乌鸦传媒

PARIS -- A first-ever single multidrug tablet including a boosted protease inhibitor for treating HIV infection was effective and well tolerated over 24 weeks, interim phase III trial results indicated.

The once-daily, fixed-dose tablet -- containing the protease inhibitor darunavir, cobicistat, emtricitabine, and a new tenofovir formulation -- maintained viral suppression in 96% of patients who switched from a multi-pill regimen, , of the University of Paris reported at .

"I think it will improve the convenience of boosted protease inhibitor-based regimens, which require many pills today. It's good to have multiple options," Molina told 乌鸦传媒.

Taking fewer daily pills helps people with HIV maintain good adherence, and treatment guidelines recommend once-daily single-tablet regimens for first-line therapy. Patients with prior treatment experience who have developed drug resistance may require stronger therapy that involves more pills.

HIV protease inhibitors have potent and durable antiviral activity and a high barrier to resistance. But to date, no single-tablet regimens containing an HIV protease inhibitor have been available.

"Boosted protease inhibitors have unique properties in terms of a high genetic barrier to resistance. That is the main characteristic of boosted PIs, and they have been unmatched by any other class of drugs so far -- even dolutegravir may not be as good in terms of resistance," Molina said.

Molina presented findings from the manufacturer-sponsored phase III , which evaluated a single-tablet regimen containing Janssen's protease inhibitor darunavir (800 mg), the boosting agent cobicistat (150 mg), emtricitabine (200 mg), and tenofovir alafenamide or TAF (10 mg) -- the latter being a new tenofovir formulation with less kidney and bone toxicity.

EMERALD included 1,141 participants from the United States and Europe. About 80% were men and the median age was 46. Mean baseline CD4 count was above 600 cells/mm³. Patients were required to have a viral load below 50 copies of HIV RNA per milliliter for at least two months and had normal kidney function at baseline.

At study entry the participants were on a multi-pill regimen including a boosted protease inhibitor plus emtricitabine and the older tenofovir disoproxil fumarate (TDF). About 70% were on boosted darunavir (Prezista), 22% were on boosted atazanavir (Reyataz), and 8% were on lopinavir/ritonavir (Kaletra); about 15% were already using cobicistat as their booster. About 40% of patients were on their first antiretroviral regimen. Prior treatment failure was permitted, but they could not have a history of darunavir failure or darunavir resistance mutations.

Participants in this open-label study were randomly assigned in a 2:1 ratio to either receive the new darunavir single-tablet regimen or stay on their current regimen for 48 weeks, at which point all patients could continue on the combination pill through 96 weeks. The primary study endpoint is the proportion of patients with HIV RNA below 50 copies/mL at 48 weeks. Molina presented 24-week interim data at the IAS meeting.

The single-tablet regimen was highly effective. Molina reported that almost all participants who switched and those who stayed on the same regimen maintained viral suppression at week 24 (96.3% versus 95.5%, respectively). Similar proportions of patients experienced viral rebound (1.8% versus 2.1%). Most viral breakthroughs were transient, and no one had confirmed viral rebound above 200 copies/mL or stopped treatment due to virological failure, he said. None of the four patients who underwent genotypic testing showed evidence of emergent drug resistance.

Treatment was generally safe and well tolerated. Only 1.2% of patients who switched to the single-tablet regimen and 0.5% who stayed on their old regimen experienced drug-related grade 3 or 4 adverse events, Molina reported. Just 2.9% of patients in both discontinued treatment early, and about 1% did so due to adverse events. The most common events were nasopharyngitis, upper respiratory tract infections, and vitamin D deficiency. Laboratory abnormalities did not differ between the two arms, Molina said.

Participants in both treatment arms saw a small decrease in estimated glomerular filtration rate (eGFR), with a slightly larger decline in the single-tablet regimen arm. This was consistent with the known effect of cobicistat on tubular creatinine secretion, which leads to a decrease in estimated GFR but has "no impact on real GFR," Molina explained. Only one person in the switch arm and two people in the continued therapy arm stopped treatment due to renal adverse events.

Bone mineral density at the hip and spine rose by about 1% in the single-pill arm, but fell 0.3% in the continued therapy arm, Molina reported.

The new combination pill "combines the safety advantages of TAF and darunavir with the known efficacy and high genetic barrier to resistance of darunavir, in a single-tablet regimen," the study investigators concluded.

"This is nothing really new -- it's still triple therapy -- but I think there's a benefit to having a single-tablet regimen with a protease inhibitor in it," , of Hôpital Pitié-Salpêtrière in Paris told 乌鸦传媒.

"It's better to have several options," Katlama said."Integrase [inhibitors] are great, but we have to fill up five decades or six decades on treatment. We need all the good drugs."

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