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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 5
Affiliation:
[1] Adolfo Lutz Inst, Retrovirus Lab, Sao Paulo - Brazil
[2] Inst Infectol Emilio Ribas, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Antimicrobial Chemotherapy; v. 70, n. 3, p. 926-929, MAR 2015.
Web of Science Citations: 7
Abstract

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)

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