Efficacy, Safety, and Tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Results Through Week 96 from IMPAACT 2014

J Pediatric Infect Dis Soc. 2023 Dec 16;12(12):602-609. doi: 10.1093/jpids/piad078.

Abstract

Background: IMPAACT 2014 study is a phase I/II, multicenter, open-label, nonrandomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed-dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks.

Methods: Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF. The efficacy endpoint was the proportion of participants with HIV-1 RNA <40 copies/mL assessed at weeks 48 and 96 using the observed failure approach. Safety and tolerability outcomes were incidence of adverse events (AEs) and treatment discontinuations.

Results: A total of 45 adolescents, median age 15 (range, 12-17) years, 58% females, were enrolled and 2 (4.4%) participants were ARV naïve. Of the 45 participants, 42 (93.3%) completed the study and 41 (91.1%) completed the study treatment. At week 48, 41/42 (97.6%; 95% confidence interval [CI], 87.4-99.9) and week 96, 37/40 (92.5%; 95% CI, 79.6-98.4) participants had achieved or maintained HIV-1 RNA <40 copies/mL. There were no treatment-related discontinuations due to AEs and no drug-related AEs ≥grade 3 or deaths.

Conclusions: We found once-daily dosing of DOR FDC to be safe and well tolerated for maintaining viral suppression through 96 weeks in adolescents living with HIV-1.

Keywords: HIV-1; MK-1439A; adolescents; doravirine.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Anti-HIV Agents* / adverse effects
  • Anti-Retroviral Agents / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • HIV Seropositivity*
  • Humans
  • Lamivudine / adverse effects
  • Male
  • RNA / therapeutic use
  • Tenofovir / adverse effects
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • doravirine
  • Lamivudine
  • RNA
  • Tenofovir