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Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03278886.

Although there is evidence of individual associations between depressive symptoms and hazardous alcohol use with suboptimal antiretroviral therapy (ART) adherence among people living with HIV (PLWH), few studies have established how the two risk factors may interact to predict viral suppression. We conducted secondary data analyses with two cohorts of Ugandan PLWH ( N = 657) to investigate the hypothesized interaction between depressive symptoms (Center for Epidemiological Studies Depression Scale) and hazardous alcohol use (Alcohol Use Disorder Identification Test -Consumption and/or Phosphatidylethanol biomarker) prior to ART initiation with viral suppression (<550 copies/ml). We were unable to detect an interaction between depressive symptoms and hazardous alcohol use prior to ART initiation with viral suppression in the first two years ( M = 19.9 months) after ART initiation ( p = 0.75). There was also no evidence of a main effect association for depressive symptoms (Adjusted Odds Ratio [AOR] = 0.88, 95% Confidence Interval [CI]: 0.50, 1.55) or hazardous alcohol use (AOR = 1.37, 95% CI: 0.80, 2.33). PLWH with depressive symptoms and/or hazardous alcohol use appear to exhibit similar levels of viral suppression as others in care; further work is needed to determine effects on HIV testing and treatment engagement.

We describe HIV providers' opioid prescribing practices and assess whether belief that chronic opioid therapy (COT) keeps people living with HIV (PLWH) engaged in care is associated with differences in these practices among providers from two HIV clinics. We conducted logistic regression to evaluate the association between the belief that COT keeps PLWH engaged in care and at least one component of guideline-recommended care (i.e., urine drug tests, treatment agreements, and/or prescription monitoring program use). The sample included 41 providers with a median age of 42 years, 63% female, 37% non-white. Routine adherence to guideline-recommended practices was: 34% urine drug tests, 27% treatment agreements, and 17% prescription monitoring program. Over half [54%] agreed that COT keeps PLWH engaged in care. There was no significant association between belief that COT keeps PLWH engaged in care and routinely providing any recommended COT care component (aOR 2.38; 95% CI 0.65-8.73). Most HIV providers do not routinely follow guidelines for opioid prescribing. We observed a positive association between belief that COT keeps PLWH engaged in care and following any guideline-recommended prescribing practices, although the result was not statistically significant. Interventions are needed to improve guideline-concordant care for COT by HIV providers.

Under-reporting of alcohol use by HIV-infected patients could adversely impact clinical care. This study examined factors associated with under-reporting of alcohol consumption by patients who denied alcohol use in clinical and research settings using an alcohol biomarker. We enrolled ART-naïve, HIV-infected adults at Mbarara Hospital HIV clinic in Uganda. We conducted baseline interviews on alcohol use, demographics, Spirituality and Religiosity Index (SRI), health and functional status; and tested for breath alcohol content and collected blood for phosphatidylethanol (PEth), a sensitive and specific biomarker of alcohol use. We determined PEth status among participants who denied alcohol consumption to clinic counselors (Group 1, n = 104), and those who denied alcohol use on their research interview (Group 2, n = 198). A positive PEth was defined as ≥8 ng/ml. Multiple logistic regression models were used to examine whether testing PEth-positive varied by demographics, literacy, spirituality, socially desirable reporting and physical health status. Results showed that, among the 104 participants in Group 1, 28.8% were PEth-positive. The odds of being PEth-positive were higher for those reporting prior unhealthy drinking (adjusted odds ratio (AOR): 4.7, 95% confidence interval (CI): 1.8, 12.5). No other factors were statistically significant. Among the 198 participants in Group 2, 13.1% were PEth-positive. The odds of being PEth-positive were higher for those reporting past unhealthy drinking (AOR: 4.6, 95% CI: 1.8, 12.2), the Catholics (AOR: 3.8, 95% CI: 1.3, 11.0) compared to Protestants and lower for the literate participants (AOR: 0.3, 95% CI: 0.1, 0.8). We concluded that under-reporting of alcohol use to HIV clinic staff was substantial, but it was lower in a research setting that conducted testing for breath alcohol and PEth. A report of past unhealthy drinking may highlight current alcohol use among deniers. Strategies to improve alcohol self-report are needed within HIV care settings in Uganda.

