Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex.
OBJECTIVE
To determine whether alternating regimens consisting of zidovudine and 2',3'-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone.


METHODS
An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared.


METHODS
Outpatient clinics of 12 AIDS Clinical Trials Units.


METHODS
One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigenemia (> or = 70 pg/mL).


METHODS
Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine.


METHODS
Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks).


RESULTS
Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P < 0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high rates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels.


CONCLUSIONS
These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.
Skowron
G
G
Division of Infectious Diseases, Roger Williams Hospital, Providence, RI 02908.
Bozzette
S A
SA
Lim
L
L
Pettinelli
C B
CB
Schaumburg
H H
HH
Arezzo
J
J
Fischl
M A
MA
Powderly
W G
WG
Gocke
D J
DJ
Richman
D D
DD
Pottage
J C
JC
Antoniskis
D
D
McKinley
G F
GF
Hyslop
N E
NE
Ray
G
G
Simon
G
G
Reed
N
N
LoFaro
M L
ML
Uttamchandani
R B
RB
Gelb
L D
LD
Sperber
S J
SJ
Murphy
R L
RL
Leedom
J M
JM
Grieco
M H
MH
Zachary
J
J
Hirsch
M S
MS
Spector
S A
SA
Bigley
J
J
Soo
W
W
Merigan
T C
TC
D000386:AIDS-Related Complex / Q000188:drug therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016655:HIV Core Protein p24 / Q000187:drug effects; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D015430:Weight Gain / Q000187:drug effects; D016047:Zalcitabine / Q000008:administration & dosage* / Q000009:adverse effects; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects
D016655:HIV Core Protein p24; D015215:Zidovudine; D016047:Zalcitabine