Background: ATV is a new protease inhibitor (PI) with excellent anti-HIV activity. ATV may be combined with EFV (a non-nucleoside reverse transcriptase inhibitor) as part of a HAART regimen.  EFV can induce cytochrome P450 (CYP) 3A and may lessen ATV exposure.  The objective was to assess the pharmacokinetic (PK) profile of ATV when co-administered with EFV.

Methods:  31 subjects received open-label drugs with a light meal as follows: 400-mg ATV qd for 6 days, followed by concomitant administration of 600-mg EFV qd for 14 more days.  Serial blood samples were collected for PK profiles on days 6 and 20.

Results: Below are non-compartmental ATV PK parameters:

 

PK parameter	ATV (day 6)	ATV + EFV (day 20)
Cmax (ng/mL)a	3369 (38)	1375 (60)
AUC(TAU)  (ng*h/mL)a	20659 (41)	5462 (60)
Tmax (h)b	2.00 (1.00, 4.00)	2.50 (1.00, 5.00)
Half-life (h)c	7.0 (2.1)	5.1 (2.3)

^aGeometric Mean (CV%); ^bMedian (Range); ^cArithmetic Mean (SD)

 

Concomitant administration of EFV and ATV resulted in ATV Cmax and AUC (TAU) values that were 41% and 26% of those following ATV alone.  The ratios of the geometric mean (90% confidence interval, C.I.) for (ATV+EFV)/ATV were 0.408 (0.329, 0.506) and 0.264 (0.217,0.322) for Cmax and AUC (TAU), respectively.  Mean EFV PK parameters were similar to literature values in HIV+ patients. No serious adverse events were noted.

Conclusion: To combine ATV with EFV, a regimen modified from a 400-mg standard ATV dose, to counter EFV’s exposure-reducing effect, is needed.