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.
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have now been replaced by a tablet formulation and only requires two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
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.
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).
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.
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.
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.
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.
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.
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.
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.
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