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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 90days 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.

Aims: This study aimed to analyze the association between any past-month cannabis use and advanced liver fibrosis. Background: Cannabinoid receptors play a role in acute and chronic liver injury, but human studies addressing the impact of cannabis use on liver fibrosis have shown mixed results. Objectives: The objective of this study was to explore and estimate the association between pastmonth cannabis use and advanced liver fibrosis (ALF) in a cohort of Russian HIV-positive individuals with heavy alcohol use and a high prevalence of hepatitis C virus (HCV) coinfection. Methods: Baseline data were analyzed from participants of the ZINC study, a trial that enrolled HIV-positive Russian patients without prior antiretroviral therapy. Cannabis use during the prior month was assessed at study entry. ALF was defined as FIB-4>3.25 and APRI>1.5. Transient elastography was used to detect advanced liver fibrosis among participants with FIB-4 values in the intermediate range (between 1.45 and 3.25). Results: Participants (n=248) were mostly male (72.6%), young (median age of 33.9 years), infected with HCV (87.9%), and did not have advanced immunosuppression (median CD4 count 465). Cannabis use was uncommon (12.4%), and the prevalence of advanced liver disease was 21.7%. The prevalence of ALF was similar among those who used cannabis compared to those who did not (25.8% vs. 21.7%). We were unable to detect an association between cannabis use and ALF (adjusted odds ratio: 1.28, 95% confidence interval: 0.53-3.12, p=0.59) in logistic regression models adjusting for age, sex, heavy drinking, BMI, and CD4 cell count. Conclusion: In this exploratory study among HIV-positive heavy drinking Russians, we did not detect an association between recent cannabis use and ALF. Larger scale studies, including more participants with cannabis use, are needed to examine this relationship further.

Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions.To compare the effects on drinking and smoking of nicotinic acetylcholine receptor partial agonists varenicline and cytisine with those of NRT.This 4-group randomized, double-blinded, placebo-controlled clinical trial was conducted from July 2017 to December 2020 in St Petersburg, Russia. Included participants were 400 individuals with HIV who engaged in risky drinking (≥5 prior-month heavy-drinking days [HDDs]) and daily smoking; they were followed up for 12 months after enrollment. Data were analyzed from May 2021 through June 2022.Participants received alcohol and tobacco counseling, 1 active medication, and 1 placebo in 1 of 4 groups: active varenicline and placebo NRT (group 1), placebo varenicline and active NRT (group 2), active cytisine and placebo NRT (group 3), or placebo cytisine and active NRT (group 4).The primary outcome was number of prior-month HDDs at 3 months. Secondary outcomes included biochemically validated abstinence from alcohol at 3 months and smoking at 6 months.Among 400 participants (263 [65.8%] men; mean [SD] age, 39 [6] years), 97 individuals (24.3%) used opioids and 156 individuals (39.1%) had depressive symptoms. These individuals had a mean (SD) CD4 count of 391 (257) cells/mm3, smoked a mean (SD) of 21 [8] cigarettes/d, and reported a mean (SD) of 9.3 (5.8) HDDs in the prior 30 days. At 3 months, the mean (SD) number of HDDs was decreased vs baseline across all groups (group 1: 2.0 [3.8] HDDs vs. 9.5 [6.1] HDDs; group 2: 2.1 [4.3] HDDs vs 9.3 [5.7] HDDs; group 3: 1.5 [3.3] HDDs vs 8.9 [5.0] HDDs; group 4: 2.4 [5.2] HDDs vs 9.6 [6.3] HDDs). There were no significant differences at 3 months between groups in mean (SD) HDDs, including group 1 vs 2 (incident rate ratio [IRR], 0.94; 95% CI, 0.49-1.79), 3 vs 4 (IRR, 0.60; 95% CI, 0.30-1.18), and 1 vs 3 (IRR, 1.29; 95% CI, 0.65-2.55). There were no significant differences at 6 months between groups in smoking abstinence, including group 1 vs 2 (15 of 100 individuals [15.0%] vs 17 of 99 individuals [17.2%]; odds ratio [OR],0.89; 95% CI, 0.38-2.08), 3 vs 4 (19 of 100 individuals [19.0%] vs 19 of 101 individuals [18.8%]; OR, 1.00; 95% CI, 0.46-2.17), and 1 vs 3 (OR, 0.79; 95% CI, 0.35-1.78). Post hoc analyses suggested lower mean (SD) HDDs (eg, at 3 months: 0.7 [1.8] HDDs vs 2.3 [4.6] HDDs) and higher alcohol abstinence (eg, at 3 months: 30 of 85 individuals [35.3%] vs 54 of 315 individuals [17.1%]) among those who quit vs continued smoking.This study found that among individuals with HIV who engaged in risky drinking and smoking, varenicline and cytisine were not more efficacious than NRT to treat risky drinking and smoking but that behavior change rates were high in all groups.ClinicalTrials.gov Identifier: NCT02797587.

