HIV-2 Integrase Polymorphisms and Longitudinal Genotypic Analysis of HIV-2 Infected Patients Failing a Raltegravir-Containing Regimen

• Autor(a) principal: Cavaco-Silva, J
• Data de Publicação: 2014
• Outros Autores: Abecasis, A, Miranda, AC, Poças, J, Narciso, J, Águas, MJ, Maltez, F, Almeida, I, Germano, I, Diniz, A, Gonçalves, MF, Gomes, P, Cunha, C, Camacho, RJ
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.17/1771
• topic: HCC INF; Drug Resistance, Viral/genetics; Genotype; HIV Infections/drug therapy; HIV Integrase/genetics; HIV Integrase Inhibitors/therapeutic use; HIV-1/drug effects; HIV-2/drug effects; HIV-2/genetics; Polymorphism, Genetic/genetics; Pyrrolidinones/therapeutic use

To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.