title: HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen.
abstract: 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.
authors.affiliation: Centro de Malária e Outras Doenças Tropicais, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Cavaco-Silva
authors.affiliation: Centro de Malária e Outras Doenças Tropicais, Unidade de Saúde Pública Internacional e Bioestatística, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Abecasis
authors.affiliation: Serviço de Doenças Infecciosas, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal.
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Miranda
authors.affiliation: Hospital de São Bernardo, Centro Hospitalar de Setúbal, Setúbal, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Poças
authors.affiliation: Hospital dos SAMS, Lisboa, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Narciso
authors.affiliation: Hospital Garcia de Orta, Almada, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Águas
authors.affiliation: Hospital Curry Cabral, Centro Hospitalar de Lisboa Central, Lisboa, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Maltez
authors.affiliation: Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Almeida
authors.affiliation: Hospital de São José, Centro Hospitalar de Lisboa Central, Lisboa, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Germano
authors.affiliation: Hospital Pulido Valente, Centro Hospitalar de Lisboa Norte, Lisboa, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Diniz
authors.affiliation: Laboratório de Microbiologia Clínica e Biologia Molecular, Serviço de Patologia Clínica (SPC), Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal.
authors.forename: Maria de Fátima
authors.initials: Mde F
authors.lastname: Gonçalves
authors.affiliation: Laboratório de Microbiologia Clínica e Biologia Molecular, Serviço de Patologia Clínica (SPC), Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal; Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal; Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Instituto Superior de Ciências da Saúde Sul, Caparica, Portugal.
authors.forename: Perpétua
authors.initials: P
authors.lastname: Gomes
authors.affiliation: Centro de Malária e Outras Doenças Tropicais, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: Celso
authors.initials: C
authors.lastname: Cunha
authors.affiliation: Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal; Rega Institute for Medical Research, Katholieke Universiteit Leuven (KU Leuven), Leuven, Belgium.
authors.forename: Ricardo Jorge
authors.initials: RJ
authors.lastname: Camacho
mesh_terms: D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase; C514802:p31 integrase protein, Human immunodeficiency virus 2