Pavlo Smyrnov

The perfect storm: incarceration and the high-risk environment perpetuating transmission of HIV, hepatitis C virus, and tuberculosis in Eastern Europe and Central Asia

Despite global reductions in HIV incidence and mortality, the 15 UNAIDS-designated countries of Eastern Europe and Central Asia (EECA) that gained independence from the Soviet Union in 1991 constitute the only region where both continue to rise. HIV transmission in EECA is fuelled primarily by injection of opioids, with harsh criminalisation of drug use that has resulted in extraordinarily high levels of incarceration. Consequently, people who inject drugs, including those with HIV, hepatitis C virus, and tuberculosis, are concentrated within prisons. Evidence-based primary and secondary prevention of HIV using opioid agonist therapies such as methadone and buprenorphine is available in prisons in only a handful of EECA countries (methadone or buprenorphine in five countries and needle and syringe programmes in three countries), with none of them meeting recommended coverage levels. Similarly, antiretroviral therapy coverage, especially among people who inject drugs, is markedly under-scaled. Russia completely bans opioid agonist therapies and does not support needle and syringe programmes-with neither available in prisons-despite the countrys high incarceration rate and having the largest burden of people with HIV who inject drugs in the region. Mathematical modelling for Ukraine suggests that high levels of incarceration in EECA countries facilitate HIV transmission among people who inject drugs, with 28-55% of all new HIV infections over the next 15 years predicted to be attributable to heightened HIV transmission risk among currently or previously incarcerated people who inject drugs. Scaling up of opioid agonist therapies within prisons and maintaining treatment after release would yield the greatest HIV transmission reduction in people who inject drugs. Additional analyses also suggest that at least 6% of all incident tuberculosis cases, and 75% of incident tuberculosis cases in people who inject drugs are due to incarceration. Interventions that reduce incarceration itself and effectively intervene with prisoners to screen, diagnose, and treat addiction and HIV, hepatitis C virus, and tuberculosis are urgently needed to stem the multiple overlapping epidemics concentrated in prisons.

Theory, measurement and hard times: some issues for HIV/AIDS research.

Economic and political instability and related “big events” are widespread throughout the globe. Although they sometimes lead to epidemic HIV outbreaks, sometimes they do not—and we do not understand why. Current behavioural theories do not adequately address these processes, and thus cannot provide optimal guidance for effective intervention. Based in part on a critique of our prior “pathways” model of big events, we suggest that cultural–historical activity theory (CHAT) may provide a useful framework for HIV research in this area. Using CHAT concepts, we also suggest a number of areas in which new measures should be developed to make such research possible.ResumenLa inestabilidad económica y política y los “grandes eventos” asociados con ella están muy extendidas en todo el mundo. Los “grandes eventos” a veces conducen a brotes epidémicos de VIH, y a veces no, y no entendemos por qué. Las actuales teorías del comportamiento no abordan adecuadamente estos procesos, y por lo tanto no pueden proveer una óptima orientación para una efectiva intervención. Basándonos en parte en una crítica a nuestro modelo de las “vías” que se interconectan durante los grandes eventos, sugerimos que la Teoría de la Actividad Histórico-Cultural (CHAT en ingles) puede proporcionar un marco útil para la investigación del VIH en esta área. Utilizamos conceptos de CHAT y también sugerimos una serie de áreas en las que las nuevas medidas se deben desarrollar para hacer posible este tipo de investigación.

