Evaluation of pharmacokinetics, safety, tolerance, and activity of combination of zalcitabine and zidovudine in stable, zidovudine-treated pediatric patients with human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 190 Team.
A double-blind phase II trial compared zalcitabine (0.03 mg/kg/day) in combination with zidovudine (720 mg/m2/day) and zidovudine monotherapy in 250 clinically stable, previously zidovudine-treated, human immunodeficiency virus-infected children. The combination was well-tolerated except for an increased incidence of neutropenia (14%) compared with that in children receiving monotherapy (5%). No differences were noted for time to first AIDS-defining illness or death, neuropsychologic status, or weight Z scores. In patients in the combination arm, the CD4 cell count decline was slower (13% per year) than in patients receiving monotherapy (25% per year) (P = .03), and quantitative peripheral blood mononuclear cell virus load remained lower at all time points (P = .08). Deaths were fewer in patients receiving combination therapy (4) compared with those in patients receiving monotherapy (10) (P = .083). Thus, administration of zidovudine with zalcitabine to children with prior zidovudine treatment did not result in a significant increase in toxicity compared with that resulting from zidovudine monotherapy and demonstrated improvement in immunologic and virologic surrogate markers.
Bakshi
S S
SS
North Shore University Hospital-Cornell University Medical College, Manhasset, New York, USA.
Britto
P
P
Capparelli
E
E
Mofenson
L
L
Fowler
M G
MG
Rasheed
S
S
Schoenfeld
D
D
Zimmer
B
B
Frank
Y
Y
Yogev
R
R
Jimenez
E
E
Salgo
M
M
Boone
G
G
Pahwa
S G
SG
D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000401:mortality; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology; D015996:Survival Rate; D013997:Time Factors; D016047:Zalcitabine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015215:Zidovudine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D015215:Zidovudine; D016047:Zalcitabine