Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa

• Type of Material: Article
• Authors: Pauli N. Amornkul, International AIDS Vaccine Initiative; Etienne Karita, Project San Francisco; Anatoli Kamali, Medical Research Council/Uganda Virus Research Unit; Wasima N. Rida, Biostatistics Consultant; Eduard J. Sanders, University of Oxford; Shabir Lakhi, Emory University; Matt A. Price, International AIDS Vaccine Initiative; William Kilembe, Zambia-Emory HIV Research Project; Emmanuel Cormier, International AIDS Vaccine Initiative; Omu Anzala, University of Nairobi; Mary H. Latka, Aurum Institute; Linda-Gail Bekker, University of Cape Town; Susan Allen, Emory University; Jill Gilmour, Imperial College London; Patricia E. Fast, International AIDS Vaccine Initiative
• Language: English
• Date: 2013-11-13
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: Lippincott Williams & Wilkins.; © 2013 Wolters Kluwer Health
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1097/QAD.0000000000000012
• Title of Journal or Parent Work: AIDS
• ISSN: 0269-9370
• Volume: 27
• Issue: 17
• Start Page: 2775
• End Page: 2786
• Grant/Funding Information: Funding source: Primary: United States Agency for International Development (USAID).; This work was made possible in part by the generous support of the American people through the United States Agency for International Development (USAID).; We also thank the study funders: Becton, Dickinson and Company; Bill and Melinda Gates Foundation; Bristol-Meyers Squibb; Canadian International Development Agency; Dutch Product Development Partnership Fund; European Commission South Africa; Foundation for the National Institute of Health; John Evans Foundation; Medical Research Council; Norwegian Agency for Development Corporation; Organization of the Petroleum Exporting Countries (OPEC) Fund for International Development; Pfizer, Inc.; Spain Ministry of Foreign Affairs; Swedish International Development Agency; United Kingdom Department for International Development; United States Agency for International Development (USAID); and World Bank.
• Keywords: Africa South of the Sahara; Middle Aged; Longitudinal Studies; AIDS; Cohort Studies; CD4+ cell count; Prospective Studies; CD4 Lymphocyte Count; HIV Infections; HIV disease progression; Viral load; Adolescent; HIV-1 subtype; Adult; Viral Load; HIV-serodiscordant couples; Disease Progression; Female; HIV-1; Young Adult; Africa; Humans; Men who have sex with men; Male
• Research Categories: Biology, Virology; Health Sciences, Immunology; Health Sciences, Public Health

Abstract

Objective: To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs). Design: Prospective cohort. Methods: Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals. Blood for lymphocyte subset and viral load determination was collected at each visit. Pol was sequenced from the first positive specimen to ascertain subtype. Preantiretroviral therapy disease progression was measured by three time-toevent endpoints: CD4 + cell count 350 cells/ml or less, viral load measurement at least 1*105 copies/ml, and clinical AIDS. Results: From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed. Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%). After adjustment for age, sex, and human leukocyte antigen alleles in Cox regression analyses, subtype C-infected participants progressed faster than subtype A to all three endpoints [CD4 + hazard ratio 1.60, 95% (confidence interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93, 95% CI 1.21, 3.09). Conclusion: Subtype-specific differences in HIV disease progression suggest that the local subtype distribution be considered when planning HIV programs and designing and defining clinical endpoints for HIV prevention trials.