Zidovudine in combination with alpha interferon and interleukin-2 as prophylactic therapy for FeLV-induced immunodeficiency syndrome (FeLV-FAIDS).
Zidovudine (3'-azido-3'-deoxythymidine; AZT) inhibited replication of an immunodeficiency-inducing strain of feline leukemia virus (FeLV-FAIDS) in vitro at concentrations of 0.5-0.005 micrograms/ml. A 25-30% additional antiviral effect was achieved in vitro when AZT was combined with human recombinant alpha interferon 2a (IFN alpha). Oral administration of AZT (20 mg/kg three times daily) to cats resulted in plasma concentrations of 3 micrograms/ml at 2 h post-administration with a T1/2 of approximately 1.60 h. Administration of AZT alone or in combination with IFN alpha or interleukin-2 (IL-2) throughout a 6-week treatment period enabled cats to resist challenge with FeLV-FAIDS. In contrast, those cats treated with IFN alpha or IL-2 alone became persistently antigenemic (core protein p27) in parallel with placebo-treated controls. Antigenemia remained undetectable in AZT-treated cats throughout an 80-day period post-inoculation (38 days after treatment was withdrawn). However, latent FeLV-FAIDS in bone marrow was detectable by in vitro culture of progenitor cells in the presence of hydrocortisone. Serial analysis of circulating p27 antigen, neutralizing antibody, and quantification of latent, reactivatable virus indicated that those animals receiving AZT in combination with IFN alpha were most able to resist FeLV-FAIDS challenge. This work provides additional evidence that early presymptomatic treatment employing combination chemoimmunotherapy can be effective in medical intervention of retroviral infection.
Zeidner
N S
NS
Department of Pathology, Colorado State University, Fort Collins 80523.
Rose
L M
LM
Mathiason-DuBard
C K
CK
Myles
M H
MH
Hill
D L
DL
Mullins
J I
JI
Hoover
E A
EA
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000382:microbiology / Q000517:prevention & control*; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D000956:Antigens, Viral / Q000032:analysis; D002415:Cats; D004359:Drug Therapy, Combination; D007153:Immunologic Deficiency Syndromes / Q000150:complications; D007370:Interferon Type I / Q000008:administration & dosage*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use; D005256:Leukemia Virus, Feline / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification; D007942:Leukemia, Experimental / Q000382:microbiology / Q000517:prevention & control*; D009500:Neutralization Tests; D011994:Recombinant Proteins; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000914:Antibodies, Viral; D000956:Antigens, Viral; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D015215:Zidovudine