HIV-1-infected patients with advanced disease failing a raltegravir-containing salvage regimen in Sao Paulo, Brazil

Author(s)

Cavalcanti, Jaqueline de Souza ^[1] ; de Paula Ferreira, Joao Leandro ^[1] ; Vidal, Jose Ernesto ^[2] ; de Souza Guimaraes, Paula Morena ^[1] ; Moreira, Denise Helena ^[1] ; de Macedo Brigido, Luis Fernando ^[1] ; Workgrp, Sao Paulo Salvage

Affiliation

^[1] Adolfo Lutz Inst, Lab Retrovirus, Virol Serv, BR-01246902 Sao Paulo - Brazil

^[2] Inst Infectol Emilio Ribas, Sao Paulo - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS; v. 43, n. 3, p. 287-291, MAR 2014.
• Web of Science Citations: 2

Abstract

Raltegravir (RAL) is the first licensed antiretroviral integrase inhibitor that may be used both for treatment-naive 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 47169 patients (68%). The most common salvage regimen, used by 56169 patients (81%), included lamivudine, tenofovir, darunavir/ritonavir and RAL. At failure, major RAL resistance mutations included Q148H/R/K (21147; 45%), N155H (14147; 30%), Y143R/H/C (3147; 6%) and E92Q (1147; 2%). Most samples with Q148H/R/K also showed G140S/A/C (21147; 45%). RAL resistance was significantly associated with less than two active drugs in the optimised background therapy regimen at failure {[}39139 (100%) vs. 9117 (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. (C) 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. (AU)

• FAPESP's process: 11/21958-2 - Genetic resistance to HIV-1 in the salvage therapy with new antiretroviral drug classes
• Grantee: Luís Fernando de Macedo Brígido
• Support Opportunities: Regular Research Grants