This study describes the self-reported prevalence of hepatitis C virus (HCV) coinfection and the HCV care continuum among persons enrolled in the St PETER HIV Study, a randomized controlled trial of medications for smoking and alcohol cessation in HIV-positive heavy drinkers and smokers in St. Petersburg, Russia. Baseline health questionnaire data were used to calculate proportions and 95% confidence intervals for self-reported steps along the HCV continuum of care. The cohort included 399 HIV-positive persons, of whom 387 (97.0% [95% CI: 95.3-98.7%]) reported a prior HCV test and 315 (78.9% [95% CI: 74.9-82.9%]) reported a prior diagnosis of HCV. Among those reporting a diagnosis of HCV, 43 (13.7% [95% CI: 9.9-17.4%]) had received treatment for HCV, and 31 (9.8% [95% CI: 6.6-13.1%]) had been cured. Despite frequent HCV testing in this HIV-positive Russian cohort, the proportion reporting prior effective HCV treatment was strikingly low. Increased efforts are needed to scale-up HCV treatment among HIV-positive Russians in St. Petersburg.

Pain is common and associated with substance use among persons with HIV (PWH), yet limited management strategies exist. We assessed the feasibility, tolerability, and safety of low-dose naltrexone and standard dose nalmefene to treat chronic pain among PWH with past-year heavy alcohol use in a randomized, double-blinded, 2-arm study (planned enrollment 8 per arm). Participants were recruited in St. Petersburg, Russia between May and October 2018 and randomized to receive either nalmefene (16 mg) or low-dose naltrexone (4.5mg) for 8 weeks. The primary outcome was tolerability of medication at 8 weeks. Study visits included assessments of pain interference and severity, as well as cold-pressor testing. All participants in the nalmefene arm (N=3) discontinued the study medication early due to side effects; nalmefene was subsequently deemed intolerable and this arm was terminated. The mean tolerability score at 8-weeks in the low-dose naltrexone arm was 90.7 (SD 22.44), median was 100 (IQR 95– 100), and median cold pain tolerance was approximately 10 seconds higher at the end of the 8 weeks. Low-dose naltrexone was well-tolerated, but nalmefene was not, in this sample. Further research is warranted to explore low-dose naltrexone’s potential efficacy as a non-addictive treatment for pain in this population.

BACKGROUND AND OBJECTIVES Previous findings on the association between hazardous drinking and HIV-risk behavior have been equivocal, varying by population and individual difference factors. This study examined associations between hazardous drinking, impulsivity, and HIV-risk behaviors among HIV-positive Russian patients with a history of injection drug use (IDU), not on antiretroviral therapy. METHODS Negative binomial regression analyses of data from a randomized controlled trial were performed (N = 241). Main independent variables were the Alcohol Use Disorders Identification Test and the Barratt Impulsiveness Scale. Outcomes were number of condomless sexual episodes (CSE; primary), number of sexual partners, and needle-sharing frequency (secondary). RESULTS Hazardous drinking was positively associated with the frequency of CSE (adjusted incidence rate ratio [aIRR] = 2.16, 95% confidence interval [CI], 1.98-2.36). Moderate (aIRR = 0.51, 95% CI, 0.46-0.56) and high (aIRR = 0.66, 95% CI, 0.60-0.73) impulsivity were associated with fewer CSE compared with low impulsivity. Hazardous drinking (aIRR = 0.64, 95% CI, 0.52-0.79) and impulsivity (aIRR = 0.95, 95% CI, 0.94-0.96) were both associated with fewer sexual partners. Hazardous drinking and impulsivity were each associated with increased needle sharing. The association between hazardous drinking and number of needle-shares was strongest at higher impulsivity levels. CONCLUSION AND SCIENTIFIC SIGNIFICANCE Hazardous drinking may be a risk factor for CSE among HIV-positive Russian patients and may influence needle sharing. Findings contribute to our understanding of the interactive associations between hazardous drinking and impulsivity with sexual risk behaviors and needle sharing among HIV-positive Russian patients with a history of IDU. (Am J Addict 2020;00:00-00).

