PMID- 15116307 OWN - NLM STAT- MEDLINE DCOM- 20040604 LR - 20201208 IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 189 IP - 9 DP - 2004 May 1 TI - 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. PG - 1688-95 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 <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. FAU - Tozzi, Valerio AU - Tozzi V AD - National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy. tozzi@inmi.it. FAU - Zaccarelli, Mauro AU - Zaccarelli M FAU - Narciso, Pasquale AU - Narciso P FAU - Trotta, Maria Paola AU - Trotta MP FAU - Ceccherini-Silberstein, Francesca AU - Ceccherini-Silberstein F FAU - De Longis, Patrizio AU - De Longis P FAU - D'Offizi, Giampiero AU - D'Offizi G FAU - Forbici, Federica AU - Forbici F FAU - D'Arrigo, Roberta AU - D'Arrigo R FAU - Boumis, Evangelo AU - Boumis E FAU - Bellagamba, Rita AU - Bellagamba R FAU - Bonfigli, Sandro AU - Bonfigli S FAU - Carvelli, Chiarina AU - Carvelli C FAU - Antinori, Andrea AU - Antinori A FAU - Perno, Carlo Federico AU - Perno CF LA - eng PT - Clinical Trial PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040413 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Alkynes) RN - 0 (Anti-HIV Agents) RN - 0 (Benzoxazines) RN - 0 (Cyclopropanes) RN - 0 (Oxazines) RN - 0 (Protease Inhibitors) RN - 0 (Reverse Transcriptase Inhibitors) RN - EC 2.7.7.49 (HIV Reverse Transcriptase) RN - JE6H2O27P8 (efavirenz) SB - IM CIN - J Infect Dis. 2004 Dec 1;190(11):2055-6; author reply 2056. PMID: 15529272 CIN - J Infect Dis. 2004 Dec 1;190(11):2056-7; author reply 2057. PMID: 15529273 MH - Adult MH - Alkynes MH - Anti-HIV Agents/pharmacology/*therapeutic use MH - Benzoxazines MH - CD4 Lymphocyte Count MH - Cohort Studies MH - Cyclopropanes MH - Drug Resistance, Viral/genetics MH - Drug Therapy, Combination MH - Female MH - HIV Infections/*drug therapy/immunology/virology MH - HIV Reverse Transcriptase/*genetics MH - HIV-1/*drug effects/enzymology/genetics MH - Humans MH - Male MH - Microbial Sensitivity Tests/methods MH - *Mutation MH - Oxazines/pharmacology/*therapeutic use MH - Protease Inhibitors/therapeutic use MH - Reverse Transcriptase Inhibitors/*pharmacology/therapeutic use MH - Treatment Outcome MH - Urban Population MH - Viral Load EDAT- 2004/04/30 05:00 MHDA- 2004/06/05 05:00 CRDT- 2004/04/30 05:00 PHST- 2003/08/02 00:00 [received] PHST- 2003/10/23 00:00 [accepted] PHST- 2004/04/30 05:00 [pubmed] PHST- 2004/06/05 05:00 [medline] PHST- 2004/04/30 05:00 [entrez] AID - JID31571 [pii] AID - 10.1086/382960 [doi] PST - ppublish SO - J Infect Dis. 2004 May 1;189(9):1688-95. doi: 10.1086/382960. Epub 2004 Apr 13.