Can we put a figure on the infectivity of HIV infection per coital act, and on the relative importance of the various determinants of transmission?
Estimates are needed in order to plan effective interventions. A recent paper, published in the Journal of Infectious Diseases (Hughes, Celum et al.), discussed by an editorial (Gray & Wawer) of the same issue, represents the latest attempt at estimating infectivity and its determinants for sub-Saharan Africa. The study was conducted on the back of a large randomized trial of HSV-2 suppression for prevention of HIV transmission between sero-discordant couples, and involved 3,293 couples at 14 sites in S and E Africa over a period of 24 months.
First the figures. Transmission per coital act was estimated at 0.0019 for male-to-female, and 0.001 for female-to-male. The major driver of transmission was HIV load in the infected partner: each log10 increment in viral load produced a 2.9 fold adjusted risk of transmission. Condom use reduced risk by 82%.
On the whole, these findings provide reassuring corroboration of the findings of earlier, smaller studies. The figure for overall infectivity is similar to that reported during the latent stage of HIV infection in low-income countries. Such a figure does not explain the rapid spread of the infection in many sub-Saharan settings – because, as Gray and Wawer point out, a study of this kind, involving stable sero-discordant couples, is unable to factor in the vastly higher levels of infectivity associated with early and late stage disease.
The figure of 2.9 for the multiplication of risk with log10 viral load increment is higher than prior estimates, and may reflect more precise estimates enabled in this study by quarterly viral load measurements (Lingappa, Hughes, Wang et al.).
Numerous earlier attempts to establish HIV infectivity and its determinants are surveyed in a recent meta-analysis (Boily, Baggaley and Wang et al.). Two things distinguish the present paper. The first is sheer scale: at 3,293 couples, the number of recruits exceeds considerably that of the next largest study (Fideli, Aldrovandi et al.), and far exceeds participation in previous studies (generally placed at <200 participant couples). The size of a study like this is an important factor because it enhances its ability to reliably estimate co-factors of transmission. The second distinguishing feature is the seriousness of the effort to estimate the number of sexual events: participant couples were interviewed about their sexual activity every month – a frequency that greatly exceeds the frequency of interviews in comparable studies. These factors, along with frequency of quarterly viral load measurements, seem to mark a considerable gain in reliability, as against earlier attempts to place a figure on latent HIV infectivity.
James P. Hughes, Connie Celum et al., “Determinants of Per-Coital-Act HIV-1 Infectivity Among African HIV-1- Serodiscordant Couples”, Journal of Infectious Diseases 205:3, January 2012
http://jid.oxfordjournals.org/content/205/3/358.full
Ronald H. Gray and Maria J. Wawer, “Probability of Heterosexual HIV-1 Transmission per Coital Act in Sub-Saharan Africa” (Editorial), Journal of infectious Diseases 205:3, January 2012
http://jid.oxfordjournals.org/content/205/3/351.full
J. R. Lingappa, J.P. Hughes, R.S. Wang et al., “Estimating the impact of plasma HIV-1 RNA reductions on herosexual HIV-1 transmission risk”, PLoS One 2010,10.1371/journal.pone.0012598
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012598
M. C. Boily, R.F. Baggaley, L. Wang et al. “Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies, Lancet Infectious Diseases 2009; vol. 9, no.2, Feb. 2009
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(09)70021-0/fulltext
U. S. Fideli, S. A. Allen, R. Musonda et al., “Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa”, AIDS Res Hum Retroviruses 2001; 17 (10): 901-10
http://www.ncbi.nlm.nih.gov/pubmed/11461676?dopt=Abstract