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Abstract LB-16. Once-Daily Atazanavir plus Saquinavir Favorably Affects Total
Cholesterol and Fasting Triglycerides in patients Failing Prior PI Therapy
Study BMS-009, week 24)
Reported by Jules Levin
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D. Haas reported today at ICAAC in Chicago 24 week safety and efficacy data
from study BMS-009. This study compares Atazanavir, a new protease inhibitor
in clinical development, taken in combination with saquinavir in a once daily
regimen compared to ritonavir+saquinavir taken twice daily in patients who
failed previous PI therapy. Atazanavir (ATZ) is taken once daily (2
capsules). In study reported yesterday at ICAAC comparing ATZ to nelfinavir
and in this study reported here cholesterol and triglycerides either did not
go up or went down for patients taking ATZ.
Patients in this study experienced prior regimen failure, had HIV-RNA >2000
and <100,000, and CD4 >100. Patients were randomized for 48-weeks to one of 3
regimens:
--ATZ 400 mg qd (once daily) + saquinavir 1200 mg qd + 2 NRTIs (n=34)
--ATZ 600 mg qd + saquinavir (SQV) 1200 mg qd + 2 NRTIs (n=27)
--ritonavir (RTV) 400 mg + saquinavir 400 mg twice daily + 2 NRTIs (n=23)
Baseline viral load was 4.50 in the 400 mg ATZ arm, 4.13 in the 600 mg ATZ a
rm, and 4.15 in the RTV/SQV arm. CD4s were 315 in the 400 ATZ arm, 290 in 600
mg ATZ arm, and 332 in RTV/SQV. 41% had AIDS diagonosis in the ATZ 400 mg
arm, 26% in the 600 mg ATZ arm, and 13% in RTV/SQV. About 67% were White
across all 3 arms. Mean fasting triglycerides (mg/dL) were 223 (n=27) in the
400 ATZ arm, 177 in the 600 mg ATZ arm (n=22), and 191 (n=18) in the RTV/SQV
arm. Mean total cholesterol (mg/dL) was 181 (n=32) in the ATZ 400 mg arm, 199
(n=27) in the 600 mg ATZ arm, and 202 in the RTV/SQV arm (n=23).
85%-88% of all patients across all arms had prior PI use. In the 400 mg ATZ
arm 50% had used IDV and 38% NFV. In the 600 mg arm, 26% used IDV and 67%
NFV. In the RTV/SQV arm, 22% used IDV and 65% NFV. In the RTV/SQV arm 30% had
previously used any NNRTI, 22% in the 600 mg ATZ study, and 19% in the 400 mg
ATZ arm.
RESULTS
There were 21% (n=7) discontinuations from study treatment in the 400 mg ATZ
arm, 25% in the ATZ 600 mg arm (n=7), and 43% (n=10) in the RTV/SQV arm.
Discontinuation due to adverse events: 9% in 400 mg ATZ arm, 11% in ATZ 600
mg arm, and 26% in RTV/SQV.
After 24 weeks, patients receiving 400 mg ATZ regimen had HIV-RNA reduced by
-1.28 log (n=29), patients receiving 600 mg ATZ had -1.17 log drop (n=22),
and RTV/SQV patients had 1.50 log drop (n=13). Haas reported that about 60%
receiving 400 mg ATZ had >1 log decrease in viral load or HIV-RNA <50
copies/ml, patients receiving 600 mg ATZ dose had about 42% with >1 log drop
or <50 copies/ml, and RTV/SQV arm had about 40% <50 copies/ml or >1 log drop
in viral load.
CD4 counts increased about 100 in RTV/SQV arm and about 50-60 in the two ATZ
arms.
Total cholesterol increased 10% from baseline to week 24 in the RTV/SQV arm
(n=13). Total cholesterol stayed the same in the 400 mg ATZ arm (n=27), and
decreased 10% in the ATZ 600 mg arm (n=20) (p<0.05, ATZ 600 mg/SQV vs RT/SQV
at 24 weeks).
Fasting triglycerides increased 90% in the RTV/SQV arm (n=8), and decreased
about 23% in the 400 mg (n=15) and the 600 mg (n=13) ATZ arms. Jaundice was
reported only in the ATZ arms (13%, 400 mg and 19% in 600 mg). Haas reported
jaundice resolved upon discontinuation of drug and was not accompanied by
changes in liver enzymes. The rate of discontinuation for these ATZ/SQV
patients was 21% and 25%, respectively.
Diarrhea was 31% in 400 mg ATZ arm, 4% in 600 mg ATZ arm, and 43% in RTV/SQV.
Nausea was 43% in RTV/SQV compared to 9% and 26% in the 400 & 600 mg ATZ
arms. Headache was 9% in the ATZ 400 mg arm, 22% in the 600 mg ATZ arm, and
17% in the RTV/SQV arm. Asthenia was 13% in 400 mg ATZ arm, 19% in 600 mg ATZ
arm, and 22% in RTV/SQV arm. Pain in abdomin was 22% in 400 mg ATZ arm, 19%
in 600 mg ATZ arm, and 0% in RTV/SQV. Peripheral neurologic symptoms were 9%
in the ATZ 400 mg arm, 15% in the 600 mg ATZ arm, and 22% in RTV/SQV.
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