title: HIV-1-infected patients with advanced disease failing a raltegravir-containing salvage regimen in São Paulo, Brazil.
abstract: Raltegravir (RAL) is the first licensed antiretroviral integrase inhibitor that may be used both for treatment-naïve human immunodeficiency virus type 1 (HIV-1) patients and for salvage therapy. The Brazilian public free access programme limits its use for salvage therapy, with scarce information regarding RAL resistance from patients failing a RAL-containing salvage regimen. This study evaluated RAL resistance mutations detected by population sequencing in 69 HIV-infected patients with advanced disease failing a RAL-containing regimen in a real-world setting. RAL resistance mutations were identified in 47/69 patients (68%). The most common salvage regimen, used by 56/69 patients (81%), included lamivudine, tenofovir, darunavir/ritonavir and RAL. At failure, major RAL resistance mutations included Q148H/R/K (21/47; 45%), N155H (14/47; 30%), Y143R/H/C (3/47; 6%) and E92Q (1/47; 2%). Most samples with Q148H/R/K also showed G140S/A/C (21/47; 45%). RAL resistance was significantly associated with less than two active drugs in the optimised background therapy regimen at failure [39/39 (100%) vs. 9/17 (53%); P<0.001] and with a longer cumulative duration with detectable viraemia (viral load >50 copies/mL) (86 weeks vs. 32 weeks; P=0.001). A high frequency of RAL mutations was observed in this study. In addition, these results reinforce the importance of close monitoring of RAL-containing regimens to reduce the time of failure and consequent resistance accumulation.
authors.affiliation: Laboratório de Retrovirus, Instituto Adolfo Lutz, Av. Dr Arnaldo 355, Virology Service, São Paulo, SP, 01246-902, Brazil.
authors.forename: Jaqueline
authors.initials: J
authors.lastname: de Souza Cavalcanti
authors.affiliation: Laboratório de Retrovirus, Instituto Adolfo Lutz, Av. Dr Arnaldo 355, Virology Service, São Paulo, SP, 01246-902, Brazil.
authors.forename: Joao Leandro
authors.initials: JL
authors.lastname: de Paula Ferreira
authors.affiliation: Instituto de Infectologia Emílio Ribas, São Paulo, Brazil.
authors.forename: Jose Ernesto
authors.initials: JE
authors.lastname: Vidal
authors.affiliation: Laboratório de Retrovirus, Instituto Adolfo Lutz, Av. Dr Arnaldo 355, Virology Service, São Paulo, SP, 01246-902, Brazil.
authors.forename: Paula Morena
authors.initials: PM
authors.lastname: de Souza Guimarães
authors.affiliation: Laboratório de Retrovirus, Instituto Adolfo Lutz, Av. Dr Arnaldo 355, Virology Service, São Paulo, SP, 01246-902, Brazil.
authors.forename: Denise Helena
authors.initials: DH
authors.lastname: Moreira
authors.affiliation: Laboratório de Retrovirus, Instituto Adolfo Lutz, Av. Dr Arnaldo 355, Virology Service, São Paulo, SP, 01246-902, Brazil. Electronic address: lubrigido@gmail.com.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: de Macedo Brigido
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000453:epidemiology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001938:Brazil / Q000453:epidemiology; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D015995:Prevalence; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D016879:Salvage Therapy / Q000379:methods*; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium
keywords: Brazil; Genotype; HIV-1; Integrase; Raltegravir; Resistance