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Abstract I-667. BMS-008 Comparative Results of Atazanavir vs Nelfinavir in
Combination With d4T (Stavudine) and 3TC (Lamivudine) in treatment-Naive,
HIV-Infected Patients
Reported by Jules Levin
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This new PI in phase III studies is the first once per day PI and the pill
burden is light (2 capsules). Studies so far show lipids (cholesterol and
triglycerides) do not go up on Atazanavir (ATZ) and this study shows that.
The length of time this drug has been studied so far is too short to evaluate
the development of lipodystrophy. But since lipids do not so far appear to go
up there is potential for benefit to lipodystrophy. As well, ATZ has a
favorable resistance profile so it will have utility for patients with a few
PI mutations. However, as more PI mutations accumulate ATZ has less antiviral
effectiveness. This study was reported at the IAS Conference this pat Summer
and NATAP reported this data which can be found on our website in the IAS
Reports. About 500 treatment-naive patients were randomized to receive either
400 or 600 mg of ATZ once per day or nelfinavir (NFV), with d4T/3TC.
Nelfinavir is taken twice daily. BMS has selected 400 mg per day to use for
future studies. Baseline HIV-RNA was 4.77-4.70 log in all 3 arms. CD4 was
260-280 in all 3 ams. 10-12% across all 3 arms had AIDS diagnosis. And about
37% of study participants were women. RESULTS: the discontinuation rate was
about the same in all 3 groups (16-19%. The discontinuation rate due to
adverse events was 5% in the 400 mg ATZ arm, 7% in the 600 mg ATZ arm, and 4%
in the NFV arm.
Discontinuation due to adverse event related to study drug: 2% in 400 mg ATZ
arm, 7% in 600 mg ATZ arm, and 4% in NFV arm. The HIV-RNA reduction at week
48 was 2.31 log for NFV patients, 2.58 for 600 mg ATZ patients, and 2.51 for
400 mg ATZ patients.
Using a randomized LOCF analysis 64% receiving the 400 mg ATZ dose had <400
copies/ml compared to 67% for the 600 mg dose and 53% for the NFV dose. Using
an observed data analysis, 74% in the 400 mg ATZ arm had <400 copies/ml
compared to 75% in the 600 mg ATZ arm, and 60% in the NFV arm. 35%
(randomized, LOCF) in the 400 mg ATZ arm had <50 copies/ml compared to 36% in
the 600 mg ATZ group and 34% in the NFV group. Using observed data analysis,
40% in the ATZ 400 mg ATZ group had <50 copies/ml compared to 41% in the 600
mg arm and 39% in the NFV arm.
CD4 increase was 234 in the 400 mg arm, 243 in the 600 mg arm, and 211 in the
NFV arm. Total cholesterol, fasting LDL (bad) cholesterol, and fasting
triglycerides were evaluated. The values did not change for the patients
receiving ATZ: total cholesterol 168 at baseline, 177 at week 48; LDL
cholesterol 101 at baseline, 107 at week 48; triglycerides 125 at baseline,
134 at week 48. But the values increased for patients receiving NFV: 165 to
206 (total cholesterol), 97 to 120 (LDL cholesterol), triglycerides 108 to
162.
BMS reported a study comparing atazanavir+saquinavir to ritonavir/saquinavir
in treatment experienced patients. The data from this study was emailed to
you and will be posted to ICAAC highlights on NATAP website. the reason
saquinavir is being studied in combination with atazanavir is because there
is data suggesting that saquinavir and atazanavir have an added benefit
pharmacologically when combined making them perhaps a potent combination
against PI resistant virus. This of course will need to be confirmed in the
clinical study.
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