Long-Term Safety and Efficacy of Dolutegravir in HIV Treatment-Experienced Adolescents
Year: 2015
Type: article
Study design: Clinical Trial
Abstract: Background. P1093 is an ongoing Phase I/II multicenter open-label study of dolutegravir (DTG) plus optimized background regimen (OBR) in age defined pediatric cohorts. DTG was safe and efficacious at a dose of ∼1 mg/kg in adolescents through Week 48. Here we report the long-term safety and efficacy of DTG. Methods. HIV infected treatment experienced children > 12 to < 18 years with an HIV RNA of ≥ 1000 copies/mL (c/mL) were enrolled. Safety and HIV-1 RNA were evaluated beyond Week 48. Virologic success was defined as achieving an HIV-1 RNA < 400 c/mL based on the FDA snapshot algorithm, with an additional secondary outcome of HIV-1 RNA < 50 c/mL at database lock. Results. Twenty three adolescents were enrolled. Demographics were as follows: 78% female, 52% African American, 35% Caucasian, 26% Hispanic. Median age (range) was 14 years (12, 17) and median weight (range) was 52.2 kg (33, 91). Median baseline CD4+ cell count was 466 cells/µL; and HIV-1 RNA log10 was 4.3 log10 c/mL. Nineteen adolescents received 50 mg/day and 4 received 35 mg/day of DTG. At database lock, the median DTG exposure (range) was 147 weeks (40, 194), 15 (65%) were on study for ≥ 144 weeks. HIV RNA < 400 c/mL was achieved in 48% (11 of 23; 95% CI: 26.8, 69.4) at Week 144. In addition, 39% (9 of 23; 95% CI: 19.7, 61.4) had an HIV RNA load < 50 c/mL at Week 144. Eight (35%) came of study, the majority due to non-compliance with study drug and study visits. Invariably, all subjects who experienced virologic failure had incomplete adherence based on 3 day pill recall. HIV genotypic drug resistance testing was available at failure in 8 subjects. Only 1 (4.3%) subject had evolution in integrase drug resistance with E138/E/K/T, S147/G and R263K at Week 132. HIV Phenotypic DTG resistance showed a 5.1-fold change. DTG was well tolerated, with 5 subjects having Grade 3 clinical adverse events, all deemed not related to treatment. There were 3 subjects experiencing Grade 3 laboratory abnormalities: one developed unconjugated bilirubin elevation while on atazanavir as part of the OBR, another developed asymptomatic lipase elevation, and one developed neutropenia, all deemed not related to treatment. Conclusion. DTG plus OBR was safe and well tolerated in HIV-infected adolescents. In addition, DTG treatment as part of an OBR provided good virologic efficacy through Week 144. Disclosures. D. Steimers, GSK: Employee, Salary; A. Buchanan, GSK: Employee, Salary; C. Vavro, GSK: Employee, Salary
Source: Open Forum Infectious Diseases
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,053
OpenAlex ID: W2290715354