naloxone and HIV-Infections

The diversion, misuse, and non-medically supervised use of buprenorphine and buprenorphine/naloxone by opioid users are reviewed. Buprenorphine and buprenorphine/naloxone are used globally as opioid analgesics and in the treatment of opioid dependency. Diversion of buprenorphine and buprenorphine/naloxone represents a complex medical and social issue, and has been widely documented in various geographical regions throughout the world. We first discuss the clinical properties of buprenorphine and its abuse potential. Second, we discuss its diversion and illicit use on an international level, as well as motivations for those activities. Third, we examine the medical risks and benefits of buprenorphine's non-medically supervised use and misuse. These risks and benefits include the effect of buprenorphine's use on HIV risk and the risk of its concomitant use with other medications and drugs of abuse. Finally, we discuss the implications of diversion, misuse, and non-medically supervised use (including potential measures to address issues of diversion); and potential areas for further research.

Topics: Buprenorphine; Drug Overdose; HIV Infections; Humans; Illicit Drugs; Motivation; Naloxone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Risk-Taking

The Centers for Disease Control and Prevention's HIV Prevention Strategic Plan Through 2005 advocated for increasing the proportion of persons with human immunodeficiency virus (HIV) infection and in need of substance abuse treatment who are successfully linked to services for these 2 conditions. There is evidence that integrating care for HIV infection and substance abuse optimizes outcomes for patients with both disorders. Buprenorphine, a recently approved medication for the treatment of opioid dependence in physicians' offices, provides the opportunity to integrate the treatment of HIV infection and substance abuse in one clinical setting, yet little information exists on the models of care that will most successfully facilitate this integration. To promote the uptake of this type of integrated care, the current review provides a description of 4 recently implemented models for combining buprenorphine treatment with HIV primary care: (1) an on-site addiction/HIV specialist treatment model; (2) a HIV primary care physician model; (3) a nonphysician health professional model; and (4) a community outreach model.

Topics: Antiretroviral Therapy, Highly Active; Buprenorphine; Centers for Disease Control and Prevention, U.S.; Delivery of Health Care, Integrated; Female; Health Resources; Health Services Needs and Demand; HIV Infections; Humans; Male; Methadone; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Selection; Primary Health Care; Program Evaluation; Risk Assessment; Substance Abuse Treatment Centers; United States

Topics: Adult; Antibody Formation; Cells, Cultured; Cytotoxicity, Immunologic; Disease Susceptibility; Endorphins; Heroin Dependence; HIV Infections; Humans; Immunologic Deficiency Syndromes; Killer Cells, Natural; Life Style; Male; Methadone; Middle Aged; Naloxone; Narcotics; Neurosecretory Systems; Opioid-Related Disorders; Stereoisomerism; T-Lymphocyte Subsets

UNAIDS recommends integrating methadone or buprenorphine treatment of opioid use disorder with HIV care to improve HIV outcomes, but buprenorphine adoption remains limited in many countries. We aimed to assess whether HIV clinic-based buprenorphine plus naloxone treatment for opioid use disorder was non-inferior to referral for methadone maintenance therapy in achieving HIV viral suppression in Vietnam.. In an open-label, non-inferiority trial (BRAVO), we randomly assigned people with HIV and opioid use disorder (1:1) by computer-generated random number sequence, in blocks of ten and stratified by site, to receive HIV clinic-based buprenorphine plus naloxone treatment or referral for methadone maintenance therapy in six HIV clinics in Vietnam. The primary outcome was HIV viral suppression at 12 months (HIV-1 RNA ≤200 copies per mL on PCR) by intention to treat (absolute risk difference [RD] margin ≤13%), compared by use of generalised estimating equations. Research staff actively queried treatment-emergent adverse events during quarterly study visits and passively collected adverse events reported during HIV clinic visits. This study is registered with ClinicalTrials.gov, NCT01936857, and is completed.. Between July 27, 2015, and Feb 12, 2018, we enrolled 281 patients. At baseline, 272 (97%) participants were male, mean age was 38·3 years (SD 6·1), and mean CD4 count was 405 cells per μL (SD 224). Viral suppression improved between baseline and 12 months for both HIV clinic-based buprenorphine plus naloxone (from 97 [69%] of 140 patients to 74 [81%] of 91 patients) and referral for methadone maintenance therapy (from 92 [66%] of 140 to 99 [93%] of 107). Buprenorphine plus naloxone did not demonstrate non-inferiority to methadone maintenance therapy in achieving viral suppression at 12 months (RD -0·11, 95% CI -0·20 to -0·02). Retention on medication at 12 months was lower for buprenorphine plus naloxone than for methadone maintenance therapy (40% vs 65%; RD -0·53, 95% CI -0·75 to -0·31). Participants assigned to buprenorphine plus naloxone more frequently experienced serious adverse events (ten [7%] of 141 vs four of 140 [3%] assigned to methadone maintenance therapy) and deaths (seven of 141 [5%] vs three of 141 [2%]). Serious adverse events and deaths typically occurred in people no longer taking ART or opioid use disorder medications.. Although integrated buprenorphine and HIV care may potentially increase access to treatment for opioid use disorder, scale-up in middle-income countries might require enhanced support for buprenorphine adherence to improve HIV viral suppression. The strength of our study as a multisite randomised trial was offset by low retention of patients on buprenorphine.. National Institute on Drug Abuse (US National Institutes of Health).

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Buprenorphine; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Random Allocation; RNA, Viral; Treatment Outcome; Vietnam; Viral Load

Understanding the role of opiate dependency treatment in risky sexual behavior could help optimize interventions for people who inject drugs (PWID).. We evaluated whether long-term medication-assisted treatment (LT-MAT) of opiate dependency with buprenorphine/naloxone influenced risky sexual behavior among HIV-uninfected PWID and identified predictors of risky sexual behavior.. We used data from HPTN 058, a randomized controlled trial of LT-MAT vs. short-term medication-assisted treatment among PWID in China and Thailand. We evaluated associations between randomized opiate dependency treatment group and self-reported risky sexual behaviors within the past month: condomless sex with primary partner, condomless sex with nonprimary partner, multiple partners, and more than 3 sexual acts. We used generalized estimating equations to conduct intention-to-treat, as-treated, and exploratory analyses of these associations.. Of 1250 participants included in the analysis, 92% were male, with median age of 34 years (interquartile range 28-39). At baseline, referring to the past month, 36% of participants reported condomless sex with primary partner, 4% reported condomless sex with nonprimary partner, 6% reported multiple sex partners, and 30% reported more than 3 sexual acts. Risky sexual behaviors did not differ significantly between treatment groups at any point. Significant predictors (P < 0.05) of condomless sex with nonprimary partner were history of incarceration and noninjection drug use. Number of needle-sharing partners, noninjection drug use, and higher income were predictors for multiple sexual partners.. LT-MAT did not significantly modify risky sexual behavior among HIV-uninfected PWID. Interventions that reduce sexual risk should target PWID with history of incarceration, alcohol use, and needle sharing.

Topics: Adult; Buprenorphine; China; Female; HIV Infections; Humans; Male; Naloxone; Opioid-Related Disorders; Risk-Taking; Sexual Behavior; Thailand; Young Adult

As resources are deployed to address the opioid overdose epidemic in the USA, it is essential that we understand the correlates of more frequent opioid injections-which has been associated not only with HIV and HCV transmission, but also with overdose risk-to inform the development and targeting of effective intervention strategies like overdose prevention and naloxone distribution programs. However, no studies have explored how characteristics of opioid use partnerships may be associated within injection frequency with opioid partnerships.. Using baseline data from a trial of a behavioural intervention to reduce overdose among opioid users in San Francisco, CA, we calculated assortativity among opioid use partnerships by race, gender, participant-reported HIV- and HCV-status, and opioids used using Newman's assortativity coefficient (NC). Multivariable generalized estimating equations linear regression was used to examine associations between individual- and partnership-level characteristics and injection frequency within opioid use partnerships.. Opioid use partnerships (n=134) reported by study participants (n=55) were assortative by race (NC=0.42, 95%CI=0.33-0.50) and participant-reported HCV-status (NC=0.42, 95%CI=0.31-0.52). In multivariable analyses, there were more monthly injections among sexual/romantic partnerships (β=114.4, 95%CI=60.2-168.7, p<0.001), racially concordant partnerships reported by white study participants (β=71.4, 95%CI=0.3-142.5, p=0.049), racially discordant partnerships reported by African American study participants (β=105.7, 95%CI=1.0-210.5, p=0.048), and partnerships in which either member had witnessed the other experience an overdose (β=81.8, 95%CI=38.9-124.6, p<0.001).. Social segregation by race and HCV-status should potentially be considered in efforts to reach networks of opioid users. Due to higher injection frequency and greater likelihood of witnessing their partners experience an overdose, individuals in sexual/romantic opioid use partnerships, white individuals in racially homogenous partnerships, and African American individuals in heterogeneous partnerships may warrant focused attention as part of peer- and network-based overdose prevention efforts, as well as broader HIV/HCV prevention strategies. Developing and targeting overdose prevention education programs that provide information on risk factors and ways to identify overdose, as well as effective responses, including naloxone use and rescue breathing, for more frequently injecting networks may help reduce opioid morbidity and mortality in these most at risk groups.

Topics: Adult; Drug Overdose; Female; Hepatitis C; HIV Infections; Humans; Interpersonal Relations; Linear Models; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pilot Projects; Racial Groups; Risk Factors; San Francisco; Sexual Partners; Substance Abuse, Intravenous

Injection opioid use plays a significant role in the transmission of HIV infection in many communities and several regions of the world. Access to evidence-based treatments for opioid use disorders is extremely limited.. HIV Prevention Trials Network 058 (HPTN 058) was a randomized controlled trial designed to compare the impact of 2 medication-assisted treatment (MAT) strategies on HIV incidence or death among opioid-dependent people who inject drugs (PWID). HIV-negative opioid-dependent PWID were recruited from 4 communities in Thailand and China with historically high prevalence of HIV among PWID. A total of 1251 participants were randomly assigned to either (1) a 1-year intervention consisting of 2 opportunities for a 15-day detoxification with buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral drug and risk counseling [short-term medication-assisted treatment (ST-MAT)] or (2) thrice-weekly dosing for 48 weeks with BUP/NX and up to 21 counseling sessions [long-term medication-assisted treatment (LT-MAT)] followed by dose tapering. All participants were followed for 52 weeks after treatment completion to assess durability of impact.. Although the study was stopped early due to lower than expected occurrence of the primary end points, sufficient data were available to assess the impact of the interventions on drug use and injection-related risk behavior. At week 26, 22% of ST-MAT participants had negative urinalyses for opioids compared with 57% in the LT-MAT (P < 0.001). Differences disappeared in the year after treatment: at week 78, 35% in ST-MAT and 32% in the LT-MAT had negative urinalyses. Injection-related risk behaviors were significantly reduced in both groups after randomization.. Participants receiving BUP/NX 3 times weekly were more likely to reduce opioid injection while on active treatment. Both treatment strategies were considered safe and associated with reductions in injection-related risk behavior. These data support the use of thrice-weekly BUP/NX as a way to reduce exposure to HIV risk. Continued access to BUP/NX may be required to sustain reductions in opioid use.

