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

PLoS Pathog. 2010 May 6;6(5):e1000876. doi: 10.1371/journal.ppat.1000876.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Evolution, Molecular
  • Family Characteristics
  • Female
  • Genetic Linkage
  • HIV Infections / epidemiology
  • HIV Infections / transmission*
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • HIV-1 / growth & development*
  • HIV-1 / pathogenicity
  • Health Surveys
  • Humans
  • Male
  • Phylogeny
  • RNA, Viral / analysis
  • Retrospective Studies
  • Uganda / epidemiology
  • Viral Load / statistics & numerical data*
  • Virulence
  • Young Adult

Substances

  • RNA, Viral