Characterization of the Transmitted Virus in an Ongoing HIV-1 Epidemic Driven by Injecting Drug Use.

Understanding features of the HIV-1 transmission process has the potential to inform biological interventions for prevention. We have examined the transmitted virus in a cohort of people who inject drugs and who are at risk of HIV-1 infection through blood contamination when injecting in a group. This study focused on seven newly infected participants in St. Petersburg, Russia, who were in acute or early infection. We used end-point dilution polymerase chain reaction to amplify single viral genomes to assess the complexity of the transmitted virus. We also used deep sequencing to further assess the complexity of the virus. We interpret the results as indicating that a single viral variant was transmitted in each case, consistent with a model where the exposure to virus during transmission was limited. We also looked at phenotypic properties of the viral Env protein in isolates from acute and chronic infection. Although differences were noted, there was no consistent pattern that distinguished the transmitted variants. Similarly, despite the reduced genetic heterogeneity of the more recent subtype A HIV-1 epidemic in St. Petersburg, we did not see reduced variance in the neutralization properties compared to isolates from the more mature subtype C HIV-1 epidemic. Finally, in looking at members of injecting groups related to the acute HIV-1 infection/early subjects, we found examples of sequence linkage consistent with ongoing and rapid spread of HIV-1 in these groups. These studies emphasize the dynamic nature of this epidemic and reinforce the idea that improved prevention methods are needed.

A Cohort Approach to Real-Time Detection of Acute HIV Infections Among People Who Inject Drugs in St. Petersburg, Russia.

To detect acute HIV infections (AHIs) in real time among people who inject drugs (PWID) in St. Petersburg, Russia and to test the feasibility of this approach. Prospective cohort study. One hundred seronegative or acutely HIV-infected at screening PWID were enrolled and followed until the end of the 12-month pilot period. Each participant was evaluated, tested, and counseled for HIV monthly. Two HIV tests were used: HIV antibody and HIV RNA PCR. If diagnosed with AHI, participants were followed weekly for a month; then, monthly for 3 months; and then, quarterly for the duration of the follow-up period. HIV risk behavior was assessed at each study visit. Most enrolled PWID were 30-39 years old, male, completed high school or more, not employed full-time, heroin users, and frequently shared injection paraphernalia. AHI prevalence at screening was 1.8% [95% confidence interval (CI): 0.4, 5.5]. Three participants with AHI at enrollment represented 3% (95% CI: 0.6, 8.5) of the 100 participants who consented to enroll. Among the HIV-uninfected participants (n = 97), the AHI incidence over time was 9.3 per 100 person-years. Persons with AHI were more likely to report alcohol intoxication within the prior 30 days. This was the first study to detect AHI using a cohort approach. The approach proved to be feasible: recruitment, retention, AHI detection, and virological endpoints were successfully reached. A cost analysis in a real-world setting would be required to determine if this strategy could be brought to scale. The study revealed continued high HIV incidence rate among PWID in St. Petersburg, Russia and the importance of prevention and treatment programs for this group.

Two Independent HIV Epidemics in Saint Petersburg, Russia Revealed by Molecular Epidemiology.

The HIV epidemic in Russia, one of the world's fastest growing, has been concentrated mostly among people who inject drugs (PWID). We sought to explore the epidemiology of the epidemic in St. Petersburg by sampling from the highest risk groups of PWID and men who have sex with men (MSM) and use viral sequencing data to better understand the nature of the city's epidemic. Serological testing confirmed an HIV prevalence among PWID in excess of 40%. All but 1 of 110 PWID whose blood samples were tested for genetic diversity were infected by subtype A virus, specifically by the AFSU strain. The remaining person was infected with a CRF-06cpx recombinant. Analysis of pairwise genetic distance among all PWID studied revealed an average of 3.1% sequence divergence, suggesting clonal introduction of the AFSU strain and/or constraints on sequence divergence. The HIV prevalence was less than 10% among MSM. All 17 sequences from HIV-infected MSM were found to be a clade B virus with a much higher average sequence diversity of 15.7%. These findings suggest two independent epidemics with little overlap between the two highest at-risk populations, which will require different HIV prevention approaches.

A peer-educator network HIV prevention intervention among injection drug users: results of a randomized controlled trial in St. Petersburg, Russia.

