Estimating the impact of plasma HIV-1 RNA reductions on heterosexual HIV-1 transmission risk.

Sexual transmission

Estimating the impact of plasma HIV-1 RNA reductions on heterosexual HIV-1 transmission risk.

The risk of sexual transmission of HIV-1 is strongly associated with the level of HIV-1 RNA in plasma making reduction in HIV-1 plasma levels an important target for HIV-1 prevention interventions. A quantitative understanding of the relationship of plasma HIV-1 RNA and HIV-1 transmission risk could help predict the impact of candidate HIV-1 prevention interventions that operate by reducing plasma HIV-1 levels, such as antiretroviral therapy, therapeutic vaccines, and other non-antiretroviral therapy interventions. The authors use prospective data collected from 2004 to 2008 in East and Southern African HIV-1 serodiscordant couples to model the relationship of plasma HIV-1 RNA levels and heterosexual transmission risk with confirmation of HIV-1 transmission events by HIV-1 sequencing. The model is based on follow-up of 3381 HIV-1 serodiscordant couples over 5017 person-years encompassing 108 genetically-linked HIV-1 transmission events. HIV-1 transmission risk was 2.27 per 100 person-years with a log-linear relationship to log(10) plasma HIV-1 RNA. The model predicts that a decrease in average plasma HIV-1 RNA of 0.74 log(10) copies/mL (95% CI 0.60 to 0.97) reduces heterosexual transmission risk by 50%, regardless of the average starting plasma HIV-1 level in the population and independent of other HIV-1-related population characteristics. In a simulated population with a similar plasma HIV-1 RNA distribution the model estimates that 90% of overall HIV-1 infections averted by a 0.74 copies/mL reduction in plasma HIV-1 RNA could be achieved by targeting this reduction to the 58% of the cohort with plasma HIV-1 levels ≥4 log(10) copies/mL. This log-linear model of plasma HIV-1 levels and risk of sexual HIV-1 transmission may help estimate the impact on HIV-1 transmission and infections averted from candidate interventions that reduce plasma HIV-1 RNA levels.

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Editors’ note: This large prospective cohort of serodiscordant couples has already informed us that herpes suppression with acyclovir at standard doses doesn’t bring down plasma viral load enough to decrease HIV transmission (http://hivthisweek.unaids.org/post/herpes-and-hiv) and that antiretroviral therapy can reduce the risk of sexual transmission by 92% (http://hivthisweek.unaids.org/post/sexual-transmission-1). Here the authors apply their data on genetically linked transmissions within couples to model population-level effects of reductions in viral load on HIV transmission. The current high cost and poor availability of plasma HIV viral load monitoring limit the application of their findings in most settings but they are nonetheless tantalizing. The model predicts that if antiretroviral therapy could be provided to the people living with HIV who have plasma viral loads above 4 log (10)/mL (less than 60% of those living with HIV), HIV transmission would decline by 50% in a population and 90% of new infections could be averted. This should spur on efforts to develop and implement low cost, accessible viral load testing. Certainly, it will help us assess the potential prevention benefit of reductions in plasma viral load achieved through treatment of concurrent infections such as herpes simplex, schistosomiasis, and other opportunisitic and endemic infections.