Socially-Integrated Transdisciplinary HIV Prevention

Current ideas about HIV prevention include a mixture of primarily biomedical interventions, socio-mechanical interventions such as sterile syringe and condom distribution, and behavioral interventions. This article presents a framework for socially-integrated transdisciplinary HIV prevention that may improve current prevention efforts. It first describes one socially-integrated transdisciplinary intervention project, the Transmission Reduction Intervention Project. We focus on how social aspects of the intervention integrate its component parts across disciplines and processes at different levels of analysis. We then present socially-integrated perspectives about how to improve combination antiretroviral treatment (cART) processes at the population level in order to solve the problems of the treatment cascade and make “treatment as prevention” more effective. Finally, we discuss some remaining problems and issues in such a social transdisciplinary intervention in the hope that other researchers and public health agents will develop additional socially-integrated interventions for HIV and other diseases.ResumenLas ideas actuales sobre prevención del VIH incluyen una mezcla de intervenciones biomédicas primariamente -, intervenciones socio-mecánicas tales como la distribución de jeringas estériles y preservativos e intervenciones conductuales. Este artículo presenta un marco transdisciplinario y socialmente integrado para la prevención del VIH que puede mejorar los esfuerzos de prevención actuales. En primer lugar, se describe un proyecto de intervención transdisciplinario socialmente integrado: Proyecto de Intervención para Reducción de Transmisión. Nos centramos en cómo los aspectos sociales de la intervención integran sus componentes en todas las disciplinas y los procesos en diferentes niveles de análisis. A continuación, presentamos las perspectivas socialmente integradas sobre cómo mejorar los procesos de tratamiento antirretroviral combinado (TARC) a nivel de la población con el fin de resolver los problemas de cascada de tratamiento y hacer “tratamiento como prevención” más eficaz. Finalmente, se discuten algunos problemas pendientes en la descrita intervención transdisciplinaria en la esperanza de que otros investigadores y agentes de salud pública desarrollen otras intervenciones socialmente integradas para el VIH y otras enfermedades.

A network intervention that locates and intervenes with recently HIV-infected persons: The Transmission Reduction Intervention Project (TRIP)

Early treatment, soon after infection, reduces HIV transmissions and benefits patients. The Transmission Reduction Intervention Project (TRIP) evaluated a network intervention to detect individuals recently infected (in the past 6 months). TRIP was conducted in Greece (2013–2015) and focused on drug injector networks. Based on HIV status, testing history, and the results of an assay to detect recent infections, TRIP classified drug injector “Seeds” into groups: Recent Seeds (RS), and Control Seeds with Long-term HIV infection (LCS). The network members of RS and LCS were traced for two steps. The analysis included 23 RS, 171 network members of the RS, 19 LCS, and 65 network members of the LCS. The per-seed number of recents detected in the network of RS was 5 times the number in the network of LCS (Ratio RS vs. LCS: 5.23; 95% Confidence Interval (CI): 1.54–27.61). The proportion of recents among HIV positives in the network of RS (27%) was approximately 3 times (Ratio RS vs. LCS: 3.30; 95% CI: 1.04–10.43) that in the network of LCS (8%). Strategic network tracing that starts with recently infected persons could support public health efforts to find and treat people early in their HIV infection.

Risk network approaches to locating undiagnosed HIV cases in Odessa, Ukraine

Providing HIV healthcare and Treatment as Prevention both depend on diagnosing HIV cases, preferably soon after initial infection. We hypothesized that tracing risk networks recruits higher proportions of undiagnosed positives than outreach‐based testing or respondent‐driven sampling (RDS) in Odessa, Ukraine.

Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects.

Objective:Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. Design:Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. Method:We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. Results:In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post–first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. Conclusion:As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID. Growing PWID populations in the developing world, where primary prevention is scarce, constitutes a public health time bomb.

Molecular Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)–Infected Individuals in a Network-Based Intervention (Transmission Reduction Intervention Project): Phylogenetics Identify HIV-1–Infected Individuals With Social Links

Background The Transmission Reduction Intervention Project (TRIP) is a network-based intervention that aims at decreasing human immunodeficiency virus type 1 (HIV-1) spread. We herein explore associations between transmission links as estimated by phylogenetic analyses, and social network-based ties among persons who inject drugs (PWID) recruited in TRIP. Methods Phylogenetic trees were inferred from HIV-1 sequences of TRIP participants. Highly supported phylogenetic clusters (transmission clusters) were those fulfilling 3 different phylogenetic confidence criteria. Social network-based ties (injecting or sexual partners, same venue engagement) were determined based on personal interviews, recruitment links, and field observation. Results TRIP recruited 356 individuals (90.2% PWID) including HIV-negative controls; recently HIV-infected seeds; long-term HIV-infected seeds; and their social network members. Of the 150 HIV-infected participants, 118 (78.7%) were phylogenetically analyzed. Phylogenetic analyses suggested the existence of 13 transmission clusters with 32 sequences. Seven of these clusters included 14 individuals (14/32 [43.8%]) who also had social ties with at least 1 member of their cluster. This proportion was significantly higher than what was expected by chance. Conclusions Molecular methods can identify HIV-infected people socially linked with another person in about half of the phylogenetic clusters. This could help public health efforts to locate individuals in networks with high transmission rates.

