Article
Emergence of an unexpected NNRTI-Resistance pattern (K103N/Y181C) in a NNRTI-naive patient during treatment interruption after only one week of treatment with Etravirin
Auftreten eines unerwarteten NNRTI-Resistenzmusters (Y181C/K103N) bei einem NNRTI-naivem Patienten während einer Therapiepause nach nur einer Woche Therapie mit Etravirin
Search Medline for
Authors
-
B. Jensen
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
-
M. Balduin
- Institut für Virologie; Universität Köln, Germany
-
N. Sichtig
- Institut für Virologie; Universität Köln, Germany
-
S. Reuter
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
-
R. Kaiser
- Institut für Virologie; Universität Köln, Germany
-
D. Häussinger
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
| Published: | June 2, 2010 |
|---|
Outline
Text
Objectives: Etravirin (ETR) is reported to have a higher genetic barrier compared with former NNRTIs. Nevertheless, considering its long half-life with slowly declining drug levels, unprotected treatment interruption might induce NNRTI-resistance. We present a NNRTI-naive patient who developed NNRTI-resistance mutations (K103N/Y181C) during treatment interruption after only one week of treatment with ETR. Additionally, the emergence of a K103N is unusual since this mutation was reported to have no impact on ETR.
Case report: A 42-year old HIV-positive patient, diagnosed in 11/00, started antiretroviral treatment (ART) in 02/01. Triple regimens containing AZT, 3TC, ABC, IDV/r and LPV/r were used in the following years. Despite an undetectable viral load ART was changed in all cases in order to simplify the treatment and improve tolerability. From 01/03 to 06/08 he received a combination therapy consisting of AZT/3TC/ABC. Because of persistent low-level viremia therapy was changed to TDF/FTC/DRV/r according to a resistance-test (04/08) showing several NRTI-mutations (D67N/K70R/M184V/K219Q). The patient had already moderately elevated transaminases (2–3-fold) for several years, diagnosed as nonalcoholic steatohepatitis. Due to 8-fold elevated transaminases since 10/08 and simultaneous diagnosis of diabetes mellitus ART was changed 12/08 to TDF/FTC/RAL/ETR. A further increase of transaminases up to >10-fold after this therapy switch led to treatment interruption after only one week. The diagnostic work-up revealed an acute Hepatitis C (HCV-RNA positive, HCV-Ab negative; 05/08+10/08 HCV-RNA negative). Resistance-testing performed 4 weeks after treatment interruption showed besides the NRTI mutations additional NNRTI-mutations (K103N/Y181C). Testing for transmitted resistant minorities with a primer-specific PCR (sensitivity 0,2%) showed no minor variants for K103N in the sample 04/08 prior to NNRTI treatment, for Y181C a very small minority of 0,3% (sensitivity 0,1%) was detected. In the meantime the patient was successfully treated with Peg-IFN/Ribavirin for Hepatitis C and restarted a ART consisting of TDF/FTC/RAL/LPV/r resulting in undetectable viral load.
Conclusions: ETR appears to be vulnerable in the setting of treatment interruption despite its higher genetic barrier as compared to first-generation NNRTIs. Whether the K103N-mutation has definitely no impact on ETR is at least arguable, as its emergence in this case may be ascribed to the ETR-treatment.
