Background:  Elvitegravir (EVG) is a potent HIV-1 integrase inhibitor undergoing Phase 3 evaluation in adults. EVG pharmacokinetics (PK) and safety were evaluated in antiretroviral (ARV)-experienced adolescents (12 to <18 years) in an ongoing, prospective, non-randomized, open-label, dose confirmation trial of EVG plus a background regimen (BR).

Methods: Patients weighing ≥40 kg either continued their BR (if screening (SCR) HIV RNA <400 copies/mL) or received a new BR (if SCR HIV RNA >1000 copies/mL); all BR included a ritonavir-boosted protease inhibitor (PI/r). Upon completion of PK and safety assessments, patients with SCR HIV RNA >1000 copies/mL could continue open label 48-week treatment. Patients received EVG 85 mg tablet once-daily when BR PI/r was lopinavir (LPV)/r or atazanavir (ATV)/r or EVG 150 mg with other PI/r, as per adult dosing, for 10 days with PK evaluation. Adverse events (AE), clinical labs, and HIV RNA were assessed.

Results:  Of the 25 patients enrolled, 23 completed EVG PK; two discontinued due to AE (vomiting, chills, and dizziness) after a single dose of study drugs. At study entry, median (range) age was 16 (12 to 17) years, weight 59 (40 to 111) kg, and years of stable ARV treatment 3.7 (0.5 to 13). BR PI(/r) (n) included darunavir (9), ATV (6), fosamprenavir (2), or LPV (8); 24 of 25 patients received ≥ 1 BR NRTI. Treatment emergent AEs included those related to gastrointestinal (56%) and nervous systems (24%). No Grade 4 or study drug related serious AEs were noted; Grade 3 AEs (n) included vomiting (2), nausea (1), chills (2), and dizziness (1). EVG 150 mg PK (mean (%CV) in Table) in adolescents was comparable to adults. The higher EVG 85 mg C_trough­ (with ATV/r or LPV/r) versus EVG 150 mg was consistent with interaction data in adults. EVG mean C_trough was 7-fold to 13-fold above the protein-binding adjusted IC₉₅ (45 ng/mL). Mean change from baseline at week 2 of -2.03 log₁₀ HIV RNA was observed in 9 subjects with HIV RNA > 1000 copies/mL at entry; all remain < 400 copies/mL through a mean of 11 weeks follow-up.

Conclusions:  In adolescent patients (12 to <18 years), EVG once-daily was well tolerated and provided comparable plasma exposures as in HIV-infected adults when added to a PI/r BR. These data support evaluation of longer term safety and efficacy of EVG in this pediatric population.