Didanosine in HIV-1-infected patients experiencing failure of antiretroviral therapy: A randomized placebo-controlled trial

Abstract

Background. The antiviral efficacy of didanosine in patients experiencing virological failure is not well known. Methods. A total of 168 patients (139 men and 29 women) receiving stable antiretroviral therapy with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 1000-100,000 copies/mL were randomly assigned to have didanosine (n = 111) or placebo (n = 57) added to their currently failing regimen for 4 weeks. The primary efficacy end point was the change in HIV-1 RNA level from baseline to week 4. Results. At baseline, the median HIV-1 RNA level was 3.8 log 10 copies/mL, the median CD4 cell count was 378 cells/mm 3, and the median number of nucleoside reverse-transcriptase inhibitor-associated mutations (NAMs) was 4. At week 4, a significant decrease in the median HIV-1 RNA level was observed in the didanosine group, compared with that in the placebo group (-0.56 vs. +0.07 log 10 copies/mL, respectively) (P < .0001). A total of 33 patients (31%) in the didanosine group, compared with 3 (6%) in the placebo group, had HIV-1 RNA levels <400 copies/ mL (P < .001). Significant antiviral activity of didanosine was observed in patients with up to 5 NAMs at baseline. Diarrhea occurred in 5 patients (5%) in the didanosine group and 2 patients (4%) in the placebo group. Conclusions. In HIV-1-infected patients experiencing failure of antiretroviral therapy, didanosine retains short-term antiviral activity. © 2005 by the Infectious Diseases Society of America. All rights reserved.