Evolution of illicit opioid use among people with HIV infection in St Petersburg, Russia, in the period 2004-2015.

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.

Methadone Matters: What the United States Can Learn from the Global Effort to Treat Opioid Addiction.

In the midst of an opioid epidemic, mortality related to opioid overdose continues to rise in the US. Medications to treat opioid use disorder, including methadone and buprenorphine, are highly effective in reducing the morbidity and mortality related to illicit opioid use. Despite the efficacy of these life-saving medications, the majority of people with an opioid use disorder lack access to treatment. This paper briefly reviews the evidence to support the use of medications to treat opioid use disorder with a specific focus on methadone. We discuss the current state of methadone therapy for the treatment of opioid use disorder in the US and present logistical barriers that limit its use. Next, we examine three international pharmacy-based models in which methadone dispensing to treat opioid use disorder occurs outside of an opioid treatment facility. We discuss current challenges and opportunities to incorporate similar methods of methadone dispensing for the treatment of opioid use disorder in the US. Finally, we present our vision to integrate pharmacy-based methadone dispensing into routine opioid use disorder treatment through collaboration between clinicians and pharmacies to improve local access to this life-saving medication.

The impact of prescribed opioids on CD4 cell count recovery among HIV-infected patients newly initiating antiretroviral therapy.

OBJECTIVES: Certain prescribed opioids have immunosuppressive properties, yet their impact on clinically relevant outcomes, including antiretroviral therapy (ART) response among HIV-infected patients, remains understudied. METHODS: Using the Veterans Aging Cohort Study data, we conducted a longitudinal analysis of 4358 HIV-infected patients initiating ART between 2002 and 2010 and then followed them for 24 months. The primary independent variable was prescribed opioid duration, categorized using pharmacy data as none prescribed, short-term (< 90 days) and long-term (≥ 90 days). Outcomes included CD4 cell count over time. Analyses adjusted for demographics, comorbid conditions, ART type and year of initiation, and overall disease severity [ascertained with the Veterans Aging Cohort Study (VACS) Index]. Sensitivity analyses examined whether effects varied according to baseline CD4 cell count, achievement of viral load suppression, and opioid properties (i.e. dose and known immunosuppressive properties). RESULTS: Compared to those with none, patients with short-term opioids had a similar increase in CD4 cell count (mean rise per year: 74 vs. 68 cells/µL; P = 0.11), as did those with long-term prescribed opioids (mean rise per year: 74 vs. 75 cells/µL; P = 0.98). In sensitivity analysis, compared with no opioids, the effects of short-term prescribed opioids were statistically significant among those with a baseline CD4 cell count ≥ 500 cells/µL (mean rise per year: 52 cells/µL for no opioids vs. 20 cells/µL for short-term opioids; P = 0.04); findings were otherwise unchanged. CONCLUSIONS: Despite immunosuppressive properties intrinsic to opioids, prescribed opioids appeared to have no effect on CD4 cell counts over 24 months among HIV-infected patients initiating ART.

Factors associated with study attrition among HIV-infected risky drinkers in St. Petersburg, Russia.

BACKGROUND: Participant attrition in HIV longitudinal studies may introduce bias and diminish research quality. The identification of participant characteristics that are predictive of attrition might inform retention strategies. OBJECTIVE: The study aimed to identify factors associated with attrition among HIV-infected Russian risky drinkers from the secondary HIV prevention HERMITAGE trial. We examined whether current injection drug use (IDU), binge drinking, depressive symptoms, HIV status nondisclosure, stigma, and lifetime history of incarceration were predictors of study attrition. We also explored effect modification due to gender. METHODS: Complete loss to follow-up (LTFU), defined as no follow-up visits after baseline, was the primary outcome, and time to first missed visit was the secondary outcome. We used multiple logistic regression models for the primary analysis, and Cox proportional hazards models for the secondary analysis. RESULTS: Of 660 participants, 101 (15.3%) did not return after baseline. No significant associations between independent variables and complete LTFU were observed. Current IDU and HIV status nondisclosure were significantly associated with time to first missed visit (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.03-1.87; AHR, 1.38; 95% CI, 1.03-1.86, respectively). Gender stratified analyses suggested a larger impact of binge drinking among men and history of incarceration among women with time to first missed visit. CONCLUSIONS: Although no factors were significantly associated with complete LTFU, current IDU and HIV status nondisclosure were significantly associated with time to first missed visit in HIV-infected Russian risky drinkers. An understanding of these predictors may inform retention efforts in longitudinal studies.

