HIV-1 Drug Resistance Trends in the Era of Modern Antiretrovirals: 2018-2024

Background Antiretroviral drug resistance limits treatment options for people living with HIV-1 (PWH) and may reduce the effectiveness of preexposure prophylaxis. Novel treatment options with enhanced efficacy and more convenient formulations have become available from 2016 to 2021. Large-scale studies of trends for plasma RNA drug resistance mutations (DRM) prevalence since 2018 are lacking and there have been no systematic studies of trends in proviral DNA DRMs. Methods We retrospectively analyzed deidentified HIV-1 plasma RNA and proviral DNA sequences from specimens submitted to a reference laboratory between January 2018 and May 2024. We analyzed the annual prevalence of DRMs with a Stanford HIV database score of ≥30 for nucleoside reverse transcriptase inhibitors (NRTI), nonnucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase strand transfer inhibitors (INSTI). Results The prevalence of resistance declined for both RNA and DNA sequences. Single-class and dual-class NRTI+NNRTI resistance declined but was higher for DNA (NRTI+NNRTI: 6.1% to 3.5% [RNA] and 12.1% to 7.8% [DNA]). Rilpivirine DRMs remained low, with 2024 prevalences of 6.3% (RNA) and 10.2% (DNA). Doravirine DRM prevalences in 2024 were 2% (RNA) and 2.9% (DNA). INSTI and dual-class NRTI+INSTI resistance also declined, but the prevalence of integrase DRM R263K increased. Conclusions Prevalence of NRTI and NNRTI resistance has declined, consistent with increased use of regimens with higher resistance barriers, improved tolerability and more convenient dosing. Proviral DNA resistance trends correlated with those for RNA. Continued advances in ART efficacy, durability and tolerability may lead to increased rates of virologic suppression and further reduce the incidence of archived resistance mutations in proviral DNA.