Molecular epidemiology reveals the role of war in the spread of HIV in Ukraine.

Significance Current conflict in the heavily HIV-affected regions of eastern Ukraine, which caused the relocation of 1.7 million people, may have increased the exportation of the virus from war-affected regions to other parts of the country. We show that the large-scale war-initiated movement of people (including those HIV-infected) was associated with patterns of HIV movement reconstructed from gene-sequence data. Our results further suggest that virus dissemination was directed to the locations with the highest prevalence of risky sexual practices in people who inject drugs (PWID). Recently, the Ukrainian HIV epidemic has been transitioning from being PWID-concentrated to sexually driven. Our study helps to understand the factors that might facilitate this shift. Ukraine has one of the largest HIV epidemics in Europe, historically driven by people who inject drugs (PWID). The epidemic showed signs of stabilization in 2012, but the recent war in eastern Ukraine may be reigniting virus spread. We investigated the movement of HIV-infected people within Ukraine before and during the conflict. We analyzed HIV-1 subtype-A pol nucleotide sequences sampled during 2012–2015 from 427 patients of 24 regional AIDS centers and used phylogeographic analysis to reconstruct virus movement among different locations in Ukraine. We then tested for correlations between reported PWID behaviors and reconstructed patterns of virus spread. Our analyses suggest that Donetsk and Lugansk, two cities not controlled by the Ukrainian government in eastern Ukraine, were significant exporters of the virus to the rest of the country. Additional analyses showed that viral dissemination within the country changed after 2013. Spearman correlation analysis showed that incoming virus flow was correlated with the number of HIV-infected internally displaced people. Additionally, there was a correlation between more intensive virus movement and locations with a higher proportion of PWID practicing risky sexual behaviors. Our findings suggest that effective prevention responses should involve internally displaced people and people who frequently travel to war-affected regions. Scale-up of harm reduction services for PWID will be an important factor in preventing new local HIV outbreaks in Ukraine.

Relying on injection drug users to prevent HIV in Ukraine - follow-up results of peer-driven interventions

Conventional harm reduction (HR) projects overlook IDUs’ capabilities in offering them services but no active roles to play in preventing HIV. In contrast, “peer-driven interventions” (PDIs) offer IDUs rewards to educate and recruit peers for services. All IDU-recruits receive the opportunity to play both roles.

Pockets of HIV Non-infection Within Highly-Infected Risk Networks in Athens, Greece

As part of a network study of HIV infection among people who inject drugs (PWID) and their contacts, we discovered a connected subcomponent of 29 uninfected PWID. In the context of a just-declining large epidemic outbreak, this raised a question: What explains the existence of large pockets of uninfected people? Possible explanations include “firewall effects” (Friedman et al., 2000; Dombrowski et al., 2017) wherein the only HIV+ people that the uninfected take risks with have low viral loads; “bottleneck effects” wherein few network paths into the pocket of non-infection exist; low levels of risk behavior; and an impending outbreak. We considered each of these. Participants provided information on their enhanced sexual and injection networks and assisted us in recruiting network members. The largest connected component had 241 members. Data on risk behaviors in the last 6 months were collected at the individual level. Recent infection was determined by LAg (SediaTM Biosciences Corporation), data on recent seronegative tests, and viral load. HIV RNA was quantified using Artus HI Virus-1 RG RT-PCR (Qiagen). The 29 members of the connected subcomponent of uninfected participants were connected (network distance = 1) to 17 recently-infected and 24 long-term infected participants. Fourteen (48%) of these 29 uninfected were classified as “extremely high risk” because they self-reported syringe sharing and had at least one injection partner with viral load >100,000 copies/mL who also reported syringe sharing. Seventeen of the 29 uninfected were re-interviewed after 6 months, but none had seroconverted. These findings show the power of network research in discovering infection patterns that standard individual-level studies cannot. Theoretical development and exploratory network research studies may be needed to understand these findings and deepen our understanding of how HIV does and does not spread through communities. Finally, the methods developed here provide practical tools to study “bottleneck” and “firewall” network hypotheses in practice.