As pharmacological antagonism of CB1 receptors caused BD rats to seize, we also evaluated the relationship between changes in anandamide levels and seizure phenomena. Our results suggest that anandamide acts as both an endogenous antidyskinetic and anticonvulsive compound, in part via interactions with the opioid system. Russia’s overall disease burden attributable to substance use is one of the highest in the world . It is among the top three countries with the largest estimated populations of persons who inject drugs . Injection drug use is the main driver of HIV transmission in Russia , a country where HIV incidence is steadily increasing. This same trend is occurring throughout parts of Eastern Europe where substance use is widespread and stands in contrast to the decline or stabilization of HIV incidence currently seen in other parts of the world , reflecting a strong relationship between injection drug use and HIV transmission. Estimates from 2017 suggest 30.4% of all PWID in Russia were living with HIV . Despite the country’s fast growing HIV epidemic, access to prevention and harm reduction services, such as needle and syringe exchange programs and opioid agonist treatment are limited and non-existent, respectively . Further, available statistics suggest the majority of Russian adults living with HIV are not on antiretroviral treatment . Numerous barriers prevent access to treatment, including the multiple steps required to enter into HIV care, discrimination towards people living with HIV overall, and conservative legislation placing restrictions on same-sex and other non-traditional relationships, drug use and sex work . Effective,vertical grow system evidence-informed prevention strategies are urgently needed in Russia to prevent both HIV acquisition and transmission.
Understanding the country’s HIV dynamics and patterns of transmission and acquisition are essential for designing approaches to reach key populations, including PWID and their sexual partners. Globally, there are more male than female PWID but available data suggest that among PWID, women have a higher HIV prevalence in many settings , including Eastern Europe. A 2012 meta-analysis including data collected from 128,745 PWID, drawn from 117 studies in 14 countries found a modest but significantly higher HIV prevalence among female PWID, relative to male PWID . Many possible explanations exist for elevated risk for HIV infection among women relative to men, irrespective of drug use behaviors. Clear biological mechanisms underlie the differential outcomes of HIV infection in women and men. For example, male-to-female HIV sexual transmission is more efficient than female-to male transmission because HIV-1 infected women have lower infectious potential . Additionally, sex hormones in women contribute to enhanced susceptibility by affecting the vaginal mucosa. It is hypothesized that women have lower viral reservoirs . It is also widely recognized that sociocultural factors, particularly as they relate to attitudes and practices surrounding sexual behaviors contribute to disparities in HIV infection and transmission between men and women, in the context of heterosexual partnerships. Further, gender-based inequalities prevent many women from protecting themselves and/or their partner against HIV infection . Less is known about the elevated risk for HIV infection and transmission among women who inject drugs. It has been found that unsafe injection practices and condomless sex heighten HIV infection risk among all PWID, but evidence suggests women who inject drugs are disproportionately more likely to engage in these behaviors, compared to men . Despite these findings, female PWID are often underrepresented in research with drug users and in studies on access to HIV care .
Evidence-based prevention measures aimed at PWID are urgently needed and have been specifically called for in Russia, where PWID account for the largest proportion of new HIV diagnoses, relative to any other risk group in the country and where evidence is limited on gender differences in HIV risk behaviors among PLHIV who have ever injected drugs. A prior study with women who inject drugs in St. Petersburg found 64% were HIVpositive and, in the past year, over 50% had two or more sexual partners, 40% transacted sex, 40% had condomless sex and 40% shared injecting needles. Transactional sex and sexual violence were both associated with increased injection drug equipment sharing and violence was associated with increased condomless sex. A second St. Petersburg study , conducted with male and female PWID living with HIV found internalized stigma surrounding HIV and drug use was correlated with poorer health outcomes and lower likelihood of service utilization. Although this study did not examine gender differences in these relationships, other research suggests that, compared to men, women who use drugs experience more stigma related to gendered cultural norms which contributes to increased risk for negative HIV outcomes . “Women-specific” research and prevention approaches have been called for to better understand the true context in which drug-using women experience health risks, and to design programs that account for the social, micro, and macro levels of women’s lives . Further, it is imperative that efforts be placed on developing gender-specific strategies for conducting research and programs to understand and reduce female PWID’s risk for both HIV acquisition from and transmission to sexual and injection drug use partners. Although a developing body of research informs our ability to design gender-tailored programs to prevent HIV infection among HIV-negative female PWID , less is known about how to effectively prevent HIV transmission by HIV-positive PWID to HIV-negative sexual partners or injection drug use partners.
