A Controlled Trial Comparing Continued Zidovudine with Didanosine in Human Immunodeficiency Virus Infection

Although zidovudine is effective in patients with human immunodeficiency virus (HIV) infection, its efficacy may decline with prolonged use. Didanosine is another inhibitor of HIV reverse transcriptase. We evaluated the effectiveness of changing anti-HIV treatment from zidovudine to didanosine. This multicenter, double-blind study involved 913 patients who had tolerated zidovudine for at least 16 weeks. The patients had the acquired immunodeficiency syndrome (AIDS), AIDS-related complex with ≤300 CD4 cells per cubic millimeter, or asymptomatic HIV infection with ≤200 CD4 cells per cubic millimeter. They were randomly assigned to receive 600 mg per day of zidovudine, 750 mg per day of didanosine, or 500 mg per day of didanosine. There were significantly fewer new AIDS-defining events and deaths among the 298 subjects assigned to 500 mg per day of didanosine than among the subjects who continued to receive zidovudine (relative risk, 1.39; 95 percent confidence interval, 1.06 to 1.82; P = 0.015). With 750 mg of didanosine, there was no clear benefit over zidovudine (relative risk, 1.10; 95 percent confidence interval, 0.86 to 1.42). The efficacy of didanosine was unrelated to the duration of previous zidovudine treatment. In the two didanosine groups, there were improvements in the number of CD4 cells (P<0.001 for both groups) and in p24 antigen levels (P = 0.03 in the 500-mg group; P = 0.005 in the 750-mg group), as compared with the zidovudine group. Changing treatment from zidovudine to 500 mg per day of didanosine appears to slow the progression of HIV disease. (N Engl J Med 1992;327:581–7.), THE nucleoside analogue zidovudine (3′-azido-3′deoxythymidine) inhibits human immunodeficiency virus (HIV) replication and is more effective than placebo in delaying death in subjects with the acquired immunodeficiency syndrome (AIDS), in delaying the development of AIDS in subjects with AIDS-related complex, and in delaying the development of AIDS or AIDS-related complex in subjects with asymptomatic HIV infection.^{1 2 3 4} Mortality was reduced with early use of zidovudine with or without prophylaxis against Pneumocystis carinii pneumonia,^{5 , 6} although these data are controversial.⁷ The duration of the clinical usefulness of zidovudine is unknown, and drug failure, manifested by the progression of HIV disease, presents a challenge in…