We evaluated the efficacy of a peer-educator network intervention as a strategy to reduce HIV acquisition among injection drug users (IDUs) and their drug and/or sexual networks. A randomized controlled trial was conducted in St. Petersburg, Russia among IDU index participants and their risk network participants. Network units were randomized to the control or experimental intervention. Only the experimental index participants received training sessions to communicate risk reduction techniques to their network members. Analysis includes 76 index and 84 network participants who were HIV uninfected. The main outcome measure was HIV sero-conversion. The incidence rates in the control and experimental groups were 19.57 (95 % CI 10.74-35.65) and 7.76 (95 % CI 3.51-17.19) cases per 100 p/y, respectively. The IRR was 0.41 (95 % CI 0.15-1.08) without a statistically significant difference between the two groups (log rank test statistic X(2) = 2.73, permutation p value = 0.16). Retention rate was 67 % with a third of the loss due to incarceration or death. The results show a promising trend that this strategy would be successful in reducing the acquisition of HIV among IDUs.

Correlates of unprotected sexual intercourse among women who inject drugs or who have sexual partners who inject drugs in St Petersburg, Russia.

OBJECTIVES: To assess risk for unintended pregnancy, this study describes the correlates of unprotected sexual intercourse (UPSI) among women who inject illicit drugs or who have sexual partners who inject drugs in St Petersburg, Russia. METHODS: Data from a cross-sectional survey and biological test results collected between 2005 and 2008 from 202 Russian women (143 drug injectors and 59 non-drug injectors) were analysed. Multivariate regression was used to investigate the correlates of UPSI occurring at the women's last sexual act. Independent variables included socio-demographics, age at sexual debut, first sexual encounter perceived as involuntary, number of pregnancies and number of children for which the participant is the primary caretaker, heavy sporadic drinking (i.e. consuming more than five drinks in 2 hours at least twice a month), at-risk drinking per the Alcohol Use Disorder Identification Test (AUDIT-C) score, and sexually transmitted infections (HIV-1, syphilis serology, Chlamydia trachomatis and Neisseria gonorrheae). RESULTS: Sixty-seven percent of women reported UPSI at last intercourse. UPSI was independently associated with heavy sporadic drinking [odds ratio (OR) 2.8, 95% CI 1.2-6.6] and having been pregnant (OR 2.25, 95% CI 1.1-4.6). CONCLUSIONS: Despite the high risk for HIV acquisition or transmission and unintended pregnancy, condom use among the study population is low. Programmes to investigate and improve contraceptive use, including condom use, among this vulnerable group of women are needed. Such programmes may require identifying and targeting female reproductive health concerns and problem drinking, particularly heavy sporadic drinking, rather than conventional measures of alcohol misuse.

HIV disclosure, condom use, and awareness of HIV infection among HIV-positive, heterosexual drug injectors in St. Petersburg, Russian Federation.

We examined the prevalence of HIV disclosure to sexual partners by HIV-positive drug injectors (IDUs) in St. Petersburg, Russia and compared the magnitude and direction of associations of condom use with awareness of one's HIV infection and disclosure to partners. Among 157 HIV-infected participants, awareness of infection at time of last intercourse was associated with condom use with partners perceived to be HIV-negative (aOR 6.68, 95% CI 1.60-27.88). Among the 70 participants aware of their infection prior to enrolment, disclosure to potentially uninfected sexual partners was independently and negatively associated with condom use (aOR 0.13, 95% CI 0.02-0.66). Disclosure was independently associated with having injected ≥ 9 years (aOR 6.04, 95% CI 1.53-23.77) and partnership with another IDU (aOR 3.61, 95% CI 1.44-9.06) or HIV-seropositive (aOR 45.12, 95% CI 2.79-730.46). Scaling up HIV testing services and interventions that increase the likelihood of individuals receiving their test results is recommended.

Estimates of HIV incidence among drug users in St. Petersburg, Russia: continued growth of a rapidly expanding epidemic.

BACKGROUND: Russia has one of the world's fastest growing HIV epidemics and it has been largely concentrated among injection drug users (IDU). St Petersburg, Russia's second largest city, is one of the country's regions that has been most affected by the HIV epidemic. To monitor the current epidemic situation, we sought to estimate recent HIV incidence among IDU in St Petersburg. METHODS: In a cross-sectional study of 691 IDU recruited during 2005-08, HIV incidence was estimated by two methods: a retrospective cohort analysis and BED capture enzyme immunoassay (EIA) results. Socio-demographic and behavioural correlates of incident infections and spatial patterns were examined. RESULTS: In the retrospective cohort analysis, the incidence rate was estimated to be 14.1/100 person-years [95% confidence interval (CI) 10.7-17.6]. Using results of BED EIA and two correction formulas for known misclassification, incidence estimates were 23.9 (95% CI 17.8-30.1) and 25.5 (95% CI 18.9-32.0) per 100 person-years. Independent correlates of being recently infected included current unemployment (P = 0.004) and not having injected drugs in the past 30 days (P = 0.03). HIV incident cases were detected in all but one district in the city, with focal areas of transmission observed to be expanding. CONCLUSIONS: High HIV incidence among IDU in St Petersburg attests to continued growth of the epidemic. The need for expansion of HIV prevention interventions targeted to vulnerable populations throughout the city is urgent. These results also suggest that the BED EIA may over-estimate incidence even after correction for low specificity.

