Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás

• Ano de defesa: 2013
• Autor(a) principal: Reis, Mônica Nogueira da Guarda
• Orientador(a): Stefani, Mariane Martins de Araújo
• Banca de defesa: Stefani, Mariane Martins de Araújo, Kipnis, André, Fonseca, Simone Gonçalves da
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)
• Departamento: Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
• País: Brasil
• Palavras-chave em Português: Gestantes; HIV-1; Enfuvirtida; Pregnant; Enfuvirtide
• Palavras-chave em Inglês: Pregnant women; HIV-1
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::MICROBIOLOGIA
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/3301

Among pregnant women infected with HIV-1, drug resistance mutations to antiretroviral drugs (ARV) represent a challenge for the prevention to HIV-1 mother-to child-transmission (MTCT) and for future maternal treatment options. The goal of this study was to assess the presence of mutations in gp41 associated with natural resistance to the fusion inhibitor T-20, polymorphisms and HIV-1 subtypes among pregnant women never treated with T-20 and under different exposure levels to other ARV. A total of 153 pregnant women infected with HIV-1 (ARV naive, under MTCT prophylaxis or under ARV treatment/HAART) was recruited from june/2008-june/2010. The env gene gp41 fragment of 766 bp (FP, HR1, HR2, TM regions) was amplified by “nested”-PCR from cDNA and sequenced among 110 patients (Big Dye Terminator Sequencing v. 3.1, Applied Biosystems, EUA; ABI Prism 3130). HIV-1 subtypes were assigned by REGA tool and by phylogenetic analyses (Neighbor-Joining, Kimura 2-P). T-20 resistance mutations were analyzed according to the IAS/USA, Stanford online HIV Drug Resistance Database and other sources. The median age of pregnant women (n=110) was 26 years (16-42 years), 16% were AIDS cases. The frequency of natural resistance (N42D, L44M and R46M) to T-20 was 5.4% (6/110). All resistance mutations were identified in HIV-1 subtype B isolates within the HR1 region of the gp41 fragment. The prevalence of compensatory mutations in HR2 region of gp41 was 20.9% (23/110): S138A (n=11), E137K (n=10) e N126K (n=2). All 110 isolates presented several polymorphisms. The following polymorphisms were observed in FP of gp41: M24I/L/V, I7M/V, and I4A/F/L/M. In 42.7% (47/110) of isolates many indels within the gp41 FP fragment were observed. Polymorphisms identified in HR1 were: K77E/L/Q/R/V, I69V, L54M, R46K/Q, N42S and Q32L/N. Polymorphisms in HR2 gp41 region were: S157D/N, E151A/K/Q, E148D, I135L, S133D/E/N/Q/R/T, H132F/Y, L130E/I/T, S129D/G/N/Q, N125A/D/E/S, R122K, N121E/D and E119Q. Moderate rate of natural resistance for T-20 and higher prevalence of polymorphisms in env gp41 region were described. Moreover higher prevalence of HIV-1 “non- B subtypes” C and F1 was observed. These molecular data may contribute to better therapeutic and MTCT preventive strategies for pregnant women infected with HIV-1.