High frequency of dolutegravir resistance in patients failing a raltegravir-containing salvage regimen
J Antimicrob Chemother
; 70(3): 926-929, 2015.
Article
in En
| LILACS, SES-SP, SESSP-IALPROD, SES-SP, SESSP-IALACERVO
| ID: biblio-1022184
Responsible library:
BR91.2
Localization: BR76.1; P
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 ANDMETHODS:
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.
Full text:
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Index:
LILACS
Main subject:
Pyrrolidinones
/
Humans
/
HIV Infections
/
HIV-1
/
Salvage Therapy
/
Treatment Failure
/
Sequence Analysis, DNA
/
Anti-HIV Agents
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Adult
/
Mutation, Missense
Language:
En
Journal:
J Antimicrob Chemother
Year:
2015
Type:
Article