ZIDOVUDINE COMPARED WITH DIDANOSINE IN PATIENTS WITH ADVANCED HIV TYPE-1 INFECTION AND LITTLE OR NO PREVIOUS EXPERIENCE WITH ZIDOVUDINE

Background: We conducted a trial to compare treatment with zidovudine or didanosine in patients with advanced human immunodeficiency virus t ype 1 (HIV-1) infection who had received little or no previous therapy with zidovudine. Methods: Six hundred seventeen patients with acquire d immunodeficiency syndrome (AIDS), advanced AIDS-related complex (CD4 cell count, less than or equal to 0.03x10(9)/L [300/mu L]), or asympt omatic HIV (CD4 cell count, less than or equal to 0.20x10(9)/L) receiv ed zidovudine, 500 mg/d of didanosine, or 750 mg/d of didanosine in a randomized, double-blind allocation, with cross-over to alternative me dication after development of an end point or serious toxic effect. To be eligible, patients must have received either no or up to 16 weeks of zidovudine therapy before entry into the study. Primary end points were development of a new AIDS-defining event or death. Secondary clin ical end points were new or recurrent AIDS-defining events, or death, and survival. Results: In the study as a whole, there were no differen ces in the relative risks (RRs) of the development of end points betwe en treatment groups. However, there was a strong interaction between t he relative efficacies of zidovudine and didanosine and previous exper ience with zidovudine. Among 380 patients with no previous zidovudine therapy, zidovudine was more effective than 750 mg/d of didanosine (RR , 1.43; 90% confidence interval [CI], 1.02 to 2.00), with a similar tr end for zidovudine compared with 500 mg/d of didanosine (RR, 1.21;90% CI, 0.86 to 1.71). However, among 118 patients with more than 8 weeks but no more than 16 weeks of previous zidovudine therapy, 500 mg/d of didanosine was more effective than zidovudine (RR, 0.48; 90% CI, 0.27 to 0.86); there was a similar trend for increased effectiveness of 750 mg/d of didanosine compared with zidovudine (RR, 0.61;90% CI, 0.36 to 1.03). Among 119 patients who had some but no more than 8 weeks of pr evious zidovudine therapy, there were no significant differences among the treatment arms. Similar findings were noted in the analysis of th e two secondary clinical end points. No significant differences were f ound in efficacy between the groups receiving 500 and 750 mg/d of dida nosine. The major toxic effect associated with zidovudine was hematopo ietic (granulocytopenia) and that associated with didanosine was pancr eatitis (dosage, 750 mg/d). Conclusions: In patients with advanced HIV disease, zidovudine appears to be more effective than didanosine as i nitial therapy; however, some patients with advanced HIV disease may b enefit from a change to didanosine therapy after as little as 8 to 16 weeks of therapy with zidovudine.