Pilot RCT comparing low-dose naltrexone, gabapentin and placebo to reduce pain among people with HIV with alcohol problems.

BACKGROUND: To estimate the effects on pain of two medications (low-dose naltrexone and gabapentin) compared to placebo among people with HIV (PWH) with heavy alcohol use and chronic pain. METHODS: We conducted a pilot, randomized, double-blinded, 3-arm study of PWH with chronic pain and past-year heavy alcohol use in 2021. Participants were recruited in St. Petersburg, Russia, and randomized to receive daily low-dose naltrexone (4.5mg), gabapentin (up to 1800mg), or placebo. The two primary outcomes were change in self-reported pain severity and pain interference measured with the Brief Pain Inventory from baseline to 8 weeks. RESULTS: Participants (N = 45, 15 in each arm) had the following baseline characteristics: 64% male; age 41 years (SD±7); mean 2 (SD±4) heavy drinking days in the past month and mean pain severity and interference were 3.2 (SD±1) and 3.0 (SD±2), respectively. Pain severity decreased for all three arms. Mean differences in change in pain severity for gabapentin vs. placebo, and naltrexone vs. placebo were -0.27 (95% confidence interval [CI] -1.76, 1.23; p = 0.73) and 0.88 (95% CI -0.7, 2.46; p = 0.55), respectively. Pain interference decreased for all three arms. Mean differences in change in pain interference for gabapentin vs. placebo, and naltrexone vs. placebo was 0.16 (95% CI -1.38, 1.71; p = 0.83) and 0.40 (95% CI -1.18, 1.99; p = 0.83), respectively. CONCLUSION: Neither gabapentin nor low-dose naltrexone appeared to improve pain more than placebo among PWH with chronic pain and past-year heavy alcohol use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT4052139).

Effects of Opioid Withdrawal on Psychobiology in People Living with HIV.

OBJECTIVE: Many 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 PARTICIPANTS: Study 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. RESULTS: HPA 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. CONCLUSIONS: Worsening 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.

Stigma and other correlates of sharing injection equipment among people with HIV in St. Petersburg, Russia.

Stigma that people with HIV who inject drugs experience negatively impacts HIV and substance use care, but stigma's association with sharing injection equipment is not known. This is a cross-sectional analysis of data from two studies of people with HIV reporting drug injection (N = 319) in St. Petersburg, Russia (September 2018-December 2020). We used logistic regression to examine associations between HIV stigma and substance use stigma scores (categorised into quartiles) and past 30-day equipment sharing, adjusting for demographic and clinical characteristics. Secondary analyses examined associations of arrest history and social support with sharing equipment. Almost half (48.6%) of participants reported sharing injection equipment. Among groups who did and did not share, mean HIV stigma (2.3 vs 2.2) and substance use stigma (32 vs 31) scores were similar. Adjusted analyses detected no significant associations between HIV stigma quartiles (global p-value = 0.85) or substance use stigma quartiles (global p-value = 0.51) and sharing equipment. Neither arrest history nor social support were significantly associated with sharing equipment. In this cohort, sharing injection equipment was common and did not vary based on stigma, arrest history, or social support. To reduce equipment sharing, investments in sterile injection equipment access in Russia should be prioritised over interventions to address stigma.

An acceptance-based, intersectional stigma coping intervention for people with HIV who inject drugs-a randomized clinical trial.

Background: People with HIV who inject drugs experience intersecting forms of stigma that adversely impact care access. This RCT aimed to evaluate effects of a behavioral intersectional stigma coping intervention on stigma and care utilization. Methods: We recruited 100 participants with HIV and past-30-day injection drug use at a non-governmental harm reduction organization in St. Petersburg, Russia, and randomized them 1:2 to receive usual services only or an additional intervention of three weekly 2-h group sessions. Primary outcomes were change in HIV and substance use stigma scores at one month after randomization. Secondary outcomes were initiation of antiretroviral treatment (ART), substance use care utilization, and changes in frequency of past-30-days drug injection at six months. The trial was registered as NCT03695393 at clinicaltrials.gov. Findings: Participant median age was 38.1 years, 49% were female. Comparing 67 intervention and 33 control group participants recruited October 2019-September 2020, the adjusted mean difference (AMD) in change in HIV and substance use stigma scores one month after baseline were 0.40, (95% CI: -0.14 to 0.93, p = 0.14) and -2.18 (95% CI: -4.87 to 0.52, p = 0.11), respectively. More intervention participants than control participants initiated ART (n = 13, 20% vs n = 1, 3%, proportion difference 0.17, 95% CI: 0.05-0.29, p = 0.01) and utilized substance use care (n = 15, 23% vs n = 2, 6%, proportion difference 0.17, 95% CI: 0.03-0.31, p = 0.02). The adjusted median difference in change in injecting drug use frequency 6 months after baseline was -3.33, 95% CI: -8.51 to 1.84, p = 0.21). Five not intervention-related serious adverse events (7.5%) occurred in the intervention group, one (3.0%) serious adverse event in the control group. Interpretation: This brief stigma-coping intervention did not change stigma manifestations or drug use behaviors in people with HIV and injection drug use. However, it seemed to reduce stigma's impact as an HIV and substance use care barrier. Funding: R00DA041245, K99DA041245, P30AI042853.

