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ObjectiveMany persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood.Method and participantsStudy participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time.ResultsHPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14.ConclusionsWorsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation.

Providers disrespect and abuse of patients is a recognized but understudied issue affecting quality of care and likely affecting healthcare utilization. Little research has examined this issue among people living with HIV (PWH) who inject drugs, despite high stigmatization of this population. No research has examined this issue in the context of Russia. This study assesses patients reports of disrespect and abuse from providers as a barrier to healthcare and examines the association between these reports and HIV care outcomes.We conducted a cross-sectional analysis of the associations between disrespect/abuse from health providers as a barrier to care and the following HIV care outcomes: (i) anti-retroviral treatment (ART) uptake ever, (ii) past 6-month visit to HIV provider, and (iii) CD4 count. Participants (N = 221) were people living with HIV who injected drugs and were not on ART at enrollment.Two in five participants (42%) reported a history disrespect/abuse from a healthcare provider that they cited as a barrier to care. Those reporting this concern had lower odds of ever use of ART (adjusted odds ratio 0.46 [95% CI 0.22, 0.95]); we found no significant associations for the other HIV outcomes. We additionally found higher representation of women among those reporting prevalence of disrespect/abuse from provider as a barrier to care compared to those not reporting this barrier (58.1% versus 27.3%).Almost half of this sample of PWH who inject drugs report disrespect/abuse from a provider as a barrier to healthcare, and this is associated with lower odds of receipt of ART but not with other HIV outcomes studied. There is need for improved focus on quality of respectful and dignified care from providers for PWH who inject drugs, and such focus may improve ART uptake in Russia.

Food insecurity (FI) impacts people with HIV (PWH) and those who use substances (i.e. drugs and alcohol). We evaluated the longitudinal association between FI and HIV transmission risks (unprotected sexual contacts and shared needles/syringes). Among 351 PWH who use substances in Russia, 51.6% reported FI and 37.0% past month injection drug use. The mean number of unprotected sexual contacts in the past 90 days was 13.4 (SD 30.1); 9.7% reported sharing needles/syringes in the past month. We did not find a significant association between mild/moderate FI (adjusted IRR = 0.87, 95% CI 0.47, 1.61) or severe FI (aIRR = 0.84, 95% CI 0.46, 1.54; global p = 0.85) and unprotected sexual contacts. We observed a significant association between severe FI and sharing needles/syringes in the past month (adjusted OR = 3.27, 95% CI 1.45, 7.39; p = 0.004), but not between mild/moderate FI and sharing needles/syringes in the past month (aOR = 1.40,95% CI 0.58, 3.38; p = 0.45). These findings suggest that severe FI could be a potential target for interventions to lower HIV transmission.

IntroductionUnhealthy alcohol use is associated with a range of adverse outcomes among people with HIV (PWH). Testing the efficacy and promoting the availability of effective interventions to address unhealthy alcohol use among PWH is thus a priority. Alcohol use outcomes in intervention studies are often measured by self-report alone, which can lead to spurious results due to information biases (eg, social desirability). Measuring alcohol outcomes objectively through biomarkers, such as phosphatidylethanol (PEth), in addition to self-report has potential to improve the validity of intervention studies. This protocol outlines the methods for a systematic review and individual participant data meta-analysis that will estimate the efficacy of interventions to reduce alcohol use as measured by a combined categorical self-report/PEth variable among PWH and compare these estimates to those generated when alcohol is measured by self-report or PEth alone.Methods and analysisWe will include randomised controlled trials that: (A) tested an alcohol intervention (behavioural and/or pharmacological), (B) enrolled participants 15 years or older with HIV; (C) included both PEth and self-report measurements, (D) completed data collection by 31 August 2023. We will contact principal investigators of eligible studies to inquire about their willingness to contribute data. The primary outcome variable will be a combined self-report/PEth alcohol categorical variable. Secondary outcomes will include PEth alone, self-report alone and HIV viral suppression. We will use a two-step meta-analysis and random effects modelling to estimate pooled treatment effects; I2 will be calculated to evaluate heterogeneity. Secondary and sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots will be used to explore publication bias.Ethics and disseminationThe study will be conducted with deidentified data from completed randomised controlled trials and will be considered exempt from additional ethical approval. Results will be disseminated through peer-reviewed publications and international scientific meetings.Prospero registration numberCRD42022373640.