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

Studies document a significant association between victimization from intimate partner violence (IPV) and sexually transmitted infections (STIs) and HIV among substance using women in Russia and elsewhere, but no study has examined IPV perpetration and STI among Russian men or HIV-infected men in Eastern Europe. This study was designed to assess the association between lifetime history of IPV perpetration and STI (lifetime and current) among substance using HIV-infected men in Russia. Cross-sectional analyses were conducted with baseline data from 415 male participants enrolled in a randomized HIV intervention clinical trial [the HERMITAGE Study]. Participants were HIV-infected men reporting recent heavy alcohol use and unprotected sex in St. Petersburg, Russia. Baseline surveys assessed demographics, IPV perpetration, risk behaviors, and STI history. Current STI was assessed via blood testing for syphilis and urine testing for gonorrhea, Chlamydia and Trichomonas. Multiple logistic regression analyses were used to assess the association between history of IPV with lifetime and current STI. Participants were aged 20-57 years. Almost half of participants (46%) reported a history of IPV perpetration; 81% reported past 30-day binge alcohol use, and 43% reported past 30-day injection drug use. Past and current STI was 41% and 12%, respectively. Men reporting a history of IPV perpetration had significantly higher odds of reporting ever having an STI (AOR=1.6, 95% CI=1.1, 2.4) but lower odds of testing positive for a current STI (AOR=0.50, 95% CI=0.26, 0.96). These findings demonstrate that a history of male IPV perpetration is common in HIV-infected Russian men and associated with a history of STI. Programmatic work toward IPV prevention is needed in Russia and may be beneficial in mitigating STIs, but more research is needed to understand how and why the association between IPV and STI changes over time in this population.

The study aim was to assess whether hepatitis C virus (HCV) was associated with painful symptoms among patients with HIV. Using data from a prospective cohort of HIV-infected adults with alcohol problems, we assessed the effects of HCV on pain that interfered with daily living and painful symptoms (muscle/joint pain, headache and peripheral neuropathy). Exploratory analyses assessed whether depressive symptoms and inflammatory cytokines mediated the relationship between HCV and pain. HCV-infected participants (n = 200) had higher odds of pain that interfered with daily living over time (adjusted odds ratio [AOR] 1.43; 95% CI: 1.02-2.01; p = 0.04) compared to those not infected with HCV. HIV/HCV co-infected participants had higher odds of muscle or joint pain (AOR 1.45; 95% CI: 1.06-1.97; p = 0.02) and headache (AOR 1.57; 95% CI: 1.18-2.07; p<0.01). The association between HCV and peripheral neuropathy did not reach statistical significance (AOR 1.33; 95% CI: 0.96-1.85; p = 0.09). Depressive symptoms and inflammatory cytokines did not appear to mediate the relationship between HCV and pain. Adults with HIV who are also co-infected with HCV are more likely to experience pain that interfered with daily living, muscle or joint pain, and headaches compared to those not co-infected. Research is needed to explore the association between HCV infection and pain, and to determine whether HCV treatment is an effective intervention.

Unhealthy alcohol use (the spectrum of risky use through dependence) is common in HIV-infected persons, yet it can interfere with HIV medication adherence, may lower CD4 cell count, and can cause hepatic injury. Carbohydrate-deficient transferrin (CDT), often measured as %CDT, can detect heavy drinking but whether it does in people with HIV is not well established. We evaluated the operating characteristics of %CDT in HIV-infected adults using cross-sectional data from 300 HIV-infected adults with current or past alcohol problems. Past 30-day alcohol consumption was determined using the Timeline Followback (TLFB), a validated structured recall questionnaire, as the reference standard. Sensitivity and specificity of %CDT (at manufacturer's cut-off point of 2.6%) for detecting both "at-risk" (≥4 drinks in a day or >7 drinks per week for women, ≥5 drinks in a day or >14 per week for men) and "heavy" drinking (≥4 drinks in a day for women, ≥5 drinks in a day for men on at least seven days) were calculated. Receiver operating characteristic (ROC) curves were estimated to summarize the diagnostic ability of %CDT for distinguishing "at risk" and "heavy" levels of drinking. Exploratory analyses that stratified by gender and viral hepatitis infection were performed. Of 300 subjects, 103 reported current consumption at "at-risk" amounts, and 47 reported "heavy" amounts. For "at-risk" drinking, sensitivity of %CDT was 28% (95% confidence interval (CI) 19%, 37%), specificity 90% (95% CI 86%, 94%); area under the ROC curve (AUC) was 0.59. For "heavy" drinking, sensitivity was 36% (95% CI 22%, 50%), specificity 88% (95% CI 84%, 92%); AUC was 0.60. Sensitivity appeared lower among women and those with viral hepatitis; specificity was similar across subgroups. Among HIV-infected adults, %CDT testing yielded good specificity, but poor sensitivity for detecting "at-risk" and "heavy" alcohol consumption, limiting its clinical utility for detecting unhealthy alcohol use in this population.