Topics: Adult; Buprenorphine; China; Female; HIV Infections; Humans; Incidence; Male; Naloxone; Opiate Substitution Treatment; Substance Abuse, Intravenous; Thailand; Treatment Outcome

Opioid-dependent patients often use the emergency department (ED) for medical care.. To test the efficacy of 3 interventions for opioid dependence: (1) screening and referral to treatment (referral); (2) screening, brief intervention, and facilitated referral to community-based treatment services (brief intervention); and (3) screening, brief intervention, ED-initiated treatment with buprenorphine/naloxone, and referral to primary care for 10-week follow-up (buprenorphine).. A randomized clinical trial involving 329 opioid-dependent patients who were treated at an urban teaching hospital ED from April 7, 2009, through June 25, 2013.. After screening, 104 patients were randomized to the referral group, 111 to the brief intervention group, and 114 to the buprenorphine treatment group.. Enrollment in and receiving addiction treatment 30 days after randomization was the primary outcome. Self-reported days of illicit opioid use, urine testing for illicit opioids, human immunodeficiency virus (HIV) risk, and use of addiction treatment services were the secondary outcomes.. Seventy-eight percent of patients in the buprenorphine group (89 of 114 [95% CI, 70%-85%]) vs 37% in the referral group (38 of 102 [95% CI, 28%-47%]) and 45% in the brief intervention group (50 of 111 [95% CI, 36%-54%]) were engaged in addiction treatment on the 30th day after randomization (P < .001). The buprenorphine group reduced the number of days of illicit opioid use per week from 5.4 days (95% CI, 5.1-5.7) to 0.9 days (95% CI, 0.5-1.3) vs a reduction from 5.4 days (95% CI, 5.1-5.7) to 2.3 days (95% CI, 1.7-3.0) in the referral group and from 5.6 days (95% CI, 5.3-5.9) to 2.4 days (95% CI, 1.8-3.0) in the brief intervention group (P < .001 for both time and intervention effects; P = .02 for the interaction effect). The rates of urine samples that tested negative for opioids did not differ statistically across groups, with 53.8% (95% CI, 42%-65%) in the referral group, 42.9% (95% CI, 31%-55%) in the brief intervention group, and 57.6% (95% CI, 47%-68%) in the buprenorphine group (P = .17). There were no statistically significant differences in HIV risk across groups (P = .66). Eleven percent of patients in the buprenorphine group (95% CI, 6%-19%) used inpatient addiction treatment services, whereas 37% in the referral group (95% CI, 27%-48%) and 35% in the brief intervention group (95% CI, 25%-37%) used inpatient addiction treatment services (P < .001).. Among opioid-dependent patients, ED-initiated buprenorphine treatment vs brief intervention and referral significantly increased engagement in addiction treatment, reduced self-reported illicit opioid use, and decreased use of inpatient addiction treatment services but did not significantly decrease the rates of urine samples that tested positive for opioids or of HIV risk. These findings require replication in other centers before widespread adoption.. clinicaltrials.gov Identifier: NCT00913770.

Topics: Adult; Buprenorphine; Emergency Service, Hospital; Female; Health Services; HIV Infections; Hospitals, Teaching; Hospitals, Urban; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Referral and Consultation; Risk; Young Adult

Compare HIV injecting and sex risk in patients being treated with methadone (MET) or buprenorphine-naloxone (BUP).. Secondary analysis from a study of liver enzyme changes in patients randomized to MET or BUP who completed 24 weeks of treatment and had 4 or more blood draws. The initial 1:1 randomization was changed to 2:1 (BUP:MET) after 18 months due to higher dropout in BUP. The Risk Behavior Survey measured HIV risk before 30 days at baseline and weeks 12 and 24.. Among 529 patients randomized to MET, 391 (74%) were completers; among 740 randomized to BUP, 340 (46%) were completers; 700 completed the Risk Behavior Survey. There were significant reductions in injecting risk (P < 0.0008) with no differences between groups in mean number of times reported injecting heroin, speedball, other opiates, and number of injections; or percent who shared needles; did not clean shared needles with bleach; shared cookers; or engaged in front/back loading of syringes. The percent having multiple sex partners decreased equally in both groups (P < 0.03). For males on BUP, the sex risk composite increased; for males on MET, the sex risk decreased resulting in significant group differences over time (P < 0.03). For females, there was a significant reduction in sex risk (P < 0.02) with no group differences.. Among MET and BUP patients who remained in treatment, HIV injecting risk was equally and markedly reduced; however, MET retained more patients. Sex risk was equally and significantly reduced among females in both treatment conditions, but it increased for males on BUP and decreased for males on MET.

Topics: Adult; Buprenorphine; Female; HIV Infections; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Risk Reduction Behavior; Substance Abuse, Intravenous; Unsafe Sex

Buprenorphine/naloxone (BUP/NX) is not licenced for use in China or Thailand and there was little clinical experience with this drug combination in these countries at the inception of HIV Prevention Trial Network (HPTN) 058, a randomized trial comparing risk reduction counselling combined with either short-term or long-term medication assisted treatment with BUP/NX to prevent HIV infection and death amongst opioid-dependent injectors.. We conducted a safety phase that included the first 50 subjects enrolled at each of the three initial study sites (N=150). Clinical and laboratory assessments were conducted at baseline and weekly for the first 4 weeks. Changes in laboratory parameters were estimated with random effects models.. BUP/NX was well tolerated by study subjects and opioid withdrawal scores decreased substantially during the 3-day induction. Two participants experienced grade 3 clinical adverse events, which were categorized as probably not related to the study drug. Grade 2 or 3 increases in alanine aminotransferase (ALT) occurred in 25 (17%) subjects. The magnitude of ALT increase over 4-week follow-up was strongly associated with baseline ALT elevation.. In Chinese and Thai opioid-dependent injectors, we found BUP/NX to be effective in reducing opioid withdrawal symptoms and safe during short-term use. ALT increases were observed over 4-week-follow-up, which are consistent with reports from Western populations. Long-term safety and efficacy evaluations are indicated.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; China; Female; Follow-Up Studies; HIV Infections; HIV Seronegativity; Humans; Male; Models, Statistical; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Thailand; Time Factors

Untreated opioid dependence adversely affects HIV outcomes. Integrating buprenorphine/naloxone into HIV treatment settings is feasible; however, the optimal level of counseling has not been established. We conducted a 12-week randomized clinical trial of physician management (PM) versus PM plus enhanced medical management (EMM) in 47 subjects. At 12 weeks, there were no differences between the two groups in percentage of opioid negative urines (63.6% PM vs. 69.0% PM+EMM, p=.5), maximum duration of continuous abstinence (4.9 weeks PM vs. 5.2 weeks PM+EMM, p=.8) or retention (80% PM vs. 59% PM+EMM, p=.1). The percentage of subjects with detectable HIV viral loads decreased from 58% at baseline to 40% at 12 weeks across both groups (p=.02 for time) with no between group differences (p=.84 and p=.27 for the interaction). Providing more extensive counseling beyond PM is feasible in an HIV clinic, but we are unable to detect an improvement in outcomes associated with these services.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Delivery of Health Care, Integrated; Feasibility Studies; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Psychotherapy, Brief; Substance Abuse Detection; Time Factors; Treatment Outcome; Viral Load

Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes.. HIV-infected, opioid-dependent subjects (N = 295) recruited from 10 clinical sites initiated buprenorphine/naloxone (BUP/NX) and were assessed at baseline and quarterly for 12 months. Primary outcomes included receiving antiretroviral therapy (ART), HIV-1 RNA suppression, and mean changes in CD4 lymphocyte count. Analyses were stratified for the 119 subjects not on ART at baseline. Generalized estimating equations were deployed to examine time-dependent correlates for each outcome.. At baseline, subjects on ART (N = 176) were more likely than those not on ART (N = 119) to be older, heterosexual, have lower alcohol addiction severity scores, and lower HIV-1 RNA levels; they were less likely to be homeless and report sexual risk behaviors. Subjects initiating BUP/NX (N = 295) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline; however, these improvements were not significantly improved by longer retention on BUP/NX. Retention on BUP/NX for three or more quarters was, however, significantly associated with increased likelihood of initiating ART (β = 1.34 [1.18, 1.53]) and achieve viral suppression (β = 1.25 [1.10, 1.42]) for the 64 of 119 (54%) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX. In longitudinal analyses, being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores (β = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (β = 0.55 [0.35, 0.97]), homeless (β = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (β = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (β = 10.27 [5.79, 18.23]). Female gender (β = 1.91 [1.07, 3.41]), Hispanic ethnicity (β = 2.82 [1.44, 5.49]), and increased general health quality of life (β = 1.02 [1.00,1.04]) were also independently correlated with viral suppression. Improvements in CD4 lymphocyte count were significantly associated with being on ART and increased over time.. Initiating BUP/NX in HIV clinical care settings is feasible and correlated with initiation of ART and improved CD4 lymphocyte counts. Longer retention on BPN/NX was not associated with improved prescription of ART, viral suppression, or CD4 lymphocyte counts for the overall sample in which the majority was already prescribed ART at baseline. Among those retained on BUP/NX, HIV treatment outcomes did not worsen and were sustained. Increasing time on BUP/NX, however, was especially important for improving HIV treatment outcomes for those not on ART at baseline, the group at highest risk for clinical deterioration. Retaining subjects on BUP/NX is an important goal for sustaining HIV treatment outcomes for those on ART and improving them for those who are not. Comorbid substance use disorders (especially alcohol), mental health problems, and quality-of-life indicators independently contributed to HIV treatment outcomes among HIV-infected persons with opioid dependence, suggesting the need for multidisciplinary treatment strategies for this population.

Topics: Alcoholism; Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; CD4 Lymphocyte Count; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Risk Factors; RNA, Viral; Treatment Outcome

Buprenorphine/naloxone allows the integration of opioid dependence and HIV treatment.. We conducted a prospective study in HIV-infected opioid-dependent patients to investigate the impact of buprenorphine/naloxone treatment on drug use. Self-report and chart review assessments were conducted every 3 months (quarters 1-4) for 1 year. Outcomes were buprenorphine/naloxone treatment retention, drug use, and addiction treatment processes.. Among 303 patients enrolled between July 2005 and December 2007, retention in buprenorphine/naloxone treatment was 74%, 67%, 59%, and 49% during Quarters 1, 2, 3, and 4, respectively. Past 30-day illicit opioid use decreased from 84% of patients at baseline to 42% in retained patients over the year. Patients were 52% less likely to use illicit opioids for each quarter in treatment (Odds ratio = 0.66; 95% CI: 0.61 to 0.72). Buprenorphine/naloxone doses and office visits approximated guidelines published by the United States Department of Health and Human Services. Urine toxicology monitoring was less frequent than recommended.. Buprenorphine/naloxone provided in HIV treatment settings can decrease opioid use. Strategies are needed to improve retention and address ongoing drug use in this treatment population.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; HIV Infections; Humans; Male; Naloxone; Narcotic Antagonists; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Treatment Outcome

Substance abuse is associated with poor medical and quality-of-life outcomes among HIV-infected individuals. Although drug treatment may reduce these negative consequences, for many patients, options are limited. Buprenorphine/naloxone, an opioid agonist treatment that can be prescribed in the United States in office-based settings, can be used to expand treatment capacity and integrate substance abuse services into HIV care. Recognizing this potential, the US Health Resources and Services Administration funded the development and implementation of demonstration projects that integrated HIV care and buprenorphine/naloxone treatment at 10 sites across the country. An Evaluation and Technical Assistance Center provided programmatic and clinical support as well as oversight for an evaluation that examined the processes for and outcomes of integrated care. The evaluation included patient-level self-report and chart abstractions as well as provider and site level data collected through surveys and in-depth interviews. Although multisite demonstrations pose implementation and evaluation challenges, our experience demonstrates that these can, in part, be addressed through ongoing communication and technical assistance as well as a comprehensive evaluation design that incorporates multiple research methods and data sources. Although limitations to evaluation findings persist, they may be balanced by the scope and "real-world" context of the initiative.

Topics: Ambulatory Care; Buprenorphine; Buprenorphine, Naloxone Drug Combination; HIV Infections; Humans; Methadone; Multicenter Studies as Topic; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; United States

HIV-infected prisoners fare poorly after release. Though rarely available, opioid agonist therapy (OAT) may be one way to improve HIV and substance abuse treatment outcomes after release. Of the 69 HIV-infected prisoners enrolled in a randomized controlled trial of directly administered antiretroviral therapy, 48 (70%) met DSM-IV criteria for opioid dependence. Of these, 30 (62.5%) selected OAT, either as methadone (N = 7, 14.5%) or buprenorphine/naloxone (BPN/NLX; N = 23, 48.0%). Twelve-week HIV and substance abuse treatment outcomes are reported as a sub-study for those selecting BPN/NLX. Retention was high: 21 (91%) completed BPN/NLX induction and 17 (74%) remained on BPN/NLX after 12 weeks. Compared with baseline, the proportion with a non-detectable viral load (61% vs 63% log(10) copies/mL) and mean CD4 count (367 vs 344 cells/mL) was unchanged at 12 weeks. Opiate-negative urine testing remained 83% for the 21 who completed induction. Using means from 10-point Likert scales, opioid craving was reduced from 6.0 to 1.8 within 3 days of BPN/NLX induction and satisfaction remained high at 9.5 throughout the 12 weeks. Adverse events were few and mild. BPN/NLX therapy was acceptable, safe and effective for both HIV and opioid treatment outcomes among released HIV-infected prisoners. Future randomized controlled trials are needed to affirm its benefit in this highly vulnerable population.

