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

Autor:	G, Tudor-Williams, P, Cahn, K, Chokephaibulkit, J, Fourie, C, Karatzios, S, Dincq, M, Opsomer, T N, Kakuda, S, Nijs, L, Tambuyzer, F L, Tomaka, Leonard, Weiner
Rok vydání:	2014
Předmět:	Male Adolescent HIV Infections Viral Load Medication Adherence Pyridazines Pyrimidines Treatment Outcome Area Under Curve Drug Resistance Viral Mutation Nitriles Humans Reverse Transcriptase Inhibitors Female Drug Eruptions Nevirapine Child
Zdroj:	HIV medicine. 15(9)
ISSN:	1468-1293
Popis:	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.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.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 (VL50 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.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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::88fe7e7a6c70f1eedfc877a9baf304ef https://pubmed.ncbi.nlm.nih.gov/24589294 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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