The influence of depressive symptoms on alcohol use among HIV-infected Russian drinkers.

BACKGROUND: Depressive symptoms have been linked to HIV progression through a number of biobehavioral mechanisms including increased alcohol use. Although research supports an association between alcohol use and depressive symptoms among HIV patients, there have been few studies that have examined whether depressive symptoms predict subsequent drinking, especially among heavy drinking HIV-infected patients. METHOD: Heavy drinking Russian HIV-infected patients (n=700) were recruited from addiction and HIV care settings for a randomized controlled trial of a risk reduction intervention [HERMITAGE]. GEE overdispersed Poisson regression analyses were conducted to assess the association between depressive symptoms and alcohol consumption 6-months later. RESULTS: In adjusted analyses, depressive symptom severity was significantly associated with drinks per day (global p=.02). Compared to the non-depressed category, mild depressive symptoms were significantly associated with more drinks per day [IRR=1.55, (95% CI: 1.14, 2.09)], while moderate [IRR=1.14, (95% CI: 0.83, 1.56)] and severe [IRR=1.48, (95% CI: 0.93, 2.34)] depressive symptoms were not. Associations between depressive symptom severity and heavy drinking days were not statistically significant (global p=.19). Secondary analyses using the BDI-II screening threshold (BDI-II>14) and the BDI-II cognitive subscale suggested an association between depressive symptoms and drinks per day over time but not heavy episodic drinking. CONCLUSIONS: Among heavy drinking HIV-infected patients, elevated depressive symptoms were associated with greater subsequent alcohol use. These findings suggest that depressive symptoms may be important to address in efforts to reduce alcohol-related risks among HIV-infected populations.

History of intimate partner violence is associated with sex work but not sexually transmitted infection among HIV-positive female drinkers in Russia.

This paper assesses the associations between intimate partner violence (IPV) and sexually transmitted infections (STIs) and sexual risks among HIV-positive female drinkers in St Petersburg, Russia. Survey and STI data were analysed from 285 women in HERMITAGE, a secondary prevention study of HIV-positive heavy drinkers. Logistic and Poisson regression analyses assessed associations of IPV with STI and risky sex. Most women (78%) experienced IPV and 19% were STI positive; 15% sold sex. IPV was not significantly associated with STI, but was with selling sex (adjusted odds ratio = 3.56, 95% confidence interval = 1.02-12.43). In conclusion, IPV is common and associated with sex trade involvement among Russian HIV-positive female drinkers.

Sexually transmitted infections among HIV-infected heavy drinkers in St Petersburg, Russia.

The objective of this study was to estimate the prevalence and identify correlates of four sexually transmitted infections (STIs) among HIV-infected Russians reporting heavy alcohol use and recent unprotected sex, we conducted a cross-sectional analysis of baseline data from the HERMITAGE study. The primary outcome was any current STI, based on urine tests for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis and serological testing for infection with Treponema pallidum. Data on potential demographic and behavioural predictors of STI were obtained from surveys administered at study entry. Of 682 participants, 12.8% (95% confidence interval [CI] 10.3, 15.3) tested positive for at least one STI. In a multivariable model adjusted for gender, age and marital status, only sex trade involvement over the last three months was significantly associated with an increased odds of STI (adjusted odds ratio [AOR] 2.00, 95% CI 1.13, 3.55). Given that STIs were common in this HIV-infected cohort, and that few patient characteristics predicted STI, the current practice of screening HIV-infected Russians for syphilis alone merits re-evaluation.

