In Vitro Antiviral Activity of Didanosine Compared with That of Other Dideoxynucleoside Analogs Against Laboratory Strains and Clinical Isolates of Human Immunodeficiency Virus

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Abstract
The in vitro activity of didanosine (2′,3′-dideoxyinosine, ddI) against the human immunodeficiency virus (HIV) is generally less potent than that of zidovudine (3′-azidothymidine, AZT) and zalcitabine (2′,3′-dideoxycytidine, ddC), often by an order of magnitude or more. However, in monocyte/macrophage cell cultures, the potency of didanosine is similar to, or greater than, that of zidovudine but still less than that of ddC. The cytotoxicity of didanosine, including cytotoxicity to bone marrow progenitor cells, is low, and endpoints are often not reached. (The concentration inhibiting 50% of the cell growth [IC50] is >100 µM.) Thus, in spite of lower potency, didanosine has a high antiviral selective index in vitro. By contrast, zidovudine and ddC are more cytotoxic, with IC50 values < 5 μM. Clinically derived HIV isolates with as high as 30-fold decreases in susceptibility to didanosine in vitro have been described. However, in studies designed to assess the frequency of resistance development after prolonged didanosine therapy, more moderate changes (2- to 5-fold) are seen in general. By contrast, isolates with a 100-fold decrease in sensitivity to zidovudine are frequently found in strains from patients who have received prolonged zidovudine therapy.

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