Comparing sexual risks and patterns of alcohol and drug use between injection drug users (IDUs) and non-IDUs who report sexual partnerships with IDUs in St. Petersburg, Russia.

BACKGROUND: To date, the great majority of Russian HIV infections have been diagnosed among IDUs and concerns about the potential for a sexual transmission of HIV beyond the IDU population have increased. This study investigated differences in the prevalence of sexual risk behaviors between IDUs and non-IDUs in St. Petersburg, Russia and assessed associations between substance use patterns and sexual risks within and between those two groups. METHODS: Cross-sectional survey data and biological test results from 331 IDUs and 65 non-IDUs who have IDU sex partners were analyzed. Multivariate regression was employed to calculate measures of associations. RESULTS: IDUs were less likely than non-IDUs to report multiple sexual partners and unprotected sex with casual partners. The quantity, frequency and intensity of alcohol use did not differ between IDUs and non-IDUs, but non-IDUs were more likely to engage in alcohol use categorized as risky per the alcohol use disorders identification test (AUDIT-C). Risky sexual practices were independently associated with monthly methamphetamine injection among IDUs and with risky alcohol use among non-IDUs. Having sex when high on alcohol or drugs was associated with unprotected sex only among IDUs. CONCLUSIONS: Greater prevalence of sexual risk among non-IDUs who have IDU sex partners compared to IDUs suggests the potential for sexual transmission of HIV from the high-prevalence IDU population into the general population. HIV prevention programs among IDUs in St. Petersburg owe special attention to risky alcohol use among non-IDUs who have IDU sex partners and the propensity of IDUs to have sex when high on alcohol or drugs and forgo condoms.

A substantial transmission bottleneck among newly and recently HIV-1-infected injection drug users in St Petersburg, Russia.

There are limited data on the genetic complexity of human immunodeficiency virus type 1 (HIV-1) after transmission among a cohort of injection drug users (IDUs). We used single-genome amplification of HIV-1 env to determine the genotypic characteristics of virus among IDUs with acute infection in St Petersburg, Russia. Our results indicate that a single variant was transmitted in a majority of cases (9 of 13 participants), which is analogous to what is observed in sexual transmission. These data are most consistent with a genetic bottleneck during transmission by injection drug use that is due to a small inoculum, which most often results in the transmission of a low-complexity viral population.

High HIV prevalence, suboptimal HIV testing, and low knowledge of HIV-positive serostatus among injection drug users in St. Petersburg, Russia.

The purpose of this analysis was to estimate human immunodeficiency virus (HIV) prevalence and testing patterns among injection drug users (IDUs) in St. Petersburg, Russia. HIV prevalence among 387 IDUs in the sample was 50%. Correlates of HIV-positive serostatus included unemployment, recent unsafe injections, and history/current sexually transmitted infection. Seventy-six percent had been HIV tested, but only 22% of those who did not report HIV-positive serostatus had been tested in the past 12 months and received their test result. Correlates of this measure included recent doctor visit and having been in prison or jail among men. Among the 193 HIV-infected participants, 36% were aware of their HIV-positive serostatus. HIV prevalence is high and continuing to increase in this population. Adequate coverage of HIV testing has not been achieved, resulting in poor knowledge of positive serostatus. Efforts are needed to better understand motivating and deterring factors for HIV testing in this setting.

Hepatitis C virus infection among drug injectors in St Petersburg, Russia: social and molecular epidemiology of an endemic infection.

