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Didanosine (ddI) and zalcitabine (ddC) provide valuable therapeutic alternatives in patients with HIV infection where previously zidovudine was the only option. Didanosine has been shown to be effective in patients with HIV infection refractory to or intolerant of zidovudine, and is also more effective than continued zidovudine therapy in patients who have previously received this drug long term. Combination therapy with both zidovudine and didanosine has synergistic antiviral effects, and the reduction in the required dosage of each agent improves tolerability. Didanosine is currently a second-line agent but if results of a direct comparison with zidovudine currently underway are favourable, it may become an alternative first-line agent.Zalcitabine also has synergistic anti-HIV activity with zidovudine but a direct comparison indicated that zidovudine was the more effective agent as monotherapy.Didanosine and zalcitabine have different tolerability profiles compared with zidovudine. The dose-limiting toxicities are pancreatitis (which may be fatal) and peripheral neuropathy, whereas the limiting toxicity of zidovudine is generally myelosuppression.Didanosine and zalcitabine have generally been priced lower than zidovudine, but lower price generic zidovudine formulations are now becoming available.