To describe sex risk behaviors of HIV-infected female sex workers (FSWs) and HIV-infected male clients of FSWs, to evaluate associations between risky transactional sex and number of unprotected transactional sex episodes, and to assess the association between unprotected transactional sex and self-reported sexually transmitted infection (STI). Adult HIV-infected FSWs (n = 211) and HIV-infected male clients (n = 205) were surveyed in Mumbai about demographics, STI, and past 90-day and past year sex and substance use histories. Gender-stratified Poisson regression models were used to evaluate associations between four risky transactional sex behaviors (number of transactional sex partners; alcohol use before transactional sex; anal transactional sex; and transactional sex with a known HIV-infected partner) and number of unprotected transactional sex episodes; logistic regression was used to assess the association between unprotected transactional sex and self-reported STI. Twenty-nine percent of females and 7% of males reported any unprotected transactional sex episodes in the past 90 days. Thirty-nine percent of females and 12% of males reported past year STI. Among males, a greater number of transactional sex partners was associated with more unprotected transactional sex episodes (adjusted incidence rate ratio [IRR] = 8.2, 95% confidence interval [CI] = 1.8-38.4 highest vs. lowest tertile), and any unprotected transactional sex was associated with a higher odds of self-reported STI in the past year (adjusted odds ratio [AOR] = 5.6, 95% CI = 1.4-22.4). For women, risky transactional sex behaviors were not associated with condom non-use, and unprotected sex was negatively associated with STI (AOR = 0.4, 95% CI = 0.2-0.9). Reports of condom use during transactional sex were high for these samples. However, standard predictors of unprotected transactional sex (i.e., greater number of partners) and STI (i.e., unprotected sex) only held true for males. Further research is needed to guide an understanding of sex risk and STI among HIV-infected FSWs in India.

The association between smoking and HIV disease progression has been examined in several studies; however, findings have been inconsistent. We examined the effect of recent cigarette smoking on CD4(+) T cell count/µl (CD4 count) and HIV RNA concentration (HIV viral load (VL)) among two HIV-infected cohorts with alcohol problems in Massachusetts in the periods 1997-2001 and 2001-2006 using a prospective cohort design and linear mixed models. Smoking groups were defined as: minimal or non-smokers, light smokers, moderate smokers, and heavy smokers. Age, alcohol use, injection drug use, depressive symptoms, gender, annual income, and antiretroviral therapy adherence were considered as potential confounders. Among 462 subjects, no significant differences in CD4 count or VL were found between smoking groups. Using minimal or non-smokers as the reference group, the adjusted mean differences in CD4 count were: 8.2 (95% confidence interval (CI): -17.4, 33.8) for heavy smokers; -0.1 (95% CI: -25.4, 5.1) for moderate smokers; and -2.6 (95% CI: -28.3, 3.0) for light smokers. For log10 VL, the adjusted differences were: 0.03 (95% CI: -0.12, 0.17) for heavy smokers; -0.06 (95% CI: -0.20, 0.08) for moderate smokers; and 0.14 (95% CI -0.01, 0.28) for light smokers. This study did not find an association between smoking cigarettes and HIV disease progression as measured by CD4 cell count and VL.

Although mortality rates among HIV-infected populations have declined with the advent of combination antiretroviral therapy (ART), patients with substance use disorders have benefited less from these therapies. While adherence to ART has been well studied, less is known about factors associated with discontinuation of ART. The aim of this study is to investigate predictors of discontinuation of ART in HIV-infected patients with alcohol problems, focusing on their substance use and depressive symptoms. The study cohort (n=266) was prospectively assessed with biannual standardised interviews between 2001 and 2005. Four predictor variables (cocaine, heroin, heavy alcohol use and substantial depressive symptoms) were assessed six months prior to the outcome (ART discontinuation). Longitudinal logistic regression models examined the association between predictor variables and ART discontinuation adjusting for age, gender, race/ethnicity, homelessness, CD4, HIV RNA and HIV Symptom Index. Subjects were 77% male; 43% black; 22% homeless; 45% used cocaine; 20% used heroin; 29% had heavy alcohol use; and 40% had substantial depressive symptoms. Discontinuation occurred in 135 (17%) of the observations (n=743). In bivariate analyses, cocaine use, heroin use and depressive symptoms were significantly associated with ART discontinuation but heavy alcohol use was not. In the multivariable model, substantial depressive symptoms (adjusted odds ratio (AOR)=1.66; 95% confidence interval (CI): 1.04, 2.65) but not cocaine (AOR=1.28; 95%CI: 0.76, 2.16) or heroin use (AOR=1.27 95%CI: 0.66, 2.44), remained significantly associated with ART discontinuation. Among HIV-infected adults with alcohol problems, depressive symptoms, but not substance use, predicted subsequent ART discontinuation. Recognition and treatment of depressive symptoms in this population may result in better maintenance of ART and its associated clinical benefits.