Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group.
OBJECTIVE
To compare the safety and efficacy of continuing zidovudine therapy with that of zalcitabine alone or zalcitabine and zidovudine used together.


METHODS
A randomized, double-blind, controlled trial.


METHODS
AIDS Clinical Trials units and National Hemophilia Foundation sites.


METHODS
1001 patients with symptomatic human immunodeficiency (HIV) disease and 300 or fewer CD4 cells/mm3 or asymptomatic HIV disease and 200 or fewer CD4 cells/mm3 who had tolerated zidovudine therapy for 6 months or more.


METHODS
Patients were randomly assigned to receive zidovudine, 600 mg/d; zalcitabine, 2.25 mg/d; or zidovudine, 600 mg/d, and zalcitabine, 2.25 mg/d.


METHODS
The primary end point was time to disease progression or death.


RESULTS
The median follow-up time was 17.7 months. The estimated 12-month event-free rates were 70%, 67%, and 73%, respectively, for the zidovudine, zalcitabine, and combination groups (P = 0.26). A trend analysis showed significantly lower progression rates for combination therapy compared with zidovudine therapy as the pretreatment CD4 cell count increased (P = 0.027). For patients with 150 or more CD4 cells/mm3, those receiving combination therapy were less likely to have disease progression or to die than were those receiving zidovudine (relative risk, 0.51; 95% CI, 0.28 to 0.93; P = 0.029). We observed no difference between the zalcitabine and zidovudine groups (relative risk, 0.74; CI, 0.40 to 1.36; P = 0.33). For patients with 50 to 150 CD4 cells/mm3 or fewer than 50 CD4 cells/mm3, we found no differences among the treatment groups (P = 0.69 and P = 0.57, respectively). Severe toxic effects occurred less frequently among patients with 150 or more CD4 cells/mm3.


CONCLUSIONS
We found no overall benefits of zalcitabine used alone or with zidovudine. However, a trend analysis suggested a better outcome for combination therapy compared with zidovudine as the pretreatment CD4 cell count increased.
Fischl
M A
MA
University of Miami School of Medicine, Department of Medicine, FL 33101.
Stanley
K
K
Collier
A C
AC
Arduino
J M
JM
Stein
D S
DS
Feinberg
J E
JE
Allan
J D
JD
Goldsmith
J C
JC
Powderly
W G
WG
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D003131:Combined Modality Therapy; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D016047:Zalcitabine / Q000009:adverse effects / Q000627:therapeutic use*; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
D016655:HIV Core Protein p24; D015215:Zidovudine; D016047:Zalcitabine