Resistência transmitida a antirretrovirais e diversidade genética do HIV-1 em pacientes dos estados do Maranhão e do Piauí

• Autor(a) principal: Moura, Maria Edileuza Soares
• Data de Publicação: 2014
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/0013000004t7n
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/4334
• topic: Epidemiologia molecular; HIV-1; Genotipagem; Molecular epidemiology; HIV-1; Genotyping; CIENCIAS DA SAUDE::MEDICINA

In a vast country, like Brazil surveillance of transmitted drug resistance to antiretroviral drugs/TDR should be continuous and extended to different locations and exposure groups. In the last decade significant geographic differences have been reported in the Brazilian AIDS epidemic: reduction in incidence of AIDS cases and related mortality in the southeast region (epicenter of the epidemic) contrasting with significant rise in both parameters in the northeast region. This study describes TDR and HIV-1 subtypes in protease-PR and reverse transcriptase-RT regions among antiretroviral (ARV) naïve patients from Piauí State (n=89) and Maranhão State (n=106), northeast, Brazil recruited between August 2011 and June 2012. HIV-1 pol gene (protease/PR and 2/3 of reverse transcriptase/RT) was sequenced from RNA. TDR was evaluated using the Calibrated Population Resistance (CPR) tool/Stanford HIV-1 Database, HIV-1 subtypes were defined by REGA software and phylogenetic analyses. Among patients from Piauí State (44 females, 45 males, 22 of them were men who have sex with men-MSM), overall TDR rate was 13.5%. TDR rate among MSM was 27.3% while among heterosexual men TDR rate was 10% and 9.1% among females. Single-class mutations to ARV (RT nucleoside and non nucleoside inhibitors NRTI/NNRTI or PR inhibitors/PI) predominated (10/12): M46L/V82F/L90M (PI), M41L/D67N (NRTI); K103NS/E138A (NNRTI). Two patients had dual class mutations: T215L (NRTI) and E138G/Y188L (NNRTI); T215N (NRTI) and F227L (NNRTI). Subtype B predominated (86.6%), non-subtype B isolates were rare: subtype F1 (n=1), subtype C (n=1). B/F1, F1/B and B/C intersubtype recombinants were observed in 11.2%. In Maranhão State females predominated (54.7%), median age was 31 years (range: 18-72); 78.3% reported heterosexual unprotected sex, 17.9% were MSM, two reported intravenous drug use/IDU. SDRM TDR rate was 3.8% (4/106). TDR was identified in adults (21-45 years), mostly males (3/4), 2 MSM, one IDU. Single-class mutations associated with NRTI (M184V; T215S) or NNRTI (K103S/N) were detected. No major PI mutation was identified; four isolates presented accessory mutations to PI (L10I/F, A71T/V). Subtype B represented 81.1% (86/106), subtype F1 1.9% (2/106), subtype C 2.8% (3/106) and 14.2% (15/106) were recombinants. The moderate frequency of BF recombinants in PI and MA where subtype F1 is rare suggests that recombinants generated in southeast/central-western were introduced and are circulating in northeast Brazil. Among patients from PI, high TDR rate observed among MSM ccontrasts with moderate rate among heterosexual patients. This result indicates that genotyping tests to detect drug resistance and TDR, mainly among MSM can contribute to define surveillance policies and to delineate prevention strategies to help control AIDS epidemic in northeast, Brazil.