Prevalence of mutations and determinants of genotypic resistance to etravirine (TMC125) in a large Italian resistance database (ARCA)

P. Di Vincenzo, S. Rusconi, F. Adorni, P. Vitiello, F. Maggiolo, D. Francisci, A. Di Biagio, L. Monno, A. Antinori, E. Boeri, G. Punzi, C. F. Perno, A. Callegaro, B. Bruzzone, M. Zazzi

Research output: Contribution to journalArticle

Abstract

Objectives: To evaluate whether etravirine (TMC125) might be effective in patients failing therapy with current nonnucleoside reverse transcriptase inhibitors (NNRTIs), we analysed the prevalence of TMC125 mutations and the possible determinants of genotypic resistance to this drug among sequences reported to a large database in Italy [Antiretroviral Resistance Cohort Analysis (ARCA)]. Methods: We analysed the prevalence of TMC125 resistance-associated mutations (RAMs) and the TMC125 weighted genotypic score (WGS) together with the determinants of genotypic resistance. A total of 5011 sequences from 2955 patients failing NNRTI therapy were evaluated. Results: Among the sequences in ARCA, 68% had at least one and 9.8% at least three TMC125 RAMs, whereas 31% had a WGS>2. Frequent RAMs were Y181C, G190A, K101E and A98G, whereas V179F, Y181V and G190S appeared in 2 was linked to higher HIV RNA values (maximum risk at >5 log10 copies/mL) and nevirapine exposure; CD4 counts ≥200 cells/μL were protective. Conclusions: The prevalence of TMC125 resistance mutations in the ARCA cohort was 68%. The DUET studies showed that at least three TMC125-associated mutations were required to impair the efficacy of the drug and Y181C/V, V179F and G190S had the greatest effect on response. The prevalence of these mutations among the patients examined in our study was low. However, WGS>2 was found for one-third of our sequences. Previous nevirapine exposure was associated with an increased risk of having WGS>2 (adjusted odds ratio 1.76).

Original languageEnglish
Pages (from-to)530-534
Number of pages5
JournalHIV Medicine
Volume11
Issue number8
DOIs
Publication statusPublished - Sep 2010

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etravirine
Cohort Studies
Databases
Mutation
Nevirapine
Reverse Transcriptase Inhibitors
CD4 Lymphocyte Count
Drug Resistance
Italy

Keywords

  • ARCA
  • Drug resistance
  • Genotype
  • HIV-1
  • TMC125

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Health Policy

Cite this

Prevalence of mutations and determinants of genotypic resistance to etravirine (TMC125) in a large Italian resistance database (ARCA). / Di Vincenzo, P.; Rusconi, S.; Adorni, F.; Vitiello, P.; Maggiolo, F.; Francisci, D.; Di Biagio, A.; Monno, L.; Antinori, A.; Boeri, E.; Punzi, G.; Perno, C. F.; Callegaro, A.; Bruzzone, B.; Zazzi, M.

In: HIV Medicine, Vol. 11, No. 8, 09.2010, p. 530-534.

Research output: Contribution to journalArticle

Di Vincenzo, P, Rusconi, S, Adorni, F, Vitiello, P, Maggiolo, F, Francisci, D, Di Biagio, A, Monno, L, Antinori, A, Boeri, E, Punzi, G, Perno, CF, Callegaro, A, Bruzzone, B & Zazzi, M 2010, 'Prevalence of mutations and determinants of genotypic resistance to etravirine (TMC125) in a large Italian resistance database (ARCA)', HIV Medicine, vol. 11, no. 8, pp. 530-534. https://doi.org/10.1111/j.1468-1293.2009.00819.x
Di Vincenzo, P. ; Rusconi, S. ; Adorni, F. ; Vitiello, P. ; Maggiolo, F. ; Francisci, D. ; Di Biagio, A. ; Monno, L. ; Antinori, A. ; Boeri, E. ; Punzi, G. ; Perno, C. F. ; Callegaro, A. ; Bruzzone, B. ; Zazzi, M. / Prevalence of mutations and determinants of genotypic resistance to etravirine (TMC125) in a large Italian resistance database (ARCA). In: HIV Medicine. 2010 ; Vol. 11, No. 8. pp. 530-534.
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abstract = "Objectives: To evaluate whether etravirine (TMC125) might be effective in patients failing therapy with current nonnucleoside reverse transcriptase inhibitors (NNRTIs), we analysed the prevalence of TMC125 mutations and the possible determinants of genotypic resistance to this drug among sequences reported to a large database in Italy [Antiretroviral Resistance Cohort Analysis (ARCA)]. Methods: We analysed the prevalence of TMC125 resistance-associated mutations (RAMs) and the TMC125 weighted genotypic score (WGS) together with the determinants of genotypic resistance. A total of 5011 sequences from 2955 patients failing NNRTI therapy were evaluated. Results: Among the sequences in ARCA, 68{\%} had at least one and 9.8{\%} at least three TMC125 RAMs, whereas 31{\%} had a WGS>2. Frequent RAMs were Y181C, G190A, K101E and A98G, whereas V179F, Y181V and G190S appeared in 2 was linked to higher HIV RNA values (maximum risk at >5 log10 copies/mL) and nevirapine exposure; CD4 counts ≥200 cells/μL were protective. Conclusions: The prevalence of TMC125 resistance mutations in the ARCA cohort was 68{\%}. The DUET studies showed that at least three TMC125-associated mutations were required to impair the efficacy of the drug and Y181C/V, V179F and G190S had the greatest effect on response. The prevalence of these mutations among the patients examined in our study was low. However, WGS>2 was found for one-third of our sequences. Previous nevirapine exposure was associated with an increased risk of having WGS>2 (adjusted odds ratio 1.76).",
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T1 - Prevalence of mutations and determinants of genotypic resistance to etravirine (TMC125) in a large Italian resistance database (ARCA)

