7th Conference - Abstract 535

Potent Antiviral Activity Using Delavirdine and Reduced-Dose Indinavir Combination Therapies: A 48-Week Analysis

J. ERON*¹, G. MCKINLEY², P. LECRERQ³, L. NIETO⁴, L. WATHEN⁵, C. PIETRANTONI⁵, C. GREENWALD⁵, M. CONKLIN⁵, L. PAXTON⁵, and W. FREIMUTH⁵. ¹Univ. of North Carolina at Chapel Hill; ²St. Luke's Roosevelt Hosp., New York; ³Hosp. Albert Michallon, La Tronche, France; ⁴Hosp. Gen. Gabriel Mancera, Mexico City, Mexico; and ⁵Pharmacia & Upjohn, Kalamazoo, MI

Introduction: A unique feature of Delavirdine (DLV) is the ability to raise plasma levels of all approved protease inhibitors (PIs). A clinical study of DLV in combination with reduced doses of indinavir (IDV) was designed to evaluate the safety, tolerability. and efficacy of PI-enhancing regimens.
Methods:Two hundred twenty-five HIV-1-infected individuals were randomized in an open-label study 0074 onto one of four arms: DLV+ZDV+IDV (600mg). DLV+3TC+IDV (600mg), DLV+ZDV+3TC+IDV (600mg) or a control arm of ZDV+3TC+IDV (800mg).
Results: Mean baseline HIV-1 RNA and CD4 cell count was =4.98 log₁₀ copies/mL and 276 cells/mm³ respectively. In 24 week on-treatment (n=155) and intent to treat (non-completer = failure. n=219) analyses. The following percentages of patients maintained HIV-1 RNA beneath 400 copies/mL:

The 98 individuals who have reached week 48 had mean reductions in HIV-1 RNA of >2.78 log₁₀ copies/mL, nearly 899 had viral burdens of <400 copies/mL, and they had a mean CD4 cell count increase from baseline of at least 168 copies/mm³. The DLV+3TC+IDV and ZDV+3TC+IDV were the best tolerated regimens.
Conclusion: In this on-going study, DLV and IDV were effective in combination with ZDV, 3TC, or ZDV+3TC and produced highly durable antiviral responses.

Key Words: delavirdine, HAART, indinavir