Abstract
BackgroundPoor adherence to either antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) can promote drug resistance, though this risk is thought to be considerably higher for ART. In the population of men who have sex with men (MSM) in San Francisco, PrEP coverage reached 9.6% in 2014 and has continued to rise. Given the risk of drug resistance and high cost of second-line drugs, the costs and benefits of initiating ART earlier while expanding PrEP coverage remain unclear.MethodsWe develop an infection–age-structured mathematical model and fit this model to the annual incidence of AIDS cases and deaths directly, and to resistance and demographic data indirectly. We investigate the impact of six various intervention scenarios (low, medium, or high PrEP coverage, with or without earlier ART) over the next 20 years.ResultsLow (medium, high) PrEP coverage with earlier ART could prevent 22% (42%, 57%) of a projected 44,508 total new infections and 8% (26%, 41%) of a projected 18,426 new drug-resistant infections, and result in a gain of 43,649 (74,048, 103,270) QALYs over 20 years compared to the status quo, at a cost of $4745 ($78,811, $115,320) per QALY gained, respectively.ConclusionsHigh PrEP coverage with earlier ART is expected to provide the greatest benefit but also entail the highest costs among the strategies considered. This strategy is cost-effective for the San Francisco MSM population, even considering the acquisition and transmission of ART-mediated drug resistance. However, without a substantial increase to San Francisco’s annual HIV budget, the most advisable strategy may be initiating ART earlier, while maintaining current strategies of PrEP enrollment.
Highlights
Poor adherence to either antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) can promote drug resistance, though this risk is thought to be considerably higher for ART
We considered only ART-mediated and not PrEP-mediated resistance, because both clinical data [42, 43] and mathematical models [44, 45] suggest that PrEP contributes less than 5% to the total burden of resistance since PrEP-selected resistant phenotypes decay below detection by 6 months after drug cessation and remain undetectable for at least 2 years thereafter [46]
Health outcomes Under baseline levels of PrEP and ART coverage, we estimate that 44,508 total new HIV infections and 18,426 new drug-resistant infections would occur among men who have sex with men (MSM) in San Francisco over the 20 years (Table 1 and Fig. 3a, b)
Summary
Poor adherence to either antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) can promote drug resistance, though this risk is thought to be considerably higher for ART. PrEP coverage among men who have sex with men (MSM) in San Francisco was estimated at 9.6% in 2014 [8]. In May 2016, more than 6000 MSM in San Francisco were reported to receive PrEP [9], suggesting a coverage of approximately 12% given that the HIV-negative MSM population is estimated at 50,000 [7, 10, 11]. In 2010, prior to this increased PrEP uptake, San Francisco was one of the first cities to institute guidelines to initiate antiretroviral therapy (ART) as early as possible postinfection rather than waiting for signs of disease progression, such as clinical symptoms or low CD4+ cell counts [12], given findings that early ART initiation improves survival while reducing the risks of transmission to others [13]. It has been hypothesized that early ART initiation might provide more time for the evolution of drug resistance and that subsequent transmission of drug-resistant HIV might reduce PrEP effectiveness [14,15,16]
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