The contribution of viral genotype to plasma viral set-point in HIV infection

TitleThe contribution of viral genotype to plasma viral set-point in HIV infection
Publication TypeJournal Article
Year of Publication2014
AuthorsHodcroft EB, Hadfield J, Fearnhill E, Phillips A, Dunn D, O’Shea S, Pillay D, Leigh Brown A.J
JournalPLoS Pathog
Volume10
Paginatione1004112
Date Published2014-05
ISBN Number1553-7366
Accession Number24789308
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Female, Genotype, HIV Infections/blood/epidemiology/*virology, HIV-1/classification/*genetics, Humans, Male, Middle Aged, Molecular Sequence Data, Phylogeny, Viral Load/*genetics, Young Adult
Abstract

Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8-8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms.

Short TitlePLoS pathogens
Alternate JournalPLoS pathogens