Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study.
OBJECTIVE
To determine the safety and efficacy of dideoxycytidine in patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex.


METHODS
A partially randomized phase I and II outpatient, dose-ranging study.


METHODS
Four university medical centers involving government-supported referral AIDS Clinical Trial Units.


METHODS
Sixty-one patients with AIDS or advanced AIDS-related complex and 100 pg/mL or more serum p24 antigen titers.


METHODS
Dideoxycytidine was administered orally at 0.06, 0.03, 0.01, or 0.005 mg/kg body weight every 4 hours for 3 to 6 months depending on tolerance and benefit.


RESULTS
In patients receiving 0.06 and 0.03 mg/kg, diffuse erythematous rash, fever, and aphthous stomatitis occurred in the first weeks of therapy, but resolved later. Hematopoietic suppression was rare. Peripheral sensory neuropathy occurred in patients receiving 0.06 mg/kg and 0.03 mg/kg and improved after discontinuation of therapy. Serum p24 antigen fell significantly (P less than 0.01) from baseline entry values in most of these patients. The CD4 lymphocytes rose transiently at the 0.03 mg/kg dosage. At the 0.005 mg/kg dosage, skin rash, fever, and aphthous stomatitis were mild or absent. Peripheral neuropathy, which occurred in all patients receiving 0.01 mg/kg was less severe than at higher dosages. At the 0.005 mg/kg dosage, peripheral neuropathy was occasionally seen. Significant suppression of serum p24 antigen was seen in most patients with AIDS-related complex receiving 0.01 mg/kg and less frequently in patients receiving 0.005 mg/kg.


CONCLUSIONS
Less toxic regimens of dideoxycytidine merit clinical assessment for advanced anti-human immunodeficiency virus-1 (HIV) infection. Several studies alternating dideoxycytidine and zidovudine are in progress.
Merigan
T C
TC
Stanford University School of Medicine, California.
Skowron
G
G
Bozzette
S A
SA
Richman
D
D
Uttamchandani
R
R
Fischl
M
M
Schooley
R
R
Hirsch
M
M
Soo
W
W
Pettinelli
C
C
D000386:AIDS-Related Complex / Q000188:drug therapy* / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D000284:Administration, Oral; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D004341:Drug Evaluation; D005260:Female; D015488:HIV Antigens / Q000032:analysis*; D016655:HIV Core Protein p24; D006801:Humans; D008297:Male; D011897:Random Allocation; D012191:Retroviridae Proteins / Q000032:analysis*; D016047:Zalcitabine
D015224:Dideoxynucleosides; D015488:HIV Antigens; D016655:HIV Core Protein p24; D012191:Retroviridae Proteins; D016047:Zalcitabine