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

Valerio Tozzi, Mauro Zaccarelli, Pasquala Narciso, Maria Paola Trotta, Francesca Caccherini-Silberstein, Patrizio Da Longis, Giampiero D'Offizi, Federica Forbici, Roberta D'Arrigo, Evangelo Boumis, Rita Bellagamba, Sandro Bonfigli, Chiarina Carvalli, Andrea Antinori, Carlo Fedarico Perno

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Pages (from-to)1688-1695
Number of pages8
JournalJournal of Infectious Diseases
Volume189
Issue number9
DOIs
Publication statusPublished - May 1 2004

Fingerprint

efavirenz
Reverse Transcriptase Inhibitors
Mutation
RNA-Directed DNA Polymerase
Protease Inhibitors
Therapeutics
Highly Active Antiretroviral Therapy
CD4 Lymphocyte Count
Human immunodeficiency virus 1 reverse transcriptase
Nucleosides

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

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. / Tozzi, Valerio; Zaccarelli, Mauro; Narciso, Pasquala; Trotta, Maria Paola; Caccherini-Silberstein, Francesca; Da Longis, Patrizio; D'Offizi, Giampiero; Forbici, Federica; D'Arrigo, Roberta; Boumis, Evangelo; Bellagamba, Rita; Bonfigli, Sandro; Carvalli, Chiarina; Antinori, Andrea; Perno, Carlo Fedarico.

In: Journal of Infectious Diseases, Vol. 189, No. 9, 01.05.2004, p. 1688-1695.

Research output: Contribution to journalArticle

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abstract = "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 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.",
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T2 - Effect on response to efavirenz-based therapy in an urban observational cohort

AU - Tozzi, Valerio

AU - Zaccarelli, Mauro

AU - Narciso, Pasquala

AU - Trotta, Maria Paola

AU - Caccherini-Silberstein, Francesca

AU - Da Longis, Patrizio

AU - D'Offizi, Giampiero

AU - Forbici, Federica

AU - D'Arrigo, Roberta

AU - Boumis, Evangelo

AU - Bellagamba, Rita

AU - Bonfigli, Sandro

AU - Carvalli, Chiarina

AU - Antinori, Andrea

AU - Perno, Carlo Fedarico

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N2 - 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 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.

AB - 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 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.

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