Introduction: Pre-exposure prophylaxis (PrEP) is an integral tool in reducing new HIV infections in national prevention strategies in the United States. Despite the efficacy of PrEP demonstrated in clinical trials, low adherence and high discontinuation rates in clinical practice may threaten the public health impact of PrEP. We assessed real-world effectiveness of PrEP on the prevention of HIV infection in clinical practice.

Methods: A retrospective cohort study using the 2012-2017 MarketScan database was conducted for patients aged ≥12 years who were prescribed ≥30 days tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) for PrEP. To ensure PrEP use, we excluded persons with diagnostic codes or prescriptions for HIV or hepatitis B virus during the year before the first TDF/FTC prescription date (index date). After the index date, exposure was ascertained on a daily basis by assessing filled prescriptions of TDF/FTC (exposed vs. non-exposed periods) with a 7-day grace period. A time-varying exposure Cox proportional hazards regression model was used to compare HIV incidence between exposed and non-exposed periods after controlling for covariates (e.g., age, sex, substance use disorders [SUDs], sexually transmitted diseases [STDs]).

Results: Among 11,960 users of PrEP (97% males) contributing 13,507 person-years, 130 new HIV cases were identified. The crude incidence rates of HIV acquisition were 0.6 and 1.7 per 100 person-years in exposed and non-exposed to PrEP, respectively. Compared to non-exposure, exposure to PrEP was associated with a 63% decreased risk of HIV infection (adjusted hazard ratios (aHR) 0.37, 95%CI 0.26-0.54). SUDs (aHR 6.01, 95%CI 2.51-14.39) and STDs (aHR 2.16, 95%CI 1.15-4.05) were associated with high risk of HIV acquisition.

Conclusions: This large population-based cohort analysis of PrEP effectiveness provides reassurance regarding the utility of this HIV prevention strategy among the commercially insured. Persons at high-risk of HIV infection (having SUDs and STDs) may benefit from targeted PrEP interventions.