Etravirine in treatment-experienced, HIV-1-infected children and adolescents : 48-week safety, efficacy and resistance analysis of the phase II PIANO study
© 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 5.2 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
HIV medicine - 15(2014), 9 vom: 04. Okt., Seite 513-24 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tudor-Williams, G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.08.2015 Date Revised 09.12.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/hiv.12141 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM236033468 |
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| 100 | 1 | |a Tudor-Williams, G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Etravirine in treatment-experienced, HIV-1-infected children and adolescents |b 48-week safety, efficacy and resistance analysis of the phase II PIANO study |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 31.08.2015 | ||
| 500 | |a Date Revised 09.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2014 British HIV Association. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a efficacy | |
| 650 | 4 | |a etravirine | |
| 650 | 4 | |a paediatrics | |
| 650 | 4 | |a safety | |
| 650 | 7 | |a Nitriles |2 NLM | |
| 650 | 7 | |a Pyridazines |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a Reverse Transcriptase Inhibitors |2 NLM | |
| 650 | 7 | |a etravirine |2 NLM | |
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| 700 | 1 | |a Chokephaibulkit, K |e verfasserin |4 aut | |
| 700 | 1 | |a Fourie, J |e verfasserin |4 aut | |
| 700 | 1 | |a Karatzios, C |e verfasserin |4 aut | |
| 700 | 1 | |a Dincq, S |e verfasserin |4 aut | |
| 700 | 1 | |a Opsomer, M |e verfasserin |4 aut | |
| 700 | 1 | |a Kakuda, T N |e verfasserin |4 aut | |
| 700 | 1 | |a Nijs, S |e verfasserin |4 aut | |
| 700 | 1 | |a Tambuyzer, L |e verfasserin |4 aut | |
| 700 | 1 | |a Tomaka, F L |e verfasserin |4 aut | |
| 700 | 0 | |a PIANO study group |e verfasserin |4 aut | |
| 700 | 1 | |a Cahn, Pedro |e investigator |4 oth | |
| 700 | 1 | |a Joao, Esaú |e investigator |4 oth | |
| 700 | 1 | |a Pilotto, Jose Henrique |e investigator |4 oth | |
| 700 | 1 | |a Mussi-Pinhata, Marisa |e investigator |4 oth | |
| 700 | 1 | |a Pinto, Jorge |e investigator |4 oth | |
| 700 | 1 | |a Karatzios, Chris |e investigator |4 oth | |
| 700 | 1 | |a Lapointe, Normand |e investigator |4 oth | |
| 700 | 1 | |a Faye, Albert |e investigator |4 oth | |
| 700 | 1 | |a Kebaili, Kamila |e investigator |4 oth | |
| 700 | 1 | |a Tudor-Williams, Gareth |e investigator |4 oth | |
| 700 | 1 | |a Welch, Steven |e investigator |4 oth | |
| 700 | 1 | |a Bernardi, Stefania |e investigator |4 oth | |
| 700 | 1 | |a Galli, Luisa |e investigator |4 oth | |
| 700 | 1 | |a Giaquinto, Carlo |e investigator |4 oth | |
| 700 | 1 | |a Principi, Nicola |e investigator |4 oth | |
| 700 | 1 | |a Zuccotti, Gian Vincenzo |e investigator |4 oth | |
| 700 | 1 | |a Scherpbier, Henriette J |e investigator |4 oth | |
| 700 | 1 | |a Marques, Laura |e investigator |4 oth | |
| 700 | 1 | |a Soares, Isabel |e investigator |4 oth | |
| 700 | 1 | |a Tavares, Margarida |e investigator |4 oth | |
| 700 | 1 | |a Acevedo, Midnela |e investigator |4 oth | |
| 700 | 1 | |a Duiculescu, Dan |e investigator |4 oth | |
| 700 | 1 | |a Rugina, Sorin |e investigator |4 oth | |
| 700 | 1 | |a Fourie, Jan |e investigator |4 oth | |
| 700 | 1 | |a Latiff, Gulam H |e investigator |4 oth | |
| 700 | 1 | |a Fortuny, Claudia |e investigator |4 oth | |
| 700 | 1 | |a Leal, Juan Antonio Leon |e investigator |4 oth | |
| 700 | 1 | |a Navarro, Marissa |e investigator |4 oth | |
| 700 | 1 | |a Ramos, Jose T |e investigator |4 oth | |
| 700 | 1 | |a Chokephaibulkit, Kulkanya |e investigator |4 oth | |
| 700 | 1 | |a Chotpitayasunondh, Tawee |e investigator |4 oth | |
| 700 | 1 | |a Kosalaraksa, Pope |e investigator |4 oth | |
| 700 | 1 | |a Ruxrungtham, Kiat |e investigator |4 oth | |
| 700 | 1 | |a Abadi, Jacobo |e investigator |4 oth | |
| 700 | 1 | |a Barton, Tess |e investigator |4 oth | |
| 700 | 1 | |a Borkowsy, William |e investigator |4 oth | |
| 700 | 1 | |a Chen, Janet |e investigator |4 oth | |
| 700 | 1 | |a Church, Joseph |e investigator |4 oth | |
| 700 | 1 | |a Flynn, Patricia |e investigator |4 oth | |
| 700 | 1 | |a Rana, Sohail |e investigator |4 oth | |
| 700 | 1 | |a Rutstein, Richard |e investigator |4 oth | |
| 700 | 1 | |a Weiner, Leonard |e investigator |4 oth | |
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