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Indinavir + AZT + ddI
Abstract 200
A Phase II Open-Label, Randomized Study of the Triple Combination of Indinavir,
Zidovudine (ZDV) and Didanosine (ddI) versus Indinavir Alone and
Zidovudine/Didanosine in Antiretroviral Naive Patients.
Authors: F Massari, M Conant, J Mellors, R Steigbigel, D Mildvan, R Greenberg, C Carpenter, R Murphy, K Squires, M Rigsby, G Drusano, G McKinley, L Gilde and M Nessly.
This study was designed to assess whether the addition of two nucleoside analogs could improve and sustain antiviral responses seen with indinavir. A total of 78 HIV-infected, antiretroviral-naive patients were randomized to receive indinavir (600 mg four times per day) plus AZT (200 mg three times per day) plus ddI (125 or 200 mg twice per day) or indinavir monotherapy or AZT plus ddI. Patients had CD4 counts of 500 cells/mm3 or fewer (median 150 cells/mm3) and viral RNA of 20,000 copies/ml or greater (median 5.01 logs or 102,000 copies/ml) at study entry. The study used a different indinavir dosing regimen than the current recommended regimen of 800 mg three times per day. Furthermore, the study was not placebo-controlled (i.e. no matching placebo for AZT or ddI).
Triple drug therapy resulted in a maximum median decline of 3.1 logs in viral RNA as compared to 1.9 logs and 1.5 logs in the indinavir and AZT/ddI groups, respectively, over 24 weeks. At 24 weeks, 60% of patients in the triple combination group had fewer than 200 copies/ml of viral RNA. There were maximum median CD4 increases of 110, 100, and 70 cells/mm3 in the triple combination, indinavir alone, and AZT/ddI groups, respectively, at week 24. Sixty percent of patients in both the triple combination and indinavir monotherapy groups achieved increases in CD4 counts of at least 50 cells/mm3 at 24 weeks.
The drugs were generally well tolerated with gastrointestinal intolerance such as nausea and vomiting in the AZT/ddI group. Hyperbilirubinemia (occurred with indinavir at an incidence of 10-50% after 1 month of therapy; they were reversible and did not cause any clinical symptoms.) There was one case of nephrolithiasis with indinavir.
Due to compliance difficulties with taking ddI, there were 7 out of 26 ddI discontinuations in the triple combination group and 3 out of 26 in the AZT/ddI group.
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