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.
Highlights
The severity of HIV-1 infection is thought to result from an interplay of factors in the host, the virus, and the environment
Previous work has shown that the most commonly observed viral load set-points are those intermediate viral load set-points which lead to the largest number of opportunities to transmit HIV-1 in an infectious person’s lifetime, balancing survival and infectiousness
This coincidence between the most common viral load set-points and the optimum for lifetime transmission could be the result of populationlevel selection acting on HIV-1
Summary
The severity of HIV-1 infection is thought to result from an interplay of factors in the host, the virus, and the environment (for instance the presence of co-infections). The existence of heritable viral factors influencing disease progression, and their contribution relative to other factors, is of interest for at least two reasons. Such factors, if they exist, have implications for how the virus influences the course of infection within an infected person. In this study we test for the existence of such factors by examining viral load set-points among transmitting couples. Viral load set-point is commonly used as a surrogate measure of the virulence of an infection since it is negatively associated with the time to AIDS and death [10]
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