Background:  Atazanavir (ATV) + fosamprenavir (FPV) is a potentially useful double-protease inhibitor (PI) combination with components that may offer a mutually beneficial resistance profile. As a formal drug interaction study of ATV+FPV has not been conducted, we evaluated the pharmacokinetics and tolerability of ATV and FPV when administered alone and in combination without ritonavir (RTV) in HIV^­ persons.

Methods:  COL100683 was a prospective, randomized, open-label, 3-way crossover study with 3-week washout periods, in which 21 HIV^­ adults received, in random order: FPV 1400 mg, ATV 400 mg, or both by mount once-daily for 14 days. At the end of each period (day 14), a 24-hour pharmacokinetic study (10 samples) was completed, including standardized diets. Drug levels (FPV reported as APV) were assayed by a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters were determined by standard noncompartmental methods and compared by paired t-test on log-transformed data. Bioequivalence was assessed by geometric mean ratios (GMR). Adverse event data were analyzed using student’s t-test.

Results:  Of the total, 21 subjects completed the study (11 men, 48% non-white) with a mean age of 31.7 (9.5 SD) years. Clinical adverse events were >99% (123 of 124) grade 1. Laboratory adverse events were not different between either agent (p = 0.3), single and dual regimens (p = 0.47) or baseline and safety follow-up (p = 0.16). Only 1 serious adverse events unrelated to study drugs (grade 3 acute pancreatitis) occurred. All grade 2 to 4 laboratory adverse events (41 of 148) represented transient increases in direct or indirect bilirubin and resolved before the next period initiation or safety follow-up visit. Pharmacokinetic parameters are reported below. No differences occurred with respect to periods or sequences.

*p <0.05; data presented as geometric mean (CV%)

Conclusions:  ATV+FPV was well tolerated. ATV significantly enhanced exposure of unboosted, once-daily FPV. ATV exposure was reduced when co-administered with FPV. The clinical relevance of these findings will remain unknown until controlled efficacy studies are completed.