We aimed to assess the association between female gender and drug risk behaviors and sex risk behaviors among a population of HIV positive men and women who had ever injected drugs in St. Petersburg, Russia. Recognizing injection drug use as a chronic condition, and that most PWID go through repeated periods of injection cessation and relapses during their injection careers , we included participants who reported past month injection drug use and/or injection drug use prior to their HIV-positive diagnosis. Alcohol use prior to sharing injecting equipment and surrounding sex were secondary outcomes in our analysis because alcohol consumption overall including by PLHIV has been associated with significantly higher drug and sex risk behaviors that heighten vulnerability for HIV acquisition, as well as transmission to others . Additionally, some of the most risky patterns of drinking have been observed in Russia and Ukraine. Based on what has been found in other studies in Russia and other settings, we hypothesized that among Russian PLHIV who had ever injected drugs, women would have higher odds of engaging in high risk drug use, sexual behaviors, and use of alcohol prior to sex or injecting drugs, relative to men. This study involved secondary analysis of data from the Russia ARCH cohort, which is part of the three site Uganda, Russia, Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS Consortium. Russia ARCH is an observational prospective cohort study conducted to assess the longitudinal association between alcohol consumption and biomarkers of microbial translocation and inflammation/ altered coagulation, which also encompasses a nested randomized controlled trial aimed at assessing the efficacy of zinc supplementation on markers of inflammation. A sample of 351 Russia ARCH participants were recruited into the study between November 2012 and June 2015 from clinical HIV and addiction care sites, non-clinical sites,indoor vertical garden systems and via snowball recruitment in St. Petersburg. Eligibility criteria for inclusion in the cohort included the following: 18-70 years old; documented HIV-infection; documented ART-naïve status; the ability to provide contact information for two contacts to assist with follow-up; stable address within St. Petersburg or districts within 100 kilometers of St. Petersburg; possession of a home or mobile phone. The current analysis was restricted to people who had ever injected drugs, defined as individuals who reported a history of injection drug use prior to HIV diagnosis, or past 30-day injection drug use at study visit. Participants were excluded from the cohort if they were not fluent in Russian or had a cognitive impairment resulting in inability to provide written informed consent. Eligibility was verified and informed consent was obtained. Participants provided a blood sample and were administered an interview assessment. Institutional Review Boards of Boston University Medical Campus and First St. Petersburg Pavlov State Medical University approved this study. The main independent variable for this study was female gender. Gender was self-reported as male or female. We did not assess other gender categories. The two primary dependent variables of interest were sharing of injecting equipment in the past 30 days and condomless sex in the past 90 days.
Condomless sex was defined as vaginal or anal sex with any sexual partner without the use of a condom or other protective barrier. Three secondary outcomes of interest were also examined, including alcohol use prior to sharing injecting equipment in past 30 days, alcohol use before or during sex in past 90 days, and reporting of both of the primary dependent variables . The following were selected as covariates for inclusion in the adjusted models, due to their potential confounding effects: age, education , income , partnered status, and recent ART use at follow-up. We also controlled for recent ART use at follow-up using data from participants’ responses to the following question about ART use at the 12 month and 24 month follow-up, “in the last 6 months, have you taken anti-retroviral medications for treating HIV?” Covariates were selected based on clinical knowledge and the literature. Partnered status was a 3 level covariate with the following categories: not partnered, partnered HIV discordant partner , and partnered HIV concordant partner . There were 21 observations over the course of the study whereby a participant reported they did not know the HIV status of their partner. Data from these observations were excluded from the analyses. Partner denoted being married, in a domestic partnership/living with a partner, or in a long-term relationship . Also measured at baseline were median income in Russian Rubles with interquartile range , mean CD4 count , heroin or other opioid use in past 30 days, and cannabis use in past 30 days. Since measures for past month heroin or opioid use did not distinguish the mode by which the drug was taken, we included data from a question assessing any injection drug use in the past 30 days . Those who indicated past 30 day injection drug use were asked to specify the type of drug injected . Heavy alcohol use in past 30 days was measured via the 30-day Timeline Follow back Method and defined as heavy if meeting NIAAA at-risk drinking amounts . Because involvement in transactional sex was associated with injection risk among women in a recent St. Petersburg study , we measured whether both male and female participants reported having given sex to a partner, received sex from a partner or both given and received sex to/from a partner in exchange for money, alcohol, drugs, or other things in the past 12 months.We assessed baseline frequencies of demographic characteristics, covariates, CD4 count, heroin or other opioid use, any injection drug use , cannabis use, heavy alcohol use and transactional sex, overall and by gender. For descriptive purposes, we assessed differences between male and female participants at baseline using chi-square and Fisher’s exact tests for categorical variables, and t-tests and Wilcoxon rank-sum tests for continuous variables. We assessed baseline, 12 month and 24 month follow-up frequencies for the primary and secondary outcomes and 12 month and 24 month follow-up frequencies for ART use in the past 6 months. To account for the correlation from using repeated observations from the same study participants, separate generalized estimating equations logistic regression models were used to evaluate the association between gender and each of the binary outcomes controlling for potential confounders. An independence working correlation was used and robust standard errors from the GEE approach are reported. Odds ratios and 95% confidence intervals are presented from the logistic regression models.We then fit a partially adjusted model controlling only for the demographic covariates specified above . Lastly, we fit the final, fully adjusted model controlling for demographic covariates and marital/partner status and respondents’ reports of ART use in the past 6 months, as recorded at the 12 and 24 month follow-up interviews. A posthoc sensitivity analysis was performed excluding observations from participants who used ARTs. All analysis was done using the statistical package SAS 9.3At baseline the sample included 291 HIV-positive participants from the Russia ARCH cohort who had ever injected drugs.