The impact of pretreatment drug resistance on ainuovirine‐based antiviral therapy in HIV‐infected patients: A subgroup analysis from the RACER study

34 Background: Pre-treatment drug resistance (PDR), particularly to non-nucleoside reverse transcriptase inhibitors (NNRTIs), presents a significant therapeutic challenge in antiretroviral treatment (ART). This study aims to evaluate the virological response to ainuovirine (ANV)-based antiviral therapy in HIV-1-infected patients with NNRTI-PDR. Materials and methods: We conducted a PDR analysis in two cohorts of the RACER study, a randomized, double-blind, double-dummy, positive parallel group, Phase 3 trial conducted in nine sites across China. The entire pol and IN genes were amplified and sequenced using HIV genotypic resistance testing. PDR was defined as detection of any mutation (potentially, low, intermediate or high resistant) by oligonucleotide ligation assay when confirmed by Sanger sequencing. All patients were followed up for 48 weeks to observe the virological outcomes of ART. The virological suppression was defined as plasma HIV-RNA < 50 copies/mL at week 48 of ART. Results: A total of 630 subjects were finally enrolled and randomly assigned (1:1) to either ANV (n = 315) or Efavirenz (EFV, n = 315) groups in the RACER study. Among the 593 included study participants, PDR was detected in 12.5% (n = 74). Of these, 69 (11.6%) were resistant to NNRTIs and 5 (0.84%) were resistant to NRTIs. The virological suppression rates of the PDR-negative group and the ANV group with NNRTI-PDR were 88.1% (37 of 42) and 88.8% (239 of 269) respectively, which were significantly higher than those in the EFV group with NNRTI-PDR (74.1%, 20 of 27). Conclusion: ANV exhibits significantly better antiviral activity compared to EFV, and the prevalence of PDR negatively impacts the outcomes of ANV-based ART. Considering the additional safety advantages of ANV over EFV, ANV is recommended for patients with NNRTI-PDR.