Topics: Anti-Retroviral Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Male; Mental Disorders; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Prisoners; Substance-Related Disorders

To assess baseline rates of and changes in HIV drug and sexual risk behavior as a function of gender and treatment in opioid-dependent youth.. One hundred fifty participants were randomly assigned to extended buprenorphine/naloxone therapy (BUP) for 12 weeks or detoxification for 2 weeks; all received drug counseling for 12 weeks. HIV risk was assessed at baseline and 4-week, 8-week, and 12-week follow-ups. Behavioral change was examined using generalized estimating equations.. Baseline rates of past-month HIV risk for females/males were 51%/45% for injection drug use (IDU) (ns), 77%/35% for injection risk (P < 0.001), 82%/74% for sexual activity (ns), 14%/24% for multiple partners (ns), and 68%/65% for unprotected intercourse (ns). IDU decreased over time (P < 0.001), with greater decreases in BUP versus detoxification (P < 0.001) and females versus males in BUP (P < 0.05). Injection risk did not change for persistent injectors. Sexual activity decreased in both genders and conditions (P < 0.01), but sexual risk did not.. Overall, IDU and sexual activity decreased markedly, particularly in BUP patients and females, but injection and sexual risk behaviors persisted. Although extended BUP seems to have favorable effects on HIV risk behavior in opioid-dependent youth, risk reduction counseling may be necessary to extend its benefits.

Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Female; HIV Infections; Humans; Male; Naloxone; Narcotic Antagonists; Patient Acceptance of Health Care; Risk Assessment; Risk-Taking; Sexual Behavior; Substance Abuse, Intravenous; Substance-Related Disorders; Young Adult

Opioid dependence is common in HIV clinics. Buprenorphine-naloxone (BUP) is an effective treatment of opioid dependence that may be used in routine medical settings.. To compare clinic-based treatment with BUP (clinic-based BUP) with case management and referral to an opioid treatment program (referred treatment).. Single-center, 12-month randomized trial. Participants and investigators were aware of treatment assignments. (ClinicalTrials.gov registration number: NCT00130819). HIV clinic in Baltimore, Maryland.. 93 HIV-infected, opioid-dependent participants who were not receiving opioid agonist therapy and were not dependent on alcohol or benzodiazepines.. Clinic-based BUP included BUP induction and dose titration, urine drug testing, and individual counseling. Referred treatment included case management and referral to an opioid-treatment program.. Initiation and long-term receipt of opioid agonist therapy, urine drug test results, visit attendance with primary HIV care providers, use of antiretroviral therapy, and changes in HIV RNA levels and CD4 cell counts.. The average estimated participation in opioid agonist therapy was 74% (95% CI, 61% to 84%) for clinic-based BUP and 41% (CI, 29% to 53%) for referred treatment (P < 0.001). Positive test results for opioids and cocaine were significantly less frequent in clinic-based BUP than in referred treatment, and study participants receiving clinic-based BUP attended significantly more HIV primary care visits than those receiving referred treatment. Use of antiretroviral therapy and changes in HIV RNA levels and CD4 cell counts did not differ between the 2 groups.. This was a small single-center study, follow-up was only moderate, and the study groups were unbalanced in terms of recent drug injections at baseline.. Management of HIV-infected, opioid-dependent patients with a clinic-based BUP strategy facilitates access to opioid agonist therapy and improves outcomes of substance abuse treatment.. Health Resources and Services Administration Special Projects of National Significance program.

Topics: Anti-HIV Agents; Baltimore; Buprenorphine; Community Health Services; Drug Therapy, Combination; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Outcome Assessment, Health Care; Referral and Consultation; Substance Abuse Treatment Centers; Treatment Outcome

HIV-infected patients with opioid dependence often require opioid replacement therapy. Pharmacokinetic interactions between HIV therapy and opioid dependence treatment medications can occur. HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone (BUP/NLX) therapy sequentially underwent baseline and steady-state pharmacokinetic evaluation of open-label, twice daily tipranavir 500 mg co-administered with ritonavir 200 mg (TPV/r). Twelve subjects were enrolled and 10 completed the study. Prior to starting TPV/r, the geometric mean BUP AUC(0-24h) and C(max) were 43.9 ng h/mL and 5.61 ng/mL, respectively. After achieving steady-state with TPV/r (> or = 7 days), these values were similar at 43.7 ng h/mL and 4.84 ng/mL, respectively. Similar analyses for norBUP, the primary metabolite of BUP, demonstrated a reduction in geometric mean for AUC(0-24h) [68.7-14.7 ng h/mL; ratio=0.21 (90% CI 0.19-0.25)] and C(max) [4.75-0.94 ng/mL; ratio=0.20 (90% CI 0.17-0.23)]. The last measurable NLX concentration (C(last)) in the concentration-time profile, never measured in previous BUP/NLX interaction studies with antiretroviral medications, was decreased by 20%. Despite these pharmacokinetic effects on BUP metabolites and NLX, no clinical opioid withdrawal symptoms were noted. TPV steady-state AUC(0-12h) and C(max) decreased 19% and 25%, respectively, and C(min) was relatively unchanged when compared to historical control subjects receiving TPV/r alone. No dosage modification of BUP/NLX is required when co-administered with TPV/r. Though mechanistically unclear, it is likely that decreased plasma RTV levels while on BUP/NLX contributed substantially to the decrease in TPV levels. BUP/NLX and TPV/r should therefore be used cautiously to avoid decreased efficacy of TPV in patients taking these agents concomitantly.

Topics: Adult; Anti-Retroviral Agents; Buprenorphine; Drug Interactions; Drug Therapy, Combination; Female; HIV Infections; HIV Seronegativity; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pyridines; Pyrones; Ritonavir; Sulfonamides; Treatment Outcome

Methadone treatment reduces human immunodeficiency virus (HIV) risk, but the effects of primary-care-based buprenorphine/naloxone on HIV risk are unknown. The purpose of this study was to determine whether primary-care-based buprenorphine/naloxone was associated with decreased HIV risk behavior. We conducted a longitudinal analysis of 166 opioid-dependent persons (129 men and 37 women) receiving buprenorphine/naloxone treatment in a primary care clinic. We compared baseline and 12- and 24-week overall, drug-related, and sex-related HIV risk behaviors using the AIDS/HIV Risk Inventory (ARI). Buprenorphine/naloxone treatment was associated with significant reductions in overall and drug-related ARI scores from baseline to 12 and 24 weeks. Intravenous drug use in the past 3 months was endorsed by 37%, 12%, and 7% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Sex while you or your partner were "high" was endorsed by 64%, 13%, and 15% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Inconsistent condom use during sex with a steady partner was high at baseline and did not change over time. We conclude that primary-care-based buprenorphine/naloxone treatment is associated with decreased drug-related HIV risk, but additional efforts may be needed to address sex-related HIV risk when present.

Topics: Adult; Buprenorphine; Female; HIV Infections; Humans; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Primary Health Care; Risk-Taking; Sexual Behavior

Untreated opioid dependence adversely affects the care of human immunodeficiency virus (HIV)-positive patients. Buprenorphine, a partial opioid agonist, is available for maintenance treatment of opioid dependence in HIV specialty settings. We investigated the feasibility and efficacy of integrating buprenorphine, along with 2 levels of counseling, into HIV clinical care.. HIV-positive, opioid-dependent patients were enrolled in a 12-week pilot study and randomized to receive daily buprenorphine/naloxone treatment along with either brief physician management or physician management combined with nurse-administered drug counseling and adherence management. Primary outcomes included treatment retention; illicit drug use, assessed by urine toxicology test and self-report; CD4 lymphocyte counts; and log(10) HIV type 1 (HIV-1) RNA levels.. Of the 16 patients who received at least 1 dose of buprenorphine, 13 (81%) completed 12 weeks of treatment. The proportion of opioid-positive weekly urine test results decreased from 100% at baseline to 32% (month 1), 20% (month 2), and 16% (month 3). Only 4 patients reported any opioid use (in the prior 7 days) during the 12-week study. CD4 lymphocyte counts remained stable over the course of the study. The mean log(10) HIV-1 RNA level (+/- standard deviation) declined significantly, from 3.66+/-1.06 log(10) HIV-1 RNA copies/mL at baseline to 3.0+/-0.57 log(10) HIV-1 RNA copies/mL at month 3 (P<.05). No significant differences based on counseling intervention were detected. All 13 patients who completed the study continued to receive treatment in an extension phase of at least 0-15 months' duration.. We conclude that it is feasible to integrate buprenorphine into HIV clinical care for the treatment of opioid dependence. Patients experienced good treatment retention and reductions in their opioid use. HIV biological markers remained stable or improved during buprenorphine/naloxone treatment.

Topics: Administration, Sublingual; Adult; Antiretroviral Therapy, Highly Active; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pilot Projects; Probability; Reference Values; Risk Factors; Treatment Outcome

The dynamics of injection drug use and higher-risk sexual practices compound the risk of HIV and HCV acquisition. Published literature on people who inject drugs (PWID) has examined risk of infection assuming homogeneity of cohort behavior. Categorizing subgroups by injection and sexual risk can inform a more equitable approach to how syringe services programs (SSPs) adapt harm reduction resources and implementation of evidence-based interventions. We explored injection and sexual risk profiles among PWID to determine significant predictors of class membership.. Data were collected from 1,272 participants at an SSP in Miami-Dade County. Latent Class Analysis (LCA) examined how 10 injection/sexual behavior indicators cluster together to create profiles. Model fit statistics and multivariable multinomial latent class regression identified the optimal class structure and significant predictors of class membership. We assessed SSP visits, naloxone access, HIV/HCV testing and prevalence, and incidence of self-reported wounds.. Understanding PWID subgroups amplifies the importance of implementing evidencebased interventions such as PrEP for those engaging in highest risk behavior, with focused interventions of antiretroviral management and access to condoms for members of the LIHS class and HCV screening with wound care for those belonging to HIMS.

Topics: Drug Users; Female; Florida; Hepatitis C; HIV Infections; Humans; Naloxone; Risk-Taking; Sexual Behavior; Substance Abuse, Intravenous

The intersecting epidemics of opioid misuse, injection drug use, and HIV/HCV have resulted in record overdose deaths and sustained high levels of HIV/HCV transmissions. Literature on social networks suggests opportunities to connect people who use drugs (PWUD) and their peers to HIV/HCV and opioid overdose prevention services. However, little evidence exists on how to design such peer referral interventions in emergency department (ED) settings.. A mixed-method study was conducted to assess the feasibility of an mHealth-facilitated 'patient to peer social network referral program' for PWUD. In-depth interviews (IDIs) and quantitative surveys were conducted with urban ED patients (n = 15), along with 3 focus group discussions (FGDs) (n = 19).. Overall, 34 participants were enrolled (71 % males, 53 % Black). 13/15 IDI participants reported a history of opioid overdose; all had witnessed overdose events; all received HIV/HCV testing. From survey responses, most would invite their peers for HIV/HCV testing and naloxone training; and anticipated peers to accept referrals (HIV: 60 %, HCV: 73 %, naloxone: 93 %). Qualitative data showed PWUD shared health-related information with each other but preferred word of mouth rather than text messages. Participants used smartphones regularly and suggested using Internet advertising for prevention services. Participants expressed enthusiasm for ED-based peer mHealth referral platform to prevention services, as well as referring their peers to proposed services, with monetary incentives.. ED-based peer referral intervention to HIV/HCV testing and naloxone training was viewed favorably by PWUD. Frequent smartphone use among PWUD suggests that the medium could be a promising mode for peer referral.

