ADDITIVE OR SEQUENTIAL NUCLEOSIDE ANALOG THERAPY COMPARED WITH CONTINUED ZIDOVUDINE MONOTHERAPY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS WITH ADVANCED DISEASE DOES NOT PROLONG SURVIVAL - AN OBSERVATIONAL STUDY

To study the effect of sequential or additive use of zalcitabine or di danosine on survival in 308 human immunodeficiency virus-infected pati ents with advanced disease treated with zidovudine, an observational s tudy using time-dependent Cox proportional hazards models was done. Ch anging to sequential or additive therapy was based on deterioration of a patient's health status, a significant drop in CD4 cell count, or i ntolerance for zidovudine. The median CD4 cell count at baseline was 1 10 X 10(6)/L; 42% Of patients had AIDS. The median count before a chan ge in therapy was 50 X 10(6)/L. Additive or sequential treatment was a ssociated with an increased risk for death (relative hazard, 1.59; 95% confidence interval [CI], 1.01-2.49; and 1.58; 95% CI, 1.10-2.37, res pectively). Adjustment of the models for prognostic factors failed to substantially affect this observation. possibly the lack of benefit in this study is because patients switched therapy at advanced stages, w hereas the switch may be more effective in early disease.