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

Scherrer, A. U. and Hasse, B. and von Wyl, V. and Yerly, S. and Böni, J. and Bürgisser, P. and Klimkait, T. and Bucher, H. C. and Ledergerber, B. and Günthard, H. F.. (2009) Prevalence of etravirine mutations and impact on response to treatment in routine clinical care : the Swiss HIV Cohort Study (SHCS). HIV medicine : the official journal of the British HIV Association (BHIVA) and the European AIDS Clinical Society (EACS), Vol. 10. pp. 647-656.

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Official URL: http://edoc.unibas.ch/dok/A6006160

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Klinische Forschung > Clinical Epidemiology and Biostatistics CEB > Klinische Epidemiologie (Bucher H)
03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Molecular Virology (Klimkait)
UniBasel Contributors:Klimkait, Thomas and Bucher, Heiner C.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Blackwell
ISSN:1464-2662
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Oct 2014 09:19
Deposited On:01 Mar 2013 11:11

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