Topics: Drug Overdose; Emergency Service, Hospital; Female; Hepatitis C; HIV Infections; Humans; Male; Naloxone; Narcotic Antagonists; Opiate Overdose; Opioid-Related Disorders; Pilot Projects; Referral and Consultation; Telemedicine

After the closure of pill mills and implementation of Florida's Prescription Drug Monitoring Program in 2010, high demand for opioids was met with counterfeit pills, heroin, and fentanyl. In response, medical students at the University of Miami Miller School of Medicine embarked on a journey to bring syringe services programs (SSPs) to Florida through an innovative grassroots approach. Working with the Florida Medical Association, students learned patient advocacy, legislation writing, and negotiation within a complex political climate. Advocacy over 4 legislative sessions (2013-2016) included committee testimony and legislative visit days, resulting in the authorization of a 5-year SSP pilot. The University of Miami's Infectious Disease Elimination Act (IDEA) SSP opened on December 1, 2016. Students identified an urgent need for expanded health care for program participants and founded a weekly free clinic at the SSP. Students who rotate through the clinic learn medicine and harm reduction through the lens of social justice, with exposure to people who use drugs, sex workers, individuals experiencing homelessness, and other vulnerable populations. The earliest success of the IDEA SSP was the distribution of over 2,000 boxes of nasal naloxone, which the authors believe positively contributed to a decrease in the number of opioid-related deaths in Miami-Dade County for the first time since 2013. The second was the early identification of a cluster of acute human immunodeficiency virus infections among program participants. Inspired by these successes, students from across the state joined University of Miami students and met with legislators in their home districts, wrote op-eds, participated in media interviews, and traveled to the State Capitol to advocate for decisive action to mitigate the opioid crisis. The 2019 legislature passed legislation authorizing SSPs statewide. In states late to adopt SSPs, medical schools have a unique opportunity to address the opioid crisis using this evidence-based approach.

Topics: Administration, Intranasal; Disease Eradication; Education, Medical; Florida; Harm Reduction; HIV Infections; Humans; Ill-Housed Persons; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Advocacy; Pilot Projects; Program Evaluation; Schools, Medical; Students, Medical; Syringes; Universities; Vulnerable Populations

The potency of a vaccine highly depends upon the nature of the adjuvant used. There are a variety of ineffective vaccines, such as HIV-1 vaccine candidates, that need to be optimized with new adjuvant formulations to improve vaccine potency and efficacy. Studies show the potency of naloxone (NLX)/alum mixture in the induction of Th1/Th2 response for vaccine. However, other immunologic patterns inducing by this adjuvant and its immunoregulatory effect is unclear. In this regard, the aim of the present study was to investigate the effect of the NLX/alum mixture, as an adjuvant, on cytokine networks and immunoregulatory activity for an HIV-1 polytope vaccine. BALB/c mice were divided into six groups (n = 6) and immunized subcutaneously with 10 μg of the vaccine formulated with NLX/alum, NLX, alum, and Freund's adjuvants. At the same time, the mice in the control groups received an equal volume of PBS or NLX. The lymphocyte proliferation assay was carried out using the BrdU method. ELISA was used to measure the levels of IFN-γ, IL-2, IL-4, IL-10, IL-12, and IL-17 cytokines, total IgG, as well as IgG1 and IgG2a subtypes in serum samples. Our findings showed that mice receiving the NLX/alum-adjuvanted vaccine exhibited increased antibody levels compared with other groups. In addition, there was a considerable difference in the levels of IgG1, IgG2a, IFN-γ, IL-2, IL-10, IL-12, and IL-17 in mice receiving the NLX/alum-adjuvanted vaccine as compared with other groups. The NLX/alum mixture, as an adjuvant, may have a positive effect on the induction of multi-cytokine responses, as well as the increased level of IL-10, showing its higher immunogenicity with a higher immunoregulatory mechanism.

Topics: Adjuvants, Immunologic; AIDS Vaccines; Alum Compounds; Animals; Antibodies, Viral; Drug Compounding; Female; HIV Infections; HIV-1; Humans; Immunization; Interferon-gamma; Interleukins; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Naloxone

Topics: Buprenorphine; HIV Infections; Humans; Maintenance; Methadone; Naloxone; Nitriles; Opioid-Related Disorders; Referral and Consultation; Vietnam

This cross-sectional study describes naloxone rescue kit receipt among people with HIV (PWH) on chronic opioid therapy (COT) and HIV clinician opioid overdose prevention care in two clinics between 2015 and 2017. Naloxone rescue kit receipt was uncommon. History of overdose was associated with receiving naloxone but having a clinician who reported providing overdose prevention care was not. This study suggests that clinicians prescribing COT to PWH should improve overdose prevention care, including naloxone co-prescribing.

Topics: Analgesics, Opioid; Cross-Sectional Studies; Drug Overdose; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

Syringe services programs (SSPs) are evidence-based interventions that are associated with decreases in prevalence and incidence rates of HIV and viral hepatitis among people who inject drugs (PWID). SSPs are also effective conduits to deliver overdose prevention resources among PWID. In December 2015, the Kanawha-Charleston Health Department (KCHD) in West Virginia implemented a SSP; however, the program was indefinitely suspended in early 2018 following policy changes that would have forced the program to operate in ways that conflicted with established best practices. The purpose of this research is to explore the public health implications of the suspension of the KCHD SSP among rural PWID.. We conducted semi-structured interviews with 27 PWID (59.3% male, 88.9% White) to explore access to sterile injection equipment and overdose prevention resources, high-risk injection practices, and HIV risk perceptions following the KCHD SSP suspension. Participants were recruited from street locations frequented by PWID. Interviews were audio-recorded and transcribed verbatim. We employed an iterative, modified constant comparison approach to systematically code and synthesize textual interview data.. Participants described the KCHD SSP as providing a variety of harm reduction services to PWID and being able to speak honestly with SSP staff about their drug use without fear of stigmatization. The suspension of the KCHD SSP fundamentally changed the public health landscape for PWID, ushering in a new era of increased risks for acquiring bloodborne infections and overdose. PWID described more frequently injecting with used syringes and engaging in a range of high-risk injection practices after the SSP was suspended. PWID also discussed having decreased access to naloxone and being less likely to get routinely tested for HIV following the KCHD SSP suspension.. This research demonstrates that the suspension of a SSP in rural West Virginia increased risks for HIV/HCV acquisition and overdose among PWID. The suspension of the SSP led to community-wide decreases in access to sterile injection equipment and naloxone among PWID. The suspension of the KCHD SSP should be viewed as a call to action for sustaining evidence-based interventions in the face of sociopolitical forces that attempt to subvert public health.

Topics: Adult; Amphetamine-Related Disorders; Drug Overdose; Female; Harm Reduction; Health Services Accessibility; Heroin Dependence; HIV Infections; Humans; Ill-Housed Persons; Male; Methamphetamine; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Needle-Exchange Programs; Opioid-Related Disorders; Public Health; Qualitative Research; Risk-Taking; Rural Health Services; Social Stigma; Substance Abuse, Intravenous; West Virginia

A community-based research (CBR) approach is critical to redressing the exclusion of women-particularly, traditionally marginalized women including those who use substances-from HIV research participation and benefit. However, few studies have articulated their process of involving and engaging peers, particularly within large-scale cohort studies of women living with HIV where gender, cultural and linguistic diversity, HIV stigma, substance use experience, and power inequities must be navigated.. Through our work on the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS), Canada's largest community-collaborative longitudinal cohort of women living with HIV (n = 1422), we developed a comprehensive, regionally tailored approach for hiring, training, and supporting women living with HIV as Peer Research Associates (PRAs). To reflect the diversity of women with HIV in Canada, we initially hired 37 PRAs from British Columbia, Ontario, and Quebec, prioritizing women historically under-represented in research, including women who use or have used illicit drugs, and women living with HIV of other social identities including Indigenous, racialized, LGBTQ2S, and sex work communities, noting important points of intersection between these groups.. Building on PRAs' lived experience, research capacity was supported through a comprehensive, multi-phase, and evidence-based experiential training curriculum, with mentorship and support opportunities provided at various stages of the study. Challenges included the following: being responsive to PRAs' diversity; ensuring PRAs' health, well-being, safety, and confidentiality; supporting PRAs to navigate shifting roles in their community; and ensuring sufficient time and resources for the translation of materials between English and French. Opportunities included the following: mutual capacity building of PRAs and researchers; community-informed approaches to study the processes and challenges; enhanced recruitment of harder-to-reach populations; and stronger community partnerships facilitating advocacy and action on findings.. Community-collaborative studies are key to increasing the relevance and impact potential of research. For women living with HIV to participate in and benefit from HIV research, studies must foster inclusive, flexible, safe, and reciprocal approaches to PRA engagement, employment, and training tailored to regional contexts and women's lives. Recommendations for best practice are offered.

Topics: Canada; Clinical Competence; Cohort Studies; Community-Based Participatory Research; Criminal Law; Drug Overdose; Epidemiologic Studies; Female; HIV Infections; Humans; Inservice Training; Longitudinal Studies; Naloxone; Narcotic Antagonists; Peer Group; Personnel Selection; Research; Research Design; Sex Factors; Social Marginalization

HIV/AIDS rates are higher in the Southern United States compared to other regions of the country. Reasons for disparities include poverty, health care access, and racism. People who inject drugs (PWID) account for 8% of HIV/AIDS incidence rates. Harm reduction can connect PWID to needed resources. AIDS United Southern REACH grantees developed the Southern Harm Reduction Coalition (SHRC) as a means to decrease HIV/AIDS and viral hepatitis rates, criminalization of drug users and sex workers, and drug overdose.. Investigators used an intrinsic case study design to examine the context of harm reduction in the Southern United States, successful strategies, and outcomes. Data collection included key informant interviews and coalition documents. The community coalition action theory was used to examine the data.. The SHRC initiated regional conferences and customized trainings. Strengths-based language and utilization of diverse strengths among coalition members were used to effect change. Coalition outcomes included syringe decriminalization legislation, syringe exchange, naloxone access, naloxone funding legislation, and 911 Good Samaritan laws, along with expanded support for PWID.. Advocacy successes can be applied to similar organizations in the Southern United States to promote harm reduction and potentially decrease HIV/AIDS burden, viral hepatitis, criminalization, and overdose.

Topics: Acquired Immunodeficiency Syndrome; Adult; Community Participation; Drug Overdose; Female; Harm Reduction; Health Services Accessibility; Health Status Disparities; Hepatitis; HIV Infections; Humans; Naloxone; Needle-Exchange Programs; Public Health; United States

Topics: Computer Simulation; Drug Overdose; Drug Tolerance; Drug Users; Drug Utilization; Emergency Service, Hospital; Facilities and Services Utilization; Female; Fentanyl; Heroin; Heroin Dependence; HIV Infections; Humans; Models, Psychological; Naloxone; Opioid-Related Disorders; Prescription Drugs; Rural Population; Social Networking; Unemployment; United States; Video Recording

In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP.. We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained.. In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a willingness-to-pay threshold of $100 000. In probabilistic sensitivity analysis, the combination of naloxone distribution, PrEP, and linkage to addiction treatment was the optimal strategy in 37% of iterations and the combination of naloxone distribution and linkage to addiction treatment was the optimal strategy in 34% of iterations.. Naloxone distribution through syringe service programmes is cost-effective compared with syringe distribution alone, but when combined with linkage to addiction treatment is cost saving compared with no additional services. A strategy that combines naloxone distribution, PrEP, and linkage to addiction treatment results in greater health benefits in people who inject drugs and is also cost-effective.. State of Connecticut Department of Public Health and the National Institute of Mental Health.

Topics: Connecticut; Cost-Benefit Analysis; HIV Infections; Humans; Models, Theoretical; Naloxone; Needle-Exchange Programs; Pre-Exposure Prophylaxis; Program Evaluation; Substance Abuse, Intravenous; Treatment Outcome

In the present study we used a fusion peptide from HIV-1 p24 and Nef as vaccine model and adjuvant activity of Naloxone/alum mixture was evaluated in a peptide vaccine model. HIV-1 p24-Nef fusion peptide was synthesized. Female BALB/c mice were divided into five groups. The first group immunized subcutaneously with the p24-Nef fusion peptide adjuvanted with Naloxone/alum mixture and boosted with same protocol. The second was immunized with fusion peptide adjuvanted in alum. The control groups were injected with NLX (Group 3), Alum (Group 4), or PBS (Groups 5) under the same conditions. To determine the type of induced immune response, sera and splenocytes were analyzed by commercial ELISA method for total IgG and isotypes and cytokine secretion (IL-4 & IFN-γ), respectively. We have also used the ELISPOT assay to monitor changes in the frequency of IFN-γ-producing T cells. The proliferation of T cells was assessed using Brdu method and T-cell cytotoxicity was assessed with CFSE method. Immunization of mice with HIV-1 p24-Nef fusion peptide formulated in Naloxone/alum mixture significantly increased lymphocyte proliferation and shifted cytokine responses toward Th1 profile compared to all other groups. Analysis of humoral immune responses revealed that administration of HIV-1 p24-Nef fusion peptide with Naloxone/alum mixture significantly increased specific IgG responses and also increased IgG1,IgG2a, IgG2b, IgG3, and IgM vs. alum-adjuvanted vaccine groups. Naloxone/alum mixture as an adjuvant could improve cellular and humoral immune response for HIV vaccine model and this adjuvant maybe useful for HIV vaccine model in human clinical trial.

