TUAB0204 - Oral Abstract Session
Safety and efficacy of etravirine in HIV-1-infected, treatment-experienced children and adolescents: PIANO 48-week results
Presented by Gareth Tudor-Williams (United Kingdom).
G. Tudor-Williams1, P. Cahn2, K. Chokephaibulkit3, J. Fourie4, C. Karatzios5, S. Dincq6, T.N. Kakuda7, S. Nijs6, L. Tambuyzer6, F. Tomaka7
1Imperial College Department of Medicine, London, United Kingdom, 2Fundación Huesped, Buenos Aires, Argentina, 3Mahidol University, Bangkok, Thailand, 4Dr Jan Fourie Medical Practice, Dundee, South Africa, 5McGill University Health Centre, Montréal, Canada, 6Janssen Infectious Diseases BVBA, Beerse, Belgium, 7Janssen Research & Development, LLC, Titusville, United States
Background: Etravirine has demonstrated efficacy and safety in treatment-experienced, HIV-1-infected adults. Pediatric development is ongoing.
Methods: PIANO (TMC125-C213; NCT00665847) is a 48-week, Phase II, open-label trial of the safety, efficacy and pharmacokinetics of etravirine 5.2mg/kg (maximum dose 200mg) bid in HIV-1-infected, treatment-experienced children (6-< 12 years) and adolescents (12-< 18 years) with screening viral load (VL) ≥500 copies/mL. All patients received an investigator-selected, optimized background regimen (OBR) of a ritonavir-boosted PI plus N(t)RTIs and optional enfuvirtide and/or raltegravir. Week 48 (W48) data are reported.
Results: Overall, 101 patients were enrolled (63% female, 49% white) and 76 (75%) completed the trial; most discontinuations were for adverse events (AEs) or trial non-compliance (8% each). At W48, 65% of patients were adherent by PENTA adherence questionnaire. By pill count, 39% (children 46%, adolescents 35%) were >95% adherent; 70% were >80% adherent. The most common drug-related AE was rash (18%) (Table). Four percent discontinued due to rash. Serious AEs were seen in 5% of patients while 14% experienced a grade 3/4 AE. Laboratory toxicities were predominantly grade 1/2. At W48, 56% of patients achieved VL < 50 copies/mL (intent-to-treat, non-completer=failure), with better responses in children than adolescents (Table). Median time to first response (VL < 50 copies/mL) was 16 weeks (children) and 24 weeks (adolescents). Forty one patients (41%) were classed as virologic failures (VF): 29 non-responders and 12 rebounders. Of 30 VFs with available genotype at endpoint, 18 (60%) developed NNRTI
resistance-associated mutations, most commonly: Y181C (n=8), E138A (n=3), L100I (n=3) and/or V90I (n=3).
Conclusions: The efficacy, safety and resistance profiles of etravirine 5.2 mg/kg bid plus OBR in this difficult-to-treat, antiretroviral-experienced pediatric population were comparable to those observed in treatment-experienced adults (DUET trials). Responses were better in children than adolescents, most likely due to less advanced disease, better adherence and less previous NNRTI use.
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