AU - Di Vincenzo, P.

AU - Rusconi, S.

AU - Adorni, F.

AU - Vitiello, P.

AU - Maggiolo, F.

AU - Francisci, D.

AU - Di Biagio, A.

AU - Monno, L.

AU - Antinori, A.

AU - Boeri, E.

AU - Punzi, G.

AU - Perno, C. F.

AU - Callegaro, A.

AU - Bruzzone, B.

AU - Zazzi, M.

PY - 2010/9

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N2 - Objectives: To evaluate whether etravirine (TMC125) might be effective in patients failing therapy with current nonnucleoside reverse transcriptase inhibitors (NNRTIs), we analysed the prevalence of TMC125 mutations and the possible determinants of genotypic resistance to this drug among sequences reported to a large database in Italy [Antiretroviral Resistance Cohort Analysis (ARCA)]. Methods: We analysed the prevalence of TMC125 resistance-associated mutations (RAMs) and the TMC125 weighted genotypic score (WGS) together with the determinants of genotypic resistance. A total of 5011 sequences from 2955 patients failing NNRTI therapy were evaluated. Results: Among the sequences in ARCA, 68% had at least one and 9.8% at least three TMC125 RAMs, whereas 31% had a WGS>2. Frequent RAMs were Y181C, G190A, K101E and A98G, whereas V179F, Y181V and G190S appeared in 2 was linked to higher HIV RNA values (maximum risk at >5 log10 copies/mL) and nevirapine exposure; CD4 counts ≥200 cells/μL were protective. Conclusions: The prevalence of TMC125 resistance mutations in the ARCA cohort was 68%. The DUET studies showed that at least three TMC125-associated mutations were required to impair the efficacy of the drug and Y181C/V, V179F and G190S had the greatest effect on response. The prevalence of these mutations among the patients examined in our study was low. However, WGS>2 was found for one-third of our sequences. Previous nevirapine exposure was associated with an increased risk of having WGS>2 (adjusted odds ratio 1.76).

AB - Objectives: To evaluate whether etravirine (TMC125) might be effective in patients failing therapy with current nonnucleoside reverse transcriptase inhibitors (NNRTIs), we analysed the prevalence of TMC125 mutations and the possible determinants of genotypic resistance to this drug among sequences reported to a large database in Italy [Antiretroviral Resistance Cohort Analysis (ARCA)]. Methods: We analysed the prevalence of TMC125 resistance-associated mutations (RAMs) and the TMC125 weighted genotypic score (WGS) together with the determinants of genotypic resistance. A total of 5011 sequences from 2955 patients failing NNRTI therapy were evaluated. Results: Among the sequences in ARCA, 68% had at least one and 9.8% at least three TMC125 RAMs, whereas 31% had a WGS>2. Frequent RAMs were Y181C, G190A, K101E and A98G, whereas V179F, Y181V and G190S appeared in 2 was linked to higher HIV RNA values (maximum risk at >5 log10 copies/mL) and nevirapine exposure; CD4 counts ≥200 cells/μL were protective. Conclusions: The prevalence of TMC125 resistance mutations in the ARCA cohort was 68%. The DUET studies showed that at least three TMC125-associated mutations were required to impair the efficacy of the drug and Y181C/V, V179F and G190S had the greatest effect on response. The prevalence of these mutations among the patients examined in our study was low. However, WGS>2 was found for one-third of our sequences. Previous nevirapine exposure was associated with an increased risk of having WGS>2 (adjusted odds ratio 1.76).

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