Phylogenetic Analysis of HIV from People Who Inject Drugs in Indonesia, Ukraine, and Vietnam: HPTN 074

Background: HPTN 074 evaluated an HIV prevention intervention for persons who inject drugs (PWID) that included support for HIV and substance use treatment. The study enrolled HIV-infected index participants and HIV-uninfected injection partners (up to five per index) in Indonesia, Ukraine, and Vietnam. Seven partners acquired HIV infection during the study. We analyzed the relationship between HIV strains in this cohort. Methods: HIV from index participants and their partners was sequenced using the ViroSeq HIV-1 Genotyping System. Phylogenetic trees were constructed using RAxML v8.2.10. Pol sequence clusters were identified that had a genetic distance ≤1.5% with ≥90% branch support. Next generation sequencing (NGS, env region) was also performed for the seven seroconverters and the corresponding index participants (index-partner pairs) and from other index participants in pol sequence clusters. Participants were classified as having linked infections if their env sequences formed a distinct monophyletic cluster with ≥90% bootstrap support Findings: Phylogenetic analysis included pol sequences from 445 of 502 index participants and all seven HIV-infected partners. The median pairwise genetic distance at the three study sites ranged from 2.9% to 3.3% with no evidence of large discrete subclades. Eighteen pol clusters were identified, including two of the seven index-partner pairs, one pair of partners enrolled with different indexes, and 15 index-only groups including 36 participants (2-7 index participants per cluster). NGS-env analysis confirmed linkage for both index-partner clusters, the partner-partner cluster, and 11 index-index clusters. Interpretation: Only two of the seven index-partner pairs in this study had genetically-linked HIV infections. Clusters were also identified that included two partners enrolled with different indexes, and groups of 2-7 index participants. These findings suggest that individuals in these PWID communities have exposure to multiple sources of HIV infection. This should be considered when designing strategies for HIV prevention in these high-risk populations. Trial Registration Number: In this report, we analyzed HIV from PWID enrolled in a randomized clinical trial conducted in Indonesia, Ukraine, and Vietnam (HIV Prevention Trials Network [HPTN] 074) Funding Statement: National Institute of Allergy and Infectious Diseases (NIAID), National Institute on Drug Abuse (NIDA), and Office of AIDS Research, of the National Institutes of Health (NIH). Declaration of Interests: None of the authors has a conflict of interest or potential conflict of interest, with the following exceptions: Susan Eshleman has collaborated on research studies with investigators from Abbott Laboratories (distributor of the ViroSeq HIV-1 Genotyping System); Abbott Laboratories has provided reagents for collaborative research studies. Ethics Approval Statement: Written informed consent was signed by each participant in the HPTN 074 trial. The study was approved by institutional review boards and ethics committees of the participating institutions in the United States and at each study site.