Topics: Adjuvants, Immunologic; AIDS Vaccines; Alum Compounds; Animals; Cell Proliferation; Cytokines; Female; HIV Core Protein p24; HIV Infections; HIV-1; Humans; Immunity, Humoral; Immunoglobulin G; Immunoglobulin M; Mice; Mice, Inbred BALB C; Naloxone; nef Gene Products, Human Immunodeficiency Virus; Recombinant Fusion Proteins

Topics: Anti-HIV Agents; Comorbidity; Drug and Narcotic Control; Drug Overdose; Harm Reduction; Health Policy; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Needle-Exchange Programs; Opiate Substitution Treatment; Substance Abuse, Intravenous; Substance-Related Disorders; United Nations

Since the 1990s, effective HIV prevention and treatment strategies have been coordinated and implemented in the United States, resulting in substantial reductions in HIV-related death and HIV transmission among people who use injection drugs. During the same period, despite substantial long-term funding of War on Drugs policies, opioid addiction, driven by increased prescription opioid use and heroin accessibility, has made overdose the leading cause of accidental injury death in the United States. This commentary describes how the prevention and treatment successes among people who use drugs in the HIV/AIDS epidemic can be applied to address the opioid overdose crisis.

Topics: Analgesics, Opioid; Drug Overdose; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; United States

The benefits of integrating primary care and substance use disorder treatment are well known, yet true integration is difficult. We developed and evaluated a team-based model of integrated care within the primary care setting for HIV-infected substance users and substance users at risk for contracting HIV. Qualitative data were gathered via focus groups and satisfaction surveys to assess patients' views of the program, evaluate key elements for success, and provide recommendations for other programs. Key themes related to preferences for the convenience and efficiency of integrated care; support for a team-based model of care; a feeling that the program requirements offered needed structure; the importance of counseling and education; and how provision of concrete services improved overall well-being and quality of life. For patients who received buprenorphine/naloxone for opioid dependence, this was viewed as a major benefit. Our results support other studies that theorize integrated care could be of significant value for hard-to-reach populations and indicate that having a clinical team dedicated to providing substance use disorder treatment, HIV risk reduction, and case management services integrated into primary care clinics has the potential to greatly enhance the ability to serve a challenging population with unmet treatment needs.

Topics: Adult; Buprenorphine; Counseling; Delivery of Health Care, Integrated; Female; Focus Groups; Health Services Needs and Demand; HIV Infections; Humans; Interviews as Topic; Male; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Satisfaction; Primary Health Care; Program Evaluation; Qualitative Research; Quality of Life; Substance-Related Disorders; Young Adult

Opioid dependence is a major risk factor for HIV infection, however, the impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV-infected opioid-dependent patients is unknown.. We conducted a longitudinal analysis of 303 HIV-infected opioid-dependent patients initiating buprenorphine/naloxone treatment. Outcomes included self-reported past 90-day needle-sharing and non-condom use. We assessed trends over the 12 months using the Cochran-Armitage trend test. Using generalized estimating equations, after multiple imputation, we determined factors independently associated with needle-sharing and non-condom use, including time-updated variables. We then conducted a mediation analysis to determine whether substance use explained the relationship between time since treatment initiation and needle-sharing.. Needle-sharing decreased from baseline to the fourth quarter following initiation of buprenorphine/naloxone (9% vs. 3%, p<0.001), while non-condom use did not (23% vs. 21%, p=0.10). HIV risk behaviors did not vary based on the presence of a detectable HIV-1 RNA viral load. Patients who were homeless and used heroin, cocaine/amphetamines or marijuana were more likely to report needle-sharing. Heroin use fully mediated the relationship between time since treatment initiation and needle-sharing. Women, patients who identified as being gay/lesbian/bisexual, those married or living with a partner and who reported heroin or alcohol use were more likely to report non-condom use. Older patients were less likely to report non-condom use.. While buprenorphine/naloxone is associated with decreased needle-sharing among HIV-infected opioid-dependent patients, sexual risk behaviors persist regardless of viral load. Targeted interventions to address HIV risk behaviors among HIV-infected opioid-dependent populations receiving buprenorphine/naloxone are needed.

Topics: Buprenorphine; Female; HIV Infections; Humans; Longitudinal Studies; Male; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Opiate Substitution Treatment; Opioid-Related Disorders; Risk-Taking; Unsafe Sex

Evaluation of State Opioid Substitution Treatment OST (methadone and buprenorphine/naloxone- Addnok-N) program in Georgia and optimization of the routine measurement instrument. Patients were recruited from 4 Tbilisi and 5 regional State Programs in May-October 2013. 2 structured self-questionnaires (one - anonymous for sensitive questions) were developed for patients to assess demographics, retention in treatment, mean drug dose, HIV and Hepatitis C and B status, illicit drug and alcohol use, social activities, crime involvement, health status, HIV risk behavior, treatment compliance and satisfaction. 608 patients (7 females) were surveyed (512 - on Methadone, 96 - on buprenorphine/naloxone). 337 (1 female) patients completed an anonymous questionnaire. Mean age - 39.43±8.7 (21-65 years). 10 (1.64%) respondents were HIV positive; 448 (73.68%) - HCV+ and 24 (3.95%) - HBV+; average methadone dose - 39.27±22.2mg; buprenorphine/naloxone - 7.4±3.6 mg; 64 (40%) of employed began working while in program; 365 (60%) have been in treatment for less than 1 year, and 146 (24%) - for 1-3 years vs. 258 (51%) out of 506 patients surveyed in 2011. 494 (81.2%) reported improvement of social status and 508 (83.5%) - of health status. 305 (90.5%) out of 337 reported no- and 30 (8.9%) - reduction of criminal activity. 467 (76.81%) patients attended individual and 200 (32.9%)-group psychotherapy sessions with various frequencies. The common adverse events: sleep disturbances - 48.84%; weakness - 50.82%; mood disturbances - 42.44%, and heaviness - 36.35%. 257 (46%) reported using of alcohol; 16 - opioids; 29 - sedative/hypnotics; 8 - marijuana and 1 - ATS past 30 days; 55 - drug injection and 11 - sharing of any injection equipment past 6 months. State OST program is effective in Georgia in terms of reduction of illegal drug use, injection risk behavior and criminal activity, and on the other hand - improving of social activity and general health. Treatment retention is less as compared with 2011 survey.

Topics: Adult; Aged; Alcoholism; Buprenorphine; Female; Georgia (Republic); Government Programs; Hepatitis B; Hepatitis C; HIV Infections; Humans; Male; Methadone; Middle Aged; Naloxone; Opiate Substitution Treatment; Patient Compliance; Patient Satisfaction; Surveys and Questionnaires; Young Adult

Topics: Buprenorphine; Female; HIV Infections; Humans; Male; Methadone; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Risk Reduction Behavior

Topics: Buprenorphine; Female; HIV Infections; Humans; Male; Methadone; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Risk Reduction Behavior

Interactions between HIV and opioid-dependence therapies are known to occur. We sought to determine if such interactions occurred between buprenorphine/naloxone and elvitegravir boosted with cobicistat.. We performed a within-subject open-labeled pharmacokinetic and pharmacodynamic study in 17 HIV-seronegative subjects stabilized on at least 2 weeks of buprenorphine/naloxone therapy. Subjects underwent baseline and steady state evaluation of the effect of elvitegravir 150 mg once daily boosted with 150 mg once daily of cobicistat (EVG/COBI) on buprenorphine/naloxone parameters. Safety was monitored throughout the study.. Compared with baseline values, buprenorphine mean AUCtau (69.0 versus 95.6 hr*ng/mL) and mean Cmax (8.4 versus 9.3 ng/mL) increased significantly in the presence of EVG/COBI. Compared with baseline values, norbuprenorphine mean AUCtau (103.4 versus 163.4 hr*ng/mL) and mean Cmax (6.9 versus 9 ng/mL) also increased significantly after achieving steady state EVG/COBI. Naloxone mean AUCtau (0.57 versus 0.45 hr*ng/mL) and mean Cmax (0.25 versus 0.16 ng/mL) decreased after the addition of EVG/COBI. The AUCtau, Cmax and Ctau of EVG and cobicistat did not significantly differ from historical controls. Opioid withdrawal or overdose was not observed among subjects in this study.. The addition of EVG/COBI to stabilized patients receiving buprenorphine/naloxone modestly increased buprenorphine and norbuprenorphine levels without affecting the opioid pharmacodynamics.

Topics: Adult; Anti-Retroviral Agents; Area Under Curve; Buprenorphine; Carbamates; Cobicistat; Drug Interactions; Female; HIV Infections; HIV Seronegativity; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Quinolones; Thiazoles

