Impact of pre-existent drug resistance on virological efficacy of single tablet regimens in people living with HIV

Despite the broad use of single tablet regimens (STRs), few real-life data are available regarding the impact of pre-existent drug resistance on virological failure (VF). Through this study we aimed to fill this gap, by analyzing a large cohort of individuals selected from the ARCA database. The impact on VF of pre-existent resistance associated mutations (RAMs) and cumulative genotypic susceptibility score (cGSS) before STR start was evaluated through survival analysis. Potential emergence of resistance at VF was also evaluated. Overall, 3916 individuals were included: 678 treatment-naïve (G1), 2309 treatment-experienced aviremic (G2), and 929 viremic (G3); 65.2% of them was treated with an STR based on efavirenz (35.2%) or rilpivirine (30%). At two years after starting STR, the overall probability of VF was 5.9% in G1, 8.7% in G2, and 20.8% in G3. No impact of pre-existent resistance on VF was found in G1. The probability of VF was higher in patients with cGSS<3 (reduced susceptibility to at least one drug) than in those with cGSS=3 (full susceptibility to STR drugs) in both G2 and G3. A higher probability of VF was also found in presence of pre-existent M184V (alone or in combination with pre-existent thymidine analogue mutations). Among patients who failed STR, a significant emergence of RAMs was found only in those exposed to EFV/FTC/TDF in G3 (specifically K103N and M184V). Our results confirm a high efficacy of STRs in clinical settings. Pre-existent resistance seems to influence virological efficacy of STR in treatment-experienced individuals (both aviremic and viremic).