Int Conf AIDS. 1996 Jul 7-12;11(Program Supplement):20 (abstract no.
Objectives: To compare the safety and efficacy of ZDV, DDI or ZDV/DDI
therapy in symptomatic HIV-infected children age 3 months to 18 years.
Methods: In this double-blind trial, 831 children who previously had no
(92%) or less than 6 weeks of antiretroviral therapy were stratified by
age (less than 30 mo. vs. greater than 30 mo.-18 yrs.) and randomly
assigned to receive ZDV (180 mg/M(2) Q6H). DDI (120 mg/M(2) Q12H), or
combination ZDV 120 mg/M(2) Q6H/DDI (90 mg/M(2) Q12H). Children were
followed for drug toxicity by clinical and laboratory parameters.
Primary endpoints were time to death or HIV-disease progression defined
by clinical outcomes. Therapy was intended to continue until the past
patient randomized completed 104 weeks. Results: the study began in
8/91; 54% of patients were less than 30 months of age at enrollment. At
interim analysis in 2/95, significantly more children assigned to ZDV
(27%) had reached a primary endpoint than the "best" (18%) of the other
two treatments. Patients in the ZDV arm were unblinded. The other two
treatment arms continued blinded until study closure (8/95) when 78% of
children had completed the study and 57% were receiving initial therapy.
The median follow-up for children receiving DDI or ZDV/DDI was 32 and 33
months, respectively. Primary endpoints were met by 67 DDI monotherapy
and 68 ZDV/DdI combination therapy recipients P=0.908; relative risk
0.98). Of the endpoints, 70 (52%) were weight growth failures, 25
(18.5%) were CNS deteriorations, and 21 (15.6) were deaths. Drug
toxicities usually were easily managed, but significantly fewer
hematological toxicities occurred in children receiving DDI than in
those treated with combination therapy. Conclusions: ZDV monotherapy was
inferior to either DDI or ZDV/DDI in the treatment of
antiretroviral-naive children with symptomatic HIV-infection ZDV
monotherapy. DDI monotherapy was less toxic than and equal in efficacy
to ZDV/DDI combination therapy in preventing death or HIV-disease
*Anti-HIV Agents/THERAPEUTIC USE *Didanosine/THERAPEUTIC USE *HIV
Infections/DRUG THERAPY *Zidovudine/THERAPEUTIC USE