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

• Published in: The Journal of infectious diseases Vol. 189; no. 9; pp. 1688 - 1695
• Main Authors: Tozzi, Valerio, Zaccarelli, Mauro, Narciso, Pasquale, Trotta, Maria Paola, Ceccherini-Silberstein, Francesca, De Longis, Patrizio, D'Offizi, Giampiero, Forbici, Federica, D'Arrigo, Roberta, Boumis, Evangelo, Bellagamba, Rita, Bonfigli, Sandro, Carvelli, Chiarina, Antinori, Andrea, Perno, Carlo Federico
• Format: Journal Article
• Language: English
• Published: Chicago, IL University Chicago Press 01-05-2004; University of Chicago Press; Oxford University Press
• Subjects: Adult; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Benzoxazines; Biological and medical sciences; CD4 Lymphocyte Count; Cohort Studies; Drug Resistance, Viral - genetics; Drug Therapy, Combination; Female; Fundamental and applied biological sciences. Psychology; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV-1 - enzymology; HIV-1 - genetics; Human immunodeficiency virus 1; Humans; Infectious diseases; Male; Medical sciences; Microbial Sensitivity Tests - methods; Microbiology; Miscellaneous; Mutation; Oxazines - pharmacology; Oxazines - therapeutic use; Protease Inhibitors - therapeutic use; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; Treatment Outcome; Urban Population; Viral Load; Virology; RNA-directed DNA polymerase; Microbiology; HIV-1 virus; Enzyme; Transferases; Retroviridae; Lentivirus; Efavirenz; Virus; Infection; Nucleotidyltransferases; Treatment; Reverse transcriptase inhibitor; Antiviral; Human immunodeficiency virus; Mutation
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/382960

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 >500 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.