Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48-week safety, efficacy and resistance analysis of the phase II PIANO study.

Autor:	Tudor‐Williams, G, Cahn, P, Chokephaibulkit, K, Fourie, J, Karatzios, C, Dincq, S, Opsomer, M, Kakuda, TN, Nijs, S, Tambuyzer, L, Tomaka, FL
Předmět:	ANALYSIS of covariance CLINICAL trials CONFIDENCE intervals DRUG resistance HIV HIV infections MATHEMATICAL statistics MULTIVARIATE analysis HEALTH outcome assessment RESEARCH RESEARCH funding MULTIPLE regression analysis PARAMETERS (Statistics) TREATMENT effectiveness DATA analysis software ADOLESCENCE ETRAVIRINE (Drug) CHILDREN THERAPEUTICS
Zdroj:	HIV Medicine; Oct2014, Vol. 15 Issue 9, p513-524, 12p
Abstrakt:	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 5.2 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 ( 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 12 h ( AUC0-12h; 5216 ng h/mL) and C0h (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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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