

Topics: Adenine; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Fluconazole; HIV Infections; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Organophosphonates; Oxazines; Positron-Emission Tomography; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adenine; Antiretroviral Therapy, Highly Active; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Oxazines; Viral Load

Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Darunavir; Deoxycytidine; Drug Combinations; Drug Resistance, Viral; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; HIV-1; Humans; Organophosphonates; Oxazines; Patient Compliance; Prognosis; Pyridines; Pyrones; Sulfonamides

Topics: Adenine; Antiretroviral Therapy, Highly Active; Clinical Trials as Topic; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Oxazines; Patient Compliance

Topics: Adenine; CD4 Lymphocyte Count; Deoxycytidine; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Oxazines

Topics: Adenine; Adult; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Deoxycytidine; Drug Approval; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; European Union; HIV Infections; Humans; Organophosphonates; Oxazines; Reverse Transcriptase Inhibitors; Tenofovir

Topics: Adenine; Anti-Retroviral Agents; Deoxycytidine; Drug Approval; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Humans; Organophosphonates; Oxazines; South Africa

Topics: Adenine; Adult; Anti-HIV Agents; Canada; Deoxycytidine; Drug Approval; Drug Combinations; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Europe; HIV Infections; HIV-1; Humans; Organophosphonates; Oxazines; United States

Topics: Adenine; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Deoxycytidine; Drug Combinations; Drug Interactions; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; HIV Infections; Humans; Organophosphonates; Oxazines; Tenofovir