Dataset Information

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.

SUBMITTER: Viani RM

PROVIDER: S-EPMC7192395 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Viani Rolando M RM Ruel Theodore T Alvero Carmelita C Fenton Terry T Acosta Edward P EP Hazra Rohan R Townley Ellen E Palumbo Paul P Buchanan Ann M AM Vavro Cindy C Singh Rajendra R Graham Bobbie B Anthony Patricia P George Kathleen K Wiznia Andrew A

Journal of the Pediatric Infectious Diseases Society 20200401 2

<h4>Background</h4>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.<h4>Methods</h4>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 onc ...[more]

PMID: 30951600

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Dataset Information

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

Background

Methods

Results

Conclusions

Clinical trials registration

Publications

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

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