Harm reduction packages for people who inject illicit drugs, including those infected with human immunodeficiency virus (HIV), are cost-effective but have not been scaled up globally. In the north-eastern Indian states of Manipur and Nagaland, the epidemic of HIV infection is driven by the injection of illicit drugs, especially opioids. These states needed to scale up harm reduction programmes but faced difficulty doing so.. In 2004, the Bill & Melinda Gates Foundation funded Project ORCHID to scale up a harm reduction programme in Manipur and Nagaland.. In 2003, an estimated 10 000 and 16 000 people were injecting drugs in Manipur and Nagaland, respectively. The prevalence of HIV infection among people injecting drugs was 24.5% in Manipur and 8.4% in Nagaland.. By 2012, the harm reduction programme had been scaled up to an average of 9011 monthly contacts outside clinics (80% of target); an average of 1709 monthly clinic visits (15% of target, well above the 5% monthly goal) and an average monthly distribution of needles and syringes of 16 each per programme participant. Opioid agonist maintenance treatment coverage was 13.7% and retention 6 months after enrolment was 63%. Antiretroviral treatment coverage for HIV-positive participants was 81%.. A harm reduction model consisting of community-owned, locally relevant innovations and business approaches can result in good harm reduction programme scale-up and influence harm reduction policy. Project ORCHID has influenced national harm reduction policy in India and contributed to the development of harm reduction guidelines.. Les kits de réduction des risques pour les personnes qui s'injectent des drogues illicites, y compris celles qui sont infectées par le virus de l'immunodéficience humaine (VIH), sont rentables, mais n'ont pas été généralisés. Dans les États du Nord-est indien de Manipur et de Nagaland, l'épidémie d'infection au VIH est induite par l'injection de drogues illicites, en particulier les opioïdes. Ces États avaient besoin d'intensifier les programmes de réduction des risques, mais ils étaient confrontés à des difficultés pour le faire.. En 2004, la Fondation Bill-et-Melinda-Gates a financé le projet ORCHID pour intensifier un programme de réduction des risques dans le Manipur et le Nagaland.. En 2003, on estimait que 10 000 à 16 000 personnes s'injectaient de la drogue dans le Manipur et le Nagaland, respectivement. La prévalence de l'infection par le VIH chez les personnes s'injectant des drogues était de 24,5% dans le Manipur et de 8,4% dans le Nagaland.. En 2012, le programme de réduction des risques a été étendu à une moyenne de 9 011 contacts par mois en dehors des cliniques (80% de la cible), pour une moyenne de 1 709 visites cliniques mensuelles (15% de l'objectif, bien au-dessus de l'objectif de 5% par mois) et pour une distribution mensuelle moyenne d'aiguilles et de seringues de 16 pour chaque participant au programme. La couverture du traitement d'entretien par agoniste opioïde était de 13,7% et la rétention 6 mois après l'inscription était de 63%. La couverture du traitement antirétroviral pour les participants séropositifs était de 81%.. Un modèle de réduction des risques, constitué d'innovations pertinentes au niveau local et appartenant à la collectivité, ainsi que d'approches commerciales, peut entraîner une extension satisfaisante du programme de réduction des risques et influencer la politique de réduction des risques. Le projet ORCHID a influencé la politique nationale de réduction des risques en Inde et a contribué à l'élaboration de recommandations en matière de réduction des risques.. Los paquetes de medidas para reducir los daños que se producen entre las personas que se inyectan drogas ilegales, incluidas aquellas infectadas por el virus de la inmunodeficiencia humana (VIH), si bien eficaces en relación con el costo, no se han ampliado a nivel global. En los estados de Manipur y Nagaland, situados en el noreste de India, la epidemia de infecciones por el VIH se debe a la inyección de drogas ilegales, en especial de opiáceos. Estos estados tuvieron que ampliar sus programas de reducción de daños pero, al hacerlo, se enfrentaron a diversas dificultades.. En el año 2004, la Bill & Melinda Foundation fundó el Proyecto ORCHID con objeto de ampliar un programa de reducción de daños en Manipur y Nagaland.. En el año 2003, se estimó que 10 000 y 16 000 personas se inyectaban drogas en Manipur y Nagaland, respectivamente. La prevalencia de la infección por el VIH entre los consumidores de drogas inyectables fue del 24,5% en Manipur y del 8,4% en Nagaland.. Hasta el año 2012, el programa de reducción de daños se amplió hasta una media de 9011 contactos mensuales fuera de clínicas (80% del objetivo); una media de 1709 visitas clínicas (15% del objetivo, muy por encima del 5% de la meta mensual) y una distribución mensual media de 16 agujas y jeringuillas por participante en el programa. La cobertura del tratamiento de mantenimiento con opioides agonistas fue del 13,7% y la permanencia 6 meses después de la inscripción, del 63%. La cobertura del tratamiento con antirretrovirales para los participantes seropositivos fue del 81%.. Un modelo de reducción de daños consistente en innovaciones basadas en la comunidad y relevantes a nivel local y en enfoques comerciales puede resultar en una ampliación positiva del programa de reducción de daños e influir en la política de reducción de daños. El proyecto ORCHID ha influido en la política nacional de reducción de daños en India y ha contribuido al desarrollo de directrices para la reducción de daños.. تعتبر حزم الحد من الأضرار للأشخاص الذين يتعاطون العقاقير غير المشروعة عن طريق الحقن، بما فيهم المصابين بعدوى فيروس العوز المناعي البشري (HIV) عالية المردود غير أنه لم يتم تعزيزها على الصعيد العالمي. وفي ولاياتي مانيبور وناغالاند في شمال شرق الهند، ينتج وباء عدوى فيروس العوز المناعي البشري عن تعاطي العقاقير غير المشروعة عن طريق الحقن، ولاسيما المواد الأفيونية المفعول. واحتاجت هاتان الولايتان إلى تعزيز برامج الحد من الأضرار ولكنهما واجهتا صعوبة في القيام بهذا.. في عام 2004، مولت مؤسسة بيل وميليندا غيتس مشروع ORCHID لتعزيز برنامج الحد من الأضرار في مانيبور وناغالاند.. في عام 2003، قُدّر عدد الأشخاص الذين يتعاطون الأدوية عن طريق الحقن في مانيبور وناغالاند بعدد 10000 و16000 شخصاً على التوالي. وبلغ معدل انتشار عدوى فيروس العوز المناعي البشري بين الأشخاص الذين يتعاطون الأدوية عن طريق الحقن 24.5 % في مانيبور و8.4 % في ناغالاند.. بحلول عام 2012، تم تعزيز برنامج الحد من الأضرار حتى وصل إلى متوسط 9011 نقطة اتصال شهرية خارج العيادات (80 % من المستهدف)؛ ومتوسط 1709 زيارة شهرية إلى العيادات (15 % من المستهدف، وهو أعلى بدرجة كبيرة من الهدف الشهري البالغ نسبته 5 %) وتوزيع شهري للإبر والمحاقن بلغ في المتوسط 16 إبرة ومحقن لكل مشارك في البرنامج. وبلغت تغطية العلاج الصياني بناهض المواد الأفيونية المفعول 13.7 % وبلغ إبقاء العلاج بعد التسجيل بستة أشهر 63 %. وبلغت تغطية العلاج بمضادات الفيروسات القهقرية للمشاركين الإيجابيين لفيروس العوز المناعي البشري 81 %.. يتمتع نموذج للحد من الأضرار يتألف من ابتكارات وأساليب عمل مملوكة للمجتمع المحلي وملائمة للظروف المحلية بالقدرة على تحسين تعزيز برنامج الحد من الأضرار والتأثير على سياسة الحد من الأضرار. وأثر مشروع ORCHID على السياسة الوطنية للحد من الأضرار في الهند وأسهم في وضع المبادئ التوجيهية للحد من الأضرار.. 针对注射违禁药物的人群的一整套减害措施具有成本效益，这套措施同样适用于感染艾滋病毒（HIV）的注射人群，但是还没有在全球范围内推广。在印度东北地区的曼尼普尔邦和那加兰邦，注射非法药物，尤其是阿片类药物加剧了艾滋病毒感染的流行。这些邦需要推广减害计划，但实施起来面临困难。. 2004 年，由比尔和梅林达·盖茨基金会资助的项目ORCHID在曼尼普尔邦和那加兰邦扩大减害计划规模。. 据估计，2003 年曼尼普尔邦和那加兰邦分别有1 万和1.6 万人注射毒品。注射毒品人群的艾滋病毒感染率在曼尼普尔邦为24.5%，在那加兰邦为 8.4%。. 2012 年，减害计划已扩大为每月平均9011 个诊所外联系人（目标人数的80%）；每月平均1709 人就诊（目标人数的15%，远高于5%的每月目标），每个计划参与者每月平均各发放16 个针头和注射器。阿片受体激动剂维持治疗覆盖率为13.7%，参加治疗之后6 个月的保持率是63%。艾滋病毒阳性参与者的抗逆转录病毒治疗的覆盖率是81%。. 由社区拥有、因地制宜的创新和商业途径组成的减害模型可以很好地推广减害计划，并影响减害政策。ORCHID项目已经对印度的国家减害政策产生了影响，对减害指导方针的发展作出了贡献。. Комплексы мер по сокращению вреда для людей, употребляющих запрещенные инъекционные наркотики, в том числе, инфицированных вирусом иммунодефицита человека (ВИЧ), оправдывают затраты, но не применяются в глобальном масштабе. Основной причиной ВИЧ-инфекции в северо-восточных индийских штатах Манипур и Нагаленд является употребление запрещенных инъекционных наркотиков, особенно опиатов. В этих штатах потребовалось более масштабное применение программ по сокращению вреда, которое, однако, столкнулось с трудностями.. В 2004 г. Фонд Билла и Мелинды Гейтсов профинансировал проект ORCHID по более масштабному применению программ сокращения вреда в штатах Манипур и Нагаленд.. В 2003 г. количество человек, употребляющих инъекционные наркотики в штатах Манипур и Нагаленд, оценивалось, соответственно, на уровне 10 000 и 16 000 человек. Уровень распространения ВИЧ-инфекции среди людей, употребляющих инъекционные наркотики, составил 24,5% в Манипуре и 8,4% в Нагаленде.. В 2012 г. было осуществлено более масштабное развертывание программы сокращения вреда в среднем до 9011 контактов за пределами клиник в месяц (80% от целевого показателя), до в среднем 1709 посещений клиники в месяц (15% от целевого показателя, на 5% выше месячной цели), а среднее количество выданных каждому участнику программы игл и шприцов составило 16 штук. Охват поддерживающей терапией с использованием агонистов опиоидных рецепторов составил 13,7%, а показатель удержания в программе через 6 месяцев после регистрации составлял 63%. Охват антиретровирусной терапией для ВИЧ-положительных участников составил 81%.. Результатом использования модели снижения вреда, включающей принадлежащие местному сообществу, актуальные для местных условий инновации и бизнес-подходы, может стать значительное расширение масштабов применения программы сокращения вреда и влияние на политику сокращения вреда. Проект ORCHID повлиял на национальную политику сокращения вреда в Индии и внес свой вклад в разработку руководящих принципов сокращения вреда.

Topics: Anti-Retroviral Agents; Community Health Services; Community Participation; Harm Reduction; HIV Infections; Humans; India; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Prevalence; Sex Workers; Substance Abuse, Intravenous

Overdose education and naloxone distribution (OEND) is an intervention that addresses overdose, but has not been studied among people who take methadone, a drug involved in increasing numbers of overdoses. This study describes the implementation of OEND among people taking methadone in the previous 30 days in various settings in Massachusetts. From 2008 to 2010, 1553 participants received OEND who had taken methadone in the past 30 days. Settings included inpatient detoxification (47%), HIV prevention programs (25%), methadone maintenance treatment programs (MMTP) (17%), and other settings (11%). Previous overdose, recent inpatient detoxification and incarceration, and polysubstance use were overdose risks factors common among all groups. Participants reported 92 overdose rescues. OEND programs are public health interventions that address overdose risk among people who take methadone and their social networks. OEND programs can be implemented in MMTPs, detoxification programs, and HIV prevention programs.

Topics: Administration, Intranasal; Adult; Drug Overdose; Female; HIV Infections; Humans; Male; Massachusetts; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Education as Topic; Pilot Projects; Risk Factors; Substance Withdrawal Syndrome; Young Adult

Buprenorphine is associated with enhanced human immunodeficiency virus (HIV) treatment outcomes including increased antiretroviral therapy initiation rates, adherence, and CD4 cell counts among HIV-infected opioid-dependent individuals. Buprenorphine facilitates hepatitis C virus (HCV) treatment in opioid-dependent patients with HCV monoinfection. Less is known about buprenorphine's role in HIV/HCV coinfection.. We conducted a retrospective chart review to evaluate HCV care for HIV-infected buprenorphine patients in the first 4 years of buprenorphine's integration into a Rhode Island HIV clinic.. Sixty-one patients initiated buprenorphine. All had HCV antibody testing; 57 (93%) were antibody-positive. All antibody-positive patients underwent HCV RNA testing; 48 (84%) were RNA-positive. Of these, 15 (31%) were not referred to HCV care. Among chronically infected patients, 3 received HCV treatment after buprenorphine; all had cirrhosis and none achieved viral eradication. At buprenorphine induction, most patients had inadequately controlled HIV infection, with detectable HIV RNA (59%) or CD4 cell count less than or equal to 350/μL (38%).. Buprenorphine has shown limited success to date as a bridge to HCV treatment within an HIV clinic. Buprenorphine's stabilization of opioid dependence and HIV disease may permit the use of HCV therapy over time.

Topics: Adult; Antiretroviral Therapy, Highly Active; Antiviral Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Hepatitis C, Chronic; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome

HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX) as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD).. From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART) for released HIV-infected prisoners; 50 (53%) selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47%) selected no BPN/NLX therapy. Maximum viral suppression (MVS), defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44) groups.. The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%), from Hartford (74.4% v 47.7%) and have higher mean global health quality of life indicator scores (54.18 v 51.40). MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1)], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1)] and negatively with being Black [AOR = 0.13 (0.03, 0.68)]. Receiving DAART or methadone did not correlate with MVS.. In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.