Transactional sex risk and STI among HIV-infected female sex workers and HIV-infected male clients of FSWs in India.

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.

Binge drinking and unsafe sex: a study of narcology hospital patients from St. Petersburg, Russia.

The purpose of this study was to assess the association between binge alcohol use and unprotected sex in Russian substance users. Participants (N = 181) were narcology hospital patients assessed on demographics, alcohol use, risky sex, and sexually transmitted disease/human immunodeficiency virus (STD/HIV) diagnoses. Adjusted generalized estimating equations (GEEs) logistic regression analysis examined the association between binge drinking and same-day unprotected sex across each of the past 30 days, per participant (N = 5430 observations). Participants were age 18 to 55 years, 75% male, and 64% binge drinking. Sex trade was reported by 27%; history of STDs by 43%; and HIV by 15%. One fourth of daily observations included sex; 88% of these involved unprotected sex. Binge drinking was not associated with same-day unprotected sex (adjusted odds ratio [OR(adj)] = 1.0, 95% confidence interval [CI] = 0.7-1.4, chi(2)(1, N = 5219) = 0.01, ns). Findings document substantial HIV/STD risk and prevalence among Russian narcology patients, but no link between binge drinking and unprotected sex in this population, possibly due to very low rates of condom use generally.

Correlates of any condom use among Russian narcology patients reporting recent unprotected sex.

The purpose of this study was to assess whether HIV/sexually transmitted infection (STI) risk factors: risky sex (multiple sex partners and sex trade involvement), past HIV or STI diagnosis and substance use (at risk drinking and injection drug use) are associated with the outcome any condom use in the past 6 months among Russian narcology hospital patients. Participants (N = 178) included only those who reported unprotected sex in the past 6 months and were aged 18-55 years and 76% male. Any condom use in the past 6 months was reported by 55% of the sample. History of STIs was reported by 43% of participants; 15% were HIV-infected. Regression analyses adjusted for demographics demonstrated that those reporting multiple sex partners (OR(adj) = 4.2, 95% CI = 2.0-8.7) and sex trade involvement (OR(adj) = 2.4, 95% CI = 1.1-5.1) in the past 6 months had significantly higher odds of reporting any condom use in this same timeframe. HIV/STI and substance use were not associated with increased odds of condom use.

Factors associated with discontinuation of antiretroviral therapy in HIV-infected patients with alcohol problems.

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.

Illicit drugs, alcohol, and addiction in human immunodeficiency virus.

Drug and alcohol use complicate both the prevention and treatment of human immunodeficiency virus (HIV) infection. Substance use is one of the major engines driving HIV transmission, directly, through the sharing of injection drug use equipment and indirectly, through increasing risky sexual behaviors. Drug and alcohol dependence compromise effective HIV treatment by influencing both access and adherence to antiretroviral therapy. Exposure to addictive substances may have direct immunosuppressive effects independent of their impact on access and adherence to treatment. Measures effective at minimizing HIV transmission attributable to drug and alcohol use include HIV testing and referral to treatment, syringe and needle exchange programs, opioid replacement therapy (i.e., methadone and buprenorphine), and behavioral interventions targeting HIV risk behaviors among both HIV-infected and HIV-uninfected people. Measures effective at optimizing HIV treatment among alcohol and drug-dependent patients include HIV testing with referral to treatment and substance use treatment that is linked to or integrated into HIV treatment. Due to the intertwining problems of substance use and HIV infection, physicians and other health care providers must address the issues of illicit drugs and alcohol use as mainstream medical problems in order to provide optimal care for HIV-infected patients.

Co-morbidity of infectious and addictive diseases in St. Petersburg and the Leningrad Region, Russia.

