title: Prevalence of resistance-associated mutations in human immunodeficiency virus type 1-positive individuals failing HAART in Rio de Janeiro, Brazil.
abstract: We investigated the occurrence of HIV-1 antiretroviral resistance in individuals failing to respond to highly active antiretroviral therapy (HAART) attended by RENAGENO from 2001-2004. One hundred and seventeen patients were selected for this study; their plasma viral RNA was extracted and the PR and RT genes sequenced to examine subtype, genetic polymorphisms and mutations associated with resistance to antiretroviral drugs. HIV-1 sequence analysis showed that 86/100 (86%) were infected with subtype B, 7/100 (7%) with subtype F and 7/100 (7%) with RT/PR hybrid forms (2 D/B, 2 F/B, 2 B/F and 1 D/F). In 14 (12%) of the samples, the subtype was not determined. The prevalence of resistance mutations was high (93.1%), mainly in the RT gene. The most prevalent resistance mutations were: M184V (60.7%), T215Y (49.6%) and M41L (46.7%) in the RT gene and L90M (19.6%), M46I (16.2%) and D30N (12.8%) in the PR gene. The frequency of resistance mutations tended to increase from the first to the second therapeutic scheme failure (p=0.079); but it stabilized after subsequent failures (p=0.875). Our finding of a high frequency of drug resistant HIV-1 samples supports the need for continuous genotypic monitoring of patients failing HAART.
authors.affiliation: Department of Infectious Diseases, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Brazil. rafael_varella@hotmail.com
authors.forename: Rafael Brandão
authors.initials: RB
authors.lastname: Varella
authors.forename: Selma Baía
authors.initials: SB
authors.lastname: Ferreira
authors.forename: Márcia Braga de
authors.initials: MB
authors.lastname: Castro
authors.forename: Marisa Dias
authors.initials: MD
authors.lastname: Tavares
authors.forename: Mariano Gustavo
authors.initials: MG
authors.lastname: Zalis
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001938:Brazil; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease