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

Abstract

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.

• Authors: Rolando M Viani, Theodore Ruel, Carmelita Alvero, Terry Fenton, Edward P Acosta, Rohan Hazra, Ellen Townley, Paul Palumbo, Ann M Buchanan, Cindy Vavro, Rajendra Singh, Bobbie Graham, Patricia Anthony, Kathleen George, Andrew Wiznia, P1093 Study Team
• Journal: Journal of the Pediatric Infectious Diseases Society (J Pediatric Infect Dis Soc) Vol. 9 Issue 2 Pg. 159-165 (Apr 30 2020) ISSN: 2048-7207 [Electronic] England
• PMID: 30951600 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

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

Topics

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