Prevalence of mutations related to HIV-1 antiretroviral resistance in Brazilian patients failing HAART

Background: Current guidelines for antiretroviral (ARV) therapy recommend at least triple-drug combination, the so-called highly active antiretroviral therapy (HAART). Not all patients respond to HAART and the development of drug resistance remains one of the most serious obstacles to sustained suppression of HIV. Objective: in an attempt to correlate the HIV therapeutic failure with reverse transcriptase (RT) and protease resistance mutations, we describe the ARV resistance profile in patients failing HAART in Brazil. We studied 267 Brazilian HIV-1 infected patients failing HAART looking for mutations in RT and protease genes. the mutation profile of the viruses infecting these individuals were deduced and correlated to laboratorial parameters. Study Design: Two different HIV-1 genomic regions were targeted for PCR amplification, the protease (pro) and pal RT (palm finger region) genes. the mutations related to drug resistance in RT gene was analyzed using a line probe assay (LIPA(R)) and pro amino acids positions 82 and 90 were screened through RFLP using HincII restriction digestion. Results: There was strong correlation between the mutation in the pro and RT genes and therapeutic failure. the main mutation found in RT gene was the M184V (48%) followed by T69D/N (47%), T215Y/F (46%), M41L (39%), and L74V (7%). in the pro gene the main mutation found was L90M (26%) followed by dual substitution in L90M and V82A (6%). All mutations profiles matched very well with the patients drug regimen. Conclusions: This study has shown that 84.7% of HIV infected subjects failing HAART for more than 3 months presented viral genomic mutations associated with drug resistance. (C) 2002 Elsevier Science B.V. All rights reserved.Univ Fed Rio de Janeiro, CCS, Inst Biol, Dept Genet,Lab Virol Mol, BR-21944970 Rio de Janeiro, BrazilBrazilian Minist Hlth, Programa Brasileiro AIDS STD, Brasilia, DF, BrazilFiocruz MS, Inst Oswaldo Cruz, Lab Imunol, BR-21045900 Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Lab Petrobras, BR-21944970 Rio de Janeiro, BrazilUniv Fed Espirito Santos, Vitoria, ES, BrazilUniv Brasilia, Virol Lab, Brasilia, DF, BrazilLab Cent Saude Publ, Recife, PE, BrazilUniv Fed Estado São Paulo, Lab Retrovirol, São Paulo, BrazilUniv São Paulo, Dept Epidemiol, São Paulo, BrazilLab Cent Saude Publ, Florianopolis, SC, BrazilUniv Fed Santa Catarina, Florianopolis, SC, BrazilUniv Fed Estado São Paulo, Lab Retrovirol, São Paulo, BrazilWeb of Scienc