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PHYLOGENETIC ANALYSIS OF HIV FROM PWID IN EASTERN EUROPE AND ASIA: HPTN074
Mariya V. Sivay1, Philip J. Palumbo1, Yinfeng Zhang1, Kate Grabowski1, Estelle Piwowar-Manning1, Xu Guo2, Erica Hamilton3, Vivian Go4, Kostyantyn Dumchev5, Zubairi Djoerban6, Brett Hanscom7, Irving Hoffman4, William C. Miller8, Susan H. Eshleman1
1Johns Hopkins University School of Medicine, Baltimore, MD,2Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA, USA,3FHI 360, Durham, NC, USA,4University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,5Ukrainian Institute on Public Health Policy, Kyiv, Ukraine,6University of Indonesia, Jakarta, Indonesia,7Fred Hutchinson Cancer Research Center, Seattle, WA, USA,8The Ohio State University, Columbus, OH, USA
HPTN 074 is evaluating the efficacy and feasibility of using an integrated intervention (support for HIV treatment and substance use treatment) to reduce HIV transmission among people who inject drugs (PWID) in Indonesia, Vietnam, and Ukraine. We used phylogenetic methods to evaluate the relationship between HIV strains in the HPTN 074 study population.
HPTN 074 enrolled HIV-infected PWID (index participants) with up to five concurrent HIV-uninfected injection partners per index. Index-partner pairs were randomized 1:3 to the integrated intervention vs. standard of care study arms. HIV genotyping (pol region) was performed using the ViroSeq-1 HIV Genotyping System for 502 index participants and 7 partners who seroconverted during the study. Phylogenetic analysis was performed using RAxML v8.10.2. Individuals were considered to form a transmission cluster if the genetic distance of their sequences was ≤0.015 with ≥90% branch support. HIV strains from participants in pol transmission clusters were also analyzed using next-generation sequencing (NGS, env region). Participants were considered to have linked infections if their env sequences formed a distinct monophyletic cluster with ≥90% bootstrap support.
Pol sequences were obtained for 452/509 HIV-infected participants (445 indexes, 7 seroconverters). Median pairwise genetic distances for sequences from each study site were 2.9%-3.3%; there was no evidence of large discrete subclades at any of the three sites. Linkage results from pol and NGS-env analyses were concordant for all 7 seroconverter cases. The index and partner were linked in 2/7 cases; in addition, two unrelated partners were linked. In addition, 15 index-index clusters were identified that included 36 indexes with 2-7 indexes per cluster (13 pairs, one triplet, one cluster of 7 indexes). Individuals in each cluster were from the same study site; the cluster of 7 indexes was from Vietnam. NGS-env data was available for 14/15 index-index clusters; this confirmed linkage for 11 (78.6%) of the 14 index-index clusters.
Analyses of HIV pol and NGS-env sequences revealed linked infections involving index-partner pairs, a partner-partner pair, and index-index groups that included 2-7 individuals. These findings suggest that there are complex patterns of HIV transmission among PWID in these communities, which should be considered when designing interventions for HIV prevention.