A pooled analysis of CD4 response to zidovudine and zalcitabine treatment in patients with AIDS and AIDS-related complex.
BACKGROUND
This article reports a meta-analysis focused on the efficacy of zalcitabine and zidovudine alone or in combination as reported by three AIDS Clinical Trial Group trials. We analyzed the log CD4 count (LCD4) response to therapy up to 1 year after the beginning of therapy. One of the purposes of this article was to illustrate a meta-analysis method that permits pooling of original data from trials with different designs.


METHODS
To effectively eliminate obvious differences due to design, we first estimated complete (1 year) individual LCD4 versus time curves using a sophisticated smoothing technique. Then several summary descriptors were computed from the completed LCD4 curves. Those descriptors were corrected for baseline covariate differences, and the corrected values were then related to measures of drug exposure.


RESULTS
Significant baseline covariates were LCD4 baseline count and AIDS-related complex or AIDS diagnosis. The predictor, corrected for baseline covariates, that correlated best with drug exposure was intensity, the initial rate of rise of LCD4, estimated as the slope of LCD4 between pretreatment and peak LCD4.


CONCLUSIONS
Using intensity as a single response measure, we found weak evidence for synergism of zalcitabine and zidovudine: combination therapy increased response by 20% over that expected from a purely additive interaction.
Gries
J M
JM
Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco 94143-0446, USA.
Troconiz
I F
IF
Verotta
D
D
Jacobson
M
M
Sheiner
L B
LB
D000386:AIDS-Related Complex / Q000188:drug therapy / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count / Q000187:drug effects*; D004359:Drug Therapy, Combination; D006801:Humans; D012044:Regression Analysis; D013997:Time Factors; D016047:Zalcitabine / Q000008:administration & dosage / Q000494:pharmacology*; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology*
D019380:Anti-HIV Agents; D015215:Zidovudine; D016047:Zalcitabine