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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.

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.

BACKGROUND: Alcohol use has been linked to worse human immunodeficiency virus (HIV) immunologic/virologic outcomes, yet few studies have explored the effects of alcohol use disorder (AUD). This study assessed whether AUD severity is associated with HIV viral suppression and CD4 count in the three cohorts of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium. METHODS: People with HIV (PWH) in Uganda (n = 301), Russia (n = 400), and Boston (n = 251), selected in-part based on their alcohol use, were included in analyses. Logistic and linear regressions were used to assess the cross-sectional associations between AUD severity (number of DSM-5 diagnostic criteria) and (1) HIV viral suppression, and (2) CD4 count (cells/mm3 ) adjusting for covariates. Analyses were conducted separately by site. RESULTS: The proportion of females was 51% (Uganda), 34% (Russia), and 33% (Boston); mean age (SD) was 40.7 (9.6), 38.6 (6.3), and 52.1 (10.5), respectively. All participants in Uganda and all but 27% in Russia and 5% in Boston were on antiretroviral therapy. In Uganda, 32% met criteria for AUD, 92% in Russia, and 43% in Boston. The mean (SD) number of AUD criteria was 1.6 (2.4) in Uganda, 5.6 (3.3) in Russia, and 2.4 (3.1) in Boston. Most participants had HIV viral suppression (Uganda 92%, Russia 57%, Boston 87%); median (IQR) CD4 count was 673 (506, 866), 351 (201, 542), and 591 (387, 881), respectively. In adjusted models, there were no associations between AUD severity and HIV viral suppression: adjusted odds ratios (AOR) (95%CI) per 1 additional AUD criterion in Uganda was 1.08 (0.87, 1.33); Russia 0.98 (0.92, 1.04); and Boston 0.95 (0.84, 1.08) or CD4 count: mean difference (95%CI) per 1 additional criterion: 5.78 (-7.47, 19.03), -3.23 (-10.91, 4.44), and -8.18 (-24.72, 8.35), respectively. CONCLUSIONS: In three cohorts of PWH, AUD severity was not associated with HIV viral suppression or CD4 count. PWH with AUD in the current era of antiretroviral therapy can achieve virologic control.

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

BACKGROUND: Both human immunodeficiency virus (HIV) infection and alcohol use predispose to autonomic/sensory neuropathy, imbalance symptoms, and cognitive impairment-conditions associated with a greater risk of falls-yet it is unclear how to identify people with HIV (PWH) whose drinking is associated with falls. Research on alcohol and falls using the same instruments in different countries could help to specify the level of alcohol use associated with fall risk. We examined whether a consumption-based measure (the Alcohol Use Disorders Identification Test-Consumption [AUDIT-C]) and/or a symptom-based measure (DSM-5 criteria for alcohol use disorder [AUD]) are associated with sustaining a fall among PWH in St Petersburg, Russia and Boston, Massachusetts in the United States. METHODS: Separate multivariate logistic regressions were used for each cohort to examine cross-sectional associations for each alcohol measure predicting fall. Potential confounders included physical functioning, depressive symptoms, and other substance use (measured with the Addiction Severity Index). RESULTS: A fall was reported by 35% (87/251) of the sample in Boston and 12% (46/400) in St Petersburg. Each additional AUD criterion-but not higher AUDIT-C score-was significantly associated with a fall in both Boston (odds ratio [OR] = 1.10; 95% confidence interval [CI] 1.02, 1.18) and St Petersburg (adjusted OR AOR = 1.10; 95% CI 1.02, 1.18). Heavy alcohol use (>6 drinks/occasion, any vs. none) was associated with more than twice the odds of a fall (AOR = 2.24; 95% CI 1.21, 4.13) in Boston. CONCLUSIONS: These findings suggest that while fall risk may vary by setting and population, heavy alcohol use and AUD symptom severity are potential targets for interventions to prevent falls. Studies in diverse global settings advance our understanding of the relationship between alcohol and falls in PWH.

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.

