HIV-1 transmitting couples have similar viral load set-points in rakai, Uganda

T. Déirdre Hollingsworth, Oliver B. Laeyendecker, George Shirreff, Christl A. Donnelly, David Serwadda, Maria J Wawer, Noah Kiwanuka, Fred Nalugoda, Aleisha Collinson-Streng, Victor Ssempijja, William P. Hanage, Thomas C Quinn, Ronald H Gray, Christophe Fraser

Research output: Contribution to journalArticle

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 setpoint 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 setpoints (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.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalPLoS Pathogens
Volume6
Issue number5
DOIs
StatePublished - May 2010

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Uganda
Viral Load
HIV-1
HIV
Viruses
Genetic Linkage
Genetic Selection
Heterosexuality
Ulcer
Virulence
Analysis of Variance

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

HIV-1 transmitting couples have similar viral load set-points in rakai, Uganda. / Hollingsworth, T. Déirdre; Laeyendecker, Oliver B.; Shirreff, George; Donnelly, Christl A.; Serwadda, David; Wawer, Maria J; Kiwanuka, Noah; Nalugoda, Fred; Collinson-Streng, Aleisha; Ssempijja, Victor; Hanage, William P.; Quinn, Thomas C; Gray, Ronald H; Fraser, Christophe.

In: PLoS Pathogens, Vol. 6, No. 5, 05.2010, p. 1-9.

Research output: Contribution to journalArticle

Hollingsworth, TD, Laeyendecker, OB, Shirreff, G, Donnelly, CA, Serwadda, D, Wawer, MJ, Kiwanuka, N, Nalugoda, F, Collinson-Streng, A, Ssempijja, V, Hanage, WP, Quinn, TC, Gray, RH & Fraser, C 2010, 'HIV-1 transmitting couples have similar viral load set-points in rakai, Uganda', PLoS Pathogens, vol. 6, no. 5, pp. 1-9. https://doi.org/10.1371/journal.ppat.1000876
Hollingsworth, T. Déirdre ; Laeyendecker, Oliver B. ; Shirreff, George ; Donnelly, Christl A. ; Serwadda, David ; Wawer, Maria J ; Kiwanuka, Noah ; Nalugoda, Fred ; Collinson-Streng, Aleisha ; Ssempijja, Victor ; Hanage, William P. ; Quinn, Thomas C ; Gray, Ronald H ; Fraser, Christophe. / HIV-1 transmitting couples have similar viral load set-points in rakai, Uganda. In: PLoS Pathogens. 2010 ; Vol. 6, No. 5. pp. 1-9.
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