The Contribution of Viral Genotype to Plasma Viral Set-Point in HIV Infection

Emma Hodcroft, Jarrod D. Hadfield, Esther Fearnhill, Andrew Phillips, David Dunn, Siobhan O'Shea, Deenan Pillay, Andrew J. Leigh Brown, Aitken Celia, Asboe David, Pozniak Anton, Patricia Cane, Castro Hannah, Dunn David, Fearnhill Esther, Porter Kholoud, Chadwick David, Churchill Duncan, Clark Duncan, Collins SimonDelpech Valerie, Douthwaite Samuel, Maria Geretti Anna, Hale Antony, Hué Stéphane, Kaye Steve, Kellam Paul, Lazarus Linda, Leigh Brown Andrew, Mbisa Tamyo, Mackie Nicola, Orkin Chloe, Nastouli Eleni, Pillay Deenan, Phillips Andrew, Sabin Caroline, Smit Erasmus, Templeton Kate, Tilston Peter, Webster Daniel, Williams Ian, Zhang Hongyi, Zuckerman Mark, Ainsworth Jonathan, Allan Sris, Anderson Jane, Babiker Abdel, Chadwick David, Dunn David, Fisher Martin, Gazzard (Chair) Brian, Gilson Richard, Gompels Mark, Hay Phillip, Hill Teresa, Johnson Margaret, Kegg Stephen, Leen Clifford, Martin Fabiola, Nelson Mark, Orkin Chloe, Palfreeman Adrian, Phillips Andrew, Pillay Deenan, Pritchard Jillian, Post Frank, Sabin Caroline, Sachikonye Memory, Schwenk Achim, Tariq Anjum, Walsh John

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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.

Original languageEnglish
Article numbere1004112
JournalPLoS Pathogens
Volume10
Issue number5
DOIs
Publication statusPublished - May 2014

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