HIV This Week

Abbas UL, Anderson RM, Mellors JW. Potential Impact of Antiretroviral Chemoprophylaxis on HIV-1 Transmission in Resource-Limited Settings. PLoS ONE 2007 Sep 19;2(9):e875.

The potential impact of pre-exposure chemoprophylaxis (PrEP) on heterosexual transmission of HIV-1 infection in resource-limited settings is uncertain. A deterministic mathematical model was used to simulate the effects of antiretroviral PrEP on an HIV-1 epidemic in sub-Saharan Africa under different scenarios (optimistic, neutral and pessimistic) both with and without sexual disinhibition (risk compensation). Sensitivity analyses were used to evaluate the effect of uncertainty in input parameters on model output and included calculation of partial rank correlations and standardized rank regressions. In the scenario without sexual disinhibition (risk compensation) after PrEP initiation, key parameters influencing infections prevented were effectiveness of PrEP (partial rank correlation coefficient (PRCC) = 0.94), PrEP discontinuation rate (PRCC = -0.94), level of coverage (PRCC = 0.92), and time to achieve target coverage (PRCC = -0.82). In the scenario with sexual disinhibition (risk compensation), PrEP effectiveness and the extent of sexual disinhibition (risk compensation) had the greatest impact on prevention. An optimistic scenario of PrEP with 90% effectiveness and 75% coverage of the general population predicted a 74% decline in cumulative HIV-1 infections after 10 years, and a 28.8% decline with PrEP targeted to the groups at highest risk of HIV exposure (16% of the population). Even with a 100% increase in at-risk behaviour from sexual disinhibition (risk compensation), a beneficial effect (23.4%-62.7% decrease in infections) was seen with 90% effective PrEP across a broad range of coverage (25%-75%). Similar disinhibition (risk compensation) led to a rise in infections with lower effectiveness of PrEP (</=50%). Mathematical modelling supports the potential public health benefit of PrEP. Approximately 2.7 to 3.2 million new HIV-1 infections could be averted in southern sub-Saharan Africa over 10 years by targeting PrEP (having 90% effectiveness) to those at highest behavioural risk and by preventing sexual disinhibition (risk compensation). This benefit could be lost, however, by sexual disinhibition (risk compensation) and by high PrEP discontinuation, especially with lower PrEP effectiveness (</=50%).

Editors’ note: There are five phase III trials of pre-exposure prophylaxis (PrEP), using tenofovir disoproxil fumarate (TDF) or Tenofovir (TDF)/emtricitabine (FTC) or both, that are either in the field or due to start within the next few months. The study populations include discordant couples, men who have sex with men, women at higher risk of HIV exposure, injecting drug users and young heterosexuals. Attempting to model population level PrEP impact in the absence of trial results is hazardous. A clear message from this exercise however is that risk compensation, where people increase their risk behaviour because they perceive themselves to be less at risk, could counterbalance any benefit – a concern for any new addition to the prevention menu.