• Once-Daily Atazanavir Plus Saquinavir Favorably Affects Total Cholesterol (TC) and Fasting Triglyceride (TG) Profiles in Patients Failing Prior PI Therapy (Trial AI424-009, Week 24)
  Abstract LB-16
  Authored by D. Haas (Vanderbilt Univ., Nashville, TN), C. Zala (Fundacion Huesped, Buenos Aires, Argentina), S. Schrader (HCRN/Montrose Clin., Houston, TX), A. Thiry (Bristol-Myers Squibb Co., Wallingford, CT), R. McGovern (Bristol-Myers Squibb Co., Wallingford, CT), S. Schnittman (Bristol-Myers Squibb Co., Wallingford, CT)
  View the original abstract

Atazanavir (BMS-232632) is an investigational protease inhibitor (PI) in Phase III trials. It is given once daily (two capsules), does not appear to increase lipids and in vitro data indicate that it has a unique resistance profile.

Clinicians who care for HIV-infected patients are aware that the salvage of protease inhibitor failure can be difficult due to cross resistance. In a study presented at the 41st ICAAC, the combination of atazanavir and saquinavir -- protease inhibitors that appear to have complementary resistance profiles and favorable pharmacokinetic interactions -- was evaluated in patients failing antiretroviral therapy. The study was a randomized, blind study that enrolled 84 adults with a median baseline viral load of 4.13-4.5 copies/mL and CD4+ T-cell count of 290-332 cells/mm³.

Therapy was with atazanavir (400 or 600mg daily) plus saquinavir (1,200mg daily) or ritonavir (400mg twice daily) plus saquinavir (400mg twice daily) plus two nucleoside reverse transcriptase inhibitors (NRTIs). This was given to patients after prior virologic failure on an antiretroviral regimen, the vast majority of which involved at least one protease inhibitor. In the three arms, seven patients (21 percent), seven patients (25 percent) and ten patients (43 percent), respectively, discontinued therapy. The observed data at 24 weeks of therapy are presented below:

The authors conclude, "In subjects failing a prior protease inhibitor regimen, atazanavir/saquinavir was safe and well tolerated and showed significant antiviral effect at week 24. Atazanavir/saquinavir lowered TC and TG levels from baseline, whereas ritonavir/saquinavir produced substantial increases."

The data from this study do provide some support for the use of atazanavir/saquinavir once daily in patients who have failed an antiretroviral regimen, although the pill burden can be onerous and the rates of success with this combination are not terribly impressive.