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. 2025 May 2;12(7):ofaf270.
doi: 10.1093/ofid/ofaf270. eCollection 2025 Jul.

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

Cissy Kityo  1 , Caitlyn McCarthy  2 , Serena P Koenig  3 , Michael D Hughes  2 , Carole L Wallis  4 , Isaac Tsikhutsu  5 , Cornelius Munyanga  6 , Noluthando Mwelase  7 , Marije Van Schalkwyk  8 , Jean Bernard Marc  3 , Kelvin Mponda  9 , Rodney Dawson  10 , Fatma F Some  11 , Lerato Mohapi  12 , Yvetot Joseph  13 , Urvi M Parikh  14 , N Sarita Shah  15 , Yukari C Manabe  16 , Catherine Godfrey  17 , Elizabeth Woolley  18 , John W Mellors  14 , Charles Flexner  16 ; ACTG A5381/Hakim Study Team
Collaborators, Affiliations

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

Cissy Kityo et al. Open Forum Infect Dis. .

Abstract

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.

Keywords: ART; Africa region; LMIC; observational prospective study; viral suppression.

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Conflict of interest statement

Potential Conflicts of Interest. C.F. has been a paid consultant in the past 3 years to Gilead Sciences, Merck, and ViiV Healthcare. Other authors do not have conflict of interest with regards to this work.

Figures

Figure 1.
Figure 1.
STROBE diagram.
See this image and copyright information in PMC

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