Changes in RPV Resistance-Related Mutations Among Antiretroviral Therapy-Naïve HIV-1-Positive Individuals - China, 2004-2023.

INTRODUCTION: Rilpivirine (RPV) is currently included in first-line antiretroviral therapy (ART) regimens in China. However, the baseline RPV resistance remains unclear, especially among different HIV-1 subtypes in China. METHODS: HIV-1 pol sequences were collected from ART-naïve HIV-infected individuals between 2004 and 2023. RPV resistance-associated mutations (RAMs) were identified and interpreted using the Stanford HIVdb algorithm. The prevalence of RPV resistance was evaluated over a 20-year study period across different HIV-1 subtypes. RESULTS: In total, 64,429 HIV-1 pol sequences from ART-naïve HIV-infected individuals were included in this analysis. The prevalence of RPV resistance increased significantly from 1.5% (2004-2007) to 3.5% (2020-2023) (P<0.001), which was driven by low-level resistance to RPV. CRF65_cpx (37.7%), CRF55_01B (8.5%), and CRF08_BC (5.0%) showed the highest rates of RPV resistance. In RPV-resistant strains, V179D/E/F/L (43.3%) and E138A/G/K/Q/R (38.0%) were the predominant RAMs. The mutations G190A/C/E/Q/S/T (12.5%) and Y181C/F/I/S/V (11.9%) were also commonly detected. Polymorphic and non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistant RAMs were identified in 66.8 and 34.8% of RPV-resistant strains, respectively. The polymorphic mutation V179D/E frequently co-occurred with other RAMs, including E138G (14.4%), K103R (7.8%), and V90I (5.5%), and conferred low- or intermediate-level RPV resistance. CONCLUSIONS: Polymorphic RAMs and NNRTI cross-resistance mutations together account for the increased RPV resistance in China. Additional phenotypic data and clinical research are needed to verify the efficacy of RPV-based ART in patients infected with subtypes CRF65_cpx, CRF55_01B, and CRF08_BC.