Access to HIV services for HIV-positive patients in addiction care is challenging in Russia, because both care systems are organized independently from each other. Strengths-based case management is an effective strategy to connect people with HIV (PHIV) to HIV care. This mixed-methods study’s objective was to investigate implementation of a case management intervention in St. Petersburg, Russia, designed to connect PHIV who inject drugs to HIV care. We analyzed survey data from 118 HIV-positive patients in addiction care and conducted six focus groups (n=38). Quantitative analyses of fidelity and satisfaction outcomes and qualitative text analysis assessed intervention implementation. Participants who linked to HIV services embraced empowerment and motivation resulting from case management as supporting self-efficacy and linkage to services. Among participants who did not link to care, drug use impeded their care engagement. Main levers to implementation were empowerment to cope with challenges of a fragmented health system and persistent stigma. Those who connected to HIV services credited case managers for facilitating linkage; those who did not link attributed it to personal issues. Implementation of case management for HIV care in Russia should focus on effective substance use treatment and empowerment, motivation and support in addressing personal and system factors.

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

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.

OBJECTIVE: We 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. METHOD: We 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. RESULTS: In 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 < .01). These findings were invariant to adjustment for covariates. CONCLUSIONS: We did not detect associations between gender and heavy drinking in cohorts of PLWH in Russia or Boston, suggesting that heavy drinking may be as common in women living with HIV as in men living with HIV in these locations. Although these cohorts were enriched with heavy drinking participants, which limits broad extrapolation to PLWH in those settings, nonetheless the findings are concerning given the significant morbidity associated with alcohol use among PLWH and women in particular.

Objectives In the late 1990s, when the current Russian opioid epidemic began, illicit opioids used in Russia consisted almost exclusively of heroin. The type of opioids used has evolved in the early 21st Century. The objective of this study was to describe the evolution of illicit opioid use among people living with HIV (PLWH) reporting recent opioid use in St Petersburg, Russia. Methods We examined baseline data from four research studies conducted in the period 2004-2015 that included PLWH who used opioids [Partnership to Reduce the Epidemic Via Engagement in Narcology Treatment (PREVENT; 2004-2005; n = 17), HIV Evolution in Russia-Mitigating Infection Transmission and Alcoholism in a Growing Epidemic (HERMITAGE; 2007-2010; n = 281), Linking Infectious and Narcology Care (LINC; 2013-2014; n = 119) and Russia Alcohol Research Collaboration on HIV/AIDS (Russia ARCH; 2012-2015; n = 121)] and reported recent use of heroin and other opioids. Results Although these studies spanned more than a decade, the participants represented similar birth cohorts; the mean age was 24.5 years in 2004 and 33.3 years in 2014. The use of opioid types, however, evolved across cohorts, with the use of any illicit drug other than heroin increasing from 6% [95% confidence interval (CI) 000.2, 29%] in PREVENT (2004-2005) to 30% (95% CI 25, 36%) in HERMITAGE (2007-2010) to 70% (95% CI 61, 78%) in LINC (2013-2014) to 77% (95% CI 68, 84%) in ARCH (2012-2015). Any heroin use consistently decreased over the 10-year period in the cohorts, from 100% (95% CI 80, 100%) in 2004-2005 to 54% (95% CI 44, 63%) in 2012-2015. Conclusions Among PLWH who use opioids in St Petersburg, Russia, illicit use of opioids other than heroin appears to be more common than heroin use.

BackgroundComorbid mental disorders in patients with tuberculosis (TB) may exacerbate TB treatment outcomes. We systematically reviewed current evidence on the association between mental disorders and TB outcomes.MethodsWe searched eight databases for studies published from 1990-2018 that compared TB treatment outcomes among patients with and without mental disorders. We excluded studies that did not systematically assess mental disorders and studies limited to substance use. We extracted study and patient characteristics and effect measures and performed a meta-analysis using random-effects models to calculate summary odds ratios (OR) with 95% confidence intervals (CI).FindingsOf 7,687 studies identified, ten were included in the systematic review and nine in the meta-analysis. Measurement of mental disorders and TB outcomes were heterogeneous across studies. The pooled association between mental disorders and any poor outcome, loss to follow-up, and non-adherence were OR 2.13 (95% CI: 0.85-5.37), 1.90 (0.33-10.91), and 1.60 (0.81-3.02), respectively. High statistical heterogeneity was present.InterpretationOur review suggests that mental disorders in TB patients increase the risk of poor TB outcomes, but pooled estimates were imprecise due to small number of eligible studies. Integration of psychological and TB services might improve TB outcomes and progress towards TB elimination.

