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Abstract N Engl J Med 1996;335:1099-106.
Zidovudine Alone or in Combination With Didanosine or Zalcitabine
in HIV-Infected Patients With the Acquired Immunodeficiency
Syndrome or Fewer Than 200 CD4 Cells per Cubic Millimeter
Authors: Saravolatz LD, Winslow, Collins G, Hodges JS, Pettinelli C, Stein DS, Markowitz N, Reves R, Loveless MO, Crane L, Thompson M, Abrams D, and investigators for the Terry Geirn Community Programs for Clinical Research on AIDS
Research has shown that a combination of zidovudine with either didanosine or zalcitabine is more effective against HIV than zidovudine alone. To determine if the combination is also more effective at delaying HIV progression, researchers compared the outcome of the therapies in 1,102 patients with AIDS or severe immune depression. After 35 months of treatment, disease progression or death was reported for 62 percent of the patients taking zidovudine and didanosine, compared to 63 percent of the patients taking zidovudine and zalcitabine, and 66 percent of those taking only zidovudine. Compared to zidovudine alone, more side effects were associated with the use of combination therapy. The authors conclude that, for patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not generally more beneficial than zidovudine alone. However, they also found that the combination therapy did offer some benefit to patients who had previously taken zidovudine for less than 12 months.
Background
We compared two combinations of nucleosides with zidovudine alone in patients with advanced human immunodeficiency virus (HIV) infection.
Methods
A total of 1102 patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter were randomly assigned to receive zidovudine alone or zidovudine combined with either didanosine or zalcitabine. Disease progression, survival, toxic effects and the CD4 cell response were assessed.
Results
After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosine, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine alone (P=0.24 ). as compared with zidovudine therapy, treatment with zidovudine plus didanosine was associated with a relative risk of disease progression or death of 0.86 (95 percent confidence interval, 0.71 to 1.03), and treatment with zidovudine plus zalcitabine was associated with a relative risk of 0.92 (95 percent confidence interval, 0.76 to 1.10). Survival was similar in the three groups.
In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously received zidovudine for 12 months or less. Therapy with zidovudine plus didanosine resulted in more gastrointestinal adverse effects, ant treatment with zidovudine plus zalcitabine, more neuropathy. The mean increases in CD4 cell counts at two months were higher with combination therapy with zidovudine alone.
Conclusions
In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not superior to zidovudine therapy alone. However, these combinations may be more effective than zidovudine monotherapy in patients with little or no previous zidovudine treatment.
For complete details consult the October 10, 1996 issue of the New England Journal of Medicine, volume 335, pages 1099-106.
Reference: 1. Saravolatz LD, Winslow, Collins G, Hodges JS, Pettinelli C, Stein DS, Markowitz N, Reves R, Loveless MO, Crane L, Thompson M, Abrams D, et al. Zidovudine alone or in combination with didanosine or zalcitabine
in HIV-infected patients with the acquired immunodeficiency
syndrome or fewer than 200 CD4 cells per cubic millimeter. N Engl J Med 1996;335:1099-106.
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