Background
Transmitted or acquired antiretroviral (ARV) drug resistance limits treatment options for people living with HIV-1 and may reduce the effectiveness of preexposure prophylaxis (PrEP). Novel treatment options with enhanced effectiveness and more convenient formulations have become available from 2016 to 2021. This study assessed the prevalence of plasma RNA and proviral DNA ARV drug resistance in the US from 2018 to 2024.
Methods
We retrospectively analyzed plasma RNA (N>50,000) or proviral DNA (N>25,000) deidentified specimens submitted to a large reference laboratory for Sanger or next generation sequencing between January 2018 and May 2024. Specimens were limited to US patients aged 1-90 with complete genotypic results for the reverse transcriptase, protease and integrase genes. We analyzed the annual prevalence of drug resistance mutations (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
From 2018 to 2024, the prevalence of resistance declined for both RNA and DNA specimens (Figure 1; p<0.0001). Single-class NRTI and NNRTI and dual-class NRTI+NNRTI resistance declined for both specimen types but was higher for DNA than RNA (NRTI+NNRTI: 6.1% to 3.5% [RNA] and 12.1% to 7.8% [DNA]). Doravirine and rilpivirine DRMs remained low, with respective 2024 prevalences of 2% (RNA) and 2.9% (DNA) and 6.3% (RNA) and 10.1% (DNA). While INSTI and dual-class NRTI+INSTI resistance also declined, the prevalence was higher for RNA than DNA. Cabotegravir DRM prevalence in 2024 was 3.8% (RNA) and 2.5% (DNA). Although low, prevalence of R263K increased over time in RNA and DNA. PI resistance remained below 3% for RNA and declined from 5.3% to 2.1% for DNA. Prevalence of triple-class resistance was <0.2% for RNA but slightly above 1% for DNA. Resistance prevalence did not differ by gender but was higher for patients in the 60-90 age group.
Conclusions
Prevalence of NRTI and NNRTI resistance declined which is consistent with increased use of regimens with higher resistance barriers, improved tolerability, and more convenient dosing, resulting in better adherence. Prevalence of INSTI DRMs was low, supporting US guidelines for limiting INSTI resistance testing to cases of treatment failure, suspected transmitted resistance, or infection during INSTI-based PrEP.
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