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Integrase strand-transfer inhibitor polymorphic and accessory resistance substitutions in patients with acute/recent HIV infection.

Integrase strand-transfer inhibitor polymorphic and accessory resistance substitutions in patients with acute/recent HIV infection.
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Ambrosioni J, Nicolás D, Manzardo C, Agüero F, Blanco JL, Mosquera MM, Peñafiel J, Gatell JM, Marcos MA, Miró JM,


Ambrosioni J, Nicolás D, Manzardo C, Agüero F, Blanco JL, Mosquera MM, Peñafiel J, Gatell JM, Marcos MA, Miró JM, (click to view)

Ambrosioni J, Nicolás D, Manzardo C, Agüero F, Blanco JL, Mosquera MM, Peñafiel J, Gatell JM, Marcos MA, Miró JM,

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The Journal of antimicrobial chemotherapy 2016 9 13() pii

Abstract
OBJECTIVES
The most recent guidelines suggest using integrase strand-transfer inhibitors (InSTIs) as the preferred antiretroviral regimens for naive HIV-infected individuals. However, resistance to InSTIs is not monitored in many centres at baseline. This study aimed to evaluate the prevalence of InSTI resistance substitutions in newly diagnosed patients with acute/recent HIV infection.

METHODS
Genotypic drug resistance tests were performed in all consecutive patients prospectively enrolled with a documented infection of <6 months, from 12 May 2015 to 12 May 2016. Sequences were obtained by high-throughput sequencing. RESULTS
Five out of 36 consecutive patients (13.89%, 95% CI = 4.67-29.5) with acute/recent HIV infection were detected to have strains carrying InSTI polymorphisms or substitutions conferring low-level resistance to raltegravir and elvitegravir. Four patients had the 157Q polymorphism and one patient had the Q95K substitution. All cases were MSM patients infected with subtype B strains. Viral loads ranged from 2.92 to 6.95 log10 copies/mL. In all cases, the mutational viral load was high. Three patients initiated dolutegravir-based regimens and became undetectable at first viral load control. There were no major viral or epidemiological differences when compared with patients without InSTI substitutions.

CONCLUSIONS
Although signature InSTI substitutions (such as Y143R/C, N155H or Q148K/R/H) were not detected, polymorphisms and substitutions conferring low-level resistance to raltegravir and elvitegravir were frequently found in a baseline genotypic test. All cases were infected with subtype B, the most frequent in Europe. In the context of primary HIV infection, virological response should be carefully monitored to evaluate the impact of these InSTI polymorphisms and substitutions.

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