Abstract

MOAX0103 - Oral Abstract Session

Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network (HPTN) 052 trial

Presented by Susan Eshleman (United States).

J. Hughes¹, S. Hudelson², A. Redd³, L. Wang⁴, R. Debes¹, Y. Chen⁴, S. Porcella⁵, E. Piwowar-Manning², M. McCauley⁶, M. Hosseinipour^7,8, J. Kumwenda⁹, J. Hakim¹⁰, S. Chariyalertsak¹¹, G. de Bruyn¹², B. Grinsztejn¹³, N. Kumarasamy¹⁴, J. Makhema¹⁵, K. Mayer¹⁶, J. Pilotto¹⁷, B. Santos¹⁸, T. Quinn^2,3, M. Cohen⁸, S. Eshleman², HPTN 052

¹University of Washington, Seattle, United States, ²Johns Hopkins University School of Medicine, Baltimore, United States, ³National Institutes of Health, Baltimore, United States, ⁴Fred Hutchinson Cancer Research Center, Seattle, United States, ⁵National Institutes of Health, Hamilton, United States, ⁶Family Health International, Arlington, United States, ⁷Kamuzu Central Hospital, Lilongwe, Malawi, ⁸University of North Carolina at Chapel Hill, Chapel Hill, United States, ⁹College of Medicine, Blantyre, Malawi, ¹⁰University of Zimbabwe, Harare, Zimbabwe, ¹¹Chiang Mai University, Chaing Mai, Thailand, ¹²University of the Witwatersrand, Johannesburg, South Africa, ¹³Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil, ¹⁴YRG Care Medical Center, Chennai, India, ¹⁵Botswana-Harvard School of Public Health AIDS Initiative Partnership, Gabarone, Botswana, ¹⁶Fenway Health, Boston, United States, ¹⁷Hospital Geral de Nova Iguaçu and Laboratorio de AIDS e Imunologia Molecular - IOC/Fiocruz, Rio de Janeiro, Brazil, ¹⁸Hospital Nossa Senhora da Conceicao, Porto Alegre, Brazil

Background: The HPTN 052 trial was designed to test whether early initiation of antiretroviral therapy (ART) reduces HIV transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. Serodiscordant couples (N=1,763, 97% heterosexual) were enrolled. HIV from index-partner pairs was analyzed to assess the genetic linkage of seroconversion events. In April 2011, a review of interim results including 39 seroconversion events demonstrated a significant benefit of early ART for prevention and treatment of HIV infection. This report describes the methods used to assess the linkage of HIV seroconversion events and the results of that analysis.
Methods: We analyzed HIV from 38 index-partner pairs (two samples / participant) and 80 unrelated index participants (controls); samples from one event were not available for analysis. The analysis included phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls. Selected samples were also analyzed using next generation sequencing (env region, gp41).
Results: Linkage status was determined for 36 of the 38 seroconversion events analyzed. In 29 (76.3%) of the 38 cases analyzed, the index was the likely source of the partner's HIV infection (linked events). In seven (18.4%) of the cases, the partner was most likely infected from a source other than the index participant (unlinked events). The linkage status of two (5.3%) of the events could not be determined based on available data.
Conclusion: Phylogenetic and Bayesian analysis of pol sequence data combined with phylogenetic analysis of env sequence data from next generation sequencing was capable of linking transmission events, allowing more accurate assessment of the efficacy of early ART for HIV prevention. Nearly one fifth of the seroconversion events in HPTN 052 were unlinked. This underscores the importance of assessing the genetic linkage of seroconversion events in HIV prevention studies.