August 17, 2006

IAC: Lexiva Measures Up to Kaletra

August 17, 2006 (AIDSmeds)—Final data from a 48-week study comparing Norvir® (ritonavir)-boosted Lexiva® (fosamprenavir) to Kaletra® (ritonavir-boosted lopinavir) reported today at the XVI International AIDS Conference (IAC) in Toronto indicate that these two protease inhibitor (PI) options have comparable safety and effectiveness. The results, which were also published in the August 5th issue of The Lancet, suggest that Norvir-boosted Lexiva may soon share the stage with Kaletra as a "preferred" PI option for HIV-positive people starting treatment for the first time.

The KLEAN study involved 878 HIV-positive patients in the United States, Europe, and Canada. All patients enrolled in the study would be starting HIV treatment for the first time. The results of the study were reported at IAC by Joe Eron, MD, of the University of North Carolina, Chapel Hill.

The patients were randomly assigned to take one 700mg Lexiva tablet plus one 100mg Norvir capsule or three Kaletra capsules (Kaletra capsules have now been replaced by a tablet formulation and only requires two pills per dose). Both Norvir-boosted Lexiva and Kaletra were taken twice a day. All patients also took an Epzicom® tablet (600mg abacavir plus 300mg lamivudine) once a day. A total of 434 patients were in the Lexiva group; 444 patients were in the Kaletra group.

The primary goal of the study was to determine the percentage of patients in each group with viral loads below 400. The researchers also looked at the percentage of patients with viral loads below 50, along with changes in CD4 cell counts (T cell counts) and side effects.

Upon entering the study, patients had relatively high viral loads, with the majority (54%) starting treatment with viral loads above 100,000. The CD4 cell count was relatively low, with a study entry CD4 count average of 192 (17% had a CD4 count below 50).

Approximately 77% of the patients completed 48 weeks of study treatment, with 12% discontinuing due to side effects in the Lexiva group and 10% discontinuing due to side effects in the Kaletra group.  

After 48 weeks of treatment, 73% of patients in the Lexiva group had viral loads below 400, compared to 71% in the Kaletra group. There was no statistically significant difference between the two groups, meaning that the slight difference wasn't due to chance. Additionally, 66% of patients in the Lexiva group and 65% of the patients in the Kaletra group had viral loads below 50.

Also of note, patients in the Lexiva group had viral load responses comparable to those in the Kaletra group, regardless of their pre-treatment viral loads. Reductions in viral load, to below 400, were similar among patients who started treatment with viral loads below 100,000 and above 100,000, with no differences between the two treatment groups.

As for immune recovery, CD4 cell counts increased by 176 in the Lexiva group after 48 weeks of treatment, compared to a 191 cell gain in the Kaletra group. Again, there were no statistically significant differences between the two groups.

In terms of side effects, diarrhea was the most common and was seen in 13% of patients in the Lexiva group and 11% in the Kaletra group. Nausea was seen in 6% and 5%, respectively, and hypersensitivity reaction to the abacavir in Epzicom was seen in 6% of patients in the Lexiva group and 4% of patients in the Kaletra group. Cholesterol and triglyceride increases, seen in 8% to 11% of patients, were also similar in both treatment groups.

Based on these results, demonstrating comparability between Norvir-boosted Lexiva and Kaletra in terms of safety and effectiveness among HIV-positive people starting therapy for the first time, it is possible that Norvir-boosted Lexiva will be promoted to a "preferred" first-line protease inhibitor option for those new to treatment.

The International AIDS Society-USA (IAS-USA) currently recommends a handful of Norvir-boosted protease inhibitor regimens for patients starting therapy for the first time, notably Lexiva, Invirase® (saquinavir), and Reyataz® (atazanavir) boosted with low-dose Norvir, as well as Kaletra.

Healthcare providers in the United States, however, appear to be more drawn to guidelines maintained by the U.S. Department of Health and Human Services (DHHS). The DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults are more conservative with their recommendations than IAS-USA, listing only Kaletra as the preferred PI for first-line therapy.

While the results of KLEAN suggest that Norvir-boosted Lexiva packs similar potency and safety as Kaletra as first-line therapy – indeed, it is the only clinical trial completed to date to show comparable results between Kaletra and another Norvir-boosted PI – it is not yet clear if this will result in Norvir-boosted Lexiva being put on equal footing with Kaletra in the eyes of the DHHS.