title: Cumulative impact of host and viral factors on HIV-1 viral-load control during early infection.
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.
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Yue
authors.forename: Heather A
authors.initials: HA
authors.lastname: Prentice
authors.forename: Paul
authors.initials: P
authors.lastname: Farmer
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Dongning
authors.initials: D
authors.lastname: He
authors.forename: Shabir
authors.initials: S
authors.lastname: Lakhi
authors.forename: Paul
authors.initials: P
authors.lastname: Goepfert
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D019562:Viral Load; D015024:Zambia
chemical_list: D015395:Histocompatibility Antigens Class I