<ABS><b>Background:</b> A previous report in healthy volunteers using a 7-day 750mg q8h regimen of NFV suggested that efavirenz (EFV) increases nelfinavir (NFV) exposure by 20%. We examined the effect of EFV on the pharmacokinetics (PK) of NFV and its active metabolite (M8) in naive, HIV-infected subjects enrolled in a PK substudy of AACTG 384, a randomized treatment strategy trial.

<b>Methods:</b> AACTG 384 was conducted in antiretroviral naïve subjects receiving a dual NRTI regimen with EFV (600 mg q24h), NFV (1,250 mg q12h), or NFV + EFV. Intensive PK studies were conducted at weeks 4 and 32. PK parameters were determined by noncompartmental analysis and statistical comparisons for NFV and M8 alone or with EFV by the Wilcoxon Rank Sum Test.

<b>Results:</b> Intensive PK data were available in 40 subjects at week (wk) 4 and 26 subjects at wk 32. No significant differences were noted for M8. Mean (±SD) PK parameters and p values for NFV are summarized in the table below.

 

Week 32
Cmax (ug/mL)	Cmin (ug/mL)	AUC12 hr (ug*h/mL)
4.7 (1.3)	1.5 (1.3)	34.3  (18)
3.7  (1.7)	0.52  (0.4)	21.4  (10)
0.08	0.04	0.07

 

 

Week 4
	Cmax (ug/mL)	Cmin (ug/mL)	AUC12 hr (ug*h/mL)
NFV	3.9 (1.1)	0.76 (0.4)	26.4 ((8.9)
NFV-EFV	3.9  (1.7)	0.61 (0.6)	24.0 (12)
p	0.71	0 .07	0.59

 

<b>Conclusions:</b> Contrary to short-term, within-subject, healthy volunteer PK data, efavirenz is associated with a trend toward decreased nelfinavir Cmax and AUC and significantly lower Cmin after 32 wks in HIV-infected subjects. Caution is required when extrapolating drug interaction and pharmacokinetic data from healthy volunteer studies to HIV-infected subjects.</ABS>