Dolutegravir/Lamivudine as a First-Line Regimen in a Test-and-Treat Setting for Newly Diagnosed People Living With HIV

Charlotte-Paige Rolle; Mezgebe Berhe; Tulika Singh; Roberto Ortiz; Anson Wurapa; Moti Ramgopal; Peter A. Leone; Jessica E. Matthews; Marybeth Dalessandro; Mark R. Underwood; Konstantinos Angelis; Brian R. Wynne; Deanna Merrill; Christopher Nguyen; Jean van Wyk; Andrew R. Zolopa


AIDS. 2021;35(12):1957-1965. 

In This Article

Abstract and Introduction


Objectives: Dolutegravir/lamivudine (DTG/3TC) is indicated for treatment-naive and experienced people with HIV; however, questions remain about its utility in a test-and-treat setting because of potential transmitted resistance and baseline hepatitis B virus (HBV) co-infection. We present feasibility and efficacy of DTG/3TC in newly diagnosed individuals in a test-and-treat setting.

Design: The single-arm STAT study evaluated DTG/3TC in a US test-and-treat setting.

Methods: Eligible adults initiated DTG/3TC 14 days or less after HIV-1 diagnosis without availability of baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance less than 30 ml/min per 1.73 m2, participants remained on study with treatment modification. Efficacy endpoints included proportions of participants with HIV-1 RNA less than 50 copies/ml at Week 24, regardless of antiretroviral regimen, among all participants (intention-to-treat exposed) and those with available HIV-1 RNA data (observed).

Results: Of 131 participants enrolled, 8% were female and 50% were non-white. Through Week 24, treatment was modified in eight participants [five with HBV co-infection, one with baseline M184V, one for adverse event (rash), one participant decision]. At Week 24, 78% (102/131) of all participants and 92% (102/111) of those with available data achieved HIV-1 RNA less than 50 copies/ml. Incidence of drug-related adverse events was low (7%); no drug-related serious adverse events occurred.

Conclusion: These data demonstrate the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting, with therapy adjustments for baseline resistance or HBV co-infection occurring safely via routine clinical care as needed [, NCT03945981; see Supplemental Digital Content 1, video abstract (Video abstract summarizing the STAT study design and results),].


Timely access to care after initial HIV diagnosis is critical to successful HIV treatment.[1] Despite wide availability of antiretroviral therapy (ART), the US Centers for Disease Control and Prevention (CDC) reported that only 80% of people diagnosed with HIV in the United States in 2018 were linked to HIV medical care 1 month or less post-diagnosis.[2]

One strategy to improve linkage of people living with HIV (PWH) to HIV care is initiation of ART immediately after a reactive HIV test, referred to as test-and-treat. The 2019 update to the Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents also recommends initiating ART at diagnosis (when possible) or soon afterward to increase ART uptake, reduce time to linkage to care and virologic suppression, and improve virologic suppression rates in recently diagnosed individuals.[3] Despite these recommendations, several barriers can prevent rapid ART initiation, including clinical conditions requiring management beforehand and concerns regarding transmitted drug resistance.[4,5]

Prevalence of transmitted integrase strand transfer inhibitor and lamivudine (3TC) resistance-associated mutations is low, occurring in up to 1% of ART-naive individuals.[6–10] These estimates are consistent with observations from the GEMINI-1/GEMINI-2 studies (conducted in 21 countries) in which three of 1974 (0.15%) participants failed screening because of transmitted M184V resistance.[11]

Dolutegravir/3TC (DTG/3TC) is a two-drug fixed-dose combination (FDC) tablet regimen indicated for treatment-naive PWH or those who are virologically suppressed on a stable ART regimen with no history of treatment failure and no known or suspected resistance to the individual components.[12] Through 144 weeks of the identically designed, phase III GEMINI trials, DTG + 3TC demonstrated non-inferior virologic efficacy, similar numbers of participants meeting virologic failure criteria, and similar safety and tolerability profiles compared with the three-drug regimen DTG + tenofovir disoproxil fumarate/emtricitabine (FTC) in ART-naive PWH.[13] However, questions remain about its utility for rapid initiation due to potential transmitted resistance, baseline hepatitis B virus (HBV) co-infection, and high viral load.

In patients with HBV co-infection, 3TC is not recommended as monotherapy because of the risk of emergent resistance-associated HBV variants.[14] Although 3TC has antiviral activity against HBV, resistance rates of 15–32% after 1 year of treatment have been reported in patients taking 3TC monotherapy, with mutations rarely detected before 36 weeks.[15]

We present results from the Week 24 primary analysis of the STAT study, evaluating DTG/3TC FDC as a first-line test-and-treat ART regimen. The strategy of allowing ART adjustment for identified HBV co-infection or underlying viral resistance was also assessed for efficacy without added risk of failure or emergent resistance due to these conditions.