335   Indinavir/Ritonavir vs Indinavir in Combination with AZT/3TC for Treatment of HIV in Nucleoside-Experienced Patients: a Randomised, Open- Label Trial.

M. Boyd*^1,4, C. Duncombe^1,4, M. Newell^1,4, C. Ungsedhapand¹, K. Ruxrungtham^1,2, M. Khongphattanayothin¹, E. Hassink^1,3, S. Ubolyam¹, T. Chuenyam¹, J. Lange^1,3, D. Cooper^1,4, and P. Phanuphak¹.
¹HIV-NAT, Bangkok, Thailand;²Chulalongkorn Univ., Bangkok, Thailand;³AMC-IATEC, Univ. of Amsterdam, The Netherlands; and⁴NCHECR, Univ. of New South Wales, Sydney, Australia.

Background:Use of IDV may be simplified by addition of RTV. This permits BID dosing of IDV and removes dietary restrictions. There is limited data on the efficacy, safety and tolerability of IDV/RTV BID.

Methods:In this prospective, open-label, 48-week study, 106 patients were randomised to either IDV 800 mg (TID) or IDV 800 mg/RTV 100 mg (BID) with AZT/3TC. All patients received at least 3 months of AZT before entry. Efficacy was determined by HIV viral load (VL) reduction and CD4⁺count response (median and [IQR]). Safety and tolerability were also assessed. Analysis (Mann-Whitney, Student's t, and Chi-square tests) is intention to treat.

Results:This study enrolled 104 patients (54 TID, 50 BID; 67 males, 37 females). At baseline both arms were comparable. Median log₁₀HIV VL was 4.0 [3.3—4.5] copies/ml and CD4 count was 168 [40—319] cells/mm³. At week 48 no significant differences were found in decrease of log₁₀HIV VL (2.0 [0.4—2.6] TID, 1.6 [0.3—2.6] BID), % of patients with VL < 50 copies (70% TID, 66% BID), or increase in CD4⁺cells (57 [-1—128] TID, 70 [-11—128] BID). Three patients died; 14 permanently ceased treatment (9 TID, 8 BID). Drug interruptions/dose reductions occurred in 34 patients (14 TID, 20 BID; p = 0.09), mostly for GI intolerance. Adverse events were evenly distributed except for nausea (48% TID, 68% BID; p = 0.04) and dry mouth (24% TID, 46% BID; p = 0.02). Hyperbilirubinaemia (>2.5*ULN), mainly unconjugated, was seen in 28 patients (20% TID, 34% BID; p = 0.09) without other LFT changes. Nephrolithiasis (+/- flank/back pain +/-haematuria +/- dysuria) was seen in 20 patients (17% TID, 22% BID; p = 0.08). No patient ceased study because of hyperbilirubinaemia or nephrolithiasis.

Conclusions:IDV/RTV BID is as effective as the TID regimen and may provide a more convenient dosing alternative. Both regimens are reasonably well tolerated, although BID patients experience more nausea and dry mouth. Nephrolithiasis and hyperbilirubinaemia occur but don't entail permanent treatment cessation.