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J Pediatric Infect Dis Soc. 2019 Apr 5. pii: piy139. doi: 10.1093/jpids/piy139. [Epub ahead of print]

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

Author information

1
Department of Pediatrics, University of California, San Diego and Rady Children's Hospital San Diego, La Jolla.
2
Division of Pediatric Infectious Diseases and Global Health, Department of Pediatrics, University of California, San Francisco.
3
Statistical and Data Analysis Center, Harvard School Public Health, Boston, Massachusetts.
4
University of Alabama at Birmingham.
5
Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
6
Columbus Technologies and Services, Contractor to the Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
7
Division of Infectious Diseases, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
8
ViiV Healthcare, Research Triangle Park, North Carolina.
9
Frontier Science Inc, Buffalo, New York.
10
University of Southern California, Los Angeles.
11
FHI 360, Durham, North Carolina.
12
Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York.

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.

KEYWORDS:

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

PMID:
30951600
DOI:
10.1093/jpids/piy139

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