title: The Decline in HIV-1 Drug Resistance in Heavily Antiretroviral-Experienced Patients Is Associated with Optimized Prescriptions in a Treatment Roll-Out Program in Mexico.
abstract: A decrease in the rate of acquired antiretroviral (ARV) drug resistance (ADR) over time has been documented in high-income settings, but data on the determinants of this phenomenon are lacking. We tested the hypothesis that in heavily ARV-experienced patients in the Mexican ARV therapy (ART) roll-out program, the drop in ADR would be associated with changes in ARV drug usage. Genotypic resistance tests obtained from 974 HIV-infected patients with virological failure and at least 2 previously failed ARV regimens from throughout the country were analyzed for the presence of nucleos(t)ide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitor (PI) resistance-associated mutations (RAMs). Patients were divided into two groups according to their first ART start date: 488 patients initiated ART before mid-2003 (group 1) and 486 after mid-2003 (group 2). The rate of RAMs, median resistance score of several sentinel ARVs, and composition of ART drugs in patient's entire treatment history were compared between both groups. Patients in group 2 were less likely to have >3 thymidine analogue-associated mutations (TAMs) and >3 PI-mRAMs [adjusted odds ratio (aOR) = 0.37; 95% confidence interval (95% CI) = 0.25-0.54; p < .001 and aOR = 0.53; 95% CI = 0.36-0.77; p = .001, respectively] and had a significantly lower resistance score for zidovudine, tenofovir, ritonavir-boosted (r)-lopinavir, r-atazanavir, and r-darunavir than group 1 patients. A significantly lower proportion of patients in group 2 used monotherapy, bitherapy, thymidine analogue-containing regimens, nonboosted PI-containing regimens, and low resistance barrier PI-containing regimens. In Mexican ARV-experienced patients, the occurrence of TAM and PI-mRAM has significantly declined over time. This can be explained by treatment optimization in the national ART roll-out program in recent years.
authors.affiliation: 1 Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, Mexico .
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Calva
authors.affiliation: 1 Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, Mexico .
authors.forename: Silvana
authors.initials: S
authors.lastname: Larrea
authors.affiliation: 2 PECEM, Faculty of Medicine, Universidad Nacional Autónoma de México , Mexico City, Mexico .
authors.forename: Marco A
authors.initials: MA
authors.lastname: Tapia-Maltos
authors.affiliation: 2 PECEM, Faculty of Medicine, Universidad Nacional Autónoma de México , Mexico City, Mexico .
authors.forename: Mauricio
authors.initials: M
authors.lastname: Ostrosky-Frid
authors.affiliation: 1 Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, Mexico .
authors.forename: Carolina
authors.initials: C
authors.lastname: Lara
authors.affiliation: 1 Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, Mexico .
authors.forename: Pedro
authors.initials: P
authors.lastname: Aguilar-Salinas
authors.affiliation: 1 Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, Mexico .
authors.forename: Héctor
authors.initials: H
authors.lastname: Rivera
authors.affiliation: 1 Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, Mexico .
authors.forename: Juan P
authors.initials: JP
authors.lastname: Ramírez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors
keywords: HIV; Mexico; antiretroviral; mutations; prescription; resistance