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

Gareth Tudor-Williams; P. Cahn; K. Chokephaibulkit; J. Fourie; C. Karatzios; S. Dincq; M. Opsomer; T. N. Kakuda; S. Nijs; L. Tambuyzer; F. L. Tomaka; Rosa Bologna; Pedro Cahn; Esaú João; José Henrique Pilotto; Marisa Mussi-Pinhata; Jorge Pinto; Chris Karatzios; 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; Jan Fourie; Gulam H. Latiff; Claudia Fortuny; Juan Antonio Leon Leal; Marissa Navarro; Jose T. Ramos; Kulkanya Chokephaibulkit; Tawee Chotpitayasunondh; Pope Kosalaraksa; Kiat Ruxrungtham; Jacobo Abadi; Tess Barton; William Borkowsy; Janet Chen; Joseph Church; Patricia Flynn; Sohail Rana; Richard Rutstein; Leonard Weiner

doi:10.1111/hiv.12141

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

Gareth Tudor-Williams, P. Cahn, K. Chokephaibulkit, J. Fourie, C. Karatzios, S. Dincq, M. Opsomer, T. N. Kakuda, S. Nijs, L. Tambuyzer, F. L. Tomaka, Rosa Bologna, Pedro Cahn, Esaú João, José Henrique Pilotto, Marisa Mussi-Pinhata, Jorge Pinto, Chris Karatzios, Normand Lapointe, Albert FayeKamila 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, Jan Fourie, Gulam H. Latiff, Claudia Fortuny, Juan Antonio Leon Leal, Marissa Navarro, Jose T. Ramos, Kulkanya Chokephaibulkit, Tawee Chotpitayasunondh, Pope Kosalaraksa, Kiat Ruxrungtham, Jacobo Abadi, Tess Barton, William Borkowsy, Janet Chen, Joseph Church, Patricia Flynn, Sohail Rana, Richard Rutstein, Leonard Weiner

Research output: Contribution to journal › Article › peer-review

Abstract

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 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 12h (AUC_0-12h; 5216ng h/mL) and C_0h (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.

Original language	English
Pages (from-to)	513-524
Number of pages	12
Journal	HIV Medicine
Volume	15
Issue number	9
DOIs	https://doi.org/10.1111/hiv.12141
Publication status	Published - 2014

Keywords

Efficacy
Etravirine
HIV
Paediatrics
Safety

ASJC Scopus subject areas

Infectious Diseases
Pharmacology (medical)
Health Policy
Medicine(all)

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10.1111/hiv.12141

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Tudor-Williams, G., Cahn, P., Chokephaibulkit, K., Fourie, J., Karatzios, C., Dincq, S., Opsomer, M., Kakuda, T. N., Nijs, S., Tambuyzer, L., Tomaka, F. L., Bologna, R., Cahn, P., João, E., Pilotto, J. H., Mussi-Pinhata, M., Pinto, J., Karatzios, C., Lapointe, N., ... Weiner, L. (2014). 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, 15(9), 513-524. https://doi.org/10.1111/hiv.12141

Etravirine in treatment-experienced, HIV-1-infected children and adolescents : 48-week safety, efficacy and resistance analysis of the phase II PIANO study. / Tudor-Williams, Gareth; Cahn, P.; Chokephaibulkit, K.; Fourie, J.; Karatzios, C.; Dincq, S.; Opsomer, M.; Kakuda, T. N.; Nijs, S.; Tambuyzer, L.; Tomaka, F. L.; Bologna, Rosa; Cahn, Pedro; João, Esaú; Pilotto, José Henrique; Mussi-Pinhata, Marisa; Pinto, Jorge; Karatzios, Chris; Lapointe, Normand; Faye, Albert; Kebaili, Kamila; Welch, Steven; Bernardi, Stefania; Galli, Luisa; Giaquinto, Carlo; Principi, Nicola; Zuccotti, Gian Vincenzo; Scherpbier, Henriette J.; Marques, Laura; Soares, Isabel; Tavares, Margarida; Acevedo, Midnela; Duiculescu, Dan; Rugina, Sorin; Fourie, Jan; Latiff, Gulam H.; Fortuny, Claudia; Leal, Juan Antonio Leon; Navarro, Marissa; Ramos, Jose T.; Chokephaibulkit, Kulkanya; Chotpitayasunondh, Tawee; Kosalaraksa, Pope; Ruxrungtham, Kiat; Abadi, Jacobo; Barton, Tess; Borkowsy, William; Chen, Janet; Church, Joseph; Flynn, Patricia; Rana, Sohail; Rutstein, Richard; Weiner, Leonard.

