HIV RNA testing to monitor oral PrEP use does not add clinical value: a real-world cohort study—United States, 2019-2023

Background The 2021 update of the CDC clinical guidelines for HIV preexposure prophylaxis (PrEP) recommended both antigen/antibody (Ag/Ab) and RNA testing at PrEP initiation and routine follow-up. We assessed real-world utilization and performance of HIV tests among oral PrEP users. Methods An oral PrEP user cohort was constructed using the HealthVerity database that included linked diagnoses, laboratory tests, and prescriptions from December 2018 to August 2023. Data was stratified by guideline pre- (2019−2021) and post-update (2022−2023) periods. For each period, we assessed the agreement between same-day HIV Ag/Ab and RNA results and calculated the false positive rate (FPR) and positive predictive values (PPV) of HIV Ag/Ab and RNA tests compared with adjudicated HIV status. Results The HIV RNA testing rate for follow-up increased from 16 per 100 person-years (PY) to 123 per 100 PYs after the guideline update. The positivity rate of HIV RNA tests decreased from 1.39% to 0.22%. Overall agreement between Ag/Ab and RNA results remained high. The FPRs of HIV Ag/Ab and RNA testing remained similar, but the PPV of HIV RNA testing for PrEP follow-up decreased from 100% to 67%. We estimated that 8,226 to 9,900 RNA tests would be needed for one HIV diagnosis earlier than would be detected with Ag/Ab testing alone. Discussion HIV RNA testing did not provide additional value to Ag/Ab testing during routine follow-up of oral PrEP users. Considering the cost and logistical complexity of HIV RNA testing, its use as a routine test during follow-up of oral PrEP users warrants reconsideration.