A RANDOMIZED TRIAL OF THE ACTIVITY AND SAFETY OF RO-24-7429 (TAT ANTAGONIST) VERSUS NUCLEOSIDE FOR HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

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/mm(3) at week 8 versus a decrease of 27 cells/mm(3) 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 log(10) reduction in infectious peripheral blood mononuclear cells, while Ro 24-7429 recipients had a mean 0.02 log(10) 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.