Virology Outcomes of Tenofovir-lamivudine-dolutegravir in Treatment-naïve and Virologically Suppressed Individuals Switching From an NNRTI-based Regimen: An Observational Analysis at 13 Sites.

Background: Tenofovir/lamivudine/dolutegravir (TLD) is widely prescribed worldwide. We report virologic and resistance outcomes for patients initiating or switching to TLD. Methods: A prospective observational study was performed at 13 AIDS Clinical Trials Group sites in 6 President's Emergency Plan for AIDS Relief-supported countries coincident with TLD rollout. This report includes results from 2 groups: group 1 (Gp1) were virally suppressed on nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) and group 2 (Gp2) were ART-naïve at TLD initiation. The primary objective was to estimate the proportions of participants with HIV-1 RNA ≤1000 copies/mL and frequency of dolutegravir resistance mutations 6 months after TLD initiation. Results: From October 2019 through July 2022, we enrolled 425 participants in Gp1 and 179 in Gp2. Two in Gp1 (0.5%) and 3 in Gp2 (1.7%) discontinued TLD by 6 months due to adverse events considered related to TLD (n = 4) and participant decision (n = 1). Ninety-three percent of participants in Gp1 and 92% in Gp2 who were still on TLD had a 6-month plasma HIV-1 RNA. Plasma HIV-1 RNA ≤1000, ≤ 200, and <50 copies/mL was achieved in 99%, 98%, and 96% in Gp1 and in 90%, 87%, and 85% in Gp2, respectively. A new integrase mutation (T97A/T) was observed in 1 participant in Gp1 and none in Gp2. Conclusions: TLD was well tolerated and achieved or maintained viral suppression (≤1000 copies/mL) in 90% of ART-naïve and 99% of participants with preswitch viral suppression. An emerging integrase strand transfer inhibitor mutation of uncertain significance was detected in only 1 participant. These data support early tolerability, virologic efficacy, and rare integrase strand transfer inhibitor resistance emergence with TLD transition or initiation in programmatic settings.