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 supp...

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Bibliographic Details
Published in:Journal of clinical virology 2002-07, Vol.25 (1), p.39-46
Main Authors: Tanuri, Amilcar, Caridea, Elena, Dantas, Maria C., Morgado, Marisa G., Mello, Daise L.C., Borges, Sandra, Tavares, Marisa, Ferreira, Selma B., Santoro-Lopes, Guilherme, Martins, Claudia R.F., Esteves, André L.C., Diaz, Ricardo S., Andreo, Sandra M.S., Ferreira, Luiz A.P., Rodrigues, Rodrigo, Reuter, Tania, Cavalcanti, Ana M.S., de Oliveira, Suelene M., de Barbosa, Heraclito B., Teixeira, Paulo R., Chequer, Pedro N.
Format: Article
Language:English
Subjects:
Antiretroviral Therapy, Highly Active
Biological and medical sciences
Brazil - epidemiology
Cross-Sectional Studies
Drug Resistance, Viral - genetics
Genotyping
HIV Infections - drug therapy
HIV Infections - epidemiology
HIV Infections - virology
HIV Protease - genetics
HIV Reverse Transcriptase - genetics
HIV-1
HIV-1 - drug effects
HIV-1 - genetics
Human viral diseases
Humans
Infectious diseases
Medical sciences
Mutation
Phenotyping
Prevalence
Protease
Reverse transcriptase
Treatment Failure
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
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Summary: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 pol RT (palm finger region) genes. The mutations related to drug resistance in RT gene was analyzed using a line probe assay (LIPA®) 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.
ISSN:1386-6532
1873-5967
DOI:10.1016/S1386-6532(01)00249-9