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

Background: Antiretroviral drug resistance limits treatment options for people with human immunodeficiency virus (HIV) 1 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 in the prevalences of plasma RNA drug resistance mutations (DRMs) 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 Drug Resistance Database score of ≥30 for nucleoside and nonnucleoside reverse-transcriptase inhibitors (NRTIs and NNRTIs), protease inhibitors, and integrase strand transfer inhibitors (INSTIs). 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, declined from 6.1% to 3.5% for RNA and from 12.1% to 7.8% for DNA). Rilpivirine DRMs remained low, with prevalences of 6.3% (RNA) and 10.2% (DNA) in 2024. The 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 were correlated with those for RNA. Continued advances in antiretroviral therapy efficacy, durability, and tolerability may lead to increased rates of virologic suppression and further reduce the incidence of archived resistance mutations in proviral DNA.