Topics: Adult; Buprenorphine; Female; HIV Infections; Humans; Male; Middle Aged; Naloxone; Opioid-Related Disorders; Prisoners; Prospective Studies; Treatment Outcome

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders

This study was part of a national, multisite demonstration project evaluating the impact of integrated buprenorphine/naloxone treatment and HIV care. The goals of this study were to describe the baseline demographic, clinical, and substance use characteristics of the participants and to explore HIV transmission risk behaviors in this group.. Nine sites across the United States participated. Data obtained by interview and chart review included demographic information, medical history, substance use, and risk behaviors.We performed a descriptive analysis of patient characteristics at entry and used logistic regression to evaluate factors associated with 1) unprotected anal or vaginal sex; and 2) needle-sharing within the previous 90 days.. Three hundred eighty-six individuals were included in the study: 303 (78.5%) received buprenorphine/naloxone; 41 (10.6%) received methadone; and 42 (10.9%) received another form of treatment. The analysis of risk behaviors was limited to those in the buprenorphine group (n = 303). Among those reporting vaginal or anal sex in the previous 90 days, 24% had sex without a condom. Factors significantly associated with unprotected sex were: having a partner; female gender; and alcohol use in previous 30 days. A total of 8.9% of participants shared needles in the previous 90 days. Factors significantly associated with needle-sharing were: amphetamine use; marijuana use; homelessness; and anxiety.. Addressing transmission risk behaviors is an important secondary HIV prevention strategy. In addition to treatment for opioid dependence, addressing other substance use, social issues, particularly housing, and mental health may have important implications for reducing HIV transmission in HIV-infected opioid-dependent patients.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Female; HIV Infections; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Risk-Taking; Unsafe Sex

Opioid dependence and HIV infection are associated with poor health-related quality of life (HRQOL). Buprenorphine/naloxone (bup/nx) provided in HIV care settings may improve HRQOL.. We surveyed 289 HIV-infected opioid-dependent persons treated with clinic-based bup/nx about HRQOL using the Short Form Health Survey (SF-12) administered at baseline, 3, 6, 9, and 12 months. We used normalized SF-12 scores, which correspond to a mean HRQOL of 50 for the general US population (SD 10, possible range 0-100). We compared mean normalized mental and physical composite and component scores in quarters 1, 2, 3, and 4 with baseline scores using generalized estimating equation models. We assessed the effect of clinic-based bup/nx prescription on HRQOL composite scores using mixed effects regression with site as random effect and time as repeated effect.. Baseline normalized SF-12 scores were lower than the general US population for all HRQOL domains. Average composite mental HRQOL improved from 38.3 (SE 12.5) to 43.4 (SE 13.2) [β 1.13 (95% CI: 0.72 to 1.54)] and composite physical HRQOL remained unchanged [β 0.21 (95% CI: -0.16 to 0.57)] over 12 months follow-up. Continued bup/nx treatment across all 4 quarters was associated with improvements in both physical [β 2.38 (95% CI: 0.63 to 4.12)] and mental [β 2.51 (95% CI: 0.42 to 4.60)] HRQOL after adjusting for other contributors to HRQOL.. Clinic-based bup/nx maintenance therapy is potentially effective in ameliorating some of the adverse effects of opioid dependence on HRQOL for HIV-infected populations.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life

Research has shown that buprenorphine/naloxone (bup/nx) is a safe and effective treatment for opioid dependence. Few reports, however, describe the patient perspective on bup/nx treatment and its integration into HIV care settings.. We conducted qualitative interviews with 33 patients to further investigate patient satisfaction and experience with bup/nx treatment and integrated care. Interviews focused on drug use/cessation history; attitudes toward and satisfaction with bup/nx treatment; and perspectives on integrated bup/nx treatment and HIV care.. Patients were overwhelmingly satisfied with the pharmacologic effects and treatment outcomes of bup/nx, including effectiveness in blocking cravings and controlling opioid use; decreased fear of withdrawal and/or missing doses; and an overall improvement in quality of life. Patients also described being more engaged with both their substance abuse treatment and HIV care, including greater ability to manage their own treatment, keep, appointments, and adhere to antiretroviral medication regimes. Counseling was seen by some patients as an important component of bup/nx treatment. Nearly all were positive about their experience with integrated care, appreciative of an improved drug treatment environment, convenience, and quality of care.. Findings suggest that patients report bup/nx to be a viable treatment and many prefer it to other opioid replacement therapies.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Data Collection; Female; HIV Infections; Humans; Interviews as Topic; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Satisfaction

The safety of buprenorphine/naloxone (bup/nx) in HIV-infected patients has not been established. Prior reports raise concern about hepatotoxicity and interactions with atazanavir.. We conducted a prospective cohort study of 303 opioid-dependent HIV-infected patients initiating bup/nx treatment. We assessed changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) over time. We compared bup/nx doses in patients receiving the antiretroviral atazanavir to those not receiving atazanavir. We conducted surveillance for pharmacodynamic interactions.. Median AST [37.0 vs. 37.0 units/liter (U/L) respective interquartile ranges (IQRs) 26-53 and 26-59] and ALT (33.0 vs. 33.0 U/L, respective IQRs 19-50 and 18-50) values did not change over time among 141 patients comparing pre-bup/nx exposure with post-bup/nx exposure measures. During bup/nx exposure, 207 subjects demonstrated no significant change in median AST (36.0 vs. 35.0 U/L, respective IQRs 25-57 and 25-61) and ALT (29.0 vs. 31.0 U/L, respective IQRs 19-50 and 18-50) values collected a median of 6 months apart. Analyses restricted to patients with hepatitis C and HIV co-infection yielded similar results, except a small but significant decrease in first to last AST, during treatment with bup/nx (P = 0.048). Mean bup/nx dose, ranging 16.0-17.8 mg, did not differ over time or with co-administration of atazanavir. No pharmacodynamic interactions were noted.. Buprenorphine/naloxone did not produce measurable hepatic toxicity or pharmacodynamic interaction with atazanavir in HIV-infected opioid-dependent patients.

Topics: Anti-HIV Agents; Atazanavir Sulfate; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chemical and Drug Induced Liver Injury; Cohort Studies; Dose-Response Relationship, Drug; Drug Interactions; HIV Infections; Humans; Naloxone; Oligopeptides; Opioid-Related Disorders; Pyridines

Cocaine use is common in opioid-dependent HIV-infected patients, but its impact on treatment outcomes in these patients receiving buprenorphine/naloxone is not known.. We conducted a prospective study in 299 patients receiving buprenorphine/naloxone who provided baseline cocaine data and a subset of 266 patients who remained in treatment for greater than or equal to one quarter. Assessments were conducted at baseline and quarterly for 1 year. We evaluated the association between baseline and in-treatment cocaine use on buprenorphine/naloxone retention, illicit opioid use, antiretroviral adherence, CD4 counts, HIV RNA, and risk behaviors.. Sixty-six percent (197 of 299) of patients reported baseline cocaine use and 65% (173 of 266) of patients with follow-up data reported in-treatment cocaine use. Baseline and in-treatment cocaine use did not impact buprenorphine/naloxone retention, antiretroviral adherence, CD4 lymphocytes, or HIV risk behaviors. However, baseline cocaine use was associated with a 14.8 (95% confidence interval [CI], 9.0-24.2) times greater likelihood of subsequent cocaine use (95% CI, 9.0-24.2), a 1.4 (95% CI, 1.02-2.00) times greater likelihood of subsequent opioid use, and higher log10 HIV RNA (P < 0.016) over time. In-treatment cocaine use was associated with a 1.4 (95% CI, 1.01-2.00) times greater likelihood of concurrent opioid use.. Given cocaine use negatively impacts opioid and HIV treatment outcomes, interventions to address cocaine use in HIV-infected patients receiving buprenorphine/naloxone treatment are warranted.

Topics: Adult; Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Female; HIV Infections; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Needle Sharing; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies; Risk Factors; Treatment Outcome; Unsafe Sex

Replication of effective practices requires detailed descriptions of implementation processes, barriers and facilitators, and lessons learned. The experiences of physicians leading the Buprenorphine HIV Evaluation and Support initiative provides valuable information for other HIV providers seeking to integrate medication-assisted treatment services into HIV clinical care.. Evaluation staff conduced site visits to the 10 funded Buprenorphine HIV Evaluation and Support programs to better understand buprenorphine/naloxone (bup/nx) integration practices; services offered; staffing; provider experiences with and perceptions of bup/nx; perceived barriers, facilitators, and sustainability; and recommendations regarding replication of integrated care program components. Interviews with site principal investigators conducted during the last year of program implementation were transcribed, coded, and analyzed according to both pre-identified and emerging themes.. Integrated bup/nx and HIV treatment was successfully introduced to community and hospital-based clinics under the direction of infectious disease, psychiatry, and general internal medicine physicians. All but 1 of the principal investigators interviewed were highly satisfied with integrated HIV and bup/nx treatment, and all anticipated continued provision of the service. Multiple prescribers were necessary to ensure sufficient coverage and a bup/nx coordinator (eg, nurse, counselor) was seen as essential to the provision of quality care. Ongoing challenges included multisubstance use and mental health issues among patients; limited adoption of bup/nx treatment among colleagues; and the necessity of incorporating new procedures, including urine toxicology testing into established practice.. Findings suggest that integrated bup/nx treatment and HIV care is acceptable to providers and feasible in a variety of practice settings.

Topics: Ambulatory Care; Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delivery of Health Care, Integrated; Health Resources; Health Services Needs and Demand; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Primary Health Care; Substance Abuse Treatment Centers; United States

Opioid-dependent HIV-infected patients are less likely to receive HIV quality of care indicators (QIs) compared with nondependent patients. Buprenorphine/naloxone maintenance therapy (bup/nx) could affect the quality of HIV care for opioid-dependent patients.. We abstracted 16 QIs from medical records at nine HIV clinics 12 months before and after initiation of bup/nx versus other treatment for opioid dependence. Summary quality scores (number of QIs received/number eligible × 100) were calculated. We compared change in QIs and summary quality scores in patients receiving bup/nx versus other participants.. One hundred ninety-four of 268 participants (72%) received bup/nx and 74 (28%) received other treatment. Mean summary quality scores increased over 12 months for participants receiving bup/nx (45.6% to 51.6%, P < 0.001) but not other treatment (48.6% to 47.8%, P = 0.788). Bup/nx participants experienced improvements in six of 16 HIV QIs versus three of 16 QIs in other participants. Improvements were mostly in preventive and monitoring care domains. In multivariable analysis, bup/nx was associated with improved summary quality score (β 8.55; 95% confidence interval, 2.06-15.0).. In this observational cohort study, HIV-infected patients with opioid dependence received approximately half of HIV QIs at baseline. Buprenorphine treatment was associated with improvement in HIV QIs at 12 months. Integration of bup/nx into HIV clinics may increase receipt of high-quality HIV care. Further research is required to assess the effect of improved quality of HIV care on clinical outcomes.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cohort Studies; Female; Guideline Adherence; HIV Infections; Humans; Male; Middle Aged; Multivariate Analysis; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Quality of Health Care

Researchers, practitioners, and policymakers have long recognized the potential benefits of providing integrated substance abuse and medical care services, particularly for special populations such as people living with HIV/AIDS. Buprenorphine, an office-based pharmacological treatment for opioid dependence, offers new opportunities for integrating drug treatment into HIV care settings. However, the historical separation between the drug treatment and medical care systems has resulted in a host of policy barriers. The Buprenorphine and HIV Care Evaluation and Support initiative, a multisite demonstration project to assess the feasibility and effectiveness of integrating buprenorphine/naloxone into HIV care settings, provided an opportunity to evaluate if and how policy barriers affect efforts to integrate HIV care and addiction treatment. We found that financing issues, workforce and training issues, and the operational consequences of some conceptual differences between HIV care and addiction treatment are barriers to the full integration of buprenorphine into HIV care. We recommend changes to financing and reimbursement policies, programs to strengthen the addiction treatment skills of physicians, and cross training between the fields of addiction, medicine, drug treatment, and HIV medicine. By addressing some of the policy barriers to integration, this promising new treatment can help the thousands of people living with HIV/AIDS who are also opioid dependent.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delivery of Health Care, Integrated; Health Policy; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; United States

Implementing integrated HIV and buprenorphine/naloxone treatment requires cost estimates to plan and obtain funding.. We identified costs incurred at HIV clinical sites participating in a cross-site evaluation of integrated care that followed patients for 1 year. Costs include labor, overhead, and urine toxicology analyses (clinic perspective), buprenorphine/naloxone (payer perspective) and patient time and transportation (patient perspective). Sites provided resource utilization quarterly, and providers estimated time required for each activity. With site as the unit of analysis, results are reported as median (range) of average site costs in 2008 US dollars.. The median number of monthly provider encounters for integrated care patients was 3.2 (1.5-13.3) compared with 1.7 (1.1-4.2) for similar patients not in integrated care, but integrated care patients had fewer physician encounters. Median monthly clinic costs per integrated care patient were $136 ($67-$677) for labor and overhead and $8 ($2-$23) for toxicology analyses, $22 higher than clinic costs for patients not in integrated care. Median monthly costs for buprenorphine/naloxone were $209 ($165-$272), and monthly patient costs in integrated care were $11 ($1-$54) higher.. Integrated HIV and buprenorphine/naloxone treatment requires different resources, including costs that are not third-party reimbursed. Implementing integrated care will require funding for training and for new staff such as buprenorphine coordinators, in addition to reimbursement for buprenorphine/naloxone. Further research is needed to identify potential cost offsets outside of the clinic setting.

