Stigma and ART initiation among people with HIV and a lifetime history of illicit drug use in Saint-Petersburg, Russia-A prospective cohort analysis.

BACKGROUND: HIV-positive people who inject drugs (PWID) are stigmatized and face more challenges in accessing ART. The natural course of stigma and its role on ART initiation in this population is unclear. We examined 1] whether HIV stigma changes over time and 2] whether HIV and substance use stigma are associated with ART initiation in a prospective cohort of HIV-positive PWID in St. Petersburg, Russia. METHODS: We used data from 165 HIV-positive PWID who were ART-naïve at enrollment andgeneralized estimating equations to assess changes in HIV stigma between baseline, 12- and 24-month study visits. Logistic regression estimated associations of HIV stigma and substance use stigma with ART initiation. All models were adjusted for gender, age, CD4 count, duration of HIV diagnosis, recent (past 30-day) drug use and depressive symptoms. RESULTS: Participants characteristics were the following: median age of 34 (Q1; Q3: 30; 37) years; 30% female; 28% with CD4 count <350; 44% reported recent drug use. During the study period, 31% initiated ART and the median time between HIV diagnosis and ART initiation was 8.5 years (Q1; Q3: 4.68; 13.61). HIV stigma scores decreased yearly by 0.57 (95% CI -1.36, 0.22). More than half (27/47 [57.4%]) of participants who were eligible for ART initiation per local ART guidelines did not initiate therapy. Total HIV stigma and substance use stigma scores were not associated with ART initiation (AOR 0.99, 95%CI 0.94-1.04; AOR 1.01, 95%CI 0.96-1.05, respectively). CONCLUSION: In this Russian cohort of HIV-positive, ART-naïve PWID, stigma did not change over time and was not associated with ART initiation. Addressing stigma alone is unlikely to increase ART initiation rates in this population. Reducing further existing structural barriers, e.g., by promoting equal access to ART and the value of substance-use treatment for ART treatment success should complement stigma-reduction approaches.

Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: a double-blind, placebo-controlled, randomised trial.

BACKGROUND: Untreated opioid addiction in people with HIV is associated with poor HIV treatment outcomes. Slow-release, long-acting, implantable naltrexone might improve these outcomes. Here, we present results of a study aimed to test this hypothesis. METHODS: We did a 48 week double-blind, double-dummy, placebo-controlled, phase 3, randomised trial with men and women addicted to opioids who were starting antiretroviral therapy (ART) for HIV and whose viral loads were higher than 1000 copies per mL. Participants were seeking treatment at two HIV and two narcology programme centres in Saint Petersburg, Russia, and the surrounding Leningrad region. The Pavlov statistical department created a table with stratification on gender distribution, viral load, and CD4 cell count. We stratified participants according to gender, viral load, and CD4 cells per µL, and randomly assigned (1:1) them to addiction treatment with a naltrexone implant and oral naltrexone placebo (implant group) or oral naltrexone and placebo implant (oral group). The primary outcome was plasma viral load of less than 400 copies per mL at 24 weeks and 48 weeks. We included all randomly assigned participants in outcome analyses (intention to treat). Treatment staff and patients were masked to group assignment. The study is complete and registered at ClinicalTrials.gov, NCT01101815. FINDINGS: Between July 14, 2011, and April 14, 2014, 238 potential participants were recruited and screened, 35 were excluded for not meeting inclusion criteria, three declined to participate, and 200 were randomly assigned to treatment (100 to each group). At week 24, 38 (38) participants in the implant group and 35 (35%) in the oral group had viral loads less than 400 copies per mL (risk ratio 1·1, 95% CI 0·76-1·56; p=0·77). At week 48, 66 participants in the implant group and 50 in the oral group had viral loads less than 400 copies per mL (risk ratio 1·32, 95% CI 1·04-1·68; p=0·045). There were seven serious adverse events: three deaths in the implant group (one due to heart disease, one trauma, and one AIDS), and four in the oral group (two overdoses, one pancreatic cancer, and one AIDS). The overdose deaths occurred 9-10 months after the last naltrexone dose. INTERPRETATION: The longer the blockade of opioid effects, the more protection an individual gets from missed ART doses and impulsive behaviours that lead to relapse and poor, even fatal, outcomes. Commercial development of implants could result in a meaningful addition to addiction treatment options. FUNDING: National Institutes of Health, National Institute on Drug Abuse, Penn Centre for AIDS Research, and Penn Mental Health AIDS Research Centre.

Anhedonia, depression, anxiety, and craving in opiate dependent patients stabilized on oral naltrexone or an extended release naltrexone implant.

BACKGROUND: Naltrexone is a µ-opioid receptor antagonist that blocks opioid effects. Craving, depression, anxiety, and anhedonia are common among opioid dependent individuals and concerns have been raised that naltrexone increases them due to blocking endogenous opioids. Here, we present data that address these concerns. OBJECTIVE: Assess the relationship between affective responses and naltrexone treatment. METHODS: Opioid dependent patients (N = 306) were enrolled in a three cell (102ss/cell) randomized, double blind, double dummy, placebo-controlled 6-month trial comparing extended release implantable naltrexone with oral naltrexone and placebo (oral and implant). Monthly assessments of affective responses used a Visual Analog Scale for opioid craving, the Beck Depression Inventory, Spielberger Anxiety Test, and the Ferguson and Chapman Anhedonia Scales. Between-group outcomes were analyzed using mixed model analysis of variance (Mixed ANOVA) and repeated measures and the Tukey test for those who remained and treatment and did not relapse, and between the last measure before dropout with the same measure for those remaining in treatment. RESULTS: Depression, anxiety, and anhedonia were elevated at baseline but reduced to normal within the first 1-2 months for patients who remained in treatment and did not relapse. Other than a slight increase in two anxiety measures at week two, there were no significant between-group differences prior to treatment dropout. CONCLUSION: These data do not support concerns that naltrexone treatment of opioid dependence increases craving, depression, anxiety or anhedonia.

Naltrexone with or without guanfacine for preventing relapse to opiate addiction in St.-Petersburg, Russia.

BACKGROUND: Stress is a key precipitant to discontinuing naltrexone and relapsing to opiate abuse. Alpha-2 adrenergic agonists like guanfacine may reduce stress induced craving and have reduced opiate relapse in small clinical trials. METHODS: This randomized, double blind double dummy placebo-controlled 6-month trial tested oral naltrexone with or without guanfacine for reducing stress and preventing opiate relapse. We randomized 301 patients to: naltrexone 50 mg/day+guanfacine 1 mg/day (n=75) (N/G), naltrexone+guanfacine placebo (N/P) (n=76), naltrexone placebo+guanfacine (n=75) (P/G), and double placebo (n=75) (P/P). RESULTS: Among the 75 patients in each group the percentage still retained on naltrexone treatment at six months was: N/G 26.7%, N/P 19.7% (p=0.258 to N/G), P/G 6.7% (p<0.05 to both N groups), and P/P 10.7% (p=0.013 to N+G). Guanfacine reduced the severity of stress particularly at weeks 10 and 18. Adverse events (AE) were infrequent (4.7%) without group differences, with most common AEs: headache, poor appetite, insomnia, and dizziness. CONCLUSIONS: Adding guanfacine to naltrexone did not improve treatment retention or opiate free urines, but it reduced both stress and craving at later time points in treatment, which may be related to stress-induced craving and the animal model of incubation of reinstatement. During treatment, HIV risk, anxiety, and depression reduced among all patients in treatment, regardless of group.

Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence.

CONTEXT Sustained-release naltrexone implants may improve outcomes of nonagonist treatment of opioid addiction. OBJECTIVE To compare outcomes of naltrexone implants, oral naltrexone hydrochloride, and nonmedication treatment. DESIGN Six-month double-blind, double-dummy, randomized trial. SETTING Addiction treatment programs in St Petersburg, Russia. PARTICIPANTS Three hundred six opioid-addicted patients recently undergoing detoxification. INTERVENTIONS Biweekly counseling and 1 of the following 3 treatments for 24 weeks: (1) 1000-mg naltrexone implant and oral placebo (NI+OP group; 102 patients); (2) placebo implant and 50-mg oral naltrexone hydrochloride (PI+ON group; 102 patients); or (3) placebo implant and oral placebo (PI+OP group; 102 patients). MAIN OUTCOME MEASURE Percentage of patients retained in treatment without relapse. RESULTS By month 6, 54 of 102 patients in the NI+OP group (52.9%) remained in treatment without relapse compared with 16 of 102 patients in the PI+ON group (15.7%) (survival analysis, log-rank test, P < .001) and 11 of 102 patients in the PI+OP group (10.8%) (P < .001). The PI+ON vs PI+OP comparison showed a nonsignificant trend favoring the PI+ON group (P = .07). Counting missing test results as positive, the proportion of urine screening tests yielding negative results for opiates was 63.6% (95% CI, 60%-66%) for the NI+OP group; 42.7% (40%-45%) for the PI+ON group; and 34.1% (32%-37%) for the PI+OP group (P < .001, Fisher exact test, compared with the NI+OP group). Twelve wound infections occurred among 244 implantations (4.9%) in the NI+OP group, 2 among 181 (1.1%) in the PI+ON group, and 1 among 148 (0.7%) in the PI+OP group (P = .02). All events were in the first 2 weeks after implantation and resolved with antibiotic therapy. Four local-site reactions (redness and swelling) occurred in the second month after implantation in the NI+OP group (P = .12), and all resolved with antiallergy medication treatment. Other nonlocal-site adverse effects were reported in 8 of 886 visits (0.9%) in the NI+OP group, 4 of 522 visits (0.8%) in the PI+ON group, and 3 of 394 visits (0.8%) in the PI+ON group; all resolved and none were serious. No evidence of increased deaths from overdose after naltrexone treatment ended was found. CONCLUSIONS The implant is more effective than oral naltrexone or placebo. More patients in the NI+OP than in the other groups develop wound infections or local irritation, but none are serious and all resolve with treatment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00678418.