Background The Zinc for INflammation and Chronic disease in HIV (ZINC) trial randomized person who live with HIV (PLWH) who engage in heavy drinking to either daily zinc supplementation or placebo. The primary outcome was change in the Veterans Aging Cohort Study (VACS) index, a predictor of mortality, between baseline and 18 months. Because adherence and follow-up were suboptimal, the intention-to-treat analysis, which was not statistically significant, may have underestimated the effect of the zinc supplementation. Objective We estimated the per-protocol effect of zinc versus placebo in the ZINC trial (i.e., the effect that would have been observed if all participants had had high adherence and none was lost to follow-up). Methods Adherence was measured as the self-reported percentage of pills taken in the previous 6 weeks and assessed at all post-baseline visits. We used inverse probability weighting to estimate and compare the change in the VACS index at 18 months in the zinc and placebo groups, had all the trial participants had high adherence (i.e., cumulative adherence ≥80% at 18 months). To examine trends by level of adherence, we rerun the analyses using thresholds for high adherence of 70% and 90% of average self-reported pill coverage. Results The estimated (95% confidence interval) change in the VACS index was − 2.16 (− 8.07, 3.59) and 5.84 (0.73, 11.80) under high adherence and no loss to follow-up in the zinc and placebo groups, respectively. The per-protocol effect estimate of the mean difference in the change between the zinc and placebo groups was − 8.01 (− 16.42, 0.01), somewhat larger than the intention-to-treat effect difference in change (− 4.68 (− 9.62, 0.25)), but it was still not statistically significant. The mean difference in the change between individuals in the zinc and placebo groups was − 4.07 (− 11.5, 2.75) and −12.34 (− 20.14, −4.14) for high adherence defined as 70% and 90% of pill coverage, respectively. Conclusions Overall, high adherence to zinc was associated with a lower VACS score, but confidence intervals were wide and crossed 0. Further studies with a larger sample size are needed to quantify the benefits of zinc supplementation in this population. Trial registration ClinicalTrials.gov NCT01934803. Registered on August 30, 2013

Author(s): Wagman, Jennifer A; Wynn, Adriane; Matsuzaki, Mika; Gnatienko, Natalia; Metsch, Lisa R; Del Rio, Carlos; Feaster, Daniel J; Nance, Robin M; Whitney, Bridget M; Delaney, Joseph AC; Kahana, Shoshana Y; Crane, Heidi M; Chandler, Redonna K; Elliott, Jennifer C; Altice, Frederick; Lucas, Gregory M; Mehta, Shruti H; Hirsch-Moverman, Yael; El-Sadr, Wafaa M; Vu, Quan; Nguyen Thanh, Binh; Springer, Sandra A; Tsui, Judith I; Samet, Jeffrey H | Abstract: ObjectivesIn high-income countries, hazardous alcohol use is associated with reduced receipt of antiretroviral therapy (ART) and viral suppression among people living with HIV (PLHIV) who inject drugs. These associations are less understood in lower middle-income countries (LMIC) and upper middle-income countries.DesignWe examined associations between hazardous alcohol use, ART receipt, and viral suppression among PLHIV who reported current or former injection drug use. Participants were from nine studies in the United States (high-income country), India (LMIC), Russia (upper middle-income country), and Vietnam (LMIC).MethodsHazardous alcohol use was measured via Alcohol Use Disorders Identification Test. Outcomes were HIV viral suppression (viral load of l1000 RNA copies/ml) and self-reported ART receipt. Logistic regression assessed associations between hazardous alcohol use and both outcome variables, controlling for age and sex, among participants with current and former injection drug use.ResultsAmong 2790 participants, 16% were women, mean age was 37.1 ± 9.5 years. Mean Alcohol Use Disorders Identification Test scores were 4.6 ± 8.1 (women) and 6.2 ± 8.3 (men); 42% reported ART receipt; 40% had viral suppression. Hazardous alcohol use was significantly associated with reduced ART receipt in India (adjusted odds ratio = 0.59, 95% confidence interval: 0.45-0.77, P l 0.001); and lower rates of viral suppression in Vietnam (adjusted odds ratio = 0.51, 95% confidence interval: 0.31-0.82, P = 0.006).ConclusionAssociations between hazardous alcohol use, ART receipt, and viral suppression varied across settings and were strongest in LMICs. Addressing hazardous alcohol use holds promise for improving HIV continuum of care outcomes among PLHIV who inject drugs. Specific impact and intervention needs may differ by setting.