The impacts of COVID-19 on structural inequities faced by people living with HIV who inject drugs: A qualitative study in St. Petersburg, Russia.

BACKGROUND: People who inject drugs (PWID) living with HIV may be disproportionately impacted by pandemic restrictions. This study qualitatively explored the impacts of the SARS-CoV-2 pandemic on PWID with HIV in St. Petersburg, Russia. METHODS: In March and April 2021, we conducted remote, semi-structured interviews with PWID with HIV, health care providers, and harm reductionists. RESULTS: We interviewed 25 PWID with HIV (aged 28-56 years, 46% female) and 11 providers. The pandemic exacerbated economic and psychological challenges experienced by PWID with HIV. Simultaneously, barriers to HIV care access, ART prescription refill and dispensing and police violence, which hindered the health and safety of PWID with HIV, were themselves hindered from normal operations by the pandemic, significantly reducing these burdens. CONCLUSION: Pandemic responses should account for the unique vulnerabilities of PWID with HIV to avoid worsening the structural violence they already experience. Wherever the pandemic decreased structural barriers, such as institutional, administrative, and bureaucratic challenges and state violence enacted by police and other elements of the criminal justice system, such changes should be protected.

Incarceration history, antiretroviral therapy, and stigma: A cross-sectional study of people with HIV who inject drugs in St. Petersburg, Russia.

BACKGROUND: The HIV epidemic is intertwined with substance use and incarceration in Russia. The relationships between incarceration history, HIV treatment history, and stigma experiences among people with HIV (PWH) who inject drugs in Russia have not been well described. METHODS: We conducted a cross-sectional study of a cohort of PWH with opioid use disorder who inject drugs (n=201) recruited at a narcology (substance use treatment) hospital in St. Petersburg, Russia from September 2018 to December 2020. The primary analysis evaluated the association between self-reported prior incarceration and prior antiretroviral therapy (ART) initiation using multivariable logistic regression to adjust for demographic, social, and clinical covariates. We used multivariable linear regression models to analyze associations between prior incarceration and two secondary outcomes: HIV stigma score (11-item abbreviated Berger scale) and substance use stigma score (21-item combination of Substance Abuse Self-Stigma Scale and Stigma-related Rejection Scale). RESULTS: Mean age was 37 (SD 5) years; 58.7% were male. Participants had been living with HIV for a mean of 13 (SD 6) years. Over two thirds (69.2%) of participants reported prior incarceration. One third (35.3%) of participants reported prior ART initiation. Prior incarceration was not significantly associated with prior ART initiation (AOR 1.76; 95% CI: 0.81, 3.83). Prior incarceration was associated with a lower HIV stigma score (adjusted mean difference in z-score: -0.50; 95%CI: -0.81, -0.19) but was not significantly associated with substance use stigma score (adjusted mean difference in z-score: -0.10; 95%CI: -0.42, 0.21). CONCLUSION: Prior incarceration was common, and rates of prior ART initiation were low even though most participants had been living with HIV for at least a decade. We did not find an association between prior incarceration and prior ART initiation, which suggests a need to explore whether opportunities to initiate ART during or after incarceration are missed. CLINICAL TRIAL NUMBER: NCT03290391.

HIV, substance use, and intersectional stigma: Associations with mental health among persons living with HIV who inject drugs in Russia.

HIV stigma is associated with negative physical and mental health outcomes. Intersectional stigma among persons living with HIV (PLHIV) results from interrelated, synergistic impacts of experiencing multiple stigma forms. Its relation with mental health outcomes is still an emerging area of study in this key population. This study aimed to evaluate associations of intersectional stigma, defined as endorsing high levels of HIV and substance use stigmas, with depressive and anxiety symptoms in a cohort of 111 PLHIV who inject drugs in St. Petersburg, Russia. Over a third of participants (37%) reported experiencing intersectional stigma (i.e., both stigma scores above the median). In adjusted analysis, lower Patient Health Questionnaire depression scale (PHQ-9) scores (beta (ß=-4.31, 95% CI: -7.11 - -1.51, p = 0.003) and Generalized Anxiety Disorders Scale (GAD-7) scores (ß=-3.64, 95% CI: -5.57 - -1.71, p < 0.001) were associated with having low scores for both HIV and substance use stigmas. Lower PHQ-9 scores (ß=-3.46, 95% CI: -5.72 - -1.19, p = 0.003) and GAD-7 scores (ß=-3.06, 95% CI: -4.62 - -1.50, p < 0.001) were also associated with high stigma on either HIV or substance use stigma scales. Controlling for demographics, depressive symptoms approximately linearly increased from both forms of stigma low to experiencing either form of stigma high to experiencing intersectional stigma, while levels of anxiety symptoms were comparable among participants with both types of stigma low and one stigma high. Participants who experienced intersectional stigma reported the greatest severity of both depressive and anxiety symptoms, as compared to individuals who endorsed low stigma scores (i.e., low stigma on both HIV and substance use stigma scales) or high scores of only one form of stigma. This suggests that intersectional stigma in this population of PLHIV who inject drugs in Russia is linked with worsened mental health outcomes, exceeding the effects of experiencing one form of stigma alone. Interventions to help people cope with intersectional stigma need to consider affective symptoms and tailor coping strategies to address impacts of multiple forms of mental health distress.

