The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in patients kept on a virologically failing regimen containing an NNRTI
Por:
Cozzi-Lepri, A, Paredes, R, Phillips, AN, Clotet, B, Kjaer, J, Von Wyl, V, Kronborg, G, Castagna, A, Bogner, JR and Lundgren, JD
Publicada:
1 ene 2012
Resumen:
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 4500 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; P50.03]. 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.
Filiaciones:
Cozzi-Lepri, A:
UCL, Dept Infect & Populat Hlth, Div Populat Hlth, London, England
Univ Minnesota, Div Biostat, Minneapolis, MN USA
:
Hosp Badalona Germans Trias & Pujol, HIV Unit, Barcelona, Spain
Hosp Badalona Germans Trias & Pujol, IrsiCaixa Retrovirol Lab, Barcelona, Spain
Phillips, AN:
UCL, Dept Infect & Populat Hlth, Div Populat Hlth, London, England
:
Hosp Badalona Germans Trias & Pujol, HIV Unit, Barcelona, Spain
Hosp Badalona Germans Trias & Pujol, IrsiCaixa Retrovirol Lab, Barcelona, Spain
Kjaer, J:
Univ Copenhagen, Panum Inst, Copenhagen HIV Programme, DK-2200 Copenhagen, Denmark
Von Wyl, V:
Univ Zurich Hosp, ETH Zurich, Div Infect Dis, Zurich, Switzerland
Univ Zurich Hosp, ETH Zurich, Hosp Epidemiol, Zurich, Switzerland
Kronborg, G:
Hvidovre Univ Hosp, Dept Infect Dis, DK-2650 Hvidovre, Denmark
Hvidovre Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark
Castagna, A:
San Raffaele Vita Salute Univ, Ist Ricovero & Cura Carattere Sci, Milan, Italy
Bogner, JR:
Univ Munich, Med Poliklin, Dept Infect Dis, Sch Med, D-8000 Munich, Germany
Lundgren, JD:
Univ Copenhagen, Panum Inst, Copenhagen HIV Programme, DK-2200 Copenhagen, Denmark
Rigshosp, Dept Infect Dis, Ctr Viral Dis, DK-2100 Copenhagen, Denmark
Bronze
|