Treatment of HIV-infected people with antiretroviral drugs for the purpose of preventing new infections is gaining support as a public health control strategy. This approach is a shift away from the normal paradigm of using antiretroviral therapy (ART) for the sole objective of keeping HIV-infected people alive, reversing AIDS-defining diseases and improving their health. We are now in a new era wherein the secondary benefits of ART can be considered. The potential population-level impact of ART for prevention has been investigated with mathematical transmission models [1–6]. Models can yield important insights when they are appropriately designed and informed by reliable empirical data. Some of the models used to explore ‘treatment as prevention’ have been criticized due to their structures, assumptions and infeasibility of their applications . However, the new model-based analysis by Johnston et al.  contributes important dimensions to the evaluation of this potential strategy. Their analysis was based on a realistic model with generally appropriate assumptions and they explored the potential population-level impact of reasonable expansions of ART to HIV-infected individuals who are treatment-eligible according to current clinical guidelines. Importantly, they also conservatively assessed that this strategy is likely to be cost-effective.
The most important parameter in any consideration of treatment as prevention is the relative reduction in transmission due to the use of ART. It is important to note that, currently, there are no data available to inform this most crucial parameter for the routes of exposure that are known to be of greatest risk. Studies that have measured associations between viral load and infectiousness or the relative reduction in incidence due to ART have all been conducted among heterosexual couples [9–12]. Currently, there is no reliable measure for the relative reduction in infectiousness due to ART associated with exposure events that are more risky than penile–vaginal sex. The rates of transmission associated with penile–anal sex [13–15] and sharing of injecting equipment or needle-stick injury [16–25] are at least one order of magnitude greater than the risk associated with penile–vaginal sex [26–27]. As ART substantially reduces HIV-RNA in plasma and genital fluids [28–31], it can be expected that infectiousness is decreased due to ART for these riskier exposure routes. However, it is plausible that the degree of reduction in risk will be different to that estimated among heterosexual couples. Emerging data from some cohorts and populations of men who have sex with men (MSM) suggest that HIV incidence has decreased with ART, but not by the extent observed among heterosexuals [31–33]. Similarly, there appears to be an association between incidence and community viral load for people who inject drugs , but the degree of reduction in infectiousness for people on ART is unknown. Consequently, the analysis of Johnston et al. , applied to British Columbia that has a concentrated epidemic with the majority of infections occurring among MSM and people who inject drugs, should be reviewed cautiously.
It is likely to be difficult to empirically estimate the relative reduction in infectiousness due to ART associated with penile–anal or injection-related transmission. These riskier transmission routes are important for the spread of HIV worldwide. Therefore, any public health strategies that may reduce these transmission risks should be considered. However, in the absence of empirical data on the effect of ART on infectiousness, any model-based evaluation should also be accompanied by an extensive uncertainty and sensitivity analysis, including assumptions that transmission rates do not decrease for transmission routes of injecting or male homosexual contact to the same extent as for heterosexual contact.
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