title: Temporal characterization of drug resistance associated mutations in HIV-1 protease and reverse transcriptase in patients failing antiretroviral therapy.
abstract: The aim of this study was to evaluate the prevalence of genotypic resistance for each drug-class, and of single resistance-mutations in 1075 HIV-1 infected multi-treated patients undergoing their first genotypic resistance-test (GRT) after virological failure, over the years 1999-2003. First GRT was requested in 2003 for patients at earlier stages of failure, with less advanced disease, higher CD4-cell-count, lower HIV-RNA, and lower drug-experience with respect to 1999. Prevalence of resistance to all three drug-classes decreased from 33.3% in 1999 to 14.8% in 2003 (p < 0.001). Patients with protease-inhibitor (PI) resistant viruses decreased from 68.1% in 1999 to 34.1% in 2003 (p < 0.001); patients with nucleoside reverse transcriptase-inhibitor (NRTI) resistant viruses remained unchanged (85.4% in 1999; 86.4% in 2003); patients with non-NRTI (NNRTI) resistant viruses increased from 36.1% in 1999 to 52.3% in 2003 (p = 0.005) (corresponding to an increased NNRTI-use and decreased PI-use). From 1999 to 2003, resistance-mutations to drugs with high genetic-barrier significantly decreased (L90M/V82A/M46I/I54V/G73S/I84V/G48V for PIs; M41L/D67N/L210W/V1181 for NRTIs, p < 0.05), while mutations to drugs with low genetic-barrier increased (D30N in protease, M184V/K103N/V108I in reverse transcriptase, p < 0.05). Taken together, earlier recruitment to first GRT in patients with less severe disease, and with lower prevalence of drug-resistant viruses may further improve therapeutic strategies aimed at longer and greater control of HIV-related disease progression.
authors.affiliation: Department of Experimental Medicine, Tor Vergata University of Rome, Italy.
authors.forename: Maria Mercedes
authors.initials: MM
authors.lastname: Santoro
authors.forename: Valentina
authors.initials: V
authors.lastname: Svicher
authors.forename: Caterina
authors.initials: C
authors.lastname: Gori
authors.forename: Mauro
authors.initials: M
authors.lastname: Zaccarelli
authors.forename: Valerio
authors.initials: V
authors.lastname: Tozzi
authors.forename: Federica
authors.initials: F
authors.lastname: Forbici
authors.forename: Roberta
authors.initials: R
authors.lastname: D'Arrigo
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Trotta
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Bellocchi
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Visco-Comandini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cenci
authors.forename: Ada
authors.initials: A
authors.lastname: Bertoli
authors.forename: Pasquale
authors.initials: P
authors.lastname: Narciso
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease