Gareth Tudor-WilliamsPedro CahnKulkanya ChokephaibulkitJan FourieChris KaratziosS. DincqM. OpsomerT. N. KakudaS. NijsL. TambuyzerF. L. TomakaRosa BolognaEsaú JoãoJosé Henrique PilottoMarisa Mussi-PinhataJorge PintoNormand LapointeAlbert FayeKamila KebailiSteven WelchStefania BernardiLuisa GalliCarlo GiaquintoNicola PrincipiGian Vincenzo ZuccottiHenriette J. ScherpbierLaura MarquesIsabel SoaresMargarida TavaresMidnela AcevedoDan DuiculescuSorin RuginaGulam H. LatiffClaudia FortunyJuan Antonio Leon LealMarissa NavarroJose T. RamosTawee ChotpitayasunondhPope KosalaraksaKiat RuxrungthamJacobo AbadiTess BartonWilliam BorkowsyJanet ChenJoseph ChurchPatricia FlynnSohail RanaRichard RutsteinLeonard WeinerImperial College LondonFundacion HuespedMahidol UniversityDr Jan Fourie Medical PracticeCentre universitaire de sante McGillJanssen Infectious Diseases BVBAJanssen2018-11-092018-11-092014-01-01HIV Medicine. Vol.15, No.9 (2014), 513-52414681293146426622-s2.0-84925954399https://repository.li.mahidol.ac.th/handle/123456789/34788© 2014 British HIV Association 15 9 October 2014 10.1111/hiv.12141 Original research Original research. © 2014 British HIV Association. Objectives: PIANO (Paediatric study of Intelence As an NNRTI Option; TMC125-C213; NCT00665847) assessed the safety/tolerability, antiviral activity and pharmacokinetics of etravirine plus an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected children (≥6 to <12 years) and adolescents (≥12 to <18 years) over 48 weeks. Methods: In a phase II, open-label, single-arm study, 101 treatment-experienced patients (41 children; 60 adolescents) with screening viral load (VL) ≥500 HIV-1 RNA copies/mL received etravirine 5.2mg/kg (maximum dose 200mg) twice a day (bid) plus OBR. Results: Sixty-seven per cent of patients had previously used efavirenz or nevirapine. At week 48, the most common treatment-related grade ≥2 adverse event (AE) was rash (13%); 12% experienced grade 3 AEs. Only two grade 4 AEs occurred (both thrombocytopaenia, not etravirine related). At week 48, 56% of patients (68% children; 48% adolescents) achieved a virological response (VL<50copies/mL; intent-to-treat, noncompleter=failure). Factors predictive of response were adherence >95%, male sex, low baseline etravirine weighted genotypic score and high etravirine trough concentration (C0h). Seventy-six patients (75%) completed the trial; most discontinuations occurred because of protocol noncompliance or AEs (8% each). Sixty-five per cent of patients were >95% adherent by questionnaire and 39% by pill count. Forty-one patients experienced virological failure (VF; time-to-loss-of-virological-response non-VF-censored algorithm) (29 nonresponders; 12 rebounders). Of 30 patients with VF with paired baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. Mean etravirine area under the plasma concentration-time curve over 12h (AUC0-12h; 5216ng h/mL) and C0h (346ng/mL) were comparable to adult target values. Conclusions: Results with etravirine 5.2mg/kg bid (with OBR) in this treatment-experienced paediatric population and etravirine 200mg bid in treatment-experienced adults were comparable. Etravirine is an NNRTI option for treatment-experienced paediatric patients. Copyright.Mahidol UniversityMedicineArticleSCOPUS10.1111/hiv.12141