Regulation and characterization of the interferon-alpha present in patients with advanced human immunodeficiency virus type 1 disease.
To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.
Swindells
S
S
Department of Medicine, University of Nebraska Medical Center, Omaha, USA.
Baldwin
T
T
Kelly
C
C
Baca-Regen
L
L
Loomis
L
L
Post
D
D
Brichacek
B
B
Stevenson
M
M
Dominguez
E A
EA
Reddy
R
R
Klein
R
R
Liao
M J
MJ
Testa
D
D
McDonald
T
T
Bellanti
J
J
Skurkovich
S
S
Gendelman
H E
HE
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000276:immunology / Q000821:virology; D000328:Adult; D001483:Base Sequence; D001781:Blood Component Removal / Q000009:adverse effects; D005260:Female; D015497:HIV-1; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014779:Virus Replication
D016898:Interferon-alpha