ObjectiveWe examined whether gender is associated with heavy drinking in three cohorts of people living with HIV (PLWH) in Mbarara, Uganda; St. Petersburg, Russia; and Boston, Massachusetts.MethodWe conducted secondary analyses of baseline data collected from three cohorts in the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) consortium. We used multiple logistic regression models to evaluate the association between gender and heavy drinking (defined in combination with self-report and phosphatidylethanol [PEth]) within each cohort.ResultsIn unadjusted logistic regression models, we found no significant association between gender and heavy drinking in Russia or Boston. In Uganda, women were less likely than men to engage in heavy drinking (odds ratio = 0.38, 95% CI [0.26, 0.58], p

Restrictive gender norms and gender inequalities are replicated and reinforced in health systems, contributing to gender inequalities in health. In this Series paper, we explore how to address all three through recognition and then with disruptive solutions. We used intersectional feminist theory to guide our systematic reviews, qualitative case studies based on lived experiences, and quantitative analyses based on cross-sectional and evaluation research. We found that health systems reinforce patients' traditional gender roles and neglect gender inequalities in health, health system models and clinic-based programmes are rarely gender responsive, and women have less authority as health workers than men and are often devalued and abused. With regard to potential for disruption, we found that gender equality policies are associated with greater representation of female physicians, which in turn is associated with better health outcomes, but that gender parity is insufficient to achieve gender equality. We found that institutional support and respect of nurses improves quality of care, and that women's empowerment collectives can increase health-care access and provider responsiveness. We see promise from social movements in supporting women's reproductive rights and policies. Our findings suggest we must view gender as a fundamental factor that predetermines and shapes health systems and outcomes. Without addressing the role of restrictive gender norms and gender inequalities within and outside health systems, we will not reach our collective ambitions of universal health coverage and the Sustainable Development Goals. We propose action to systematically identify and address restrictive gender norms and gender inequalities in health systems.

Among persons who inject drugs, women have a higher HIV prevalence (than men) in many settings. Understanding how gender affects risk for infection among HIV-negative, and transmission among HIV-positive people who currently or previously injected drugs is key to designing effective prevention and treatment programs. We analyzed data from 291 persons living with HIV who had ever injected drugs. Participants were drawn from the Russia Alcohol Research Collaboration on HIV/AIDS cohort (2012-2015) to examine associations between female gender and HIV transmission risk. Primary outcomes were sharing drug injecting equipment (e.g., needle/syringes) and condomless sex. Secondary outcomes were alcohol use before sharing drug injecting equipment; before condomless sex; and both sharing drug injecting equipment and condomless sex. Logistic regression models assessed associations between gender and outcomes, controlling for demographics, partner HIV status and use of antiretroviral treatment. Female gender was not significantly associated with sharing drug injecting equipment [aOR = 1.45, 95% confidence interval (CI) 0.85-2.46, p value = 0.18] but was associated with condomless sex (aOR = 1.91, 95% CI 1.12-3.23, p = 0.02) in adjusted models. Female gender was not significantly associated with any secondary outcomes. Better understanding of risky sex and drug use behaviors among people who currently or previously injected drugs can support the design of effective gender-tailored HIV prevention interventions.

BackgroundResearch studies rely on accurate assessment of entry criteria in order to maintain study integrity and participant safety, however, challenges can exist with HIV studies in international settings.ObjectiveExamine the unexpectedly high proportion of study participants with an undetectable HIV viral load found in Ugandan and Russian research cohorts meeting antiretroviral therapy (ART)-naïve entry criteria.MethodsRussian participants with documented HIV and ART-naïve status were recruited between 2012 and 2015 from clinical and non-clinical sites in St. Petersburg. Participants in Uganda were recruited from Mbarara Regional Referral Hospital from 2011 to 2014 with documented HIV infection via rapid diagnostic testing and recorded ART-naïve in the clinic database. HIV viral load testing of baseline samples was performed; the lower limit of detection was 500 copies/mL in Russia and 40 in Uganda. Due to an unexpectedly high proportion of participants with undetectable viremia, additional tests were performed: enzyme-linked immunosorbent assay HIV testing and testing for ART.ResultsIn Russia, 16% (58/360) had undetectable viremia; 3% (9/360) re-tested HIV-seronegative and 4% (13/360) tested positive for ART. In Uganda 11% (55/482) had undetectable viremia; 5% (26/482) re-tested HIV-seronegative, while

