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Long-term safety, tolerability and antiviral activity of rilpivirine in antiretroviral-naïve adolescents living with HIV-1, aged 12 to less than 18 years: Week 240 findings of a phase 2, open-label study, PAINT.

Introduction: This Phase-2 study investigated long-term safety and efficacy of rilpivirine (RPV)+two investigator-selected nucleos(t)ide reverse-transcriptase inhibitors (NRTIs), in HIV-1-infected antiviral therapy-naïve adolescents. Methods: Participants (≥12to <18 years) were treated with RPV 25mg qd+2 NRTIs who entered treatment extension period for up to 240 weeks with visits every 3 months. Long-term safety (analysis of adverse events [AEs], laboratory results), efficacy (virologic-response and outcome for patients with viral load <50 and <400 by time to loss of virologic-response (TLOVR) and FDA Snapshot methods, and CD4+ cell count), and adherence (by pill-count) for up to 240 weeks are presented. Results: 24 of 36 entered treatment extension period and 21 completed week 240. At week 240, viral load <50 copies/mL was achieved by 14/32 (43.8%) participants; virologic-response by TLOVR was higher in participants with baseline viral load≤100,000 copies/mL (48.0%) versus viral load >100,000 copies/mL (28.6%). By FDA Snapshot, viral load < 50 copies/mL at week 240 was 53.1% (17/32) in participants with baseline viral load ≤100,000 copies/mL. Higher response was observed in participants with adherence >95% and baseline viral load ≤100,000 copies/mL. Through week 240, 16/32 participants (50.0%) experienced virologic-failure, including seven who developed treatment-emergent RPV resistance-associated mutations (RAMs; frequently E138K); all 7 had ≥1 treatment-emergent NRTI RAM. No serious AEs after week 48, no discontinuations due to AEs between week 48 and week 240 and no new safety signals were observed. RPV did not affect pubertal development/adolescent growth. Conclusions: At the 5-year follow-up, efficacy was low in adolescents, particularly those with poor adherence and/or high baseline viral load >100,000 copies/mL. To limit the risk of virologic failure, Edurant is restricted to patients with a baseline VL ≤100,000 copies/mL in most countries. In addition, adequate treatment adherence to RPV treatment is imperative for long-term viral suppression and should be emphasized in the management of adolescents living with HIV. RPV exhibited favorable long-term safety profile for adolescents living with HIV-1 with adequate adherence. Clinical Trial Number: NCT00799864.