High frequency of dolutegravir resistance in patients failing a raltegravir-containing salvage regimen

Autor(es)

Cavalcanti, Jaqueline de Souza ^[1] ; de Paula Ferreira, Joao Leandro ^[1] ; de Souza Guimaraes, Paula Morena ^[1] ; Vidal, Jose Ernesto ^[2] ; de Macedo Brigido, Luis Fernando ^[1]

Afiliação do(s) autor(es)

^[1] Adolfo Lutz Inst, Retrovirus Lab, Sao Paulo - Brazil

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

• Tipo de documento: Artigo Científico
• Fonte: Journal of Antimicrobial Chemotherapy; v. 70, n. 3, p. 926-929, MAR 2015.
• Citações Web of Science: 7

Resumo

Objectives: Dolutegravir is a second-generation integrase strand transfer inhibitor (InSTI) that has been recently approved by the FDA to treat antiretroviral therapy-naive as well as treatment-experienced HIV-infected individuals, including those already exposed to the first-generation InSTI. Despite having a different mutational profile, some cross-resistance mutations may influence its susceptibility. The aim of this study was to evaluate the impact of a raltegravir-containing salvage regimen on dolutegravir activity. Patients and methods: Blood samples of 92 HIV-infected individuals with virological failure (two or more viral loads >50 copies/mL after 6 months of treatment) using raltegravir with optimized background therapy were sequenced and evaluated according to the Stanford University HIV Drug Resistance Database algorithm. Results: Among the 92 patients analysed, 32 (35%) showed resistance to dolutegravir, in most cases associated with the combination of Q148H/R/K with G140S/A mutations. At genotyping, patients with resistance to dolutegravir had viral load values closer to the highest previously documented viral load. Conclusions: Changes in viraemia during virological failure may indicate the evolution of raltegravir resistance and may predict the emergence of secondary mutations that are associated with a decrease in dolutegravir susceptibility. Early discontinuation of raltegravir from failing regimens might favour subsequent salvage with dolutegravir, but further studies are necessary to evaluate this issue. (AU)

• Processo FAPESP: 11/21958-2 - Resistência genotípica no resgate terapêutico de pacientes infectados pelo HIV-1 com novas classes de antirretrovirais
• Beneficiário: Luís Fernando de Macedo Brígido
• Modalidade de apoio: Auxílio à Pesquisa - Regular