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


Primary results from the STAT study demonstrate the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat approach. When using a test-and-treat approach, baseline genotypic and laboratory data are not available before therapy initiation; therefore, transmitted resistance and HBV co-infection are important considerations. In STAT with participants treated within 15 days of diagnosis, including same-day ART initiation in 34 (26%) participants, few required ART modifications for HBV co-infection (n = 5) or baseline 3TC resistance (n = 1). All participants who switched from the initial DTG/3TC regimen with available data at Week 24 achieved HIV-1 RNA less than 50 copies/ml. The one participant with baseline M184V achieved HIV-1 RNA less than 50 copies/ml by Week 8, before ART adjustment. Although the number of ART modifications was minimal, these results suggest that appropriate therapy adjustments in the presence of baseline resistance or HBV co-infection can be performed safely via routine clinical care and careful follow-up in a test-and-treat setting with DTG/3TC and that this would be required in a small proportion of US patients.

The observed analysis, which included all 111 participants with available Week 24 HIV-1 RNA data, demonstrated achievement of HIV-1 RNA less than 50 copies/ml in 92% (n = 102), irrespective of ART received. The observed analysis is critical to answering the clinical practice question – whether a test-and-treat approach using DTG/3TC, which allowed for ART adjustment for identified HBV co-infection or underlying viral resistance, could provide efficacy without added risk of failure or de novo resistance due to these conditions.

The ITT-E missing = failure analysis evaluates the probability of a newly diagnosed individual with HIV-1 immediately initiating DTG/3TC, remaining in care, and being suppressed (HIV-1 RNA < 50 copies/ml) 24 weeks later regardless of ART regimen. Among all participants, 78% (102/131) had HIV-1 RNA less than 50 copies/ml at Week 24, irrespective of ART (ITT-E missing = failure). Seven (5%) participants were lost to follow-up, more than previous studies (GEMINI trials, 2%)[18] or other test-and-treat studies (DIAMOND, 3%) at Week 24,[19] but evaluation of these withdrawals showed no specific pattern. Two (2%) participants had false-positive HIV tests at diagnosis and therefore withdrew.

Thirteen of 19 participants with HIV-1 RNA at least 500 000 copies/ml at baseline (including 8/10 with ≥1000 000 copies/ml) were suppressed to less than 50 copies/ml at Week 24, and two discontinued. Of the four remaining on study with HIV-1 RNA at least 50 copies/ml at Week 24, three achieved HIV-1 RNA less than 200 copies/ml. The relatively short observation period may not have allowed adequate time for virologic suppression in some participants with very high baseline viral loads. These results are consistent with those in participants with high baseline viral load from the pooled GEMINI trials, in which 13 of 716 (2%) participants had HIV-1 RNA more than 500 000 copies/ml at baseline, with eight (62%) suppressed to HIV-1 RNA less than 50 copies/ml by Week 24.[20]

Another recent phase 3 prospective study with a test-and-treat approach was the DIAMOND trial (NCT03227861), which assessed darunavir/cobicistat/FTC/TAF (DRV/COBI/FTC/TAF).[21] However, in DIAMOND, participants discontinuing DRV/COBI/FTC/TAF also discontinued from study, not allowing for efficacy evaluation in those requiring treatment modification for any reason. DIAMOND participants had a median age of 28 years, 87% were male, 40% were non-white, and median (range) baseline viral load was 38 700 (19–144 000 000) copies/ml. Overall, 90% (88/98) of participants with available 24-week assessments in DIAMOND achieved HIV-1 RNA less than 50 copies/ml, and 92% (97/106 on DTG/3TC) achieved HIV-1 RNA less than 50 copies/ml in STAT.[19]

A limitation of STAT is that it only evaluated DTG/3TC in a test-and-treat approach in the United States, and results may not be generalizable to other geographic regions with greater HIV burden, increased prevalence of transmitted resistance and HBV co-infection, and fewer healthcare resources. Generalizability may also be limited by the single-arm, non-comparative study design; however, this trial was primarily intended to assess the feasibility of using DTG/3TC in a rapid ART initiation approach. The primary evaluation of efficacy in treatment-naive adults comes from the GEMINI studies, but STAT provides additional data.