People with HIV (PWH) who inject drugs often experience coexisting HIV- and substance use-related stigma manifestations. We assessed correlates of HIV stigma (Berger HIV stigma scale), substance use stigma (Substance Abuse Self-stigma scale) and intersectional HIV and substance use stigma in a cohort of PWH with a lifetime history of drug use in St. Petersburg, Russia. Intersectional stigma was defined as having a score greater than the median for both forms of stigma. Of the 208 participants, 56 (27%) had intersectional stigma. Depressive symptoms and alcohol dependence were significantly associated with a higher HIV and substance stigma score, but not with intersectional stigma. Individual and community interventions to reduce the impact of HIV stigma and substance use stigma affecting PWH who inject drugs should consider assessing and addressing mental health and unhealthy substance use. Further work with longitudinal data is needed to understand mechanisms leading to intersectional stigma.

This study evaluated the association between impulsivity and linkage to HIV care among Russians living with HIV recruited from an inpatient narcology hospital. Linking Infectious and Narcology Care (LINC) study participants who completed the Barratt Impulsiveness Scale (BIS) were included in these analyses. The primary independent variable was impulsivity score which was categorized as high impulsivity (BIS score > 71) vs. low impulsivity (BIS score

Abstract Background With HIV prevalence estimated at 20% among female injecting drug users (IDUs) in St. Petersburg, Russia, there is a critical need to address the HIV risks of this at-risk population. This study characterized HIV risks associated with injecting drug use and sex behaviors and assessed the initial feasibility and efficacy of an adapted Woman-Focused intervention, the Women's CoOp, relative to a Nutrition control to reduce HIV risk behaviors among female IDUs in an inpatient detoxification drug treatment setting. Method Women (N = 100) were randomized into one of two one-hour long intervention conditions--the Woman-Focused intervention (n = 51) or a time and attention-matched Nutrition control condition (n = 49). Results The results showed that 57% of the participants had been told that they were HIV-positive. At 3-month follow-up, both groups showed reduced levels of injecting frequency. However, participants in the Woman-Focused intervention reported, on average, a lower frequency of partner impairment at last sex act and a lower average number of unprotected vaginal sex acts with their main sex partner than the Nutrition condition. Conclusion The findings suggest that improvements in sexual risk reduction are possible for these at-risk women and that more comprehensive treatment is needed to address HIV and drug risks in this vulnerable population.

Little is known about the intersection of HIV stigma and substance use stigma. Using data from 188 HIV-positive people who inject drugs (PWID) in Russia, we examined the associations of these stigmas and their interaction with access and utilization of healthcare. While substance use stigma was significantly associated with poor access to care (AOR 2.31, 95%CI 1.50-3.57), HIV stigma was not. HIV stigma was associated with lower inpatient care utilization (AOR 0.32, 95%CI 0.14-0.65), while substance use stigma was not. We did not detect a significant interaction between the two forms of stigma for either of the primary outcomes. However, those with high levels of both substance use stigma and HIV stigma had higher odds of poor general access to healthcare (AOR 1.86, 95%CI 1.19-2.92), and lower odds of recent general outpatient (AOR 0.52, 95%CI 0.32-0.85) and any inpatient (AOR 0.48, 95%CI 0.22-0.99) care utilization compared to those with low levels of both types of stigma. Interventions addressing both substance use and HIV stigma in general healthcare settings might improve care in this HIV key population.

Abstract Background Opioid overdose in Russia is a problem that has grown more severe as heroin abuse expanded over the past decade, yet few studies have explored it in detail. In order to gain a clearer understanding of the situation, 60 drug users, both in and out of drug treatment in St. Petersburg, were interviewed concerning their overdose experience and knowledge about overdose recognition and prevention. Methods Using a semi-structured interview, we sought to identify and describe local attitudes, knowledge and experience (both self-sustained and witnessed) of opioid overdose. Bi-variate and multiple logistic regressions were performed in order to identify the relationship between overdose experience and sociodemographic factors, risk behaviors, and clinical psychiatric measures. Results We found that having experienced or witnessed an opioid overdose within the previous year was common, overdose knowledge was generally high, but nearly half the participants reported low self-efficacy for effectively intervening in an overdose situation. In bivariate analyses, self-reported family problems (i.e., perceived problematic family interactions) were positively associated with both experiencing (t56 = 2.49; p < 0.05) and with witnessing a greater number of overdoses in the previous year (rhos = 0.31; p < 0.05). Having previously overdosed [Adjusted Risk Ratio (ARR) 1.7, 95% Confidence Interval (CI) 1.1–2.6] and higher SCL-90-R somatization scores (ARR 1.2, 95% CI 0.96 – 1.5) were independently associated in multivariable analyses with self-sustained overdose experience in the past year. Greater perceived likelihood of experiencing a future overdose and concern about medical problems were independently associated with witnessing a higher number of overdoses within the previous year. Over two thirds of the participants expressed interest in receiving training in overdose prevention and response. Conclusion Opioid overdose experience is very common among drug users in St. Petersburg, Russia, and interest in receiving training for overdose recognition and prevention was high. Future research should target the development of effective overdose recognition and prevention interventions, especially ones that include naloxone distribution and involve drug users' families.

