The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in patients kept on a virologically failing regimen containing an NNRTI
Autor: | Cozzi-Lepri, A, Paredes, R, Phillips, AN, Clotet, B, Kjaer, J, Von Wyl, V, Kronborg, G, Castagna, A, Bogner, JR, Lundgren, JD |
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Přispěvatelé: | Cozzi lepri, A., Paredes, R., Phillips, A. N., Clotet, B., Kjã¦r, J., Von Wyl, V., Kronborg, G., Castagna, Antonella, Bogner, J. R., Lundgren, J. D., University of Zurich, Cozzi-Lepri, A |
Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Adult
Benzoxazine Male 610 Medicine & health Rate of accumulation 10234 Clinic for Infectious Diseases Poisson regression DNA Mutational Analysi Young Adult Drug Resistance Viral 2736 Pharmacology (medical) HIV Infection Pharmacology (medical) Nevirapine Aged Ongoing viraemia Health Policy Anti-HIV Agent 2725 Infectious Diseases Middle Aged Viral Load 2719 Health Policy Reverse Transcriptase Inhibitor Prospective Studie Infectious Diseases Mutation Female Nonnucleoside reverse transcriptase inhibitor mutation Human |
Zdroj: | HIV Medicine; Vol |
Popis: | 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 >500HIV-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. © 2011 British HIV Association. |
Databáze: | OpenAIRE |
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