Resistência primária aos antirretrovirais e diversidade genética do HIV-1 em pacientes do estado do Tocantins.

• Ano de defesa: 2011
• Autor(a) principal: CARVALHO, Bruna Coelho
• Orientador(a): STEFANI, Mariane Martins de Araújo
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Mestrado em Medicina Tropical
• Departamento: Medicina
• País: BR
• Palavras-chave em Português: Genotipagem; resistência primária; diversidade genética; HIV-1
• Palavras-chave em Inglês: Genotypin; primary resistance; genetic diversity; HIV-1
• Área do conhecimento CNPq: CNPQ::CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tde/1796

Regional differences in the molecular epidemiology of HIV-1 have been reported in Brazil, where there is scarce publication about the epidemic in north region. Despite the large number of antiretroviral drugs (ARV) belonging to nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI and NNRTI) and protease inhibitors (PI) classes, the selection of resistance-associated mutations may compromise the therapeutic efficacy. Primary resistance mutations, present prior to ARV use, occur mainly due to the transmission of resistant virus. This study describes the prevalence and profile of primary resistance mutations to ARV and the molecular epidemiology of HIV-1 in ARV naive patients from Tocantins State. For HIV-1 genotyping of the entire protease gene (PR) and 750 bp of reverse transcriptase (RT) gene, plasma RNA was extracted, reverse transcribed into cDNA) and used as the target for nested polymerase chain reaction (K1/K2 and F2/DP10 primers) and fragments were sequenced (kit DYEnamic ET Dye Terminator, GE Healthcare; ABI Prism 3130). The sequences were edited by the Staden Package software. Primary drug resistance was analyzed using the Calibrated Population Resistance (CPR) tool employing the Stanford Surveillance Drug Resistance Mutation (SDRM). The susceptibility profile of ARV mutations was analyzed by Stanford HIV Drug Resistance Database (hivdb.stanford.edu). HIV-1 genetic subtypes were identified by REGA HIV-1 and SIMPLOT softwares and by phylogenetic inference. Naïve patients (n=52) were recruited in LACEN/Palmas/TO between 2008-2010. The majority of investigated patients (59.6%) were males and 73.1% reported heterosexual exposure. Primary mutations that confer resistance to ARV were identified in 11.5% (06/52) of the isolates: BRTO08-43: M41L, L210W, T215D (NRTI); BRTO02-83: Y181C (NNRTI); BRTO13-83: D67G, K219E (NRTI); BRTO20-83: V108I, Y181C (NNRTI); BRTO02-66: M46L (PI); e BRTO13-66: V90I, K103N (NNRTI). Isolates with concordant subtypes in PR/RT regions represented 86.5% (45/52): subtype BPRBRT=78.8% (41/52), subtype CPRCRT=5.8% (3/52), subtype F1PRF1RT=1.9%. Isolates with discordant subtypes in PR and RT genes indicating intersubtype recombination represented 13.5% (07/52): BPRF1TR=1.9% (01/52); BPRBF1TR=7.7% (04/52) e CPRCF1TR=3.9% (02/52). Our study among naive patients from Tocantins State describes moderate prevalence of primary resistance to ARV, the predominance of subtype B that co-circulates with subtype C and a significant number of B/F1 and C/F1 recombinant forms. These results indicate the transmission of ARV resistant HIV-1 isolates among patients from a small inland city in north Brazil, where the epidemic is more recent. In this context, it is important to monitor the prevalence of primary drug resistance in order to assess the need and the cost-benefit of the implementation of pre-treatment genotipic tests aiming to optimize the choice of the ARV regimen among naive patients from Tocantins State.