BACKGROUND: Russia continues to have an uncontrolled HIV epidemic and its per capita alcohol consumption is among the highest in the world. Alcohol use among HIV-positive individuals is common and is associated with worse clinical outcomes. Alcohol use and HIV each lead to microbial translocation, which in turn results in inflammation. Zinc supplementation holds potential for lowering levels of biomarkers of inflammation, possibly as a consequence of its impact on intestinal permeability. This paper describes the protocol of a double-blinded randomized placebo-controlled trial of zinc supplementation in St. Petersburg, Russia. METHODS: Participants (n=254) were recruited between October 2013 and June 2015 from HIV and addiction clinical care sites, and non-clinical sites in St. Petersburg, Russia. Participants were randomly assigned, to receive either zinc (15 mg for men; 12 mg for women) or placebo, daily for 18 months. The following outcomes were assessed at 6, 12, and 18 months: 1) mortality risk (primary outcome at 18 months); 2) HIV disease progression; 3) cardiovascular risk; and 4) microbial translocation and inflammation. Adherence was assessed using direct (riboflavin) and indirect (pill count, self-report) measures. CONCLUSION: Given the limited effectiveness of current interventions to reduce alcohol use, zinc supplementation merits testing as a simple, low cost intervention to mitigate the consequences of alcohol use in HIV-positive persons despite ongoing drinking. TRIAL REGISTRATION: NCT01934803

Limited research examines family planning for HIV-infected women with a history of injection drug use. We describe modern contraceptive use and its association with heavy drinking and recent injection for HIV-infected females in St. Petersburg, Russia (N = 49): 22.4% (n = 11) used traditional methods and 30.6% (n = 15) reported modern contraceptive use, which consisted primarily of condoms (26.5%, n = 13). Over 63% (n = 31) had an abortion. Observed associations for heavy alcohol use (AOR = 2.36, CI = 0.53, 12.41) and recent injection drug use (AOR = 2.88, CI = 0.60, 16.92) were clinically notable, but not statistically significant. Prioritizing family planning for HIV-infected women with a history of substance use is urgently needed.

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.

Reproducible outcomes in clinical trials depend on adherence to study protocol. Short message service (also known as text message) reminders have been shown to improve clinical trial adherence in the United States and elsewhere. However, due to systematic differences in mobile data plans, languages, and technology, these systems are not easily translated to international settings.To gauge technical capabilities for international projects, we developed SMSMessenger, an automated Android application that uses a US server to send medication reminders to participants in a clinical trial in St. Petersburg, Russia (Zinc for HIV disease among alcohol users-a randomized controlled trial in the Russia Alcohol Research Collaboration on HIV/AIDS cohort). The application is downloaded once onto an Android study phone. When it is time for the text message reminders to be sent, study personnel access the application on a local phone, which in turn accesses the existing clinical trial database hosted on a US web server. The application retrieves a list of participants with the following information: phone number, whether a message should be received at that time, and the appropriate text of the message. The application is capable of storing multiple outgoing messages. With a few clicks, text messages are sent to study participants who can reply directly to the message. Study staff can check the local phone for incoming messages. The SMSMessenger application uses an existing clinical trial database and is able to receive real-time updates. All communications between the application and server are encrypted, and phone numbers are stored in a secure database behind a firewall. No sensitive data are stored on the phone, as outgoing messages are sent through the application and not by messaging features on the phone itself. Messages are sent simultaneously to study participants, which reduces the burden on local study staff. Costs and setup are minimal. The only local requirements are an Android phone and data plan.The SMSMessenger technology could be modified to be applied anywhere in the world, in any language, script, or alphabet, and for many different purposes. The novel application of this existing low-cost technology can improve the usefulness of text messaging in advancing the goals of international clinical trials.

Objectives Among Russians living with HIV/AIDS who inject drugs, we examined the incidence of fatal and non-fatal overdoses following discharge from a narcology hospital and the associations with more advanced HIV infection. Design Prospective cohort study of data collected at baseline, 3 and 6 months from HIV-infected patients with a history of injection drug use who were not treated with anti-retroviral therapy. Participants were recruited between 2012–2014 from a narcology (addiction) hospital in St. Petersburg, Russia. Methods Fatal overdose was determined based on contact reports to study staff in the year after discharge. Non-fatal overdose was self-reported at the 3- and 6-month assessments. The main independent variable for HIV severity was CD4 cell count at the baseline interview ( 3 ≥200cells/mm 3 ). Secondary analyses assessed time since HIV diagnosis and treated with anti-retroviral treatment (ART) prior to enrolment as independent variables. We fit Cox proportional hazards models to assess whether HIV severity is associated with either fatal or non-fatal overdose. Results Among 349 narcology patients, 18 participants died from overdose within one year after discharge (8.7%, 95% CI 3.4–14.2 by Kaplan–Meier); an estimated 51% [95% CI 34–68%] reported at least one non-fatal overdose within 6 months of discharge. HIV severity, time since HIV diagnosis and ever ART were not significantly associated with either fatal or non-fatal overdose events. Conclusion Fatal and non-fatal overdose are common among Russians living with HIV/AIDS who inject drugs after narcology hospital discharge. Overdose prevention interventions are urgently warranted among Russian narcology patients with HIV infection.

