麻豆传媒

SAN DIEGO -- Patients switching to a four-drug, single-pill HIV regimen from already-successful therapy were able to maintain control of the virus over a 48-week study, a researcher said here.

And they did so with improvements in safety and no evidence of the development of drug resistance, according to Joseph Eron, MD, of the University of North Carolina at Chapel Hill.

The investigational four-drug regimen is based on the protease inhibitor darunavir (Prezista), which is known to have a high genetic barrier to resistance, Eron said at the annual IDWeek meeting, sponsored jointly by the (IDSA), the (PIDS), the (SHEA), and the (HIVMA).

The study was simultaneously published online in.

The single-pill regimen has just been and is under review in the U.S.

The regimen also includes the recently approved tenofovir alafenamide fumarate (TAF), a nucleotide reverse transcriptase inhibitor (NRTI) with less bone and kidney toxicity than the earlier tenofovir disoproxil fumarate (TDF), he said.

The combination of high resistance to mutation, better safety, and the convenience of the single-pill, once-daily formulation makes the regimen an attractive choice, Eron told 麻豆传媒. It would be the first single-pill regimen based on a protease inhibitor

While initial treatment is more and more tending to be based on integrase inhibitors, the four-drug pill is likely to have a role for some people, commented Rajesh Gandhi, MD, of Massachusetts General Hospital and the Ragon Institute in Boston, the IDWeek session co-moderator.

For instance, some people can't take integrase inhibitors for one reason or another, he told 麻豆传媒.

For patients already doing well on a protease inhibitor-based regimen, this would be attractive -- if it's approved -- because they're likely to maintain good virologic control with an additional safety advantage, Gandhi noted.

The barrier to resistance is also important, but at least one of the integrase inhibitors, dolutegravir, also is unlikely to develop resistance, Gandhi said, and so the use of the novel combination is likely to come down to patient and physician choice.

The four-drug combination consists of darunavir (800 mg), TAF (10 mg), the NRTI emtricitabine (200 mg), and cobicistat (150 mg), a drug that boosts the potency of darunavir.

In the EMERALD trial, 1,141 patients whose HIV was well controlled on a protease inhibitor-based regimen were randomly assigned on a two-to-one basis, to stay on their current regimen or switch to the single pill. Interestingly, most of the comparator regimens were darunavir-based and all included TDF and emtricitabine.

In interim data reported in July, the researchers said that the two arms had maintained similar rates of viral suppression over 24 weeks.

But the study's primary endpoint was something slightly different -- to see if the proportion of patients who lost viral control over 48 weeks while on the single pill was non-inferior to the proportion whose virus rebounded while on the original regimen.

Virologic rebound was defined as a confirmed viral RNA load of 50 copies/mL of plasma or premature discontinuations, with the last viral load above that level.

The pre-specified non-inferiority margin was 4%, which Eron said was "appropriate" given that patients in the study already had well controlled HIV.

At 48 weeks, 19 of the 763 (2.5%) patients in the study group and eight of the 378 control patients (2.1%) had reached that endpoint. The difference was 0.4% (95% CI -1.5% to 2.5%), "well within" the non-inferiority margin, Eron said.

Importantly, the investigators saw no resistance to darunavir or to any study drug.

Few patients stopped therapy for adverse events -- 1% in each arm -- and grade 3 or 4 adverse events were also similar, 7% in the study group and 8% in the control group.

Patients in the study group saw improvements in bone density, a reflection of the lower bone toxicity seen with TAF compared with TDF, Eron noted.

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