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The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in patients kept on a virologically failing regimen containing an NNRTI*.

Abstract：

BACKGROUND:Virological failure of first-generation nonnucleoside reverse transcriptase inhibitors (NNRTIs) can compromise the efficacy of etravirine as a result of the accumulation of NNRTI resistance mutations. How quickly NNRTI resistance accumulates in patients with a delayed switch from nevirapine or efavirenz despite virological failure, when these drugs are used as a component of combination antiretroviral therapy (cART), remains unclear. METHODS:The rate of NNRTI resistance accumulation was estimated in patients in EuroSIDA with at least two available genotypic resistance tests (GRTs), provided that (1) the date of the first GRT (t0) was after the date of the first virological failure (VF) of an NNRTI, and (2) patients were receiving an NNRTI and HIV RNA was >500 HIV-1 RNA copies/mL in all measurements between GRTs. RESULTS:A total of 227 patients were included in the study, contributing 467 GRT pairs. At baseline-t0, a median of 3 months after VF, 66% of patients had at least one NNRTI mutation: 103N (34%), 181C (22%) and 190A (20%) were the most common mutations. Overall, 180 additional NNRTI mutations were found to have accumulated over 295 years [1 new/1.6 years; 95% confidence interval (CI) 1.5-1.8]. The rate of accumulation was faster in the first 6 months from VF (1 new/1.1 years), and slower in patients exposed to nevirapine vs. those receiving efavirenz [relative risk (RR) 0.66; 95% CI 0.46-0.95; P=0.03]. CONCLUSIONS:There is an initial phase of rapid accumulation of NNRTI mutations close to the time of VF followed by a phase of slower accumulation. We predict that it should take approximately one year of exposure to a virologically failing first-generation NNRTI-based cART regimen to reduce etravirine activity from fully susceptible to intermediate resistant, and possibly longer in patients kept on a failing nevirapine-containing regimen.

journal_name

HIV Med

journal_title

HIV medicine

authors

Cozzi-Lepri A,Paredes,Phillips AN,Clotet B,Kjaer J,Von Wyl V,Kronborg G,Castagna A,Bogner JR,Lundgren JD,EuroSIDA in EuroCoord.

doi

10.1111/j.1468-1293.2011.00943.x

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

62-72

issue

eissn

1464-2662

issn

1468-1293

journal_volume

pub_type

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The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in patients kept on a virologically failing regimen containing an NNRTI*.