Hollingsworth, T. Déirdre, Laeyendecker, Oliver, Shirreff, George, Donnelly, Christl A., Serwadda, David, Wawer, Maria, Kiwanuka, Noah, Nalugoda, Fred, Collinson-Streng, Aleisha, Ssempijja, Victor, Hanage, William P., Quinn, Thomas C., Gray, Ronald H. and Fraser, Christophe (2010) HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda. PLoS Pathogens, Volume 6 (Number 5). Article no. e1000876. doi:10.1371/journal.ppat.1000876 ISSN 1553-7374.

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Abstract

It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD) were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the ‘couple effect’). Individuals with suspected intra-couple transmission (97 couples) had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted) and the couple effect explained 16% of variance in viral loads (23% adjusted). The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted) and the size of the effect was 27% (37% adjusted). Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR355 Virology R Medicine > R Medicine (General) R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Science > Mathematics
Library of Congress Subject Headings (LCSH):	HIV-positive persons, HIV infections, Microbiology, Sexually transmitted diseases, AIDS (Disease), HIV infections -- Research -- Methodology
Journal or Publication Title:	PLoS Pathogens
Publisher:	PLOS
ISSN:	1553-7374
Official Date:	2010
Dates:	Date Event 2010 Published
Volume:	Volume 6
Number:	Number 5
Page Range:	Article no. e1000876
DOI:	10.1371/journal.ppat.1000876
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	23 December 2015
Date of first compliant Open Access:	23 December 2015
Funder:	Royal Society (Great Britain), Wellcome Trust (London, England), Medical Research Council (Great Britain) (MRC), National Institute of Allergy and Infectious Diseases (U.S.) (NIAID), Imperial College, London

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