Sustained Virologic Suppression With Dolutegravir/Lamivudine in a Test-and-Treat Setting Through 48 Weeks

Abstract

Background: We assessed the efficacy and safety of dolutegravir/lamivudine (DTG/3TC) in a US test-and-treat setting at a secondary 48-week time point of the multicenter, single-arm, phase IIIb STAT study.

Methods: Participants were eligible adults newly diagnosed with human immunodeficiency virus (HIV)-1 and had started once-daily DTG/3TC within 14 days of diagnosis, before laboratory results were available. Antiretroviral therapy (ART) was modified if baseline testing indicated DTG or 3TC resistance, hepatitis B virus (HBV) coinfection, or creatinine clearance <30 mL/min per 1.73 m², and these participants remained in the study. A proportion with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48 was calculated among all participants (intention-to-treat-exposed [ITT-E] missing = failure analysis) and those with available data (observed analysis).

Results: At Week 48, 82% of all participants regardless of ART (107 of 131; ITT-E missing = failure) and 97% with available data (107 of 110; observed analysis) achieved HIV-1 RNA <50 copies/mL. High proportions of virologic response were seen overall, including in participants with high viral load (≥500 000 copies/mL; 89%) or low CD4⁺ cell count (<200 cells/mm³; 78%) at baseline. Ten participants had treatment modification (baseline HBV coinfection, n = 5; participant/proxy decision, n = 2; baseline M184V resistance mutation, adverse event [AE; rash], and pregnancy, n = 1 each) before Week 48. Two participants met confirmed virologic failure criteria. No treatment-emergent resistance was observed. Ten participants reported drug-related AEs (all grade 1-2); no serious drug-related AEs occurred.

Conclusions: Results demonstrated high proportions of participants with sustained virologic suppression, no treatment-emergent resistance, and good safety over 48 weeks, supporting first-line use of DTG/3TC in a test-and-treat setting.

Keywords: 2-drug regimen; DTG/3TC; first-line regimen; rapid initiation; virologic suppression.

Figure 1.

(A) Virologic outcomes and (B) detailed summary of virologic outcomes at Week 48. Intention-to-treat exposed (ITT-E) missing = failure analysis: all participants included; missing data considered human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) ≥50 copies/mL. Observed analysis: only participants with available data at time of visit included. US Food and Drug Administration (FDA) Snapshot analysis: all participants included; only participants with HIV-1 RNA <50 copies/mL AND still on dolutegravir/lamivudine (DTG/3TC) considered HIV-1 RNA <50 copies/mL. ^aOne participant missed HIV-1 RNA assessment at Week 48 because of the coronavirus disease 2019 (COVID-19) pandemic. ^bEight due to lost to follow up; 6 withdrew consent (3 relocations, 2 incarcerations; 1 no subreason). ^cAll due to physician decision (2 HIV negative, 2 did not show up to several scheduled appointments). ART, antiretroviral therapy.

Figure 2.

(A) Intention-to-treat exposed (ITT-E) missing = failure analysis and (B) observed analysis by baseline (BL) viral load (VL) and CD4⁺ cell count. Change from baseline in plasma human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) (log₁₀ copies/mL) by visit and baseline viral load (C) under any antiretroviral therapy (ART) regimen and (D) under dolutegravir/lamivudine (DTG/3TC) (post hoc analysis). The ITT-E missing = failure analysis: all participants included; missing data considered HIV-1 RNA ≥50 copies/mL. Observed analysis: only participants with available data at time of visit included. US Food and Drug Administration (FDA) Snapshot analysis: all participants included; only participants with HIV-1 RNA <50 copies/mL AND still on DTG/3TC considered HIV-1 RNA <50 copies/mL. BL, baseline; VL, viral load.

Figure 3.

Human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) across visits for participants with baseline viral load ≥500 000 copies/mL. Values after “/” denote viral load at retesting. ^aParticipant confirmed many missed doses before Week 12 and withdrew consent due to incarceration. ^bParticipant switched to darunavir/cobicistat/emtricitabine (FTC)/tenofovir alafenamide (TAF) at Week 12 (Day 92) due to adverse event (rash); participant switched again to bictegravir/FTC/TAF at Week 12 (Day 113) due to a different rash. ^cParticipant withdrew at Week 4 due to physician decision. ^dParticipant had a remote visit without laboratory testing (hence HIV-1 RNA assessment was missed) due to coronavirus disease 2019. ART, antiretroviral therapy; NA, not available.

Figure 4.

Percentage change from baseline in weight overall and by baseline (BL) viral load (post hoc analysis) and CD4⁺ cell count under dolutegravir/lamivudine.