Mutations in HIV-1 reverse transcriptase potentially associated with hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors: effect on response to efavirenz-based therapy in an urban observational cohort
| Autor: | Evangelo Boumis, Andrea Antinori, Pasquale Narciso, Carlo Federico Perno, Roberta D'Arrigo, Patrizio De Longis, Federica Forbici, Chiarina Carvelli, Giampiero D'Offizi, Rita Bellagamba, Valerio Tozzi, Sandro Bonfigli, Mauro Zaccarelli, Maria Paola Trotta, Francesca Ceccherini-Silberstein |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Cyclopropanes
Adult Male Efavirenz Urban Population Anti-HIV Agents Drug Resistance HIV Infections Drug resistance Microbial Sensitivity Tests Cohort Studies chemistry.chemical_compound Drug Therapy immune system diseases Drug Resistance Viral Oxazines medicine Immunology and Allergy Humans Protease inhibitor (pharmacology) Protease Inhibitors Viral CD4 Lymphocyte Count HIV-1 Reverse Transcriptase Inhibitors Viral Load Drug Therapy Combination Treatment Outcome HIV Reverse Transcriptase Mutation Benzoxazines Female biology Reverse-transcriptase inhibitor virus diseases biology.organism_classification Resistance mutation Settore MED/07 - Microbiologia e Microbiologia Clinica Virology Reverse transcriptase Infectious Diseases chemistry Alkynes Lentivirus Combination Viral load medicine.drug |
| Popis: | Background. Hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was described in association with reverse-transcriptase (RT) mutations conferring resistance to nucleoside reverse-transcriptase inhibitors (NRTIs). We evaluated the effect of RT mutations associated with hypersusceptibility to NNRTIs on the response to efavirenz-based therapy. Methods. We analyzed an observational database of patients for whom highly active antiretroviral therapy failed and who received genotypic resistance testing–guided therapy, either efavirenz or protease inhibitor (PI) based. Study end points were achievement of virus load !80 copies/mL, achievement of virus load !80 copies/mL without rebound to 1500 copies/mL, and changes in CD4 cell counts. Results. The baseline RT mutations M41L, M184V, L210W, and T215Y and the M41L/T215Y and M41L/ T215Y/M184V combinations were associated with virological suppression for efavirenz-treated patients, whereas, for PI-treated patients, only the M184V mutation was associated with virological suppression, and the L210W mutation showed a negative correlation; no correlation was found between any mutation and virological response without rebound. Conclusions. The M41L, M184V, L210W, and T215Y mutations were associated with a better, although transient, virological outcome in patients treated with efavirenz-based regimens. Two classes of inhibitors of the HIV-1 reverse transcriptase (RT) gene have been approved so far: nucleoside reverse-transcriptase inhibitors (NRTIs) and nonnucleoside reverse-transcriptase inhibitors (NNRTIs). Both NRTIs and NNRTIs act on the same viral enzyme, the HIV-1 RT, but they inhibit the enzyme through different mechanisms. NNRTIs are noncompetitive in |
| Databáze: | OpenAIRE |
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