Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015 Nov;34(11):1207-13.
doi: 10.1097/INF.0000000000000848.

Safety, Pharmacokinetics and Efficacy of Dolutegravir in Treatment-experienced HIV-1 Infected Adolescents: Forty-eight-week Results from IMPAACT P1093

Rolando M Viani  1 , Carmelita Alvero, Terry Fenton, Edward P Acosta, Rohan Hazra, Ellen Townley, Debra Steimers, Sherene Min, Andrew Wiznia; P1093 Study Team
Collaborators, Affiliations
Clinical Trial

Safety, Pharmacokinetics and Efficacy of Dolutegravir in Treatment-experienced HIV-1 Infected Adolescents: Forty-eight-week Results from IMPAACT P1093

Rolando M Viani et al. Pediatr Infect Dis J. 2015 Nov.

Abstract

Objective: To assess the pharmacokinetics (PK), safety and efficacy of dolutegravir plus optimized background regimen in HIV-infected treatment-experienced adolescents.

Methods: Children older than 12 to younger than 18 years received dolutegravir weight-based fixed doses at approximately 1.0 mg/kg once daily in a phase I/II multicenter open label 48-week study. Intensive PK evaluation was done at steady state after dolutegravir was added to a failing regimen or started at the end of a treatment interruption. Safety and HIV RNA and CD4 cell count assessments were performed through week 48.

Results: Twenty-three adolescents were enrolled and 22 (96%) completed the 48-week study visit. Median age and weight were 15 years and 52 kg, respectively. Median [interquartile range (IQR)] baseline CD4+ cell count was 466 cells/μL (297, 771). Median (IQR) baseline HIV-1 RNA log10 was 4.3 log10 copies/mL (3.9, 4.6). Dolutegravir geometric mean of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing (AUC0-24) and 24 hour postdose concentration (C24) were 46.0 μg hours/mL and 0.90 μg/mL, respectively, which were within the study targets based on adult PK ranges. Virologic success with an HIV RNA <400 copies/mL was achieved in 74% [95% confidence interval (CI): 52-90%] at week 48. Additionally, 61% (95% CI: 39-80%) had an HIV RNA <50 copies/mL at week 48. Median (IQR) gain in CD4 cell count at week 48 was 84 cells/μL (-81, 238). Dolutegravir was well tolerated, with no grade 4 adverse events, serious adverse events or discontinuations because of serious adverse events.

Conclusions: Dolutegravir achieved target PK exposures in adolescents. Dolutegravir was safe and well tolerated, providing good virologic efficacy through week 48.

Trial registration: ClinicalTrials.gov NCT01302847.

PubMed Disclaimer

Conflict of interest statement

Disclosures: The authors have no conflict of interest or funding to disclose, except for Debra Steimers and Sherene Min who are GSK employees and own stock and/or stock options in the company.

Figures

Figure 1
Figure 1
Study design OBR; optimized background regimen, DTG; dolutegravir
Figure 2
Figure 2
a Proportion of participants with HIV RNA<400 copies/mL b Proportion of participants with HIV RNA <50 copies/mL
Figure 2
Figure 2
a Proportion of participants with HIV RNA<400 copies/mL b Proportion of participants with HIV RNA <50 copies/mL
See this image and copyright information in PMC

References

    1. Mocroft A, Ledergerber B, Katlama C, et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet. 2003;362:22–29. - PubMed
    1. Gortmaker SL, Hughes M, Cervia J, et al. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med. 2001;345:1522–1528. - PubMed
    1. Viani RM, Araneta MR, Deville JG, Spector SA. Decrease in hospitalization and mortality rates among children with perinatally acquired HIV type 1 infection receiving highly active antiretroviral therapy. Clin Infect Dis. 2004;39:725–731. - PubMed
    1. Resino S, Resino R, Maria Bellon J, et al. Clinical outcomes improve with highly active antiretroviral therapy in vertically HIV type-1-infected children. Clin Infect Dis. 2006;43:243–252. - PubMed
    1. Kourtis AP, Bansil P, Posner SF, Johnson C, Jamieson DJ. Trends in hospitalizations of HIV-infected children and adolescents in the United States: analysis of data from the 1994–2003 Nationwide Inpatient Sample. Pediatrics. 2007;120:e236–e243. - PubMed

Publication types

Associated data