Efficacy of Lamivudine plus Dolutegravir versus Dolutegravir-based Three-drugs Regimens in Virologically-suppressed People Living with HIV

Abstract Background Lamivudine+dolutegravir maintenance dual therapy (DT) could be less effective than three-drug therapies (TT) in the context of resistance-associated mutations (RAMs) to nucleoside reverse transcriptase inhibitors (NRTIs). The “ARCA” database was queried to test this hypothesis with a trial-emulation strategy. Methods People living with HIV on 2NRTI plus either a protease inhibitor or a non-NRTI, switching to DT or dolutegravir-based TT, were followed-up from the first HIV-RNA<50 cps/mL (baseline) to virological failure (VF, i.e., 2 consecutive HIV-RNA≥50 cps/ml or one HIV-RNA≥200 cp/mL). Those switching to DT within 6 months were assigned to the “treatment”-arm, all other patients to the “control”-arm. Each participant was also cloned, assigned to the opposite strategy, and censored at the time of deviation from that strategy. By using inverse-probability of censoring weight (IPCW)-Cox regression models, we calculated hazard-ratios of VF for DT versus TT, stratified for the presence of RAMs. Results Overall, 626 people (204 on DT, 422 on TT; 73% men, mean age 44 years) were analyzed. Ten and 31 VF occurred with DT and TT, respectively, over a median of 5.8 years. Compared with a fully-active TT, the DT had similar efficacy (aHR: 0.88, 95% CI 0.29-2.61; p=0.812) when full susceptibility was confirmed at historical genotype. When in both groups previous M184V/I was present, the risk of VF was higher for DT but not statistically significant (versus TT, aHR 3.06, 95% CI 0.45-20.84; p=0.252). Conclusions DT was not associated with a statistically significant higher risk of VF than dolutegravir-based TT.