BackgroundIf Russia is to achieve the UNAIDS 90-90-90 HIV targets, better approaches to engage, effectively treat, and retain patients in care are needed. This paper describes the protocol of a randomized controlled trial (RCT) testing the effectiveness of LINC-II, a strength-based case management program for HIV-positive people who inject drugs (PWID) to increase rates of HIV viral suppression, ART initiation, and opioid abstinence.MethodsThis RCT will enroll and randomize 240 participants, recruited from a narcology (addiction care) hospital in St. Petersburg, Russia. Participants are randomized to the intervention or control arms. Those in the intervention arm receive: (1) strengths-based HIV case management supporting coordinated care; (2) rapid ART initiation; and (3) pharmacotherapy for opioid use disorder. We will evaluate the intervention’s effectiveness compared to standard of care on the following outcomes: (1) undetectable HIV viral load at 12 months (primary); (2) initiation of ART within 28 days of randomization; (3) change in CD4 count from baseline to 12 months; (4) retention in HIV care (i.e., ≥ 1 visit to medical care in 2 consecutive 6 month periods); (5) undetectable HIV viral load at 6 months; and (6) past 30-day opioid abstinence (at 6 and at 12 months).DiscussionThis RCT will assess the LINC-II intervention in an urban Russian setting. If effective, it will offer a new approach for increasing the uptake of both HIV and opioid use disorder treatment and coordination of these modalities in standard Eastern European clinical settings.Trial registrationThis study was registered with ClinicalTrials.gov through the National Institutes of Health, NCT03290391. Registered 19 September 2017,https://clinicaltrials.gov/ct2/show/NCT03290391

Objective: To determine whether the Linking Infectious and Narcology Care strengths-based case management intervention was more effective than usual care for linking people who inject drugs (PWID) to HIV care and improving HIV outcomes. Design: Two-armed randomized controlled trial. Setting: Participants recruited from a narcology hospital in St. Petersburg, Russia. Participants: A total of 349 HIV-positive PWID not on antiretroviral therapy (ART). Intervention: Strengths-based case management over 6 months. Main outcome measures: Primary outcomes were linkage to HIV care and improved CD4+ cell count. We performed adjusted logistic and linear regression analyses controlling for past HIV care using the intention-to-treat approach. Results: Participants (N = 349) had the following baseline characteristics: 73% male, 12% any past ART use, and median values of 34.0 years of age and CD4+ cell count 311 cells/μl. Within 6 months of enrollment 51% of the intervention group and 31% of controls linked to HIV care (adjusted odds ratio 2.34; 95% confidence interval: 1.49–3.67; P

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.

Importance Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. Objective To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. Design, Setting, and Participants This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy–naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. Intervention Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo. Main Outcomes and Measures The primary outcome was mortality risk measured as a change in Veterans Aging Cohort Study (VACS) Index score between baseline and 18 months. The VACS Index scores range from 0 to 164, with higher scores indicating higher mortality risk. Secondary outcomes were change in CD4 cell count between baseline and 18 months, the assessment of cardiovascular disease risk (Reynolds Risk Score, which ranges from 0% to 100%, with higher scores indicating higher risk), and changes in inflammatory or microbial translocation biomarkers at 18 months. Adjusted linear regression analyses were performed. Results A total of 254 participants (184 men [72%]; mean [SD] age, 34 [6] years) were enrolled in the trial; 126 were randomized to receive zinc, and 128 were randomized to receive placebo. Participants had high CD4 cell counts (mean [SD], 521 [292] cells/mm3), and 188 (74%) reported heavy drinking in the past week. In the main analyses, zinc supplementation did not affect changes in the VACS Index score at 18 months (change for zinc, mean [SD], 0.49 [14.6]; median [interquartile range], 0.0 [−7.0 to 6.0]; change for placebo, mean [SD], 5.5 [17.2]; median [interquartile range], 6.0 [−6.0 to 14.0]; adjusted mean difference [AMD], −4.68; 95% CI, −9.62 to 0.25;P = .06) or any secondary outcomes, including change in CD4 cell count (AMD, 41.8 cells/mm3; 95% CI, −20.3 to 103.8 cells/mm3;P = .19), Reynolds Risk Score (AMD, −0.014; 95% CI, −0.167 to 0.139;P = .85), interleukin-6 level (AMD, −0.13 pg/mL; 95% CI, −0.38 to 0.11 pg/mL;P = .30), dimerized plasmin fragment D level (AMD, −0.21 μg/mL fibrinogen equivalent units; 95% CI, −0.48 to 0.07 μg/mL fibrinogen equivalent units;P = .14), soluble CD14 level (AMD, −38.01 ng/mL; 95% CI, −166.90 to 90.88 ng/mL;P = .56), intestinal fatty acid binding protein level (AMD, 0.08 pg/mL; 95% CI, −0.07 to 0.22 pg/mL;P = .32), and lipopolysaccharide binding protein level (AMD, −0.09 ng/mL; 95% CI, −0.23 to 0.06 ng/mL;P = .24). In the per-protocol analyses, zinc supplementation statistically significantly affected changes in the VACS Index score at 18 months (AMD, −7.49; 95% CI, −13.74 to −1.23;P = .02); however, the adherence rate to zinc supplementation was 51%. Conclusions and Relevance Zinc supplementation did not reduce mortality risk, CD4 cell counts, cardiovascular disease risk, and levels of inflammation or microbial translocation in people with heavy alcohol use who are living with HIV/AIDS. Zinc supplementation did not change the VACS Index score but may have been limited by low adherence. Trial Registration ClinicalTrials.gov Identifier:NCT01934803

