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

Tenofovir/lamivudine/dolutegravir (TLD) is widely prescribed worldwide. We report virologic and resistance outcomes for patients initiating or switching to TLD.

A prospective observational study was performed at 13 AIDS Clinical Trials Group (ACTG) sites in six PEPFAR-supported countries coincident with TLD rollout. This report includes results from two groups: Gp1 were virally suppressed on NNRTI-based ART and 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 DTG resistance mutations 6 months after TLD initiation.

From 10/2019-7/2022, we enrolled 425 participants in Gp1 and 179 in Gp2. Two in Gp1 (0.5%) and three 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 one participant in Gp1 and none in Gp2.

TLD was well tolerated and achieved or maintained viral suppression (≤1000 copies/mL) in 90% of ART-naïve and 99% of participants with pre-switch viral suppression. An emerging INSTI mutation of uncertain significance was detected in only one participant. These data support early tolerability, virologic efficacy, and rare INSTI resistance emergence with TLD transition or initiation in programmatic settings.