Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. AIDS Clinical Trials Group (ACTG) Study 152 Team.
BACKGROUND
Zidovudine has been the drug of choice for the initial treatment of symptomatic children infected with the human immunodeficiency virus (HIV). This trial was designed to assess the efficacy and safety of treatment with zidovudine alone as compared with either didanosine alone or combination therapy with zidovudine plus didanosine.


METHODS
In this multicenter, double-blind study, symptomatic HIV-infected children 3 months through 18 years of age were stratified according to age (<30 months or > or =30 months) and randomly assigned to receive zidovudine, didanosine, or zidovudine plus didanosine. The primary end point was length of time to death or to progression of HIV disease.


RESULTS
Of the 831 children who could be evaluated, 92 percent had never received antiretroviral therapy and 90 percent had acquired HIV perinatally. An interim analysis (median follow-up, 23 months) showed a significantly higher risk of HIV-disease progression or death in patients receiving zidovudine alone than in those receiving combination therapy (relative risk, 0.61; 95 percent confidence interval, 0.42 to 0.88; P=0.007). The study arm with zidovudine alone was stopped and unblinded; the other two treatment arms were continued. At the end of the study, didanosine alone had an efficacy similar to that of zidovudine plus didanosine (median follow-up, 32 months) (relative risk of disease progression or death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.91). A significantly lower risk of anemia or neutropenia was seen in patients receiving didanosine alone (P=0.036).


CONCLUSIONS
In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity.
Englund
J A
JA
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Baker
C J
CJ
Raskino
C
C
McKinney
R E
RE
Petrie
B
B
Fowler
M G
MG
Pearson
D
D
Gershon
A
A
McSherry
G D
GD
Abrams
E J
EJ
Schliozberg
J
J
Sullivan
J L
JL
D000293:Adolescent; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D016049:Didanosine / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D016896:Treatment Outcome; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D015215:Zidovudine; D016049:Didanosine