Dolutegravir-based regimen maintains virological success in a patient with archived mutations to integrase inhibitors

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Excerpt

Dolutegravir (DTG) is the latest integrase inhibitor (INI) to be approved for the treatment of HIV-1 infection, with a high antiviral effect, excellent efficacy and safety profile [1,2]. Although DTG seems to show a high genetic barrier, its resistance profile has not yet been established, particularly in patients with failure on an INI-based regimen [3]. The VIKING-3 study among patients with INI-resistant virus reported that the maximum reduction in DTG susceptibility occurred when Q148 was accompanied by at least two other major mutations. For these patients, the odds of achieving HIV-RNA less than 50 copies/ml were 96% lower than those of patients with no evidence of Q148 mutations, even when DTG was dosed twice a day (BID) [4,5]. Moreover, the role of archived integrase mutations is still unknown and generally the clinical significance of drug resistance mutations (DRMs) in proviral DNA remains controversial. Several studies showed that DRMs in proviral DNA may be implicated in therapy failure, whereas others reported that genotypic resistance tests on peripheral blood mononuclear cells (PBMCs) did not provide useful information for assessing the risk of virological failure [6–8].
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