Zidovudine plus interferon-alpha versus zidovudine alone in HIV-infected symptomatic or asymptomatic persons with CD4+ cell counts > 150 x 10(6)/L: results of the Zidon trial. Zidon Study Group.
OBJECTIVE
To evaluate the efficacy and safety of zidovudine (ZDV) and lymphoblastoid interferon (IFN)-alpha combination therapy compared with ZDV monotherapy in HIV-infected subjects with CD4+ cell counts between 150 and 500 x 10(6)/l.


METHODS
Open, randomized controlled trial with subjects stratified by the Centers for Disease Control and Prevention (CDC) 1986 classification of HIV disease (group II/III or IV). The study was amended to a sequential design in February 1992 to allow interim analyses to be conducted.


METHODS
Outpatient clinics in 45 hospitals in Europe, Australia and Canada.


METHODS
A total of 402 previously untreated subjects with symptomatic HIV infection (CDC group IV) and CD4+ count 150-500 x 10(6)/l or asymptomatic HIV infection (CDC group II/III) with CD4+ count 150-350 x 10(6)/l.


METHODS
ZDV 250 mg twice daily with or without 3 MU subcutaneous injections of lymphoblastoid IFN-alpha three times per week.


METHODS
Time to development of a study endpoint defined as: progression from CDC group II/III to group IV, group IV non-AIDS to AIDS, or group IV AIDS to a second AIDS-defining condition; also CD4+ count to < 50 x 10(6)/l on two occasions at least 1 month apart or HIV-related death irrespective of CDC group on entry.


RESULTS
There was no reduction in the rate of disease progression for patients receiving ZDV plus IFN-alpha compared with patients receiving ZDV alone. No major differences between the groups were seen for CD4+ counts or percentages, or p24 antigenaemia. In a subset of 70 patients, a similar proportion from both dose groups showed evidence of ZDV resistance after 48 weeks of treatment. More adverse experiences were seen in the ZDV/IFN-alpha group.


CONCLUSIONS
Combination therapy with low dose lymphoblastoid IFN-alpha and ZDV revealed no clinical benefit compared with ZDV monotherapy.
Fernández-Cruz
E
E
Department of Immunology, General Hospital Gregorio Marañón, Madrid, Spain.
Lang
J M
JM
Frissen
J
J
Furner
V
V
Châteauvert
M
M
Boucher
C A
CA
Dowd
P
P
Stevens
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count / Q000187:drug effects*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects
D016655:HIV Core Protein p24; D016898:Interferon-alpha; D015215:Zidovudine