The Russian health care system is organized around specific diseases, with relatively little focus on integration across specialties to address co-morbidities. This organizational structure presents new challenges in the context of the recent epidemics of injection drug use (IDU) and HIV. This paper uses existing and new data to examine the prevalence of reported new cases of drug dependence (heroin) and HIV over time as well as associations between drug dependence and alcoholism, hepatitis B and C, and tuberculosis in the City of St. Petersburg and the Leningrad region. We found a sharp rise in reported cases of IDU beginning in 1991 and continuing until 2002/2003, followed by a sharp rise in newly reported cases of HIV. These rises were followed by a drop in new cases of HIV and drug addiction in 2002/2003 and a drop in the proportion of HIV-positive individuals with IDU as a risk factor. Infection with hepatitis B and C were common, especially among injection drug users (38 and 85%, respectively), but also in alcoholics (7 and 14%). Tuberculosis was more common in alcoholics (53%) than in persons with alcoholism and drug dependence (10%), or with drug dependence alone (4%). Though these data have many limitations, they clearly demonstrate that drug dependence and/or alcoholism, HIV, hepatitis, and tuberculosis frequently co-occur in St. Petersburg and the Leningrad Region. Prevention and treatment services across medical specialties should be integrated to address the wide range of issues that are associated with these co-morbidities.

Physical and sexual violence and health care utilization in HIV-infected persons with alcohol problems.

We examined interpersonal violence and its association with health care utilization and substance use severity among a cohort of 349 HIV-infected men and women with histories of alcohol problems assessed biannually up to 36 months. Data included demographics, lifetime interpersonal violence histories, age at first violence exposure, recent violence (prior six months), substance use severity and health care utilization (ambulatory visits, Emergency Department (ED) visits, hospitalizations) and adherence to HIV medication. Kaplan-Meier survival curves estimated the proportion of subjects experiencing recent violence. Generalized estimating equation regression models evaluated the relationship between recent violence, utilization and substance use severity over time, controlling for demographics, CD4 counts and depressive symptoms. Subject characteristics included: 79% male; mean age 41 years; 44% black, 33% white and 23% other. Eighty percent of subjects reported lifetime interpersonal violence: 40% physical violence alone, and 40% sexual violence with or without physical violence. First violence occurred prior to age 13 in 46%. Twenty-four (41%) of subjects reported recent violence by 24 and 36 months, respectively. In multivariate analyses, recent violence was associated with more ambulatory visits, ED visits and hospitalizations and worse substance use severity, but not medication adherence. Due to the high incidence and associated increased health care services utilization, violence prevention interventions should be considered for HIV-infected patients with a history of alcohol problems.

The onset of HIV infection in the Leningrad region of Russia: a focus on drug and alcohol dependence.

OBJECTIVES: Within 5 years, 5 million Russians may be infected with HIV. Currently, injection drug use is the major risk factor for HIV. As Russia's alcohol consumption per capita is among the highest in the world, alcohol-associated behaviours may be an important contributor to the HIV epidemic. Our objective was to examine the prevalence of HIV infection among drug- and alcohol-dependent patients in a regional narcology hospital and in the general population in Leningrad. METHODS: All patients in the Narcology Hospital, Leningrad Regional Center of Addictions (LRCA), were tested for HIV antibody between 1997 and 2001. We reviewed these clinical records (i.e. serostatus, gender, age, and addiction) and data from the HIV/AIDS Center in the Leningrad Region (1997-2001). RESULTS: From 1997 to 2001, HIV prevalence at the LRCA increased from 0 to 12.7% overall, 33.4% among drug-dependent patients and 1.2% among alcohol-dependent patients. During the same 5-year period (1997-2001), 2826 persons were registered at the HIV/AIDS Center: 6, 6, 51, 780, and 1983 persons in 1997, 1998, 1999, 2000 and 2001, respectively. CONCLUSIONS: HIV infection is exploding in the Leningrad Region, currently in injection drug users (IDUs) but potentially more broadly. The known high per capita alcohol intake in Russia heightens concern regarding the sexual transmission of HIV. Interventions to prevent such a development should include use, and assessment of the effectiveness, of known HIV prevention measures for at-risk and infected individuals.

