The Lancet has published final data from two key clinical trials of Prezista™ (darunavir), Tibotec's new protease inhibitor, indicating that the drug offers prolonged treatment effects for HIV-positive people with limited treatment options. The complete results demonstrate that patients with extensive treatment experience who take Prezista in combination with an optimized background regimen stand a good chance of keeping their viral loads undetectable for at least a year.

Prezista was approved by the FDA in June 2006 based largely on early results from two phase IIb clinical trials called POWER 1 and POWER 2. The two studies enrolled 588 HIV-positive people who had previously been treated with at least one protease inhibitor (PI), one non-nucleoside reverse transcriptase inhibitor (NNRTI), and one nucleoside reverse transcriptase inhibitor (NRTI). Patients also needed evidence, by way of drug-resistance testing, of one or more HIV mutations known to contribute to resistance to older protease inhibitor options.

The study participants were randomized to one of two groups. In the first group, 131 patients are taking Norvir® (ritonavir)-boosted Prezista (600mg plus 100mg Norvir) twice daily plus an optimized background regimen (OBR). In the second group – the control group – 124 patients are taking an approved Norvir-boosted protease inhibitor plus OBR.

Preliminary 48-week data were reported at the XVI International AIDS Conference, this past summer in Toronto, by Sharon Walmsley, MD, a POWER researcher and Senior Scientist at the Toronto General Research Institute. Final data from studies, in an article prepared by Bonaventura Clotet, MD, of the Hospital Universitari Germans Trias i Pujol in Barcelona and his POWER colleagues, have now been published in The Lancet. 

After 48 weeks of treatment, 61% of patients taking a Prezista-based regimen had viral loads that were at least 1 log below their pre-study levels. In the control groups, only 15% had a similar viral load response after 48 weeks of treatment. As for undetectable viral loads, 45% of the Prezista-treated patients had viral loads below 50 after 48 weeks, compared to 10% of the control patients.

Encouraging CD4 count data were reported as well. After almost a year of treatment, Prezista-treated patients experienced, on average, a 102-cell increase, compared to an approximate 19-cell increase in the control groups.

Thus far, the most common side effects in the Prezista-treated patients, compared to those in the control group, include diarrhea (20% in the Prezista group vs. 28% in the control group), nausea (18% vs. 13%), headache (15% vs. 20%), and fatigue (12% vs. 17%). While increases in cholesterol and triglycerides have been noted in patients participating in the studies, these increases do not appear to be any more common in the Prezista-treated patients compared to those in the control groups.

Rodger MacArthur, MD, of Wayne State University in Detroit writes in an accompanying article that clinical endpoint studies – clinical trials evaluating the effects of Prezista-based therapy on disease progression and survival over a two- to three-year period – are needed to fully establish the efficacy of the drug. He also suggests that a comparison of Prezista with Aptivus®, Boehringer Ingelheim's PI for patients with drug-resistant HIV, is also needed. 

But Dr. MacArthur added: "For now, all of us treating HIV-infected individuals in clinical practice will probably rejoice in the availability of darunavir, since it seems to be a safe, well tolerated, and truly effective agent against multi-drug resistant HIV."