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.

Research 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.Examine 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.Russian 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.In 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 1% (4/482) tested positive for ART.In both RussiaUganda, undetectable viremia was much higher than would be expected for an HIV-infected ART-naïve cohort. Misclassification of study participants was due to misdiagnosis of HIV with rapid diagnostic testing and inaccurate accounting of ART use. Confirmatory HIV testing could improve accuracy of participants meeting entry criteria for HIV infection as might increased scrutiny of medication use in an ART-naïve cohort.

Introduction Globally, persons with HIV infection, depression and substance use disorders have a higher smoking prevalence and smoke more heavily than other populations. These associations have not been explored among Russian smokers with HIV infection and substance use disorders. The purpose of this study was to examine the relationship between the presence of depressive symptoms and smoking outcomes in an HIV-positive cohort of Russian smokers with a history of substance use disorders (alcohol and/or drug use disorders). Methods We performed a cross-sectional secondary data analysis of a cohort of HIV-positive regular smokers with a history of substance use disorders recruited in St. Petersburg, Russia in 2012–2015. The primary outcome was heavy smoking, defined as smoking > 20 cigarettes per day. Nicotine dependence (moderate-very high) was a secondary outcome. The main independent variable was a high level of depressive symptoms in the past 7 days (defined as CES-D > = 24). We used multivariable logistic regression to examine associations between depressive symptoms and the outcomes, controlling for age, sex, education, income, running out of money for housing/food, injection drug use, and alcohol use measured by the AUDIT. Results Among 309 regular smokers, 79 participants (25.6%) had high levels of depressive symptoms, and 65 participants (21.0%) were heavy smokers. High levels of depressive symptoms were not significantly associated with heavy smoking (adjusted odds ratio [aOR] 1.50, 95% CI 0.78–2.89) or with moderate-very high levels of nicotine dependence (aOR 1.35, 95% CI 0.75–2.41). Conclusions This study did not detect an association between depressive symptoms and smoking outcomes among HIV-positive regular smokers in Russia.

Background Engaging people who drink alcohol or inject drugs in HIV care can be challenging, particularly in Eastern Europe. Healthcare facilities in Russia are organized by specialty; therefore linking patients from addiction care to HIV hospitals has been difficult. The HIV care cascade outlines stages of HIV care (e.g., linkage to care, prescribed antiretroviral therapy [ART], and achieving HIV viral suppression). We hypothesized that unhealthy alcohol use, injection drug use, and opioid craving are associated with unfavorable HIV care cascade outcomes. Methods We analyzed data from a cohort (n = 249) of HIV-positive Russians who have been in addiction hospital treatment in the past year and had a lifetime history of injection drug use (IDU). We evaluated the association between unhealthy alcohol use (AUDIT score > 7 [both hazardous drinking and dependence]), past-month injection drug use (IDU), and opioid craving (visual analogue scale from 1 to 100) with HIV care cascade outcomes. The primary outcome was linkage to HIV care within 12 months. Other outcomes were prescription of ART (secondary) and achievement of undetectable HIV viral load (HVL

The link between HIV stigma with substance use is understudied. We characterized individuals with high HIV stigma and examined whether HIV stigma contributes to substance use among HIV-positive Russians reporting risky alcohol use. We analyzed data from HERMITAGE, a randomized controlled trial of 700 people living with HIV/AIDS (PLWHA) with past 6-month risky sex and risky alcohol use in St. Petersburg, Russia (2007-2011). Participants who were female and reported depressive symptoms and lower social support were more likely to endorse high HIV stigma (all p's

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 128days (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.