AIMS: To understand the epidemiology and transmission patterns of hepatitis C virus (HCV), the predominant blood borne-pathogen infecting injection drug users (IDUs), in a part of the former Soviet Union. DESIGN: Cross-sectional respondent-driven sample of IDUs. SETTING: St Petersburg, Russia. PARTICIPANTS: A total of 387 IDUs were recruited in late 2005 and throughout 2006. MEASUREMENTS: Participants were surveyed to collect demographic, medical and both general and dyad-specific drug injection and sexual behaviors. A blood sample was collected to detect antibodies to hepatitis C and to amplify viral RNA for molecular analysis. The molecular data, including genotypes, were analyzed spatially and linkage patterns were compared to the social linkages obtained by respondent-driven sampling (RDS) for chains of respondents and among the injection dyads. FINDINGS: HCV infection was all but ubiquitous: 94.6% of IDUs were HCV-seropositive. Among the 209 viral sequences amplified, genotype 3a predominated (n = 119, 56.9%), followed by 1b (n = 61, 29.2%) and 1a (n = 25, 11.9%). There was no significant clustering of genotypes spatially. Neither genotypes nor closely related sequences were clustered within RDS chains. Analysis of HCV sequences from dyads failed to find associations of genotype or sequence homology within pairs. CONCLUSIONS: Genotyping reveals that there have been at least five unique introductions of HCV genotypes into the IDU community in St Petersburg. Analysis of prevalent infections does not appear to correlate with the social networks of IDUs, suggesting that simple approaches to link these networks to prevalent infections, rather than incident transmission, will not prove meaningful. On a more positive note, the majority of IDUs are infected with 3a genotype that is associated with sustained virological response to antiviral therapy.

The rate of epidemiological and virological changes during the transition from nascent to concentrated HIV epidemic stage in the former Soviet Union countries.

The rate of processes accompanying the transition of the HIV-1 epidemic from nascent stage to concentrated one in the Former Soviet Union (FSU) during intravenous drug user (IDU)-associated HIV infection outbreaks in 1994-1999 has not been analyzed. To define the rates, we studied susceptible populations and circulating viruses before, during, and after the outbreaks. Our findings included the following: (1) the pattern of high HIV-1 genetic diversity characteristic of the nascent epidemic changed to a concentrated one within 1 year in St. Petersburg and in Moscow; (2) different FSU regions were at different stages of the HIV-1 epidemic in 1994-1996; (3) the change of serotypic patterns characteristic of different stages of the HIV/AIDS epidemic for the non-IDU risk group occurred within 1 year in Moscow, suggesting an extremely high rate of IDU-associated epidemic pattern distributions in regions and susceptible populations in the FSU.

HIV prevalence, sociodemographic, and behavioral correlates and recruitment methods among injection drug users in St. Petersburg, Russia.

OBJECTIVE: In St. Petersburg, Russia, we sought to describe the characteristics of active high-risk injection drug users (IDUs) to evaluate the associations between behavioral and demographic characteristics and HIV-1 infection and to describe 3 discrete recruitment methods. METHODS: Active high-risk IDUs were recruited in 3 ways: through street outreach, at facilities serving IDUs, and by network-based chain referral. Recruits were screened, counseled, and tested for HIV-1. Sociodemographic and behavioral data were collected. HIV-1 prevalence was analyzed as a function of sociodemographic and behavioral variables. RESULTS: During the 10-month recruitment period, data from 900 participants were collected: median age was 24 years, and in the previous month, 96% used heroin and 75% shared needles with others. The baseline HIV prevalence was 30% (95% confidence interval [CI]: 27 to 33). Recruitment through social networks was the most productive strategy. HIV-positive individuals were younger, but none of the other sociodemographic or behavioral characteristics differed significantly by HIV status. CONCLUSIONS: The estimated HIV prevalence of 30% places St. Petersburg among the worst IDU-concentrated epidemics in Europe. Recruitment through network-based chain referral is a useful method for recruiting active IDUs. Sociodemographic and behavioral links to prevalent HIV infection remain to be elucidated.

HIV incidence and factors associated with HIV acquisition among injection drug users in St Petersburg, Russia.

BACKGROUND: The Russian HIV-1 epidemic has been driven by injection drug use. OBJECTIVE: To determine HIV incidence and identify demographic and behavioral correlates of infection to facilitate the development of longitudinal HIV prevention programs. METHODS: In 2002, a cohort of 520 injection drug users (IDU) in St Petersburg, Russia were recruited and tested and counseled for HIV-1. HIV-seronegative IDU were enrolled and reevaluated at 6 and 12 months. HIV testing was performed and sociodemographic and behavioral data were collected during each study visit. The relationship of sociodemographic and behavioral factors to HIV-1 incidence was assessed. RESULTS: Most enrolled subjects were young, male, living at home, educated, heroin users, and frequently shared needles and other injection paraphernalia. The retention rate at the 12 month follow-up was 80%. The HIV-1 incidence rate was 4.5/100 person-years. In univariate analysis, psychostimulant use, especially frequent use, three or more sex partners in the past 6 months, and females selling sex were associated with HIV seroconversion. In the multivariate analysis, psychostimulant use three or more times per week was the only factor still associated with HIV seroconversion. CONCLUSIONS: The high incidence of HIV infection places St Petersburg among the worst IDU-concentrated epidemics in Europe. Interventions targeting psychostimulant and heroin users and their accompanying behaviors such as frequent injections and increased sexual activity are needed immediately.