Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing : final results of the PIANO study
BACKGROUND: We assessed etravirine resistance in treatment-experienced, HIV-1-infected children (n=41)/adolescents (n=60) who received twice-daily etravirine 5.2 mg/kg and a background regimen (boosted protease inhibitor plus nucleoside/nucleotide reverse transcriptase inhibitors, optional enfuvirtide/raltegravir) in a Phase II, open-label, multicentre trial (PIANO).
METHODS: In addition to phenotypes, viral genotypes were assessed by population and deep sequencing (PS and DS) in virological failures (VFs; baseline and end point) and responders (baseline). Minority resistance-associated mutations (RAMs) were defined as those with frequencies above 1% and not detected with PS.
RESULTS: By week 48, 41/101 (40.6%) patients experienced VF; 17/41 (41.5%) VFs and 22/54 (40.8%) responders had ≥1 baseline etravirine RAM by PS, mainly A98G, K101E, V106I and G190A. Baseline minority etravirine RAMs (n) were detected in 8/40 VFs (V90I [2], A98G [1], L100I [1], V106I [1], E138G [1] and Y181C [2]) and 5/38 responders (V90I [3], A98G [1], V106I [1] and E138G [1]). The most frequent emerging non-nucleoside reverse transcriptase inhibitor RAMs detected by PS (≥3 VFs; n) were the etravirine RAMs Y181C (8), V90I (3), L100I (3) and E138A (3). In 15 of 29 (51.7%) VFs with baseline DS/PS and end point PS data, ≥1 emerging etravirine RAM was detected by PS, which was not detected at baseline by DS in most cases (12/15 [80.0%]). In 10/26 (38.5%) VFs with baseline/end point DS data, ≥1 additional emerging minority etravirine RAM was detected.
CONCLUSIONS: Patterns of etravirine resistance in adults, adolescents and children experiencing VF are similar. The presence of minority etravirine RAMs at baseline was not consistently associated with treatment failure. ClinicalTrials.gov: NCT00665847.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Antiviral therapy - 21(2016), 4 vom: 07., Seite 317-27 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tambuyzer, Lotke [VerfasserIn] |
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| Links: |
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| Themen: |
0C50HW4FO1 |
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| Anmerkungen: |
Date Completed 19.01.2018 Date Revised 09.12.2020 published: Print-Electronic ClinicalTrials.gov: NCT00665847 Citation Status MEDLINE |
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| doi: |
10.3851/IMP3011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM254615201 |
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| 100 | 1 | |a Tambuyzer, Lotke |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing |b final results of the PIANO study |
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| 500 | |a Date Revised 09.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT00665847 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: We assessed etravirine resistance in treatment-experienced, HIV-1-infected children (n=41)/adolescents (n=60) who received twice-daily etravirine 5.2 mg/kg and a background regimen (boosted protease inhibitor plus nucleoside/nucleotide reverse transcriptase inhibitors, optional enfuvirtide/raltegravir) in a Phase II, open-label, multicentre trial (PIANO) | ||
| 520 | |a METHODS: In addition to phenotypes, viral genotypes were assessed by population and deep sequencing (PS and DS) in virological failures (VFs; baseline and end point) and responders (baseline). Minority resistance-associated mutations (RAMs) were defined as those with frequencies above 1% and not detected with PS | ||
| 520 | |a RESULTS: By week 48, 41/101 (40.6%) patients experienced VF; 17/41 (41.5%) VFs and 22/54 (40.8%) responders had ≥1 baseline etravirine RAM by PS, mainly A98G, K101E, V106I and G190A. Baseline minority etravirine RAMs (n) were detected in 8/40 VFs (V90I [2], A98G [1], L100I [1], V106I [1], E138G [1] and Y181C [2]) and 5/38 responders (V90I [3], A98G [1], V106I [1] and E138G [1]). The most frequent emerging non-nucleoside reverse transcriptase inhibitor RAMs detected by PS (≥3 VFs; n) were the etravirine RAMs Y181C (8), V90I (3), L100I (3) and E138A (3). In 15 of 29 (51.7%) VFs with baseline DS/PS and end point PS data, ≥1 emerging etravirine RAM was detected by PS, which was not detected at baseline by DS in most cases (12/15 [80.0%]). In 10/26 (38.5%) VFs with baseline/end point DS data, ≥1 additional emerging minority etravirine RAM was detected | ||
| 520 | |a CONCLUSIONS: Patterns of etravirine resistance in adults, adolescents and children experiencing VF are similar. The presence of minority etravirine RAMs at baseline was not consistently associated with treatment failure. ClinicalTrials.gov: NCT00665847 | ||
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| 650 | 7 | |a Nitriles |2 NLM | |
| 650 | 7 | |a Pyridazines |2 NLM | |
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