HIV Pre-exposure Prophylaxis (PrEP) Effectiveness in the Real World: A Nested Case-control Study Among 46,706 Men at High Risk of HIV Infection in France

Background: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate—emtricitabine has proved to be a highly effective means of HIV prevention in clinical trials, reducing HIV infection risk by 90-95%. However, few observational studies confirmed its level of effectiveness when prescribed in common practice to diverse profiles of users.

Objectives: To assess real-world PrEP effectiveness among adult men at high risk of HIV infection in France.

Methods: Based on information of the French National Health Data System (SNDS), we conducted a nested case-control study among adult men identified at high risk of HIV infection between January 2016 and June 2020. Newly HIV-infected cases identified until December 2020 were individually matched on age, socioeconomic status, place of residence, calendar year and follow-up duration with up to five controls, using risk set sampling. Conditional logistic regression was used to calculate adjusted odds-ratios (aOR) of HIV infection associated with PrEP use. PrEP effectiveness, computed as 1-aOR, was estimated overall, by PrEP use modalities and by individuals' sociodemographic characteristics.

Results: A total of 46,706 men aged 18-65 years were identified at high risk of sexually-acquired HIV infection (61% PrEP users and 39% non-PrEP users). Among them, 256 cases were identified and matched with 1,213 controls. PrEP users accounted for 29% of cases and 49% of controls. Overall estimate of PrEP effectiveness was 60% (95% confidence interval, 46%-71%). PrEP effectiveness increased with PrEP level of coverage, ranging from 18% (-18% to 43%) for a low coverage to 93% (84% to 97%) for a high coverage, and reached 86% (78%-92%) when excluding periods of PrEP withdrawal. PrEP effectiveness was significantly reduced in subjects aged < 30 years and those socioeconomically deprived, who showed low levels of PrEP coverage and high rates of PrEP discontinuation.

Conclusions: PrEP effectiveness appears lower in real-world conditions than reported in clinical trials as a result of frequent sub-optimal PrEP coverage and treatment discontinuations. Close monitoring of compliance to treatment is essential to ensure PrEP efficacy, especially among young and deprived users, who will be more and more numerous as PrEP continues to scale-up.