The human immunodeficiency virus (HIV) epidemic in Russia, driven by injection drug use, has seen a steady rise in the past two decades. Hepatitis C virus (HCV) infection is highly prevalent in people who inject drugs (PWID). The study aimed to describe the current frequency of HCV testing and treatment among HIV-infected PWID in St. Petersburg, Russia. This study examined baseline data from the “Linking Infectious and Narcology Care” (LINC) and “Russia Alcohol Research Collaboration on HIV/AIDS” (Russia ARCH) studies. Participants included in this analysis were HIV-infected with a history of injection drug use. Descriptive statistics were performed to assess frequency of HCV testing and treatment. Participants (n = 349 [LINC], 207 [Russia ARCH]) had a mean age of 33.8 years (IQR: 31–37) in LINC and 33.0 (IQR: 30–36) in Russia ARCH; 26.6 % (LINC) and 29.0 % (Russia ARCH) were female; 100 % were Caucasian. Nearly all participants had been tested for HCV (98.9 % in LINC, 97.1 % in Russia ARCH). Almost all reported being diagnosed HCV positive (98.9 % in LINC, 97.1 % in Russia ARCH). Only 2.3 % of LINC and 5.0 % of Russia ARCH participants reported ever receiving HCV treatment. Among these cohorts of HIV-infected PWID in St. Petersburg, Russia, as of 2015 nearly all reported being tested for HCV and testing positive, while only 3.3 % received any HCV treatment. In this new era of effective HCV pharmacotherapy, an enormous chasm in the HCV treatment cascade in Russia exists providing substantial opportunities for curing HCV in HIV-infected Russians with a history of injection drug use. The studies described were registered with ClinicalTrials.gov through the National Institutes of Health: Linking Infectious and Narcology Care in Russia (LINC) - NCT01612455 , registered 1 June 2012, first participant enrolled 3 July 2012; Alcohol’s Impact on Inflammatory Markers in HIV Disease - Russia ARCH Cohort - NCT01614626 , registered 25 May 2012, first participant enrolled 15 November 2012.

BackgroundBiomarkers of monocyte activation (soluble CD14 [sCD14]), inflammation (interleukin-6 [IL-6]), and altered coagulation (D-dimer) are associated with increased mortality risk in people with HIV. The objective of the Russia Alcohol Research Collaboration on HIV/AIDS (ARCH) study was to evaluate the association between heavy alcohol use and inflammatory biomarkers over time.MethodsThe study sought antiretroviral therapy naive participants with HIV (n = 350) and assessed them at baseline, 12 and 24 months. Linear mixed effects models were used to determine whether heavy drinking (self-report augmented by phosphatidylethanol [PEth], an alcohol biomarker) was longitudinally associated with IL-6, sCD14 and D-dimer adjusting for potential confounders (e.g., demographics, HIV factors, comorbid conditions).ResultsParticipants' baseline characteristics were as follows: 71% male; mean age of 34 years; 87% self-reported hepatitis C; and 86% current smokers. Mean log10 (HIV RNA) was 4.3 copies/mL. Heavy alcohol use, based on National Institute of Alcohol Abuse and Alcoholism risky drinking criteria and PEth (versus non-heavy alcohol use) was associated with higher sCD14 (adjusted mean difference 125 ng/mL [95% CI: 42, 209]), IL-6 (ratio of means 1.35 [95% CI: 1.17, 1.55] pg/mL), and D-dimer (ratio of means 1.20 [95% CI: 1.06, 1.37] ug/mL) across the two-year follow-up.ConclusionAmong HIV+ adults, current heavy alcohol use is associated with higher sCD14, IL-6 and D-dimer over time. Since these biomarkers are associated with mortality, interventions to mitigate effects of heavy drinking on these immune processes merit consideration.

We analyzed baseline data from an observational cohort of HIV-infected ART-naive patients in St. Petersburg, Russia to explore whether pain was associated with HIV risk behaviors. The primary outcomes were (1) unprotected vaginal or anal sex in the past 90 days and (2) sharing of needles or equipment in the past month. Secondary outcomes included: use of alcohol prior to sex, current injection drug use, number of unprotected sex and sharing episodes, and days injected in the past month. The main independent variable was any past week pain. Multivariable regression models were fit for outcomes. After adjustment, the association with unprotected sex was of borderline significance (AOR = 2.06; 95 % CI 0.98–4.36, p = 0.058); there was no significant association between any past week pain and sharing of needles/equipment (AOR = 1.52; 95 % CI 0.65–3.59, p = 0.33). Participants with pain had higher odds of reporting alcohol use prior to sex (AOR = 2.42; 95 % CI 1.10–5.28, p = 0.03).

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 12months 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.