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Etravirine in treatment‐experienced, HIV ‐1‐infected children and adolescents: 48‐week safety, efficacy and resistance analysis of the phase II PIANO study
Author(s) -
TudorWilliams G,
Cahn P,
Chokephaibulkit K,
Fourie J,
Karatzios C,
Dincq S,
Opsomer M,
Kakuda TN,
Nijs S,
Tambuyzer L,
Tomaka FL
Publication year - 2014
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/hiv.12141
Subject(s) - etravirine , medicine , tolerability , efavirenz , regimen , viral load , nevirapine , adverse effect , rash , gastroenterology , human immunodeficiency virus (hiv) , immunology , antiretroviral therapy
Objectives PIANO ( P aediatric study of I ntelence A s an NNRTI O ption; 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 5.2 mg/kg (maximum dose 200 mg) 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 <50 copies/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 ( C 0h ). 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 12 h ( AUC 0–12h ; 5216 ng h/mL) and C 0h (346 ng/mL) were comparable to adult target values. Conclusions Results with etravirine 5.2 mg/kg bid (with OBR ) in this treatment‐experienced paediatric population and etravirine 200 mg bid in treatment‐experienced adults were comparable. Etravirine is an NNRTI option for treatment‐experienced paediatric patients.