Timing and source of subtype-C HIV-1 superinfection in the newly infected partner of Zambian couples with disparate viruses

• Type of Material: Article
• Authors: Colleen S Kraft, Emory University; Debby Basu, Emory University; Paulina A Hawkins, Emory University; Peter T Hraber, Los Alamos National Laboratory; Elwyn Chomba, Zambia Emory HIV Research Project; Joseph Mulenga, Zambia Emory HIV Research Project; William Kilembe, Zambia Emory HIV Research Project; Naw H Khu, Emory University; Cynthia Derdeyn, Emory University; Susan A Allen, Emory University; Olivier Manigart, Emory University; Eric Hunter, Emory University
• Language: English
• Date: 2012-03-20
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: ©2012 Kraft et al; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.ncbi.nlm.nih.gov/pubmed/22433432
• Title of Journal or Parent Work: Retrovirology
• Volume: 9
• Start Page: 22
• End Page: 22
• Grant/Funding Information: The Fogarty AITRP grant (D43 TW001042) sponsored WK.; The work was supported by grants from the National Institutes of Health (AI-51231; MH-66767; HD-40951) and the International AIDS Vaccine Initiative.; An NRSA Institutional Postdoctoral Training Grant T32 AI-007470 through the Emory Microbiology and Molecular Genetics Program and National Institutes of Health/National Center for Research Resources KL2 RR-025009 supported CSK.; The Virology Core of the Emory Center for AIDS Research (P30 AI050409) provided support for viral load testing.; Funding institutions played no role in the conduct of these studies or in the preparation, review or approval of the manuscript.; NIH AI-0678501 supported PTH.
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Public Health

Abstract

Background HIV-1 superinfection occurs at varying frequencies in different at risk populations. Though seroincidence is decreased, in the negative partner of HIV-discordant couples after joint testing and counseling in the Zambia Emory HIV Research Project (ZEHRP) cohort, the annual infection rate remains relatively high at 7-8%. Based on sequencing within the gp41 region of each partner's virus, 24% of new infections between 2004 and 2008 were the result of transmission from a non-spousal partner. Since these seroconvertors and their spouses have disparate epidemiologically-unlinked viruses, there is a risk of superinfection within the marriage. We have, therefore, investigated the incidence and viral origin of superinfection in these couples. Results Superinfection was detected by heteroduplex mobility assay (HMA), degenerate base counting of the gp41 sequence, or by phylogenetic analysis of the longitudinal sequences. It was confirmed by full-length env single genome amplification and phylogenetic analysis. In 22 couples (44 individuals), followed for up to five years, three of the newly infected (initially HIV uninfected) partners became superinfected. In each case superinfection occurred during the first 12 months following initial infection of the negative partner, and in each case the superinfecting virus was derived from a non-spousal partner. In addition, one probable case of intra-couple HIV-1 superinfection was observed in a chronically infected partner at the time of his seroconverting spouse's initial viremia. Extensive recombination within the env gene was observed following superinfection. Conclusions In this subtype-C discordant couple cohort, superinfection, during the first year after HIV-1 infection of the previously negative partner, occurred at a rate similar to primary infection (13.6% [95% CI 5.2-34.8] vs 7.8% [7.1-8.6]). While limited intra-couple superinfection may in part reflect continued condom usage within couples, this and our lack of detecting newly superinfected individuals after one year of primary infection raise the possibility that immunological resistance to intra-subtype superinfection may develop over time in subtype C infected individuals.