Cavaco-Silva, JAbecasis, AMiranda, ACPoças, JNarciso, JÁguas, MJMaltez, FAlmeida, IGermano, IDiniz, AGonçalves, MFGomes, PCunha, CCamacho, RJ2014-04-022014-04-022014PLoS One. 2014 Mar 28;9(3):e92747http://hdl.handle.net/10400.17/1771To 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.engHCC INFDrug Resistance, Viral/geneticsGenotypeHIV Infections/drug therapyHIV Integrase/geneticsHIV Integrase Inhibitors/therapeutic useHIV-1/drug effectsHIV-2/drug effectsHIV-2/geneticsPolymorphism, Genetic/geneticsPyrrolidinones/therapeutic usejournal article