In: HIV Medicine, Vol. 15, No. 9, 2014, p. 513-524.

Research output: Contribution to journal › Article › peer-review

Tudor-Williams, G, Cahn, P, Chokephaibulkit, K, Fourie, J, Karatzios, C, Dincq, S, Opsomer, M, Kakuda, TN, Nijs, S, Tambuyzer, L, Tomaka, FL, Bologna, R, Cahn, P, João, E, Pilotto, JH, Mussi-Pinhata, M, Pinto, J, Karatzios, C, Lapointe, N, Faye, A, Kebaili, K, Welch, S, Bernardi, S, Galli, L, Giaquinto, C, Principi, N, Zuccotti, GV, Scherpbier, HJ, Marques, L, Soares, I, Tavares, M, Acevedo, M, Duiculescu, D, Rugina, S, Fourie, J, Latiff, GH, Fortuny, C, Leal, JAL, Navarro, M, Ramos, JT, Chokephaibulkit, K, Chotpitayasunondh, T, Kosalaraksa, P, Ruxrungtham, K, Abadi, J, Barton, T, Borkowsy, W, Chen, J, Church, J, Flynn, P, Rana, S, Rutstein, R & Weiner, L 2014, '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, pp. 513-524. https://doi.org/10.1111/hiv.12141

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

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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",

abstract = "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 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.",

keywords = "Efficacy, Etravirine, HIV, Paediatrics, Safety",

author = "Gareth Tudor-Williams and P. Cahn and K. Chokephaibulkit and J. Fourie and C. Karatzios and S. Dincq and M. Opsomer and Kakuda, {T. N.} and S. Nijs and L. Tambuyzer and Tomaka, {F. L.} and Rosa Bologna and Pedro Cahn and Esa{\'u} Jo{\~a}o and Pilotto, {Jos{\'e} Henrique} and Marisa Mussi-Pinhata and Jorge Pinto and Chris Karatzios and Normand Lapointe and Albert Faye and Kamila Kebaili and Steven Welch and Stefania Bernardi and Luisa Galli and Carlo Giaquinto and Nicola Principi and Zuccotti, {Gian Vincenzo} and Scherpbier, {Henriette J.} and Laura Marques and Isabel Soares and Margarida Tavares and Midnela Acevedo and Dan Duiculescu and Sorin Rugina and Jan Fourie and Latiff, {Gulam H.} and Claudia Fortuny and Leal, {Juan Antonio Leon} and Marissa Navarro and Ramos, {Jose T.} and Kulkanya Chokephaibulkit and Tawee Chotpitayasunondh and Pope Kosalaraksa and Kiat Ruxrungtham and Jacobo Abadi and Tess Barton and William Borkowsy and Janet Chen and Joseph Church and Patricia Flynn and Sohail Rana and Richard Rutstein and Leonard Weiner",

year = "2014",

doi = "10.1111/hiv.12141",

language = "English",

volume = "15",

pages = "513--524",

journal = "HIV Medicine",

issn = "1464-2662",

publisher = "Blackwell Publishing Ltd",

number = "9",

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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 - Tudor-Williams, Gareth

AU - Cahn, P.

AU - Chokephaibulkit, K.

AU - Fourie, J.

AU - Karatzios, C.

AU - Dincq, S.

AU - Opsomer, M.

AU - Kakuda, T. N.

AU - Nijs, S.

AU - Tambuyzer, L.

AU - Tomaka, F. L.

AU - Bologna, Rosa

AU - Cahn, Pedro

AU - João, Esaú

AU - Pilotto, José Henrique

AU - Mussi-Pinhata, Marisa

AU - Pinto, Jorge

AU - Karatzios, Chris

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 - Fourie, Jan

AU - Latiff, Gulam H.

AU - Fortuny, Claudia

AU - Leal, Juan Antonio Leon

AU - Navarro, Marissa

AU - Ramos, Jose T.

AU - Chokephaibulkit, Kulkanya

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

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 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 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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JF - HIV Medicine

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ER -

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

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