Abstract Form

BID FIRSTLINE RITONAVIR/INDINAVIR (RTV/IDV) 100/800 IN A GERMAN MULTICENTER STUDY: 48 WEEK RESULTS

Author: Voigt E ,Wickesberg A, Gute P¹, Locher L¹, Salzberger B², Wöhrmann A², Schröer K P², Adam A³, Weitner L³, and Rockstroh J K
¹Dep. of Int. Med., Univ. of Bonn, Germany; priv. pract., Frankfurt, Germany; ²Dep. of Int. Med., Univ. of Cologne, Germany; ³priv. pract., Hamburg, Germany

Background: Protease inhibitor (PI) combination with low dose RTV enhances plasma concentrations of the chosen PI by inhibiting its metabolism via cytochrome P-450, thereby allowing b.i.d. dosing.

Objective: To evaluate safety and efficacy of RTV/IDV 100/800 mg b.i.d. plus 2 – 3 nucleosid analogues (NRTI) in antiretroviral (ARV) naïve patients.

Methods: Monthly determination of viral load (VL), CD4 cell count, triglyceride and cholesterol under the new ARV regimen up to 48 weeks.

Results: 56 patients were enrolled in the study. Most patients showed advanced HIV disease with CDC stadium C (63,6%). At baseline median VL was 308,000 cps/ml (range 170-3,01Mio cps/ml; 5,49log), median CD4 cells were 50/µl (range 0–400/µl). VL decreased by a median of 3,79log until week 24 and week 48 respectively. At week 48 22/56 (39,3%; intent to treat, last observation carried forward) patients showed a VL below 80 cps/ml. In parallel median CD4 cells increased up to 291/µl (range 51–702/µl) at week 48. The metabolic assessments showed an increase of median triglycerides from baseline 161 mg/dl to 218 mg/dl at week 48, median cholesterol increased from 166 mg/dl at baseline to 233mg/dl at week 24. 23/56 patients are still on treatment, while 27 (48,2%) patients discontinued study treatment, 6 patients are lost to follow up. Discontinuation of study treatment were due to kidney stones in 19 (34%) patients, 3 (5,4%) were due to diarrhea. One patient showed recurrent paronychia, one suffered from dry skin, one from CNS-toxicity. 2 patients changed ARV regimen due to virological failure.

Conclusion: The combination of RTV/IDV 100/800 mg b.i.d. appears to be effective up to 48 weeks, despite high baseline VL and low CD4 counts in ARV naïve patients. However, discontinuation due to adverse events, especially nephrotoxicity, is frequent and limits treatment duration. Therefore extra hydration appears inevitible. However dosing regimens with lower drug levels should be considered in future treatment concepts and will be examined by the authors‘ group.

Esther Voigt, MD Immunologische Ambulanz, Med. Universitätsklinik, Sigmund Freud Str. 25, 53105 Bonn, Germany