ICAAC: Darunavir and Lopinavir Equal in Naive HIV Patients

CHICAGO, Sept. 19 -- In patients newly diagnosed with HIV, the novel protease inhibitor darunavir (Prezista) has been found to be as effective as the standard lopinavir (Kaletra).

And in patients with very high levels of HIV -- at least 100,000 copies of viral RNA per milliliter of plasma -- darunavir is actually more effective, reported Edwin DeJesus, M.D., of the Orlando (Fla.) Immunology Clinic, at the Interscience Conference on Anti-microbial Agents and Chemotherapy here.

The findings come after 48 weeks of a head-to-head trial of the two drugs, each boosted with ritonavir, Dr. DeJesus said.

The so-called ARTEMIS study is important because it gives clinicians "information regarding the potential use of a once daily (darunavir) regimen for the treatment of adult patients who have never taken HIV medications before," Dr. DeJesus said.

Darunavir was given accelerated approval last year to treat patients with experience of several antiretroviral drugs, but is not yet FDA-approved for treatment-nave patients.

In this study, researchers enrolled 639 patients with a viral load of greater than 5,000 copies per milliliter of plasma who had not yet been treated for the infection.

They were randomized to receive:

• 800 milligrams daily of darunavir, combined with 100 milligrams of ritonavir.
• Either 800 milligrams of lopinavir plus 200 milligrams of ritonavir daily or 400 milligrams plus 100 taken twice a day.
• In both arms, the background was a fixed dose combination of emtricitabine (Emtriva) and tenofovir (Viread).

The primary endpoint of the study was the proportion of patients with a viral load of less than 50 copies of HIV RNA per milliliter of blood -- the so-called undetectable level -- at the end of 48 weeks.

The trial was designed as a non-inferiority study, in which the two drugs would be judged equivalent if there was less than a 12% difference in efficacy between the study arms, Dr. DeJesus said.

In the per-protocol analysis of 689 patients, 84% of patients in the darunavir arm met the endpoint, compared with 78% of patients in the lopinavir arm. For the purposes of the non-inferiority analysis, Dr. DeJesus said, the difference was estimated to be 5.6% -- within the 12% margin and significant at P

The trial results were "very impressive," said Roy Gulick, M.D., of Weill Medical College of Cornell University in New York, a leading researcher in the field who was not involved in the study.

"Everybody in that trial did well on treatment," he said, so that clinicians can now begin to think about adding darunavir to their list of potent drugs for nave patients.

The drug is also delivered in a single daily dose, he said, "so that's great to see."

The difference in efficacy, which seems to favor darunavir, is probably driven by the toxicity issue, Dr. Gulick said. Darunavir is "a little better tolerated" than lopinavir, which may make it a bit easier for patients to stick to their medication.

He added that he's intrigued by the lack of resistance among patients who failed therapy and is hoping that researchers will find an explanation.