Dynamics of viremia in primary HIV-1 infection in Africans: Insights from analyses of host and viral correlates

• Type of Material: Article
• Authors: Heather A. Prentice, University of Alabama Birmingham; Matthew A. Price, International AIDS Vaccine Initiative; Travis R. Porter, University of Alabama Birmingham; Emmanuel Cormier, International AIDS Vaccine Initiative; Michael J. Mugavero, University of Alabama Birmingham; Anatoli Kamali, MRC/UVRI Uganda Virus Research Unit on AIDS; Etienne Karita, Projet San Francisco; Shabir Lakhi, Zambia-Emory HIV Research Project; Eduard J. Sanders, Kenya Medical Research Institute; Omu Anzala, Kenya AIDS Vaccine Initiative; Pauli N. Amornkul, International AIDS Vaccine Initiative; Susan Allen, Emory University; Eric Hunter, Emory University; Richard A. Kaslow, University of Alabama Birmingham; Jill Gilmour, International AIDS Vaccine Initiative; Jianming Tang, University of Alabama Birmingham
• Language: English
• Date: 2014-01-20
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2013.11.024
• Title of Journal or Parent Work: Virology
• ISSN: 0042-6822
• Volume: 449
• Start Page: 254
• End Page: 262
• Grant/Funding Information: This work was funded by (i) the United States Agency for International Development (USAID) (to IAVI); (ii) United States National Institute of Allergy and Infectious Diseases (NIAID), through two R01 grants (AI071906 to R.A.K./J.T. and AI064060 to E.H.); (iii) Fogarty AIDS International Training and Research Program (AITRP) (grant FIC 2D43 TW001042 to S.L.).
• Keywords: Virology; HETEROSEXUAL TRANSMISSION; HIV-1; DISEASE PROGRESSION; PLASMA; SUBTYPE-A; Life Sciences & Biomedicine; SEROCONVERSION; LOAD; Science & Technology; Statistical models; Subtype; IMMUNODEFICIENCY-VIRUS TYPE-1; HLA; Africa; CLASS-I ALLELES; ANTIRETROVIRAL THERAPY; Viral load; ANTIGEN CLASS-I
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Pathology; Biology, Virology

Abstract

In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B*53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2-3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies.