SURVIVAL EFFECTS OF ZDV, DDI, AND DDC IN PATIENTS WITH CD4-LESS-THAN-OR-EQUAL-TO-50 CELLS MM(3)/

Seven major clinical trials for the treatment of HIV-ififected individ uals are investigated. The treatments used in these trials were zidovu dine, dideoxyinosine, dideoxycytosine, and one combination for patient s with CD4 cell counts <500 cells/mm3. Patients in each trial are part itioned into two subgroups based on their baseline CD4 cell counts: pa tients with CD4 less than or equal to 50 cells/mm(3) and patients with CD4 >50 cells/mm(3). The difference between treatment effects, using survival as a measure of effect, within each subgroup is calculated se parately for each trial; this difference is referred to as ''subgroup response.'' For each trial the difference between the subgroup respons es is calculated and standardized. A meta-analysis is conducted over a ll seven trials for the differences between subgroup responses; the co nsistency of responses is evaluated across all trials among patients w ithin baseline CD4 subgroups. Based on the result of this meta-analysi s we conclude that there is no evidence that the treatment effects in patients with CD4 less than or equal to 50 cells/mm(3) are different f rom those among patients with CD4 >50 cellsimm3. This result is observ ed in patients with different antiviral experience and different basel ine characteristics. Risk ratios as well as chi(2) statistics are used to quantify the response rates in different subgroups. Kaplan-Meier c urves of survival for these trials are depicted for all patients and e ach subgroup separately. In most of the trials the Kaplan-Meier curves for the patients with CD4 less than or equal to 50 cells/mm(3) resemb le those for all patients. This finding implies that most of the clini cal events, and therefore statistical power, in the analyses of these trials came from patients with CD4 less than or equal to 50 cells/mm(3 ). Therefore, the exclusion of patients with CD4 less than or equal to 50 cells/mm(3) may result in prolonged and/or larger clinical trials.