Pharmacokinetics, Safety and Antiviral Activity of Rilpivirine in Antiretroviral-naïve Children With HIV ≥6 to <12 Years Old: Week 48 and Final Analysis of Cohort 2 From the Open-label, Phase 2 PAINT Study

Background: Rilpivirine has shown adequate antiviral activity, consistent pharmacokinetics and safety in adults and adolescents living with HIV-1. Pharmacokinetics, safety, and antiviral activity of rilpivirine were assessed in children, following at least 48 weeks of treatment.

Methods: Cohort 2 of the open-label, phase 2 PAINT study (NCT00799864) included antiretroviral-naïve children living with HIV-1 ≥6 to <12 years old, with a viral load ≤100,000 RNA copies/mL. Participants received weight-based doses of rilpivirine in combination with a background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).

Results: Of the 18 children enrolled, 17 completed the 48-week treatment period. Participants were mostly boys (61%), median (range) age of 9.0 years (6–11 years) and weight of 25.0 kg (17–51 kg). Most children [14/18 (78%)] were adherent (>95%) to the treatment. Pharmacokinetic exposures were similar across the recommended weight-based doses and within a range comparable to exposures seen in adult studies. At week 48, 13/18 (72%) children achieved virologic response (HIV-1 RNA <50 copies/mL, FDA Snapshot). The mean (SE) increase from baseline to week 48 in CD4+ count was 213.4 (77.80) cells/μL. Overall postbaseline, 2 participants experienced virologic failure, of which 1 carried treatment-emergent rilpivirine resistance-associated mutations (RAMs); 3 of 5 participants with suspected virologic failure carried rilpivirine and NRTI RAMs. No new safety signals were identified in this population.

Conclusions: At week 48, rilpivirine achieved adequate viral suppression in antiretroviral-naïve children ≥6 to <12 years of age. The pharmacokinetic, safety and virologic profile of rilpivirine in this age group was consistent with observations in adults and adolescents living with HIV-1.