Long-Term Safety and Efficacy of Dolutegravir in Treatment-Experienced Adolescents With Human Immunodeficiency Virus Infection: Results of the IMPAACT P1093 Study

J Pediatric Infect Dis Soc. 2020 Apr 30;9(2):159-165. doi: 10.1093/jpids/piy139.


Background: P1093 is an ongoing phase I/II multicenter open-label study of dolutegravir plus an optimized background regimen in age-defined pediatric cohorts; here we report the long-term safety and virologic efficacy outcomes for the oldest cohort.

Methods: The study enrolled human immunodeficiency virus type 1 (HIV-1)-infected treatment-experienced adolescents aged 12 to <18 years, with an HIV-1 RNA level ≥1000 copies/mL . Cumulative safety and HIV-1 RNA outcomes were assessed once the last enrolled participant reached 144 weeks of follow-up.

Results: Among 23 adolescents enrolled, 16 remained in the study at least 144 weeks; the median follow-up was 153 weeks (range, 55-193 weeks). Dolutegravir was well tolerated, with grade 3 clinical adverse events in 5 participants, grade 3 laboratory abnormalities in 3, and grade 4 laboratory abnormalities in 1; none of the adverse events or abnormalities were judged to be treatment related. In an-intent-to-treat analysis, an HIV-1 RNA level <400 copies/mL at week 144 was achieved in 43% (10 of 23 participants; 95% confidence interval, 23.2%-65.5%); in addition, 35% (8 of 23; 16.4%-57.3%) had an HIV-1 RNA level <50 copies/mL. Nine participants (39%) discontinued study treatment before 144 weeks, but none because of adverse events or drug intolerance. All participants with sustained virologic control had excellent adherence; most who experienced virologic failure had adherence levels <90%. HIV-1 genotypic drug resistance testing was available at time of failure from 6 participants; 1 had evolution in integrase resistance with E138T, S147G, and R263K mutations at week 192 and phenotypic dolutegravir resistance of a 5.1-fold change.

Conclusions: Dolutegravir plus an optimized background regimen seemed safe, well tolerated, and efficacious in this cohort of treatment-experienced HIV-1-infected adolescents. Adherence remains problematic in this population.

Clinical trials registration: NCT01302847.

Keywords: Adolescent; Antiretroviral agents; Dolutegravir; HIV-1 integrase inhibitors; long-term follow-up.

Publication types

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

MeSH terms

  • Adolescent
  • Anti-Retroviral Agents / therapeutic use
  • Child
  • Drug Resistance, Viral / genetics*
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Integrase Inhibitors / adverse effects
  • HIV Integrase Inhibitors / therapeutic use*
  • HIV-1* / genetics
  • HIV-1* / isolation & purification
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Male
  • Medication Adherence
  • Mutation*
  • Oxazines / adverse effects
  • Oxazines / therapeutic use*
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Pyridones / adverse effects
  • Pyridones / therapeutic use*
  • RNA, Viral / blood
  • Treatment Outcome
  • Viral Load


  • Anti-Retroviral Agents
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • RNA, Viral
  • dolutegravir

Associated data

  • ClinicalTrials.gov/NCT01302847