331   A Pilot Study of Combinations of Delavirdine (DLV), Zidovudine (ZDV), Lamivudine (3TC) & Saquinavir- SGC (Fortovase, FTV) as Initial Antiretroviral Therapy: Virologic and Pharmacokinetic Considerations.

B. Conway*, A. Chu, J. Tran, C. Petersen, L. Tye, S. Grubb, L. Nieto, C. Rivera, M. Wolff, J. Echevarria, J. Benetucci, P. Cahn, N. Gilmore, and K. Williams for the 0081 Study Group.
Univ. of British Columbia, Vancouver, Canada.

Background:Our objective was to evaluate the efficacy and safety of four different antiretroviral therapy regimens administered to HIV-1-infected individuals recruited from Canadian, Mexican and Latin American centers.

Methods:Patients with baseline plasma viral load >5,000 copies/mL who were treatment-naïve were assigned to receive one of four regimens: FTV 1400/DLV 600 administered bid (group 1), FTV 1000/DLV 400 tid (group 2) given with 3TC 150 bid, FTV/3TC/ZDV tid at standard doses (group 3), or FTV 1400/3TC 150/DLV 600/ZDV 300 bid (group 4); they were evaluated over 24 weeks. DLV & FTV plasma levels were obtained after four weeks.

Results:The study is fully enrolled (n = 97), with 94 patients evaluable at 24 weeks (24, 21, 24 and 25 in groups 1—4). Mean baseline CD4 counts ranged from 224—280 cells/mL, and plasma viral loads ranged from 4.7—4.9 log₁₀copies/mL, depending on the group. At 24 weeks, 75—100% of patients had plasma viral loads <400 copies/mL and 63—83% had <50 copies/mL (on-treatment analysis). In an intent-to-treat analysis (ITT), 39/94 (41%) subjects had <400 copies/mL, with 33/94 (35%) having <50 copies/mL. Patients in group 1 showed the most favorable responses, with 10/24 (42%) having <50 copies/mL at 24 weeks (ITT). FTV exposure resulting from the bid regimen with DLV was similar or superior to the standard tid regimen without DLV, while DLV exposures were similar between the bid and tid regimens. By week 24, 20/97 patients had withdrawn, including three who never started treatment. There were 8 patients with grade 3-4 laboratory abnormalities and 19 with grade 3-4 clinical events, including a single DLV-associated rash.

Conclusions:A twice-daily regimen including DLV and FTV was safe and showed substantial virologic efficacy over 24 weeks. This was associated with an excellent pharmacokinetic profile of these two agents. DLV combined with a PI is an attractive option as it adds pharmacokinetic enhancement to the antiretroviral activity of the NNRTI/PI combination.