The contribution of viral genotype to plasma viral set-point in HIV infection
File(s)
Author(s)
Type
Journal Article
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.
Date Issued
2014-05-01
Online Publication Date
2019-05-08T13:53:27Z
Date Acceptance
2014-03-22
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Pathogens
Volume
10
Issue
5
Copyright Statement
© 2014 Hodcroft et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000337732300028&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
HUMAN-IMMUNODEFICIENCY-VIRUS
CD4 CELL COUNTS
DISEASE PROGRESSION
RNA LEVELS
REVERSE-TRANSCRIPTASE
TEMPORAL TRENDS
LYMPHOCYTE COUNTS
MIXED MODELS
TRANSMISSION
SEROCONVERSION
Adolescent
Adult
Aged
Aged, 80 and over
Female
Genotype
HIV Infections
HIV-1
Humans
Male
Middle Aged
Molecular Sequence Data
Phylogeny
Viral Load
Young Adult
UK HIV Drug Resistance Database
UK CHIC Study
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Article Number
e1004112
Date Publish Online
2014-05-01