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

PLoS One. 2010 Sep 13;5(9):e12598. doi: 10.1371/journal.pone.0012598.

Abstract

Background: 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 (ART), therapeutic vaccines, and other non-ART interventions.

Methodology/principal findings: We 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.

Conclusions/significance: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa, Eastern
  • Africa, Southern
  • Anti-HIV Agents / therapeutic use
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy
  • HIV Infections / prevention & control*
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • HIV-1 / physiology
  • Heterosexuality*
  • Humans
  • Male
  • RNA, Viral / blood*
  • RNA, Viral / genetics
  • Risk Factors
  • Sexual Partners
  • Viral Load

Substances

  • Anti-HIV Agents
  • RNA, Viral