Efficacy and Safety of the Two-Drug Regimen Dolutegravir–Lamivudine in Adolescents Living With HIV-1 Naive to Antiretroviral Therapy at 48 Weeks (DANCE): A Single-Arm, Open-Label, Phase 3b Trial

Abstract

Background: Dolutegravir–lamivudine is recommended for initial antiretroviral therapy (ART) in adults living with HIV-1; however, no clinical trials have assessed this regimen in adolescents, a potentially more challenging population to treat. We evaluated efficacy, safety, and pharmacokinetics of dolutegravir–lamivudine as initial ART in adolescents living with HIV-1. Setting: Nine centers in Thailand, Kenya, and South Africa. Methods: In the single-arm, open-label, phase 3b DANCE study (NCT03682848), adolescents naive to ART aged ≥12 to <18 years, weighing ≥25 kg, with plasma HIV-1 RNA 1000 to ≤500,000 copies/mL received single once-daily dolutegravir–lamivudine fixed-dose combination tablet orally for 48 weeks (treatment phase). The primary endpoint was proportion of participants with HIV-1 RNA <50 copies/mL at Week 48 [Snapshot; intention-to-treat–exposed (ITT-E) population]. Safety outcomes were evaluated in the safety population. Both the ITT-E and safety populations consisted of participants who received ≥1 dose of dolutegravir–lamivudine (N = 32). A sensitivity analysis was performed using data from all but 2 participants who were withdrawn before Week 48 because of site closure (n = 30). Results: At Week 48, 26 of 32 (81%; 95% CI: 64 to 93) participants had HIV-1 RNA <50 copies/mL; in sensitivity analyses, 26 of 30 (87%; 95% CI: 69 to 96) participants achieved virologic suppression. No confirmed virologic withdrawals or deaths were reported. One drug-related adverse event was reported (grade 3 decreased glomerular filtration rate) and was the only adverse event leading to study withdrawal at data cut. Pharmacokinetic parameters were comparable with adult systemic exposure ranges. Conclusions: Dolutegravir–lamivudine demonstrated efficacy and safety as initial ART in adolescents with HIV-1 through 48 weeks.