Cumulative Impact of Host and Viral Factors on HIV-1 Viral-Load Control during Early Infection

• Authors: Ling Yue, Emory University; Heather A. Prentice, University of Alabama at Birmingham; Paul Farmer, Emory University; Wei Song, University of Alabama at Birmingham; Dongning He, University of Alabama at Birmingham; Shabir Lakhi, Emory University; Paul Goepfert, University of Alabama at Birmingham; Jill Gilmour, International AIDS Vaccine Initiative; Susan A Allen, Emory University; Jianming Tang, University of Alabama at Birmingham; Richard A. Kaslow, University of Alabama at Birmingham; Eric Hunter, Emory University
• Journal Title: Journal of Virology
• Volume: Volume 87, Number 2
• Publisher: American Society for Microbiology | 2013-01, Pages 708-715
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1128/JVI.02118-12
• Subjects: Health Sciences, Pathology; Biology, Virology

Abstract

In HIV-1 infection, the early set-point viral load strongly predicts both viral transmission and disease progression. The factors responsible for the wide spectrum of set-point viral loads are complex and likely reflect an interplay between the transmitted virus and genetically defined factors in both the transmitting source partner and the seroconverter. Indeed, analysis of 195 transmission pairs from Lusaka, Zambia, revealed that the viral loads in transmitting source partners contributed only ∼2% of the variance in early set-point viral loads of seroconverters (P = 0.046 by univariable analysis). In multivariable models, early set-point viral loads in seroconverting partners were a complex function of (i) the viral load in the source partner, (ii) the gender of the seroconverter, (iii) specific HLA class I alleles in the newly infected partner, and (iv) sharing of HLA-I alleles between partners in a transmission pair. Each of these factors significantly and independently contributed to the set-point viral load in the newly infected partner, accounting for up to 37% of the variance observed and suggesting that many factors operate in concert to define the early virological phenotype in HIV-1 infection.