Abstract Background Economic theory and limited empirical data suggest that costs per unit of HIV prevention program output (unit costs) will initially decrease as small programs expand. Unit costs may then reach a nadir and start to increase if expansion continues beyond the economically optimal size. Information on the relationship between scale and unit costs is critical to project the cost of global HIV prevention efforts and to allocate prevention resources efficiently. Methods The "Prevent AIDS: Network for Cost-Effectiveness Analysis" (PANCEA) project collected 2003 and 2004 cost and output data from 206 HIV prevention programs of six types in five countries. The association between scale and efficiency for each intervention type was examined for each country. Our team characterized the direction, shape, and strength of this association by fitting bivariate regression lines to scatter plots of output levels and unit costs. We chose the regression forms with the highest explanatory power (R2). Results Efficiency increased with scale, across all countries and interventions. This association varied within intervention and within country, in terms of the range in scale and efficiency, the best fitting regression form, and the slope of the regression. The fraction of variation in efficiency explained by scale ranged from 26% – 96%. Doubling in scale resulted in reductions in unit costs averaging 34.2% (ranging from 2.4% to 58.0%). Two regression trends, in India, suggested an inflection point beyond which unit costs increased. Conclusion Unit costs decrease with scale across a wide range of service types and volumes. These country and intervention-specific findings can inform projections of the global cost of scaling up HIV prevention efforts.

Food insecurity (FI) has been associated with HIV disease progression among people on antiretroviral therapy (ART), presumably a consequence of poor medication adherence. We assessed whether there is a longitudinal association between FI and two primary outcomes reflecting on HIV disease progression (i.e., CD4 count and time to ART initiation) among people not on ART. Analyses used linear mixed effects and Cox models controlling for confounders. In this cohort (n = 310) FI was common (53%). Most (71.3%) reported past month heavy alcohol use and 37.1% reported past month injection drug use. Only 50 participants initiated ART during the study and mean time to ART was 128 days (SD 120). There were no significant differences in CD4 cell count between the groups with mild/moderate FI or severe FI versus those with no FI [adjusted mean difference, mild/moderate insecurity versus no FI -32.5 (95% CI -94.3, 29.3); severe versus no FI -45.5 (95% CI -124.1, 33.0); global p = 0.42]. We found no significant association between FI and longer time to ART initiation (p = 0.36). Food security is a desirable goal for overall health and shown beneficial for those on ART, however it does not appear to be associated with HIV disease progression among those with high prevalence of substance use and not yet on ART.

Food insecurity (FI) is a documented problem associated with adverse health outcomes among HIV-infected populations. Little is known about the relationship between alcohol use and FI. We assessed whether heavy alcohol use was associated with FI among HIV-infected, antiretroviral therapy (ART)-naïve cohorts in Uganda and Russia. Inverse probability of treatment weighted logistic regression models were used to evaluate the association using cross-sectional baseline data. FI was experienced by half of the Russia cohort (52 %) and by a large majority of the Uganda cohort (84 %). We did not detect an association between heavy alcohol use and FI in either cohort (Russia: AOR = 0.80, 95 % CI 0.46, 1.40; Uganda: AOR = 1.00, 95 % CI 0.57, 1.74) or based on the overall combined estimate (AOR = 0.89, 95 % CI 0.60, 1.33). Future studies should explore the determinants of FI in HIV-infected populations to inform strategies for its mitigation.

