Results from a Phase III clinical trial indicate that Prezista (darunavir) plus Norvir (ritonavir) is more effective than Kaletra (lopinavir/ritonavir) in treatment-experienced HIV-positive patients. The results were published in a special issue of The Lancet focusing on the HIV/AIDS pandemic, coinciding with the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention scheduled to begin on July 22nd in Sydney, Australia.

Prezista (600 mg), taken twice daily in combination with Norvir (100 mg), was approved by the U.S. Food and Drug Administration (FDA) in June 2006 specifically for treatment-experienced HIV-positive patients, notably those with multiple-drug-resistant virus (i.e., resistance to more than one protease inhibitor). These new data suggest that Prezista/Norvir may be a better bet than Kaletra for patients with less treatment experience, including those starting a protease inhibitor (PI) for the first time.

The ongoing study, known as TITAN (TMC114/r In Treatment-Experienced Patients Naïve to lopinavir/ritonavir), has enrolled 595 treatment-experienced patients. Participants enrolled in the study had not yet used Kaletra, had a viral load of at least 1,000 copies, and had previously failed an HIV treatment combination after at least 12 weeks (or were taking a break from treatment). Approximately 31 percent of the patients enrolled had never used a protease inhibitor in the past and 82% had HIV susceptible to four or more protease inhibitors.

Patients were randomized to receive standard, twice-daily doses of either Prezista/Norvir or Kaletra in combination with an optimized background regimen (OBR). OBR was individualized for each patient, based on resistance testing and prior treatment history, and included a combination of nucleoside reverse transcriptase inhibitors (NRTIs) with or without non-nucleoside reverse transcriptase inhibitors (NNRTIs).

In the analysis of 554 patients, 77% of those randomized to receive Prezista/Norvir had viral loads below 400 copies, compared to 68% of those randomized to receive Kaletra. The nine percent difference between the two groups was statistically significant, meaning that it wasn't likely due to chance. Viral loads below 50 copies—"undetectable" by today's testing standards—after 48 weeks of treatment were seen in 71% of the Prezista/Norvir-treated patients and 60% of the Kaletra-treated patients. These data were also statistically significant.

It is also worth noting that more patients stopped Kaletra (11 percent) than Prezista/Norvir (1%) due to virologic failure. What's more, fewer patients in the Prezista/Norvir group (21 percent), compared to those in the Kaletra group (36 percent) developed new mutations typically associated with resistance to PIs. Taken together, these data suggest that Prezista/Norvir may be associated with even more durable virologic responses than Kaletra, in light of what appears to be a greater barrier against the emergence of resistance mutations.

It is not yet known how Prezista/Norvir compared to other PIs, include Kaletra, in HIV-positive patients starting antiretroviral therapy for the first time.

Approximately 7 percent of patients in both groups discontinued their assigned treatment due to side effects. In the Prezista/Norvir group, the most frequently reported side effects were diarrhea (32 percent), nausea (18 percent), inflamed sinuses and sore throats (nasopharyngitis) (12 percent), headache (11 percent), and upper respiratory tract infection (10 percent). In the Kaletra group, the most frequently reported side effects were diarrhea (42 percent), nausea (21 percent) and nasopharyngitis (11 percent).

Moderate-to-severe diarrhea occurred in 8 percent of patients taking Prezista/Norvir compared with 15 percent of patients taking Kaletra. Skin rashes, however, were more common in the Prezista/Norvir group (16% vs. 8% among Kaletra takers).

As for lipid levels, increases in total cholesterol were similar between the two groups after 48 weeks (32% in the Prezista/Norvir group and 29% in the Kaletra group), whereas triglyceride increases were more common among those taking Kaletra compared to those taking Prezista (25% vs. 19%).

According to Daniel Berger, MD, Clinical Assistant Professor of Medicine at the University of Illinois in Chicago, "This is exciting new information that adds to the body of knowledge on Prezista in a much broader group of treatment-experienced patients."