Purpose of this Document
NIAID is providing these preliminary data to you as a health care provider so that you may make informed decisions in managing your patients. This document provides information on the preliminary results of ACTG 290, a phase II study of the virologic and immunologic effects of various antiretroviral drugs alone and in various combinations in patients who had previously taken ZDV for at least 12 weeks. An interim analysis of this study revealed that the average CD4+ T cell count in patients taking the combination of d4T and ZDV decreased from the time they entered the study. NIAID recommends that physicians closely monitor the CD4+ T cell counts of patients taking this combination.
Study Description and Results
The study, ACTG 290, is being conducted by the AIDS Clinical Trials Group (ACTG), a research network supported by the National Institute of Allergy and Infectious Diseases (NIAID). In this study 98 percent of the subjects had taken ZDV for more than 24 weeks (median 34 months). The CD4+ T cell counts of volunteers at study entry ranged form 300 to 600/mm3. Subjects were randomly assigned to one of four arms: (1) d4T (40 mg b.i.d.) And ZDV (200 mg t.i.d.), (2) d4T (40 mg b.i.d.) And ZDV placebo. (3) didanosine [ddI] (200 mg b.i.d.) And ZDV (200 mg t.i.d.), and (4) ddI (200 mg b.i.d.) And ZDV placebo.
An interim analysis of 129 subjects indicated that the average CD4+ T cell count of volunteers in the d4T/ZDV arm decreased after they entered the study. The median decrease from baseline at all follow-up visits ranged form 20 cells/mm3 at week 4 to 82 cells/mm3 at week 36. This decrease was significant (p-value .006 at week 24) when compared to the d4T/ZDV placebo arm. No unexpected changes in average CD4+ T cell counts occurred in the other arms of the study. No significant differences in adverse events, serious laboratory toxicities or HIV-related clinical events were observed among the four treatment groups. Viral load is still being analyzed and data are not currently available.
On the basis of these results, the ACTG 290 Protocol Team is closing the d4T/ZDV arm of the study. In an effort to understand this observation and its possible clinical significance, subjects in this arm will be offered the opportunity to enroll in a new arm of the study containing only d4T for an additional eight weeks, with very close monitoring of their CD4+ T cell count and plasma viral load. The study will continue until April 1997.
Studies are under way that may help us understand this observation. Data have been analyzed from patients in a similar study (ACTG 298) who have CD4+ T cell counts in the same range (300-600/mm3) as ACTG 29+0, but with fewer than seven days prior experience with ZDV or other antiviral nucleoside drugs. Participants in that study are randomized o receive either ZDV or d4T or ZDV+ d4T. After 12 weeks those on ZDV monotherapy have 3TC added. An interim review of ACTG 298 did not reveal an average CD4+ T cell count decline in any of the arms. At this time, the only apparent difference between these two study populations is the previous length of time on ZDV. At this time, no information is available on viral burden, drug resistance or pharmacology for either of these ongoing studies.
A decline in average CD4+ T cell counts was observed in participants who had received prior ZDV when they were treated with the combination of d4T and ZDV. Data from ACTG 298 thus far suggest that this observation may only apply to participants with substantial (more than six months) prior ZDV experience. Because these data are preliminary and based on a small number of individuals, additional conclusions are not possible at this time. Physicians should, however, closely monitor the CD4+ T cell counts of patients taking this drug combination.
For further information about ACTG 290, please call 1-800-TRIALS-A, Monday through Friday, 9 a.m. to 7 p.m., EST.
National Institutes of Health National Institute of Allergy and Infectious Diseases Betesda, Maryland 20892