Background
Early results of BMS 045, presented in July 2003 at the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment, showed that a regimen containing the combination of atazanavir and low-dose ritonavir had very good efficacy in treatment-experienced patients. This poster presents 48-week results from that study.
Atazanavir-Ritonavir Similar in Efficacy to Lopinavir-Ritonavir in Treatment-Experienced Patients
Efficacy and Safety of Atazanavir with Ritonavir or Saquinavir vs Lopinavir/Ritonavir in Patients Who Have Experienced Virologic Failure on Multiple HAART Regimens: 48-Week Results from BMS A1424-045
Abstract: DeJesus E, Grinsztejn B, Rodriguez C, et al. Efficacy and Safety of Atazanavir with Ritonavir or Saquinavir vs Lopinavir/Ritonavir in Patients Who Have Experienced Virologic Failure on Multiple HAART Regimens: 48-Week Results from BMS A1424-045. 11th CROI, Abstract 547.
Description: 358 patients with three-class antiretroviral experience and virologic failure of at least two combination regimens were randomized to one of three treatment arms: atazanavir + ritonavir once daily, lopinavir + ritonavir twice daily, or atazanavir + saquinavir once daily, each combined with tenofovir and one nucleoside analogue. At baseline, the median HIV viral load was approximately 4.44 log10 copies/mL and median CD4 was 283-317 cells/mm3 in each group.
Results: By intent-to-treat analysis, 48-week results are as follows:
| | Atazanavir + Ritonavir | Lopinavir + Ritonavir | Atazanavir + Saquinavir |
| HIV RNA <400 copies/mL (% of subjects) | 56% | 58% | 38% |
| HIV RNA <50 copies/mL (% of subjects) | 38% | 46% | 26% |
| CD4 increase (cells/mm3) | 110 | 121 | 72 |
The differences in viral load and CD4 responses between the atazanavir + ritonavir and the lopinavir + ritonavir arms were not statistically significant.
Overall, adverse event rates were similar among treatment groups. However, diarrhea was more frequent in the lopinavir group and jaundice was more common in the atazanavir groups. Analysis of lipid levels showed modest decreases in all lipid parameters, including HDL, in the atazanavir groups, and increases in total cholesterol and triglycerides in the lopinavir group.
Comment: These results suggest that ritonavir-boosted atazanavir is similar in potency to boosted lopinavir in patients with moderate treatment experience, though lopinavir + ritonavir may be more effective in patients with multiple protease inhibitor (PI) mutations.Either of these boosted PIs is superior to the dual-PI combination of atazanavir + saquinavir. It should be noted that each of the regimens contained tenofovir, which is known to lower atazanavir levels, particularly in the absence of ritonavir boosting.(1) It is unclear whether the use of tenofovir adversely affected the outcomes of the atazanavir treatment arms. All regimens were relatively well tolerated, with more favorable lipid effects and less gastrointestinal toxicity in the atazanavir groups.
References
1. Taburet AM, Piketty C, Gerard L, Vincent I, Chazallon C, Clavel F, Calvez V, Aboulker JP, Girard PM. Pharmacokinetic Parameters of Atazanavir/Ritonavir when Combined to Tenofovir in HIV Infected Patients with Multiple Treatment Failures: A Sub-study of Puzzle2-ANRS 107 Trial. 10th CROI, Abstract 537. February 2003.
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