Colebunders R, Van Hove D, Peeters M, Kestens L, Vercauteren G, Fransen K, Stoffels P, Cauwenbergh G, Piot P; International Conference on AIDS.

Int Conf AIDS. 1992 Jul 19-24; 8: B89 (abstract no. PoB 3014).

Institute of Tropical Medicine, Antwerp, Belgium.

OBJECTIVES: To assess the in vivo antiviral activity of R 18893 in patients with AIDS. METHODS: R 18893 400 mg t.i.d. was administered orally during 3 months to 15 patients with AIDS (HIV-1) intolerant or refractory to zidovudine. Antiviral activity was assessed by determination of p24 Ag levels and by quantitative HIV cultures from peripheral blood mononuclear cells and plasma. Differences between groups were evaluated by the Wilcoxon Two-Sample Test. Pharmacokinetics of R 18893 were followed in 7/15 patients during 8 days. RESULTS: Fifteen patients between 25 and 62 years (median age 39, 14 M, 1 F) were included in the study. At enrollment the median CD4 count was 8 cells/microliter blood (0-117) and the median p24 Ag level 52.5 pg/ml (0-375). Ten of 15 patients completed the 3 months study period. In 4 the dose was reduced to 200 mg t.i.d. because of intolerance. Five patients discontinued therapy; 3 for intolerance and 2 on their own request. Ten patients could be evaluated for efficacy parameters. At the end of the 3 months the median p24 Ag level increased to 210 pg/ml (0-492) (p = NS) and the median CD4 level was 12 cells/microliters blood (0-89). Quantitative HIV cultures showed no significant difference between start and end of treatment with R 18893. Three patients with KS continued to develop new lesions during therapy. Plasma levels of R 18893 (-) were in the range of the IC50 of R 18893 for HIV-1 (10 ng/ml). Following side effects were observed: drug fever 1; rash 2; diarrhoea 2; myalgia 5; tinnitus 3; nausea 2; headache 2. Side effects were more frequent in the patients receiving concomitant ketoconazole and were associated with higher plasma levels of R 18893. All side effects disappeared after discontinuation of treatment with R 18893. No drug related laboratory abnormalities were observed. CONCLUSION: In this study, among patients with advanced AIDS, no therapeutic effect of R 18893 could be demonstrated.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Antigens, CD4
• Antiviral Agents
• CD4 Lymphocyte Count
• Clinical Trials, Phase II as Topic
• Drug Therapy, Combination
• HIV Infections
• HIV Seropositivity
• HIV-1
• Humans
• Zidovudine
• drug therapy
• immunology
• therapy

Other ID:

• 92401652

UI: 102199365

From Meeting Abstracts