ObjectiveTo describe the frequency of being partnered and having an HIV-negative partner, and whether this differed by gender, among a cohort of persons living with HIV (PLWH) who have ever injected drugs; to describe awareness of HIV pre-exposure prophylaxis (PrEP) and perceived partner interest in PrEP.SettingSecondary analyses of an observational cohort study of PLWH who have ever injected drugs in St. Petersburg, Russia.MethodsPrimary outcomes were 1) being partnered and 2) being in a serodiscordant partnership. The main independent variable was gender. Multivariable GEE logistic regression models were fit for binary outcomes, adjusted for age, income, education, and recent opioid use. Descriptive analyses were performed for partners' HIV status, substance use, sex risk behaviors, and awareness of PrEP for a subset of participants.ResultsAt baseline, 50% (147/296) reported being in a partnership, and of those, 35% were in a serodiscordant partnership. After adjustment, women had significantly higher odds of being partnered compared to men (aOR = 3.12; 95% CI: 1.77, 5.51), but there were no significant gender differences in the odds of being in a serodiscordant partnership (aOR = 0.58; 95% CI: 0.27, 1.24). Among a sub-sample of participants queried (n = 56), 25% were aware of PrEP for prevention of sexual HIV transmission and 14% for prevention of injection-related transmission.ConclusionAlthough half of our sample were partnered and one third of these partnerships were serodiscordant, PrEP awareness was low. Substantial opportunities for HIV prevention exist among PLWH who have ever injected drugs in Russia and their HIV-negative partners. Given the high proportion of HIV-negative partners among this ART-naïve sample, efforts to address the associated inherent risks, such as couples-based interventions, are needed to increase condom use, PrEP awareness, or uptake of other HIV-prevention modalities (e.g., ART for the HIV-positive partner).

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.

In HIV-infected drinkers, alcohol types more likely to cause inflammation could plausibly increase the risk of HIV disease progression. We therefore assessed the association between alcohol type and plasma HIV RNA level (HIV viral load) among HIV-infected drinkers not on antiretroviral therapy (ART) in Russia and Uganda. We analyzed the data of participants from cohorts in Russia and Uganda and assessed their HIV viral load at enrollment by the alcohol type predominantly consumed. We defined predominant alcohol type as the alcohol type contributing >50% of total alcohol consumption in the 1 month (Russia) or 3 months (Uganda) prior to enrollment. Using multiple linear regression, we compared log10 HIV viral load by predominant alcohol type, controlling for age, gender, socioeconomic status, total number of standard drinks, frequency of drinking ≥6 drinks/occasion, and in Russia, history of injection drug use. Most participants (99.2% of 261 in Russia and 98.9% of 352 in Uganda) predominantly drank one alcohol type. In Russia, we did not find evidence for differences in viral load levels between drinkers of fortified wine (n = 5) or hard liquor (n = 49), compared to drinkers of beer/low-ethanol-content cocktails (n = 163); however, wine/high-ethanol-content cocktail drinkers (n = 42) had higher mean log10 viral load than beer/low-ethanol-content cocktail drinkers (β = 0.38, 95% CI 0.07-0.69; p = 0.02). In Uganda, we did not find evidence for differences in viral load levels between drinkers of locally-brewed beer (n = 41), commercially-distilled spirits (n = 38), or locally-distilled spirits (n = 43), compared to drinkers of commercially-made beer (n = 218); however, wine drinkers (n = 8) had lower mean log10 HIV viral load (β = -0.65, 95% CI -1.36 to 0.07, p = 0.08), although this did not reach statistical significance. Among HIV-infected drinkers not yet on ART in Russia and Uganda, we observed an association between the alcohol type predominantly consumed and the HIV viral load level in the Russia sample. These exploratory results suggest that, in addition to total number of drinks and drinking patterns, alcohol type might be a dimension of alcohol use that merits examination in studies of HIV and alcohol related outcomes.

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.

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.