BACKGROUND The virologic and immunologic efficacy of the combination of zidovudine (ZDV) and didanosine (DDI) was examined in 27 HIV-infected patients. METHODS 27 HIV-infected patients, 15 of whom were naive for antiretroviral drugs. The remaining 12 subjects had been exposed to ZDV for at least 16 weeks. Mean plasma viral load was of 4.7 logs and 4.5 logs, respectively. All patients had less than 350 x 10(6)/l CD4+ T lymphocytes at baseline. RESULTS Significant reductions in viremia (> 0.5 logs) were seen at the first and third months, respectively, in 71.4% and 64.3% of naive patients. In contrast, it occurred only in 10% and 0%, respectively, of pre-treated patients. Moreover, the CD4 count only increased significantly (> 15%) in naive individuals. Changes in serum p24 antigenemia were not significant in both groups neither at the first nor at the third months of began therapy. CONCLUSIONS The antiviral efficacy of the ZDV plus DDI combination is limited and transient in patients with advanced HIV disease, and disappears in subjects already exposed to ZDV.