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 A sensitivity analysis was performed using data from all but two participants who were withdrawn before Week 48 due to site closure (n=30).

Results: At Week 48, 26/32 (81%; 95% CI, 64%-93%) participants had HIV-1 RNA <50 copies/mL; in sensitivity analyses, 26/30 (87%; 95% CI, 69%-96%) 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 to adult systemic exposure ranges.

Conclusion: Dolutegravir/Lamivudine demonstrated efficacy and safety as initial ART in adolescents with HIV-1 through 48 weeks.