Background: While 1400 SQV mg BID resulted in adequate SQV levels without Itra, adequate levels may be produced with lower SQV doses plus Itra. This prospective randomized open-label substudy investigates the PK of 800 and 1200 mg SQV BID plus 100 mg Itra qd compared to 1400 mg SQV BID without Itra.

Methods: HIV-1-infected patients received 2 nucleoside reverse transcriptase inhibitors (AZT/3TC or d4T/ddI) and 1400 mg BID SQV for 2 years. A subset of 17 randomly selected patients were switched from 1400 mg SQV without Itra to 800 mg or 1200 mg SQV BID plus Itra 100 mg qd. Steady-state SQV PK was determined while on the triple regimen with 1400 mg BID SQV without Itra and after 2 weeks of therapy with the lower SQV doses plus Itra. SQV plasma concentrations were determined just before, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 12 hours after taking drugs by a sensitive and validated RP-HPLC method. A non-compartmental model was applied to calculate area under the plasma concentration versus time curve (AUC), maximum (Cmax) and minimum (Cmin) concentration, time to Cmax (Tmax) and elimination half-life (t_1/2).

Results: The median (IQR) steady-state PK parameters for SQV are:

 

SQVdose-BID	patients	AUC0-12h·mg/L	Cmax (mg/L)	Tmax (h)	Cmin (mg/L)	t1/2 (h)
1400 mg	17	3.33 (1.96-7.34)	1.05(0.69-2.48)	2.0(1.8-3.0)	0.09(0.04-0.13)	4.6(4.0-6.0)
1200 mg +itra	9	4.29 (3.14-7.67)	1.42(0.60-2.19)	2.0(1.5-2.5)	0.11(0.06-0.14)	5.0(4.-7.5)
800 mg +itra	8	4.07 (2.76-4.49)	0.98(0.84-1.21)	2.6(1.9-3.3)	0.08(0.06-0.08)	5.1(4.7-6.1)

 

There were no significant SQV exposure differences found with Kruskal-Wallis 1-way ANOVA (AUC _[0-12]p=0.68; Cmax p=0.78 and Cmin p=0.45).

Conclusions:  Lower doses of SQV (800 or 1200 mg BID) boosted with 100 mg Itra qd resulted in adequate PK parameters equivalent to SQV 1400 mg BID. Lower SQV doses boosted with Itra maintained therapeutic SQV levels, an important benefit in the developing world where drug access/affordability is a major obstacle in treating patients.