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.


METHODS
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(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.
Tanuri
Amilcar
A
Departamento de Genética, Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, sala 121, 2o andar, Rio de Janeiro, RJ, Cep: 21944-970, Brazil. atanuri@biologia.ufrj.br
Caridea
Elena
E
Dantas
Maria C
MC
Morgado
Marisa G
MG
Mello
Daise L C
DL
Borges
Sandra
S
Tavares
Marisa
M
Ferreira
Selma B
SB
Santoro-Lopes
Guilherme
G
Martins
Claudia R F
CR
Esteves
André L C
AL
Diaz
Ricardo S
RS
Andreo
Sandra M S
SM
Ferreira
Luiz A P
LA
Rodrigues
Rodrigo
R
Reuter
Tania
T
Cavalcanti
Ana M S
AM
de Oliveira
Suelene M
SM
de Barbosa
Heraclito B
HB
Teixeira
Paulo R
PR
Chequer
Pedro N
PN
D023241:Antiretroviral Therapy, Highly Active; D001938:Brazil / Q000453:epidemiology; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D015995:Prevalence; D017211:Treatment Failure
D054303:HIV Reverse Transcriptase; D016333:HIV Protease