BackgroundRussia and Eastern Europe have one of the fastest growing HIV epidemics in the world. While countries in this region have implemented HIV testing within addiction treatment systems, linkage to HIV care from these settings is not yet standard practice. The Linking Infectious and Narcology Care (LINC) intervention utilized peer-led strengths-based case management to motivate HIV-infected patients in addiction treatment to obtain HIV care. This paper describes the protocol of a randomized controlled trial evaluating the effectiveness of the LINC intervention in St. Petersburg, Russia.Methods/designParticipants (n = 349) were recruited from the inpatient wards at the City Addiction Hospital in St. Petersburg, Russia. After completing a baseline assessment, participants were randomly assigned to receive either the LINC intervention or standard of care. Participants returned for research assessments 6 and 12 months post-baseline. Primary outcomes were assessed via chart review at HIV treatment locations.DiscussionLINC holds the potential to offer an effective approach to coordinating HIV care for people who inject drugs in Russia. The LINC intervention utilizes existing systems of care in Russia, minimizing adoption of substantial infrastructure for implementation. Trial Registration NCT01612455.

ObjectivesOnce-monthly intramuscular extended-release naltrexone (XR-NTX) has demonstrated efficacy for the prevention of relapse in opioid dependence, providing an alternative to agonist or partial agonist maintenance (ie, methadone and buprenorphine). The question remains, for whom is this unique treatment most efficacious and can patient-treatment matching factors be identified?MethodsA moderator analysis was conducted on a previously reported 24-week, placebo-controlled, multisite, randomized controlled trial of XR-NTX (n = 126) versus placebo (n = 124) among recently detoxified opioid-dependent adults in Russia, which showed XR-NTX superior to placebo in proportion of opioid abstinent weeks. The moderator analysis examined a dichotomous indicator of good clinical response-achieving at least 90% of weeks abstinent over the 24-week trial. A series of logistic regression models were fit for this outcome as functions of treatment (XR-NTX vs placebo), each baseline moderator variable, and their interactions. The 25 baseline variables included demographics, clinical severity (Addiction Severity Index, SF-36, and Clinical Global Impression-Severity), functioning (EQ-5D), craving, and HIV serostatus (HIV+).ResultsMore XR-NTX patients achieved 90% abstinence (64/126, 51%) versus placebo (39/124, 31%; P = 0.002). There were no significant interactions between baseline variables and treatment. There was a significant main effect of Clinical Global Impression-Severity score (P = 0.02), such that higher severity score was associated with a lower rate of Good Clinical Response.ConclusionsThe absence of significant baseline by treatment interactions indicates that no patient-treatment matching variables could be identified. This suggests that XR-NTX was effective in promoting abstinence from opioids across a range of demographic and severity characteristics.

AimsThis study assessed the effectiveness of HERMITAGE (HIV's Evolution in Russia-Mitigating Infection Transmission and Alcoholism in a Growing Epidemic), an adapted secondary HIV prevention intervention, compared with an attention control condition in decreasing sexually transmitted infections (STIs) and sex and drug risk behaviors among Russian HIV-infected heavy drinkers.DesignWe conducted a single-blinded, two-armed, randomized controlled trial with 12-month follow-up.SettingThe study was conducted in St Petersburg, Russia. Participants were recruited from four HIV and addiction clinical sites. The intervention was conducted at Botkin Infectious Disease Hospital.ParticipantsHIV-infected individuals with past 6-month risky sex and heavy alcohol consumption (n = 700) were randomized to the HERMITAGE intervention (n = 350) or an attention control condition (n = 350).InterventionA Healthy Relationships Intervention stressing disclosure of HIV serostatus and condom use, adapted for a Russian clinical setting with two individual sessions and three small group sessions.MeasurementsThe primary outcome was incident STI by laboratory test at 12-month follow-up. Secondary outcomes included change in unprotected sex and several alcohol and injection drug use (IDU) variables.FindingsParticipants had the following baseline characteristics: 59.3% male, mean age 30.1, 60.4% past year IDU, 15.4% prevalent STI and mean CD4 cell count 413.3/μl. Assessment occurred among 75 and 71% of participants at 6 and 12 months, respectively. STIs occurred in 20 subjects (8.1%) in the intervention group and 28 subjects (12.0%) in the control group at 12-month follow-up; logistic regression analyses found no significant difference between groups (adjusted odds ratio 0.63; 95% confidence interval = 0.34-1.18; P = 0.15). Both groups decreased unsafe behaviors, although no significant differences were found between groups.ConclusionsThe HERMITAGE HIV risk reduction intervention does not appear to reduce sexually transmitted infections and HIV risk behaviors in Russian HIV-infected heavy drinkers compared with attention controls.

