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

Issued Date

2014-01-01

Resource Type

Article

ISSN

14681293
14642662

DOI

10.1111/hiv.12141

Other identifier(s)

2-s2.0-84925954399

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

HIV Medicine. Vol.15, No.9 (2014), 513-524

Suggested Citation

Gareth Tudor-Williams, Pedro Cahn, Kulkanya Chokephaibulkit, Jan Fourie, Chris Karatzios, S. Dincq, M. Opsomer, T. N. Kakuda, S. Nijs, L. Tambuyzer, F. L. Tomaka, Rosa Bologna, Esaú João, José Henrique Pilotto, Marisa Mussi-Pinhata, Jorge Pinto, Normand Lapointe, Albert Faye, Kamila Kebaili, Steven Welch, Stefania Bernardi, Luisa Galli, Carlo Giaquinto, Nicola Principi, Gian Vincenzo Zuccotti, Henriette J. Scherpbier, Laura Marques, Isabel Soares, Margarida Tavares, Midnela Acevedo, Dan Duiculescu, Sorin Rugina, Gulam H. Latiff, Claudia Fortuny, Juan Antonio Leon Leal, Marissa Navarro, Jose T. Ramos, Tawee Chotpitayasunondh, Pope Kosalaraksa, Kiat Ruxrungtham, Jacobo Abadi, Tess Barton, William Borkowsy, Janet Chen, Joseph Church, Patricia Flynn, Sohail Rana, Richard Rutstein, Leonard Weiner Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48-week safety, efficacy and resistance analysis of the phase II PIANO study. HIV Medicine. Vol.15, No.9 (2014), 513-524. doi:10.1111/hiv.12141 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/34788

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Title

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)

Gareth Tudor-Williams
 Pedro Cahn
 Kulkanya Chokephaibulkit
 Jan Fourie
 Chris Karatzios
 S. Dincq
 M. Opsomer
 T. N. Kakuda
 S. Nijs
 L. Tambuyzer
 F. L. Tomaka
 Rosa Bologna
 Esaú João
 José Henrique Pilotto
 Marisa Mussi-Pinhata
 Jorge Pinto
 Normand Lapointe
 Albert Faye
 Kamila Kebaili
 Steven Welch
 Stefania Bernardi
 Luisa Galli
 Carlo Giaquinto
 Nicola Principi
 Gian Vincenzo Zuccotti
 Henriette J. Scherpbier
 Laura Marques
 Isabel Soares
 Margarida Tavares
 Midnela Acevedo
 Dan Duiculescu
 Sorin Rugina
 Gulam H. Latiff
 Claudia Fortuny
 Juan Antonio Leon Leal
 Marissa Navarro
 Jose T. Ramos
 Tawee Chotpitayasunondh
 Pope Kosalaraksa
 Kiat Ruxrungtham
 Jacobo Abadi
 Tess Barton
 William Borkowsy
 Janet Chen
 Joseph Church
 Patricia Flynn
 Sohail Rana
 Richard Rutstein
 Leonard Weiner

Other Contributor(s)

Imperial College London
 Fundacion Huesped
 Mahidol University
 Dr Jan Fourie Medical Practice
 Centre universitaire de sante McGill
 Janssen Infectious Diseases BVBA
 Janssen

Abstract

© 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.

Keyword(s)

Medicine

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https://repository.li.mahidol.ac.th/handle/123456789/34788

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