HIV and Hepatitis.com Coverage of the 15th
Conference on Retroviruses and Opportunistic Infections (CROI 2008) February
3 - 6, 2008, Boston, MA
The
material posted on HIV and Hepatitis.com about CROI 2008 is not approved by
nor is it a part of CROI 2008.
Boosted
Atazanavir (Reyataz) and Lopinavir/ritonavir (Kaletra) Have Similar Efficacy,
but Different Side Effects: CASTLE Study
Kaletra
Tablet
Atazanavir
Capsule
As
antiretroviral therapy had
improved, there are now multiple drug regimens that can produce full HIV suppression.
However other factors -- including immediate side effects, long-term toxicities,
and convenience -- may vary considerably.
At the 15th Conference on Retroviruses
and Opportunistic Infections this week in Boston, researchers reported data from
the CASTLE trial, which compared 2 of the most widely used protease inhibitors,
ritonavir-boosted atazanavir
(Reyataz) and lopinavir/ritonavir
(Kaletra), in treatment-naive participants. Past studies have shown that the
drugs are similarly effective in treatment-experienced patients; atazanavir produces
less blood lipid elevation, but often causes increased bilirubin.
CASTLE
is an ongoing randomized, open-label, 96-week study assessing non-inferiority
of 300/100 mg once-daily atazanavir/ritonavir versus 400/100 mg twice-daily lopinavir/ritonavir,
both in combination with fixed-dose tenofovir
plus emtricitabine (Truvada). The non-inferiority threshold was 10%.
A
total of 883 treatment-naive patients were randomized and 878 were treated. Baseline
demographics and characteristics were similar in both treatment arms. About 70%
were men, the median age was 35 years, and 13% had hepatitis
B or C coinfection. Median CD4 count was
just over 200 cells/mm3 and median plasma HIV RNA was about 5 log10 copies/mL.
The primary study endpoint was the proportion of patients with HIV RNA
< 50 copies/mL at week 48. Planned secondary assessments included percentage
with HIV RNA < 400 copies/mL, CD4
cell count change, and safety parameters.
Result
•
At 48 weeks, 78% of patients in the atazanavir/ritonavir
arm and 76% in the lopinavir/ritonavir arm achieved HIV viral load < 50 copies/mL
(difference estimate 1.7).
•
Baseline HIV RNA < 100,000 copies/mL: 82%
vs 81%, respectively; •
Baseline HIV RNA > 100,000 copies/mL:
74% vs 72%, respectively;
•
In the subset of patients with < 50 cells/mm3
at baseline, 78% and 63%, respectively, achieved HIV RNA < 50 copies/mL.
•
The respective percentages with CD4 count
< 400 copies/mL were 86% an 82% (difference estimate 3.3).
•
At week 48, the mean CD4 count increases from
baseline were 203 cells/mm3 in the atazanavir/ritonavir arm and 219 cells/mm3
in the lopinavir/ritonavir arm.
•
9% in the atazanavir/ritonavir arm and 13%
in the lopinavir/ritonavir arm discontinued therapy prior to week 48.
•
Jaundice: 4% vs 0%; •
Nausea: 4% vs 8%; •
Diarrhea: 2% vs 11%; •
Rash: 3% vs 2%.
•
12% in the atazanavir/ritonavir arm and 10%
in the lopinavir/ritonavir arm experienced serious adverse events:
•
Bilirubin > 2.5 x upper limit of normal
(ULN): 34% vs <1%; •
ALT elevation > 5 x ULN: 2% vs 1%; •
Elevated total cholesterol > 240
mg/dL: 7% vs 18%; •
Elevated triglycerides > 751 mg/dL:
<1% vs 4%; •
Elevated glucose > 251 mg/dL: <1%
in both arms.
•
Mean percentage increases in fasting plasma
lipid levels in atazanavir/ritonavir and lopinavir/ritonavir arms, respectively,
were as follows:
•
Total cholesterol: 12% vs 24% •
LDL ("bad") cholesterol: 12% vs
15%; •
HDL ("good") cholesterol: 27% vs
32%; •
Non-HDL: 7% vs 21%; •
Triglycerides: 13% vs 51%.
•
Proportions of patients with a total cholesterol-to-HDL
ratio > 5 were 12% in the atazanavir/ritonavir arm and 20% in the lopinavir/ritonavir
arm.
•
Fewer patients on atazanavir/ritonavir (2%)
compared with lopinavir/ritonavir (7%) started lipid-lowering therapy.
Conclusion
"In
treatment-naive patients, atazanavir/ritonavir demonstrated similar efficacy,
a lower incidence of gastrointestinal-related adverse events, and a significantly
better lipid profile (total cholesterol, triglycerides, non-HDL) compared to lopinavir/ritonavir,"
the investigators concluded.
"In combination with tenofovir
and [emtricitabine], both atazanavir/ritonavir
and lopinavir/ritonavir were
well tolerated with few discontinuations through 48 weeks," they added. Once-daily
atzanavir/ritonavir is an appropriate therapeutic option for treatment-naive patients."
Hosp
St Louis, Paris, France; Hosp Civil de Guadalajara, Mexico; Hosp Natl Cayetano
Heredia, Lima, Peru; Khonkaen Univ, Thailand; Hosp Intl Gral de Agudos Oscar Alende,
Buenos Aires, Argentina; Brooklyn Med Ctr, Western Cape, South Africa; and Bristol-Myers
Squibb R&D, Wallingford, CT.
2/5/08
Reference J-M
Molina, J Andrade-Villanueva, J Echevarria, and others.Efficacy and Safety of
Once-daily Atazanavir/Ritonavir Compared to Twice-daily Lopinavir/Ritonavir, Each
in Combination with Tenofovir and Emtricitabinein ARV-naive HIV-1-infected Subjects:
The CASTLE Study, 48-week Results. CROI 2008. Boston, MA. February 3-6, 2008.
Abstract 37.
Boosted
Atazanavir (Reyataz) and Lopinavir/ritonavir (Kaletra) Have Similar Efficacy,
but Different Side Effects: CASTLE Study 
