The investigational integrase inhibitor dolutegravir has been studied in treatment-naive patients and in treatment-experienced patients with integrase inhibitor-associated resistance. The present study (SAILING) evaluates dolutegravir in 715 patients who had resistance to at least 2 ARV classes and incomplete viral suppression on their current regimen but were naive to integrase inhibitors. The patients were randomized to dolutegravir (50 mg once daily) or raltegravir (400 mg BID), each with an optimized background regimen of 2 agents (at least 1 fully active) selected by the investigators. The baseline median HIV RNA was 4.2 log10 copies/mL (30% in each arm had HIV RNA levels of >50,000 copies/mL), median CD4 count was 200 cells/µL, and 50% of the patients had resistance to at least 3 ARV classes.
At the interim 24-week analysis (intention to treat), 79% of the dolutegravir group and 70% of the raltegravir group had HIV RNA suppressed to <50 copies/mL (95% confidence interval [CI]: 3.4, 15.9; p = .003); in those with baseline HIV RNA >50,000 copies/mL, virologic suppression was seen in 70% and 63% of the treatment groups, respectively. CD4 count increases were similar in the two groups: 114 cells/µL and 106 cells/µL, respectively.
Virologic failure was seen less frequently in the dolutegravir arm (4% vs 9%), and integrase inhibitor resistance emerged less frequently in the dolutegravir arm (in 2 vs 10 subjects). The 2 subjects in the dolutegravir group developed an R263K mutation but did not have phenotypic resistance (fold change IC50 of <2 for both dolutegravir and raltegravir). On the other hand, raltegravir recipients with new integrase mutations had expected raltegravir-associated mutations (Y143, Q148, and/or N155) with high-level phenotypic resistance.
Adverse events were similar in frequency and type, though more immune reconstitution inflammatory syndrome (IRIS) events were observed in the dolutegravir group.
Clinical Bottom Line
This study will continue through the primary endpoint of 48 weeks, so much more data on efficacy, safety, and emergent resistance should be forthcoming. Dolutegravir continues to be a very promising ARV--it is highly effective and tolerable, is dosed once daily, does not require PK boosting with ritonavir or cobicistat, and has a higher barrier to resistance than raltegravir. Approval by the FDA is anticipated to occur later this year.