Lopinavir/Ritonavir Demonstrates Significantly Greater Reduction
in HIV RNA Than Unboosted Atazanavir in Patients with Prior Protease
Inhibitor Failure
This study sought to compare the long-term effects of
the protease
inhibitor (PI) atazanavir (Reyataz) with that of ritonavir-boosted
lopinavir (Kaletra) in 300 HIV patients who had
failed a prior PI-based regimen.
Investigators of the Community Research Initiative of
New England in Boston
compared the change from baseline in HIV
RNA and fasting low-density
lipoprotein (LDL) cholesterol levels
in PI-experienced patients receiving unboosted atazanavir
400 mg once daily versus lopinavir 400 mg boosted with ritonavir
100 mg twice daily, with two nucleoside
reverse transcriptase inhibitors (NRTIs).
Secondary objectives included virologic response, CD4 cell count
changes, other lipid changes,
safety, and tolerability.
This
was a multinational,andomized, open-label, 48-week study in patients
with one PI-regimen failure, HIV RNA >/= 1000 copies/mL, and
CD4 count >/= 50 cells/mm(3).
Results
Three hundred patients were randomized;
290 treated (144 atazanavir, 146 lopinavir/ritonavir).
Lopinavir/ritonavir
resulted in a significantly greater reduction in HIV RNA than
unboosted atazanavir (-2.02 vs -1.59 log(10) copies/mL, p <
0.001) at week 48.
Secondary
efficacy endpoints also favored lopinavir/ritonavir;
The differences in
efficacy between regimens were also observed in secondary analyses
comparing those subjects who were susceptible and those subjects
who were resistant to their respective PIs at baseline.
However,
both regimens were equally effective in subjects who had no baseline
NRTI mutations.
From
baseline to week 48, atazanavir resulted in either no change or
decreases in fasting LDL cholesterol, total
cholesterol, and fasting triglycerides
(-6%, -2%, and +1%), whereas lopinavir/ritonavir resulted in increases
(+3%, +12%, and +53%) (p
< 0.05, all between-treatment comparisons).
Fewer patients were administered
lipid-lowering therapy in the atazanavir arm (6% vs 20% for lopinavir/ritonavir).
Both regimens were safe
and well tolerated.
In
conclusion the study authors write, “While both treatments demonstrated
good antiviral efficacy, relatively greater antiviral suppression
was observed with lopinavir/ritonavir.”
“In
those patients with no NRTI mutations at baseline, both regimens
demonstrated comparable virologic
suppression.”
“Atazanavir-treated
patients demonstrated a superior lipid profile and required less
frequent lipid-lowering treatment.”
Community
Research Initiative of New England, Boston,
Massachusetts,USA.
10/31/05
Reference
C
Cohen and others (on behalf of the BMS AI424-043
Study Group). Comparison of atazanavir with lopinavir/ritonavir
in patients with prior protease inhibitor failure. Current
Medical Research and Opinion 21(10): 1683-9162. October 2005.
