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Ritonavir-boosted
Reyataz (atazanavir) Regimen Produces HIV Viral Load Decrease Comparable
to Kaletra (lopinavir/ritonavir) Regimen at 24 Weeks
Twenty-four (24)-week data suggest that a
treatment regimen comprised of Reyataz
(atazanavir) plus low-dose ritonavir provides potency against HIV
that is comparable to a Kaletra
(lopinavir/ritonavir)-based regimen in treatment-experienced patients.
The
data were presented 7/15/03 at the 2nd International
AIDS Society Conference on HIV Pathogenesis and Treatment (July
13-16, Paris, France).
Reyataz
is the recently-approved (6/20/03) protease inhibitor (PI) from
Bristol-Myers Squibb and is the first once-daily PI. Kaletra, also
a protease inhibitor, is a potent anti-HIV drug that has demonstrated
durable suppression of the virus. According to its manufacturer,
Abbott Labs, Kaletra
is currently the most widely used PI in the US and Europe.
“More
and more physicians are prescribing multiple protease inhibitor-containing
regimens in treatment-experienced patients….This early evidence
that Reyataz, when boosted with [low dose] ritonavir, is comparable
to Kaletra is very encouraging,” said Bonaventura Clotet, PhD, Director
of the Retrovirology Laboratory and HIV Unit at the Hospital Universitari
Germans Trias I Pujol and Associate Professor of Medicine at the
Universitat Autónoma de Barcelona (UAB), Spain.
Additional
data from the study suggest Reyataz-containing regimens have a more
favorable lipid profile compared to the Kaletra regimen. The lipid
profiles were evaluated by mean percent changes from baseline in
total cholesterol, fasting LDL cholesterol, and fasting serum triglyceride
concentrations
Study
Results
The 24-week
interim analysis of this 48-week study examined 358 randomized patients
who were highly treatment-experienced – meaning they had failed
two or more HAART (Highly Active Antiretroviral Therapy) regimens,
including at least one agent from each class of oral HAART.
The primary
objective of the triple-arm study was to compare the magnitude of
plasma HIV RNA reduction from baseline of a regimen containing once-daily
Reyataz 300 mg boosted with 100 mg of ritonavir to a regimen containing
twice-daily Kaletra and a regimen containing once-daily Reyataz
400 mg with 1200 mg of saquinavir, all in combination with once-daily
tenofovir 300 mg and one nucleoside reverse transcriptase inhibitor
(NRTI).
Secondary
objectives of the study included the effect of each regimen on the
proportion of patients with HIV RNA levels below 400 copies/mL and
50 copies/mL, CD4 cell count changes from baseline, serum lipid
changes from baseline, and safety and tolerability.
Results through
week 24 demonstrated that the ritonavir-boosted Reyataz regimen
had comparable antiviral activity to the Kaletra-containing regimen.
The dual-PI combination arm of Reyataz and saquinavir showed less
antiviral activity than the other two regimens at the interim 24-week
analysis. *
Both boosted
regimens resulted in similar decreases from baseline in HIV RNA,
with mean changes of -1.86 log10 copies/mL for the ritonavir-boosted
Reyataz arm (N=120) and -1.89 log10 copies/mL for the
Kaletra arm (N=123).
However, the
Reyataz/saquinavir arm produced less of a decrease than the boosted
regimens with a mean change of -1.52 log10 copies/mL
(N=115).
The proportion
of patients with HIV RNA levels below 400 copies/mL and 50 copies/mL
using an intent-to-treat analysis were similar in the Reyataz/ritonavir
(64% and 39%) and Kaletra (62% and 42%) arms, but were lower in
the Reyataz/saquinavir arm (44% and 23%).
Mean
increases from baseline in CD4 cell counts through week 24 were
similar between the ritonavir-boosted Reyataz (83 cells/mm3)
and Kaletra (90 cells/mm3) regimens and less for the
Reyataz/saquinavir regimen (59 cells/mm3).
Adverse
Effects
Moderate to
severe adverse events (AEs) occurred with comparable frequency across
all regimens and were consistent with the known safety profiles
of the study drugs.
The most commonly
observed AE in the Reyataz/ritonavir arm was jaundice, which occurred
in six percent of patients and was not associated with an increased
risk of liver injury or treatment discontinuation.
Other common
side effects in the Reyataz/ritonavir and Reyataz/ saquinavir arms
were nausea (2%, 7%), diarrhea (3%, 5%), scleral icterus (3%, 0%)
and vomiting (0%, 4%).
The
most common side effect in the Kaletra arm was diarrhea (11%).
Sources
B
Clotet and others. Atazanavir
with ritonavir or saquinavir vs lopinavir/ritonavir in patients
with multiple virologic failures: 24 week results from BMS A1424-045.
Abstract 118. Abstracts of the 2nd IAS Conference
on HIV Pathogenesis and Treatment. July 13-16, 2003. Paris,
France.
Bristol-Myers
Squibb. Regimen containing ritonavir-boosted
Reyataz (atazanavir sulfate) demonstrates comparable viral load
reduction through week 24 to a regimen containing Kaletra (lopinavir/ritonavir)
in highly treatment-experienced HIV/AIDS patients. Press Release.
July 15, 2003.
R
Baker. FDA Approves
Bristol-Myers Squibb's Once Daily Protease Inhibitor Reyataz (atazanavir)
for HIV Infection. HIV and Hepatitis.com. June 21, 2003.
FDA
Product Label Atazanavir / Reyataz. HIV and Hepatitis.com
B
Boyle. Kaletra (lopinavir/ritonavir) Summary
on HIV and Hepatitis.com
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