Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS).

Details

Serval ID
serval:BIB_B84EFF5C0653
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS).
Journal
HIV Medicine
Author(s)
Scherrer A.U., Hasse B., von Wyl V., Yerly S., Böni J., Bürgisser Philippe, Klimkait T., Bucher H.C., Ledergerber B., Günthard H.F.
ISSN
1468-1293[electronic]
Publication state
Published
Issued date
2009
Volume
10
Number
10
Pages
647-656
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
OBJECTIVES: Etravirine (ETV) is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs, which has been primarily studied in randomized clinical trials and not in routine clinical settings. METHODS: ETV resistance-associated mutations (RAMs) were investigated by analysing 6072 genotypic tests. The antiviral activity of ETV was predicted using different interpretation systems: International AIDS Society-USA (IAS-USA), Stanford, Rega and Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS). RESULTS: The prevalence of ETV RAMs was higher in NNRTI-exposed patients [44.9%, 95% confidence interval (CI) 41.0-48.9%] than in treatment-naïve patients (9.6%, 95% CI 8.5-10.7%). ETV RAMs in treatment-naïve patients mainly represent polymorphism, as prevalence estimates in genotypic tests for treatment-naïve patients with documented recent (<1 year) infection, who had acquired HIV before the introduction of NNRTIs, were almost identical (9.8%, 95% CI 3.3-21.4). Discontinuation of NNRTI treatment led to a marked drop in the detection of ETV RAMs, from 51.7% (95% CI 40.8-62.6%) to 34.5% (95% CI 24.6-45.4%, P=0.032). Differences in prevalence among subtypes were found for V90I and V179T (P<0.001). Estimates of restricted virological response to ETV varied among algorithms in patients with exposure to efavirenz (EFV)/nevirapine (NVP), ranging from 3.8% (95% CI 2.5-5.6%) for ANRS to 56.2% (95% CI 52.2-60.1%) for Stanford. The predicted activity of ETV decreased as the sensitivity of potential optimized background regimens decreased. The presence of major IAS-USA mutations (L100I, K101E/H/P and Y181C/I/V) reduced the treatment response at week 24. CONCLUSIONS: Most ETV RAMs in drug-naïve patients are polymorphisms rather than transmitted RAMs. Uncertainty regarding predictions of antiviral activity for ETV in NNRTI-treated patients remains high. The lowest activity was predicted for patients harbouring extensive multidrug-resistant viruses, thus limiting ETV use in those who are most in need.
Pubmed
Web of science
Open Access
Yes
Create date
24/11/2009 0:34
Last modification date
20/08/2019 15:26
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