Investigational HIV Treatment Promising (CME/CE)
The investigational anti-HIV drug dolutegravir outperformed raltegravir (Isentress) in a randomized trial among patients needing salvage therapy, a researcher said here.
After 48 weeks of therapy, HIV patients who had failed earlier regimens were significantly more likely to control their virus if they were taking dolutegravir, according to Pedro Cahn, MD, of Fundación Huesped in Buenos Aires.
At the same time, there were no major differences in the rate of adverse events in the so-called SAILING trial, Cahn reported at the 7th International Aids Society Conference on HIV Pathogenesis, Treatment, and Prevention.
Both drugs are members of a relatively new class of anti-HIV drugs, the integrase inhibitors. Raltegravir was the first approved integrase inhibitor, and a second drug in the class, elvitegravir, is so far only approved as part of a fixed-dose combination.
Dolutegravir is regarded as an attractive alternative because it is given once daily, at 50 milligrams, compared with 400 milligrams twice a day for raltegravir.
To test the comparative efficacy of the two drugs, Cahn and colleagues enrolled 715 treatment-experienced patients who had not yet been given an integrase inhibitor for a randomized, double-blinded, double-dummy trial.
The primary endpoint was the proportion of patients who reached an undetectable level of plasma RNA, defined as fewer than 50 copies per milliliter.
Along with the integrase inhibitor, patients were given an optimized two-drug background in which at least one drug had to be fully active, Cahn told reporters.
After 48 weeks of treatment, he said, 64% of patients taking raltegravir had reached the primary endpoint, compared with 71% of those taking dolutegravir (P
=0.03).
The treatment difference was significant, Cahn said, allowing the investigators to conclude that "superiority can be claimed for dolutegravir on a statistical basis."
Interestingly, among patients whose background regimen included the protease inhibitor darunavir (Prezista) -- and who had no resistance to the drug -- there was no difference in efficacy between raltegravir and dolutegravir, Cahn told MedPage Today
.
That's probably because darunavir itself is very potent in salvage therapy, Cahn said, so that its benefit swamps any difference between the integrase inhibitors.
Both integrase inhibitors are "extremely safe," he said, with very few patients stopping therapy because of adverse events -- 3% in the dolutegravir arm and 4% in the raltegravir arm.
The most commonly reported adverse events were diarrhea and upper respiratory tract infection, which occurred at similar rates in the two treatment arms, Cahn reported.
The study adds to the "very promising data" on dolutegravir, commented Jintanat Ananworanich, MD, PhD, of the Thai Red Cross AIDS Research Center in Bangkok, who was not part of the study but who moderated a press conference at which some details were presented.
The drug has shown very rapid reductions in viral load at low doses, Ananworanich told MedPage Today
, which might allow it to be used at lower cost than other members of the class.
As a pediatrician, she added, she's following it closely because it also appears to very effective in children.
The study was supported by GlaxoSmithKline. Cahn has previously disclosed financial relationships with Abbott, Avexa, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Pfizer, Pharmasset, Schering-Plough, and Tibotec.
Ananworanich made no disclosures.
Primary source: International AIDS Society
Source reference:
Cahn P, et al "Dolutegravir (DTG) is superior to raltegravir (RAL) in ART-experienced, integrase naive subjects: week 48 results from SAILING" IAS
2013; Abstract WELBB03.
