icon_folder.gif   Conference Reports for NATAP  
  ICAAC 41st Interscience Conference on Antimicrobial Agents and Chemotherapy
Chicago, Illinois, December 16-19
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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
  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.