Potential Risks and Benefits of Low-Barrier Access and Monitoring for HIV Preexposure Prophylaxis: A Modeling Study

PrEP prevents HIV acquisition, but its population-level impact is limited by access barriers. Low-barrier delivery of daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), such as over-the-counter (OTC) availability, could improve access by eliminating clinic visits, though reduced monitoring may increase risks including drug resistance, renal toxicity, and hepatitis B virus (HBV) reactivation. We estimated the benefits and risks of OTC PrEP.

Using a stochastic network-based model of HIV/STI transmission among gay, bisexual, and other men who have sex with men (GBMSM) in Atlanta, we simulated two delivery pathways: clinic-based PrEP and OTC PrEP with simplified initiation and reduced monitoring. We modeled 10-50% increases in PrEP coverage over 10 years. Outcomes included HIV infections averted, STI incidence, contraindicated PrEP use (GFR < 60 mL/min/1.73 m2), HBV reactivations, and drug resistance.

By expanding coverage, OTC PrEP reduced HIV incidence across all scenarios. A 50% coverage increase averted 15.4% of HIV infections. However, clinical risks increased: renal impairment exposure rose from 2.5% to 4.8%; HBV reactivations reached 2.27 per 100 person-years; and TDF/FTC resistance rose from 0.68 to 8.40 events per 100 incident HIV infections. In sensitivity analyses, confirming HIV-negative status at initiation reduced resistance by >90% without reducing prevention benefits, and frequent renal monitoring reduced renal risk.

OTC PrEP could produce population-level HIV prevention benefits if it expands coverage beyond clinic-based care. However, its net public health impact depends on implementation choices that preserve safety functions, particularly HIV testing at initiation and renal monitoring, without undermining access gains.