HIV preexposure prophylaxis in the United States: impact on lifetime infection risk, clinical outcomes, and cost-effectiveness

Abstract

Background: The combination of tenofovir and emtricitabine shows promise as HIV preexposure prophylaxis (PrEP). We sought to forecast clinical, epidemiologic, and economic outcomes of PrEP, taking into account uncertainties regarding efficacy, the risks of developing drug resistance and toxicity, behavioral disinhibition, and drug costs.

Methods: We adapted a computer simulation of HIV acquisition, detection, and care to model PrEP among men who have sex with men and are at high risk of HIV infection (i.e., 1.6% mean annual incidence of HIV infection) in the United States. Base-case assumptions included 50% PrEP efficacy and monthly tenofovir-emtricitabine costs of $753. We used sensitivity analyses to examine the stability of results and to identify critical input parameters.

Results: In a cohort with a mean age of 34 years, PrEP reduced lifetime HIV infection risk from 44% to 25% and increased mean life expectancy from 39.9 to 40.7 years (21.7 to 22.2 discounted quality-adjusted life-years). Discounted mean lifetime treatment costs increased from $81,100 to $232,700 per person, indicating an incremental cost-effectiveness ratio of $298,000 per quality-adjusted life-year gained. Markedly larger reductions in lifetime infection risk (from 44% to 6%) were observed with the assumption of greater (90%) PrEP efficacy. More-favorable incremental cost-effectiveness ratios were obtained by targeting younger populations with a higher incidence of infection and by improvements in the efficacy and cost of PrEP.

Conclusions: PrEP could substantially reduce the incidence of HIV transmission in populations at high risk of HIV infection in the United States. Although it is unlikely to confer sufficient benefits to justify the current costs of tenofovir-emtricitabine, price reductions and/or increases in efficacy could make PrEP a cost-effective option in younger populations or populations at higher risk of infection. Given recent disappointments in HIV infection prevention and vaccine development, additional study of PrEP-based HIV prevention is warranted.

FIGURE 1. One-Way Sensitivity Analyses

A “tornado diagram” summarizes the results of a series of 1-way sensitivity analyses on the incremental cost-effectiveness of PrEP. Each horizontal bar represents the full range of costeffectiveness ratios produced by varying a given model parameter across its entire plausible range, as described in the Methods section. The bar denoting the “HIV testing frequency” variable, for example, summarizes the results we obtained using all of the following frequencies: never; once every 10 years; once every 5 years; once every 3 years; once every 2 years; and annually. The vertical line denotes the base case incremental cost-effectiveness estimate ($298,000/QALY). Note: The horizontal axis should be understood to extend beyond $500,000/QALY and to include instances where the PrEP intervention is dominated (i.e., it costs more and confers fewer QALYs than its comparator). PrEP = pre-exposure prophylaxis; QALY = quality-adjusted life-year; ART = antiretroviral therapy; TDF = tenofovir.

FIGURE 2. Multi-Way Sensitivity Analyses

The figure reports ranges of incremental cost-effectiveness for PrEP as a function of the four influential parameters identified via the one-way sensitivity analyses in Figure 1: PrEP efficacy, PrEP cost, and the age and HIV incidence in the target population. In each of the six panels, the horizontal axis denotes PrEP efficacy (measured as a % reduction in infections) and the vertical axis denotes the average annual HIV incidence in the target population. The top three panels consider a target population with mean age 34 years; the lower three panels consider a younger target cohort (mean age = 20 years). Moving from left to right, the three columns of panels consider decreasing annual PrEP costs, ranging from $9,000 to $2,000. The shading denotes the resultant ICER, ranging from >$200,000/QALY through cost-saving.