Recurrence of post-traumatic stress disorder symptoms after initiation of antiretrovirals including efavirenz: a report of two cases.

BACKGROUND: Some antiretrovirals has been reported to cause a wide range of psychiatric symptoms. However, reappearance of post-traumatic stress disorder (PTSD) symptoms has not been described in relation to these medications. DESIGN: Case report. SETTINGS: The Boston Medical Center, a tertiary care academic centre. FINDINGS: Two HIV-infected refugees re-experienced symptoms of PTSD after starting therapy with efavirenz (EFV) and zidovudine (ZDV). The two patients had no typical factors present to account for the PTSD exacerbation. In both patients, the symptoms of PTSD gradually subsided to baseline within the first 4 weeks of antiretroviral treatment. CONCLUSIONS: We believe that EFV, a non-nucleoside reverse transcriptase inhibitor, with ZDV, may be manifesting its known neuropsychiatric toxicities in a heretofore unreported presentation of PTSD exacerbation.

Improving participation in HIV clinical trials: impact of a brief intervention.

PURPOSE: To determine if a brief intervention that provides information about AIDS clinical trials to HIV-infected patients at the initiation of primary care increases the participation of women, persons of color, and injection drug users (IDUs) in clinical trials. METHOD: 196 outpatients beginning HIV primary care at a municipal hospital were followed from September 1994 to April 1996. During the intake assessment, each patient met briefly with a research assistant who described the purpose, role, and availability of clinical trials. Contacts for further information about trials were given to patients who expressed interest. At the end of the 20-month period, enrollment rates of all patients, including women, persons of color, and IDUs, into clinical trials were compared with previously published enrollment rates of patients at the same hospital but prior to the development of this brief intervention. RESULTS: The characteristics of the 196 HIV-infected patients were: 27% women; 47% IDUs; 14% gay/bisexual men; and 76% persons of color. Overall enrollment in AIDS clinical trials was 14.8% during the 20-month follow-up period. There was no significant difference in participation rates between males and females (p =.20), whites and persons of color (p =.71), and IDUs compared with non-IDUs (p =.90), whereas previously published data had shown significantly higher enrollment rates among males, whites, and non-IDUs. CONCLUSION: Providing all HIV-infected patients with information about the meaning, role, and availability of AIDS clinical trials at the initiation of HIV primary care reduces differences in participation rates by gender, race, and history of drug use.

Understanding delay to medical care for HIV infection: the long-term non-presenter.

OBJECTIVE: To examine delayed presentation for HIV testing and primary care in the second decade of the AIDS epidemic. DESIGN: Cohort study in two urban hospitals in the USA between February 1994 and April 1996. METHODS: A total of 203 consecutive outpatients on initial HIV primary care presentation were interviewed about sociodemographic characteristics, alcohol and drug use, social support, sexual practices, HIV testing, awareness of possible HIV infection, and CD4 cell count. MAIN OUTCOME MEASURE: Duration of delay to medical presentation in years based on CD4 cell count, factors independently associated with low CD4 cell counts, frequency of awareness of HIV risk before testing. RESULTS: The estimated mean duration between acquiring HIV infection and initial presentation to primary care was 8.1 years (95% CI 7.5, 8.6) based on our cohort's median initial CD4 cell count of 280/microl. Male sex, older age, and no jail time were associated with lower CD4 cell counts; 34% reported not being aware that they were at risk of HIV before testing. Heterosexual intercourse as a risk behavior for HIV was the most statistically significant factor for personal unawareness of HIV risk. Of those who acknowledged awareness, the mean time between awareness of HIV risk and testing was 2.5 years (median 1.0 year). CONCLUSION: In the pre-highly active antiretroviral therapy era, HIV-infected patients frequently initiated primary medical care years after initial infection, at a time of advanced immunosuppression. Over one-third of HIV-infected patients were not cognisant of their HIV risk before testing, a condition significantly associated with heterosexual intercourse as the only HIV risk behavior.