title: HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.
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.
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: T Déirdre
authors.initials: TD
authors.lastname: Hollingsworth
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: George
authors.initials: G
authors.lastname: Shirreff
authors.forename: Christl A
authors.initials: CA
authors.lastname: Donnelly
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.forename: Noah
authors.initials: N
authors.lastname: Kiwanuka
authors.forename: Fred
authors.initials: F
authors.lastname: Nalugoda
authors.forename: Aleisha
authors.initials: A
authors.lastname: Collinson-Streng
authors.forename: Victor
authors.initials: V
authors.lastname: Ssempijja
authors.forename: William P
authors.initials: WP
authors.lastname: Hanage
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.forename: Christophe
authors.initials: C
authors.lastname: Fraser
mesh_terms: D000293:Adolescent; D000328:Adult; D019143:Evolution, Molecular; D005191:Family Characteristics; D005260:Female; D008040:Genetic Linkage; D015658:HIV Infections / Q000453:epidemiology / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development* / Q000472:pathogenicity; D006306:Health Surveys; D006801:Humans; D008297:Male; D010802:Phylogeny; D012367:RNA, Viral / Q000032:analysis; D012189:Retrospective Studies; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load / Q000706:statistics & numerical data*; D014774:Virulence; D055815:Young Adult
chemical_list: D012367:RNA, Viral
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