Julio S.G. Montaner, MD; Martin T. Schechter, MD, PhD; Anita Rachlis, MD; John Gill, MD; Raymond Beaulieu, MD; Chris Tsoukas, MD; Janet Raboud, PhD; Bill Cameron, MD; Horacio Salomon, PhD; Lisa Dunkle, MD; Laurie Smaldone, MD; Mark A. Wainberg, PhD; The Canadian HIV Trials Network Protocol 002 Study Group*
To compare the safety and efficacy of didanosine with that of continued zidovudine therapy in persons with human immunodeficiency virus (HIV) infection who had received zidovudine for at least 6 months and had CD4 cell counts of 200 to 500 CD4 cells/mm3.
Double-blind, randomized, controlled trial.
10 Canadian university-affiliated specialty clinics.
246 patients were assigned to receive standard doses of either zidovudine or didanosine.
The primary clinical end point was the occurrence of a new, previously undiagnosed acquired immunodeficiency syndrome (AIDS)-defining illness or death.
245 of 246 patients were eligible (118 receiving didanosine and 127 receiving zidovudine). Sixty-six percent were asymptomatic, 30% had AIDS-related complex, and 4% had AIDS. The median baseline CD4 count was 320 cells/mm3. The median previous duration of zidovudine therapy was 471 days. Nine new AIDS-defining illnesses developed during the study; all but one were in the zidovudine group (relative risk, 7.9 [95% CI, 1.0 to 63.3; P = 0.02]). A change to didanosine led to a statistically significant increase in CD4 counts by week 2 that persisted until the end of the study at week 48 (P < equals 0.01). Viral sensitivity studies (done in 102 patients) showed that 28% of the zidovudine group and 21% of the didanosine group had high-level in vitro resistance to zidovudine (50% inhibitory concentration greater than 0.8 µm) at baseline (P = 0.49). Only one patient in the didanosine group developed high-level resistance to zidovudine during the study. In the zidovudine group, the cumulative probability of developing high-level resistance to zidovudine was 59% at 1 year (P = 0.01). Abdominal pain, leukopenia, and neutropenia were more frequent in the zidovudine group, and hyperuricemia was more frequent in the didanosine group (P < 0.05).
In clinically stable patients with 200 to 500 CD4 cells/mm3 who had tolerated zidovudine for at least 6 months, a change to didanosine led to a decrease in the rate of disease progression, a sustained increase in CD4 counts, and a decrease in the chances of developing high-level resistance to zidovudine. Both drugs were generally well tolerated.
*For additional members of the Canadian HIV Trials Network Protocol 002 Study Group, see the Appendix.
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Montaner JS, Schechter MT, Rachlis A, Gill J, Beaulieu R, Tsoukas C, et al. Didanosine Compared with Continued Zidovudine Therapy for HIV-Infected Patients with 200 to 500 CD4 Cells/mm3: A Double-Blind, Randomized, Controlled Trial. Ann Intern Med. 1995;123:561–571. doi: 10.7326/0003-4819-123-8-199510150-00001
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Published: Ann Intern Med. 1995;123(8):561-571.
HIV, Infectious Disease.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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