TY - JOUR
T1 - Etravirine in treatment-experienced, HIV-1-infected children and adolescents
T2 - 48-week safety, efficacy and resistance analysis of the phase II PIANO study
AU - PIANO study group
AU - Tudor-Williams, Gareth
AU - Cahn, Pedro
AU - Chokephaibulkit, Kulkanya
AU - Fourie, Jan
AU - Karatzios, Chris
AU - Dincq, S.
AU - Opsomer, M.
AU - Kakuda, T. N.
AU - Nijs, S.
AU - Tambuyzer, L.
AU - Tomaka, F. L.
AU - Bologna, Rosa
AU - João, Esaú
AU - Pilotto, José Henrique
AU - Mussi-Pinhata, Marisa
AU - Pinto, Jorge
AU - Lapointe, Normand
AU - Faye, Albert
AU - Kebaili, Kamila
AU - Welch, Steven
AU - Bernardi, Stefania
AU - Galli, Luisa
AU - Giaquinto, Carlo
AU - Principi, Nicola
AU - Zuccotti, Gian Vincenzo
AU - Scherpbier, Henriette J.
AU - Marques, Laura
AU - Soares, Isabel
AU - Tavares, Margarida
AU - Acevedo, Midnela
AU - Duiculescu, Dan
AU - Rugina, Sorin
AU - Latiff, Gulam H.
AU - Fortuny, Claudia
AU - Leal, Juan Antonio Leon
AU - Navarro, Marissa
AU - Ramos, Jose T.
AU - Chotpitayasunondh, Tawee
AU - Kosalaraksa, Pope
AU - Ruxrungtham, Kiat
AU - Abadi, Jacobo
AU - Barton, Tess
AU - Borkowsy, William
AU - Chen, Janet
AU - Church, Joseph
AU - Flynn, Patricia
AU - Rana, Sohail
AU - Rutstein, Richard
AU - Weiner, Leonard
N1 - Publisher Copyright:
© 2014 British HIV Association 15 9 October 2014 10.1111/hiv.12141 Original research Original research. © 2014 British HIV Association.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Efficacy
KW - Etravirine
KW - HIV
KW - Paediatrics
KW - Safety
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U2 - 10.1111/hiv.12141
DO - 10.1111/hiv.12141
M3 - Article
C2 - 24589294
AN - SCOPUS:84925954399
SN - 1464-2662
VL - 15
SP - 513
EP - 524
JO - HIV Medicine
JF - HIV Medicine
IS - 9
ER -