Topics: Anti-HIV Agents; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Delivery of Health Care, Integrated; Health Care Costs; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders

By recounting the making of the office that contributed to the implementation of the harm reduction policy in Taiwan, this paper aims to answer two questions: Who and what assembled to make this policy possible? Which conceptual tool works best to understand what this policy-making was all about?. The research was designed as a multi-sited qualitative study whose materials were collected through archival research, in-depth interviews, and direct field observation. The data were analysed on the basis of the constructivist version of grounded theory.. Formulating the office as an assemblage with heterogeneous components and shifting territories, the present work endeavours to show how it was constituted by way of guanxi, or webs of social relationship that blur the boundary between the private and the public, the governmental and the social.. This "studying up" approach is hoped to elicit more research on the office in which harm reduction policies are made into the backdrop of drug users on the street.

Topics: Administrative Personnel; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug and Narcotic Control; Drug Users; Government Regulation; Harm Reduction; Health Policy; HIV Infections; Humans; Incidence; Methadone; Naloxone; Needle-Exchange Programs; Opiate Substitution Treatment; Policy Making; Private Sector; Qualitative Research; Social Behavior; Speech; Substance Abuse, Intravenous; Taiwan

Topics: Anti-HIV Agents; Buprenorphine; Chemical and Drug Induced Liver Injury; HIV Infections; Humans; Naloxone; Opioid-Related Disorders

This study was conducted to examine the pharmacokinetic interactions between buprenorphine/naloxone (BUP/NLX) and lopinavir/ritonavir (LPV/r) in HIV-seronegative subjects chronically maintained on BUP/NLX.. This study was an open labeled pharmacokinetic study in twelve HIV-seronegative subjects stabilized on at least 3 weeks of BUP/NLX therapy. Subjects sequentially underwent baseline and steady-state pharmacokinetic evaluation of once-daily LPV/r (800/200 mg).. Compared to baseline values, BUP AUC0-24h (46.8 vs. 46.2 ng*hr/mL) and Cmax (6.54 vs. 5.88 ng/mL) did not differ significantly after achieving steady-state LPV/r. Similar analyses of norBUP, the primary metabolite of BUP, demonstrated no significant difference in norBUP AUC0-24 hours (73.7 vs. 52.7 ng x h/mL); however, Cmax (5.29 vs. 3.11 ng/mL) levels were statistically different (P < 0.05) after LPV/r administration. Naloxone concentrations were similarly unchanged for AUC0-24 hours (0.421 vs. 0.374 ng x hr/mL) and Cmax (0.186 vs. 0.186 ng/mL). Using standardized measures, no objective opioid withdrawal was observed. The AUC0-24 hours and Cmin of LPV in this study did not significantly differ from historical controls (159.6 vs. 171.3 microg x hr/mL) and (2.3 vs. 1.3 microg/mL).. The addition of LPV/r to stabilized patients receiving BUP/NLX did not affect buprenorphine pharmacokinetics but did increase the clearance of norbuprenorphine. Pharmacodynamic responses indicate that the altered norbuprenorphine clearance did not lead to opioid withdrawal. Buprenorphine/naloxone and LPV/r can be safely coadministered without need for dosage modification.

Topics: Adult; Analgesics, Opioid; Anti-HIV Agents; Buprenorphine; Drug Interactions; Female; HIV Infections; Humans; Lopinavir; Male; Metabolic Clearance Rate; Middle Aged; Naloxone; Pyrimidinones; Ritonavir

The cytokine tumor necrosis factor alpha (TNFalpha) is a key factor in several inflammatory diseases and its levels increase in response to a variety of internal or external stimuli. The regulation of the TNFalpha promoter is mediated by several transcription factors including the nuclear factor kappa B protein (NF-kappaB). This study examines the role of NF-kappaB in the regulation of TNFalpha production by morphine in microglia. Using reverse transcriptase polymerase chain reaction, we demonstrated the presence of morphine receptors in these cells. We next demonstrated the ability of morphine to promote TNFalpha production and secretion by these cells using a cytokine array assay. Transient transfection experiments led to the identification of the region located between nucleotides -751 and -615 within the TNFalpha promoter as being responsive to morphine treatment. The DNA sequence of this region contains a motif indicative of a potential NF-kappaB binding site. The use of a small interfering RNA directed against p65, a subunit of NF-kappaB, demonstrated that TNFalpha induction by morphine is NF-kappaB-dependent. All of the effects of morphine were reversed by the morphine inhibitor, naloxone. These data provide important insights into the effects of morphine on microglia.

Topics: Analgesics, Opioid; Astrocytes; Blotting, Western; Cells, Cultured; HIV Infections; HIV-1; Humans; Microglia; Morphine; Naloxone; Narcotic Antagonists; Neuroglia; NF-kappa B; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Transfection; Tumor Necrosis Factor-alpha; U937 Cells

Assessing social risks has proven difficult for IRBs. We undertook a novel effort to empirically investigate social risks before an HIV prevention trial among drug users in Thailand and China. The assessment investigated whether law, policies and enforcement strategies would place research subjects at significantly elevated risk of arrest, incarceration, physical harm, breach of confidentiality, or loss of access to health care relative to drug users not participating in the research. The study validated the investigator's concern that drug users were subject to serious social risks in the site localities, but also suggested that participation in research posed little or no marginal increase in risk and might even have a protective effect. Our experience shows that it is feasible to inform IRB deliberations with actual data on social risks, but also raises the question of whether and when such research is an appropriate use of scare research resources.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; China; Confidentiality; Conflict of Interest; Counseling; Ethics Committees, Research; Ethics, Research; Female; Financing, Government; Health Services Accessibility; HIV Infections; Human Rights; Humans; Informed Consent; International Cooperation; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Selection; Randomized Controlled Trials as Topic; Research Design; Research Subjects; Risk Assessment; Risk Reduction Behavior; Social Environment; Thailand; United States; Vulnerable Populations

HIV-1 affects microglia and astroglia, which subsequently contributes to the neurodegenerative changes. Viral proteins cause neurotoxicity by direct action on the CNS cells or by activating glial cells to cause the release of cytokines, chemokines or neurotoxic substances. Opioid abuse has been postulated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) infection and AIDS. HIV-induced pathogenesis is exacerbated by opiate abuse and that the synergistic neurotoxicity is a direct effect of opiates on the CNS. Chemokines and their receptors have been implicated in the pathogenesis of neuroAIDS. Herein we describe the effects of morphine and/or gp120 on the expression of the genes for the beta-chemokine MIP-1beta and its receptors CCR3 and CCR5 by the U373 cells which are a human brain-derived astrocytoma/glioblastoma cell line. Our results indicate that treatment of U373 cells with morphine significantly downregulated the gene expression of the beta chemokine, MIP-1 beta, while reciprocally upregulating the expression of its specific receptors, CCR3 and CCR5 suggesting that the capacity of mu-opioids to increase HIV-1 co-receptor expression may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression. Additionally, opiates can enhance the cytotoxicity of HIV-1 viral protein gp120 via mechanisms that involve intracellular calcium modulation resulting in direct actions on astroglia, making them an important cellular target for HIV-opiate interactions.

Topics: AIDS Dementia Complex; Astrocytes; Calcium; Cell Line, Tumor; Chemokine CCL4; Chemokines; Gene Expression; HIV Envelope Protein gp120; HIV Infections; HIV-1; Humans; Immunologic Factors; In Vitro Techniques; Macrophage Inflammatory Proteins; Morphine; Naloxone; Narcotic Antagonists; Receptors, CCR3; Receptors, CCR5; Receptors, Chemokine; Receptors, Opioid, mu

Topics: Buprenorphine; Drug Therapy, Combination; HIV Infections; Humans; Naloxone; Narcotic Antagonists; Needle-Exchange Programs; Substance Abuse, Intravenous

All HIV-1 strains studied to date use CCR5, CXCR4, or both receptors to enter cells. Simian immunodeficiency virus (SIV) infection of non-human primates has served as a useful model for understanding AIDS pathogenesis in humans. Research on several genetically divergent SIV isolates has revealed that SIV uses CCR5, and not CXCR4, for entry. CEM x174, a human lymphoid cell line, has been routinely used to cultivate and maintain various SIV strains. However, questions have arisen about how CEM x174, which reportedly was unable to express detectable amounts of CCR5 transcripts, efficiently supports the growth of SIV. In searching for an answer, we resorted to a sensitive competitive reverse transcriptase-polymerase chain reaction procedure in an attempt to detect as well as quantify the amount of CCR5 expression. Here we present our findings, which indicate that CEM x174 indeed expresses CCR5 and that the amount of CCR5 is increased in cells pretreated with morphine. These results correlate well with our previous observations that morphine treatment causes CEM x174 cells to be more susceptible to SIV infection. Similar morphine effect was not observed on CEM x174 cells infected with simian retroviruses, which do not depend on CCR5 for entry. These findings suggest a plausible mechanism whereby opiate drug users render themselves more susceptible to HIV infection, thereby explaining the vast prevalence of HIV infection among endemic drug use populations.

Topics: B-Lymphocytes; Blotting, Western; Cell Line; Dose-Response Relationship, Drug; Flow Cytometry; Gene Expression; HIV Infections; Humans; Kinetics; Lymphocytes; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Receptors, CCR5; Receptors, Chemokine; Receptors, CXCR6; Receptors, Cytokine; Receptors, G-Protein-Coupled; Receptors, Peptide; Receptors, Virus; Reverse Transcriptase Polymerase Chain Reaction; Simian Acquired Immunodeficiency Syndrome; Substance-Related Disorders; T-Lymphocytes; Time Factors

Intravenous opiate abusers are susceptible to develop heroin and HIV-associated nephropathies; however, the role of opiates in the development of these kidney lesions is not clear. Patients with opiate addiction are prone to recurrent infections.. The effect of morphine was studied on the generation of TNF-alpha with or without LPS (lipopolysaccharide) by cultured mouse mesangial cells. In addition, the effect of morphine was evaluated on mesangial cell nitrite production. To evaluate the role of opiate receptors, we studied the effect of naloxone and naltrexone on mesangial cell TNF-alpha and nitrite production. To determine the role of TNF-alpha on mesangial cell nitrite production, we examined the effect of anti-TNF-alpha antibody on morphine-induced nitrite production. Assay of TNF-alpha and nitrite production was carried by ELISA and Griess method respectively.. Morphine alone did not enhance the generation of TNF-alpha by mesangial cells, however, an enhanced (P < 0.001) TNF-alpha production was observed when mesangial cells were first treated with morphine for 18 h and then activated further with LPS. Maximum release of TNF-alpha was seen at a concentration of 10(-12) M of morphine. Opiate receptor antagonists (naloxone and naltrexone) inhibited the effect of morphine. Morphine also amplified (P < 0.0002) the effect of LPS on mesangial cell nitrite production. Anti-TNF-alpha antibody attenuated morphine induced nitrite generation.. We conclude that morphine stimulates the generation of TNF-infinity by LPS-activated mesangial cells. This effect of morphine seems to be opiate receptor mediated and has a downstream effect in the form of mesangial cell nitrite generation. The present in vitro study provides the basis for a hypothesis that morphine may be playing a role in the development of heroin and HIV-associated nephropathies.

Topics: Animals; Antibodies, Monoclonal; Cell Line, Transformed; Dose-Response Relationship, Drug; Drug Synergism; Enzyme Inhibitors; Gene Expression Regulation; Glomerular Mesangium; Glomerulosclerosis, Focal Segmental; Heroin Dependence; HIV Envelope Protein gp120; HIV Infections; Lipopolysaccharides; Macrophages; Mice; Morphine; Muscle, Smooth, Vascular; Naloxone; Naltrexone; Narcotic Antagonists; NG-Nitroarginine Methyl Ester; Nitrites; Tumor Necrosis Factor-alpha

Topics: Animals; Female; Hemocyanins; HIV Envelope Protein gp120; HIV Infections; HIV-1; Hypersensitivity, Delayed; Immunity, Cellular; Immunosuppressive Agents; Mice; Mice, Inbred C3H; Morphine; Naloxone