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

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  • معلومة اضافية
    • Corporate Authors:
      Antiretroviral Resistance Cohort Analysis (ARCA) Collaborative Group
    • المصدر:
      Publisher: Wiley Country of Publication: England NLM ID: 100897392 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-1293 (Electronic) Linking ISSN: 14642662 NLM ISO Abbreviation: HIV Med Subsets: MEDLINE
    • بيانات النشر:
      Publication: Oxford : Wiley
      Original Publication: Oxford : Blackwell Science, c1999-
    • الموضوع:
      Mutation*; Anti-Retroviral Agents/*pharmacology ; Drug Resistance, Viral/*genetics ; HIV Infections/*virology ; HIV-1/*genetics ; Pyridazines/*pharmacology; Adult ; Anti-Retroviral Agents/therapeutic use ; Female ; Genotype ; HIV Infections/drug therapy ; HIV Reverse Transcriptase/genetics ; HIV-1/drug effects ; Humans ; Italy/epidemiology ; Male ; Multivariate Analysis ; Nitriles ; Prevalence ; Pyridazines/therapeutic use ; Pyrimidines ; Retrospective Studies ; Treatment Failure
    • نبذة مختصرة :
      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 <5% of sequences. Multivariate analysis revealed a higher risk of developing at least three TMC125 RAMs associated with both nevirapine and efavirenz exposure, whereas CD4 counts > or = 200 cells/microL retained their protective effect. An increased risk of WGS>2 was linked to higher HIV RNA values (maximum risk at >5 log(10) copies/mL) and nevirapine exposure; CD4 counts > or = 200 cells/microL 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).
    • الرقم المعرف:
      0 (Anti-Retroviral Agents)
      0 (Nitriles)
      0 (Pyridazines)
      0 (Pyrimidines)
      0C50HW4FO1 (etravirine)
      EC 2.7.7.49 (HIV Reverse Transcriptase)
    • الموضوع:
      Date Created: 20100319 Date Completed: 20110105 Latest Revision: 20201209
    • الموضوع:
      20231215
    • الرقم المعرف:
      10.1111/j.1468-1293.2009.00819.x
    • الرقم المعرف:
      20236364