A randomized trial of the activity and safety of Ro 24-7429 (Tat antagonist) versus nucleoside for human immunodeficiency virus infection. The AIDS Clinical Trials Group 213 Team.
Ro 24-7429, a Tat antagonist, dosed at 75, 150, or 300 mg/day, was compared with nucleoside analogue (zidovudine or didanosine) for 12 weeks in 96 human immunodeficiency virus (HIV)-infected patients to assess safety and activity. The primary adverse effect of Ro 24-7429 was rash, which necessitated treatment discontinuation in 6 of 71 patients. Nucleoside analogue treatment produced an average increase in CD4 cell count of 28 cells/mm3 at week 8 versus a decrease of 27 cells/mm3 in recipients of Ro 24-7429 (P < .001). Serum HIV p24 antigen levels decreased by an average of 111 pg/mL in nucleoside recipients at week 8 compared with an increase of 41 pg/mL in recipients of Ro 24-7429 (P = .007). Nucleoside-treated patients had a mean 0.66 log10 reduction in infectious peripheral blood mononuclear cells, while Ro 24-7429 recipients had a mean 0.02 log10 reduction (P = .02). No dose-response relationships were observed in the Ro 24-7429 groups. In this study, Ro 24-7429 treatment showed no evidence of antiviral activity.
Haubrich
R H
RH
Department of Medicine, University of California, San Diego.
Flexner
C
C
Lederman
M M
MM
Hirsch
M
M
Pettinelli
C P
CP
Ginsberg
R
R
Lietman
P
P
Hamzeh
F M
FM
Spector
S A
SA
Richman
D D
DD
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use* / Q000633:toxicity*; D001569:Benzodiazepines / Q000627:therapeutic use* / Q000633:toxicity*; D018791:CD4 Lymphocyte Count / Q000187:drug effects*; D016049:Didanosine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D015696:Gene Products, tat / Q000037:antagonists & inhibitors; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011758:Pyrroles; D013997:Time Factors; D015215:Zidovudine / Q000627:therapeutic use; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D015696:Gene Products, tat; D016655:HIV Core Protein p24; D011758:Pyrroles; D054322:tat Gene Products, Human Immunodeficiency Virus; D001569:Benzodiazepines; C070024:Ro 24-7429; D015215:Zidovudine; D016049:Didanosine