Overdoses and HIV infection are common among Russians who inject drugs, yet risk factors have not been studied. We analyzed baseline data of 294 participants with 30-day injection drug use from an HIV secondary prevention trial for persons reporting "heavy" alcohol use (National Institute on Alcohol Abuse and Alcoholism [NIAAA] risky drinking definition) and risky sex in the past 6 months. The outcome was any self-reported overdose in the previous 3 months. We examined demographic, HIV-related, criminal justice, mental health, substance use, and injection risk factors. Participants' characteristics included median age 29 years, 117/294 (40%) female, and median CD4 cell count 345/µl. Over three quarters 223/294 (76%) reported a history of overdose and 47/294 (16%) reported overdose in the past 3 months. Past month injection frequency (adjusted odds ratio [AOR] 4.77, 95% confidence interval [CI]: 1.63-14.0 highest vs. lowest quartile; AOR 3.58, 95% CI: 1.20-10.69 second highest vs. lowest quartile) and anti-retroviral therapy (ART) at time of interview (AOR 3.96 95% CI: 1.33-11.83) were associated with 3-month overdose. Nonfatal overdose among HIV-infected Russians who inject drugs is common. Risk factors include injection frequency and anti-retroviral therapy (ART), which warrant further study. Overdose prevention efforts are needed among HIV-infected Russians who inject drugs.

IntroductionDrug law enforcement is part of the HIV risk environment among people who inject drugs (PWID). Punitive policing practices such as extrajudicial arrests for needle possession and police planting of drugs have been described anecdotally in Russia, but these experiences and their associations with risky drug behaviours have not been quantified. This study aims to quantify the burden of extrajudicial police arrests among a cohort of HIV-positive PWID in Russia and to explore its links to drug-related health outcomes.MethodsIn a cross-sectional study of 582 HIV-positive people with lifetime injection drug use (IDU) in St. Petersburg, Russia, we estimated the prevalence of self-reported extrajudicial police arrests. We used multiple logistic regression to evaluate associations between arrests and the following outcomes: overdose, recent IDU and receptive needle sharing.FindingsThis cohort's mean age was 29.8 years, 60.8% were male; 75.3% reported non-fatal drug overdose, 50.3% recent IDU and 47.3% receptive needle sharing. Extrajudicial arrests were reported by more than half (60.5%, 95% confidence interval [CI]: 56.5-64.5) and were associated with higher odds of non-fatal drug overdose (AOR 1.52, 95% CI: 1.02-2.25) but not with recent IDU (AOR 1.17, arrests were associated with receptive needle sharing (AOR 1.84, 95% CI: 1.09-3.09).ConclusionsExtrajudicial police arrests were common among this cohort of Russian HIV-positive PWID and associated with non-fatal overdose and, among those with recent IDU, receptive needle sharing. As a part of the HIV risk environment of PWIDs, these practices might contribute to HIV transmission and overdose mortality. Further research is needed to relate these findings to the operational environment of law enforcement and to better understand how police interventions among PWIDs can improve the HIV risk environment.

BackgroundEconomic theory and limited empirical data suggest that costs per unit of HIV prevention program output (unit costs) will initially decrease as small programs expand. Unit costs may then reach a nadir and start to increase if expansion continues beyond the economically optimal size. Information on the relationship between scale and unit costs is critical to project the cost of global HIV prevention efforts and to allocate prevention resources efficiently.MethodsThe "Prevent AIDS: Network for Cost-Effectiveness Analysis" (PANCEA) project collected 2003 and 2004 cost and output data from 206 HIV prevention programs of six types in five countries. The association between scale and efficiency for each intervention type was examined for each country. Our team characterized the direction, shape, and strength of this association by fitting bivariate regression lines to scatter plots of output levels and unit costs. We chose the regression forms with the highest explanatory power (R2).ResultsEfficiency increased with scale, across all countries and interventions. This association varied within intervention and within country, in terms of the range in scale and efficiency, the best fitting regression form, and the slope of the regression. The fraction of variation in efficiency explained by scale ranged from 26-96%. Doubling in scale resulted in reductions in unit costs averaging 34.2% (ranging from 2.4% to 58.0%). Two regression trends, in India, suggested an inflection point beyond which unit costs increased.ConclusionUnit costs decrease with scale across a wide range of service types and volumes. These country and intervention-specific findings can inform projections of the global cost of scaling up HIV prevention efforts.