Correlates of Intersectional HIV and Substance Use Stigma Affecting People with HIV and Substance Use in St. Petersburg, Russia.

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.

RESUMEN: Las personas infectadas por el VIH que se inyectan drogas a menudo experimentan manifestaciones de estigma relacionadas con el uso de sustancias y el propio VIH. En este estudio evaluamos los correlatos de estigma asociado al VIH (escala de estigma asociado al VIH de Berger), el estigma asociado al uso de sustancias ("Substance Abuse Self-stigma Scale") y el estigma interseccional del VIH y el uso de sustancias en una cohorte de personas infectadas por el VIH con antecedente de uso de drogas en San Petersburgo, Rusia. El estigma interseccional se definió como una puntuación superior a la mediana para ambas formas de estigma. De los 208 participantes, 56 (27%) tenían estigma interseccional. Los síntomas depresivos y la dependencia del alcohol se asociaron significativamente con una puntuación más alta de estigma relacionado con el VIH y las sustancias, pero no con el estigma interseccional. Las intervenciones individuales y comunitarias para reducir el impacto del estigma asociado al VIH y al uso de sustancias que afectan a las personas con VIH que se inyectan drogas deben tener en cuenta la salud mental y el uso nocivo de sustancias. Se necesitan estudios con datos longitudinales para comprender mejor los mecanismos que conducen al estigma interseccional.

Pilot study of tolerability and safety of opioid receptor antagonists as novel therapies for chronic pain among persons living with HIV with past year heavy drinking: a randomized controlled trial.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03278886.

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.

Addressing intersectional stigma as a care barrier for HIV-positive people who inject drugs: Design of an RCT in St. Petersburg, Russia.

BACKGROUND: HIV-positive people who inject drugs (PWID) experience stigma related to their substance use and HIV, with adverse consequences to their health care utilization and mental health. To help affected individuals cope with their intersectional stigma and reduce its negative impact on health and health care, we adapted a behavioral stigma coping intervention for this HIV key population. OBJECTIVE: To conduct a randomized controlled trial (RCT) testing the 'Stigma Coping to Reduce HIV risks and Improve substance use Prevention and Treatment' (SCRIPT) intervention, a community-based, adapted form of Acceptance and Commitment Therapy (ACT), for PWID living with HIV in St. Petersburg, Russia. METHODS: We recruited 100 PWID living with HIV from civil society organizations (CSO) delivering harm reduction and HIV prevention services in St. Petersburg, Russia. We randomized participants 2:1 to receive either the intervention (three adapted ACT sessions in a group format over one month and usual CSO care) or usual CSO care alone. ACT aims to help affected individuals cope with stigma by increasing their psychological flexibility to handle stigma-related negative expectations, emotions and experiences. The primary outcomes were satisfaction with the intervention, and changes in HIV and substance use stigma scores. CONCLUSIONS: Stigma coping interventions targeting HIV-positive PWID outside of formal health care settings may help them confront negativities in their lives originating from intersectional stigma and reduce stigma's impact as a health care barrier.

HIV and Substance Use Stigma, Intersectional Stigma and Healthcare Among HIV-Positive PWID in Russia.

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.

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.

Community reentry challenges after release from prison among people who inject drugs in St. Petersburg, Russia.

PURPOSE: Little is known about the context of the post-release risk environment among formerly incarcerated people who inject drugs (PWID) in Russia. The purpose of this paper is to explore these challenges as they relate to reentry, relapse to injection opioid use, and overdose. DESIGN/METHODOLOGY/APPROACH: The authors conducted 25 in-depth semi-structured interviews among PWID living in St Petersburg, Russia who had been incarcerated within the past two years. Participants were recruited from street outreach (n=20) and a drug treatment center (n=5). FINDINGS: Emergent themes related to the post-release environment included financial instability, negative interactions with police, return to a drug using community, and reuniting with drug using peers. Many respondents relapsed to opioid use immediately after release. Those whose relapse occurred weeks or months after their release expressed more motivation to resist. Alcohol or stimulant use often preceded the opioid relapse episode. Among those who overdosed, alcohol use was often reported prior to overdosing on opioids. PRACTICAL IMPLICATIONS: Future post-release interventions in Russia should effectively link PWID to social, medical, and harm reduction services. Particular attention should be focussed on helping former inmates find employment and overdose prevention training prior to leaving prison that should also cover the heightened risk of concomitant alcohol use. ORIGINALITY/VALUE: In addition to describing a syndemic involving the intersection of incarceration, injection drug use, poverty, and alcohol abuse, the findings can inform future interventions to address these interrelated public health challenges within the Russian setting.