With regard to costs, opportunity costs, and ethical considerations, the desirability of orally administered PrEP must be established. We have argued that randomized clinical trials may not provide all the needed evidence when the intervention under consideration is one for which the outcome depends not only on physiologic responses to treatment but also on behavioral responses. In the case of PrEP, clinical trials may demonstrate physiologic efficacy but are unlikely to provide definitive information on adherence levels and risk compensation, key parameters in determining whether PrEP will lead to increased rather than decreased HIV transmission.
Significant opportunity costs exist. Available models of cost-effectiveness suggest that including the secondary benefits of reducing community viral load, TNT/TLC+, and PrEP may achieve similar cost per QALY subject to the caveat that models of PrEP did not fully account for the cost of maintaining counseling and compliance monitoring at levels provided in the randomized clinical trials. Such expenditure would be necessary to gain the level of clinical results indicated by the randomized clinical trials. Public health concerns underscore the importance of extensive active surveillance for resistant strains that could undermine existing treatment regimens. Compromising the effectiveness of current antiretroviral agents could impose huge societal costs.
Implementing PrEP at the expense of TNT/TLC+ would impose a large opportunity cost because TNT/TLC+ involves a relatively low-cost HIV test given to a large population with treatment of the small number of those who test positive. By contrast, PrEP involves dosing large numbers of uninfected individuals with costly medications for an extended period of time.
Studies suggest that PrEP could be cost-effective if targeted to "core transmitters" of HIV. However, success of a targeted strategy depends not only on the efficacy of PrEP, but also on levels of risk compensation. Targeted high-risk individuals may well exhibit more risky behaviors than the highly selected sample of randomized clinical trial participants. The randomized clinical trials provide behavioral risk counseling and incentives to adhere to the ARVs. At the same time, participants may practice safer behaviors because they are uncertain if they are receiving ARVs or placebo medications. The conditions of large-scale implementation of PrEP are substantially different from those in a randomized clinical trial and policy decisions must be made with consideration to cost-effectiveness, opportunity costs, and ethical issues of PrEP in practice.
Additional results from the randomized trials of PrEP are eagerly anticipated, and the CDC and NIH have begun designing communication and adherence strategies, developing eligibility criteria, and planning for the strategic monitoring of drug resistance.6,10
However, as many others have pointed out, it would be a mistake to treat PrEP or any other biomedical intervention as a silver bullet, applicable to all populations and desirable in all settings.
Orally administered PrEP expands the number of options that a successful prevention program could offer. However, the strategy cannot succeed if made at the expense of consistent reductions in risk-taking behaviors. Combination prevention is desirable, but in a world of limited resources, more spending on PrEP clearly implies less on other effective interventions. Findings from the randomized clinical trials that PrEP is efficacious should mark the beginning of the policy discussion, and not its end.