New HIV Drug - A Match To Preceeding Standards

The recently approved anti-HIV medication dolutegravir (Tivicay) has equivalent efficacy to boosted darunavir (Prezista), a researcher said.

Indeed, in 48-week results from an open-label trial, dolutegravir, an integrase inhibitor, appeared statistically superior to the older drug, according to Judith Feinberg, MD, of the University of Cincinnati and an investigator with the AIDS Clinical Trials Unit there.




So far in the 96-week study, there has been no sign of developing resistance, Feinberg said here at the annual Interscience Conference on Anti-Microbial Agents and Chemotherapy.

The report is the first new data on the drug since it was approved in August but the open-label design of the so-called FLAMINGO trial drew criticism from participants in the late-breaking oral session.

In answer to a question, Feinberg conceded that most such studies are performed in a blinded fashion, but she said organizers were concerned that the number of pills involved in a placebo-controlled, double-dummy study would be too much for participants.

The design is not a major hurdle, however, commented Joseph Eron, MD, of the University of North Carolina Chapel Hill, who was not involved in the study but who co-moderated the session.
"I think they could have blinded it, to be honest," he told MedPage Today later, but "there have been other open-label studies that we have taken to the bank."

And, he added, there have been other studies of dolutegravir, conducted in a blinded fashion, that have yielded similar efficacy results to the FLAMINGO trial.

Feinberg reported that she and colleagues studied outcomes for 484 treatment-naive patients randomly assigned to get either dolutegravir or darunavir once a day, in combination with a backbone of two nucleoside reverse transcriptase inhibitors (NRTIs).

The primary outcome was the proportion of patients at 48 weeks with a plasma viral load of fewer than 50 copies of HIV RNA per milliliter, with a minus 12% noninferiority margin.

In that so-called snapshot analysis, she said, 90% of those treated with dolutegravir and 83% of those getting darunavir met the primary endpoint. The difference, adjusted for baseline viral load and the concomitant NRTI backbones, was nine percentage points and the 95% confidence interval of the difference ranged from 7.1 to 13.2.

In other words, Feinberg said, the confidence interval not only showed noninferiority by excluding minus 12%, it suggested statistical superiority by excluding zero.

That apparent superiority was driven by two factors, she said: Fewer dolutegravir patients withdrew because of adverse events or other reasons and fewer nonresponders among those who started with a very high plasma viral load of greater than 100,000 copies of HIV RNA per milliliter.

Only two patients in each arm had virologic failure, defined by the study protocol as two consecutive viral loads greater than 200 copies per milliliter, on or after week 24, Feinberg said.

And none of the four showed resistance mutations to any of the three drug classes involved in the study, she said.

Eron said he "wouldn't put too much weight" on the statistical superiority. The bottom line, he said, is that "for treatment-naive patients, dolutegravir is as good as darunavir."

For his part, he said, the key finding is the lack of resistance. "The longer we go without resistance," he said, "the more dolutegravir will eat into the boosted protease inhibitors."

source: www.medpagetoday.com