Zidovudine-interferon-alpha combination therapy in patients with advanced human immunodeficiency virus type 1 infection: biphasic response of p24 antigen and quantitative polymerase chain reaction.
In an open-label dose-ranging pilot trial, 13 homosexual men with human immunodeficiency virus type 1 (HIV-1) p24 antigenemia after at least 6 weeks of zidovudine monotherapy were continued on zidovudine and given interferon-alpha, 1.25-7.5 x 10(6) units/m2 subcutaneously three times/week. Plasma p24 antigen levels demonstrated a biphasic response, falling initially in 11 patients by a mean of 50% (95% confidence interval, 36%-64%; P = .001) at a median of 11 weeks, but rising steadily thereafter (P = .001). CD4+ cell counts fell by a mean of 7.1 cells/mm3/week (P = .01). Higher initial CD4+ counts predicted greater p24 antigen reductions. At higher interferon doses no greater reductions in p24 antigen occurred, but side effects were more severe and CD4+ lymphocyte counts fell faster. Polymerase chain reaction quantification of HIV-1 DNA in 3 patients showed a biphasic pattern paralleling the p24 antigen response. In sum, although evidence of short-term effects was found, the combination showed no evidence of lasting antiviral activity beyond that achieved with zidovudine alone in patients with advanced HIV-1 infection.
Edlin
B R
BR
Division of HIV/AIDS, Centers for Disease Control, Atlanta, Georgia 30333.
Weinstein
R A
RA
Whaling
S M
SM
Ou
C Y
CY
Connolly
P J
PJ
Moore
J L
JL
Bitran
J D
JD
D000386:AIDS-Related Complex / Q000188:drug therapy / Q000628:therapy; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000628:therapy; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D017024:Chemotherapy, Adjuvant; D004279:DNA, Viral / Q000032:analysis; D005500:Follow-Up Studies; D016655:HIV Core Protein p24 / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification*; D006716:Homosexuality; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D016896:Treatment Outcome; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
D004279:DNA, Viral; D016655:HIV Core Protein p24; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015215:Zidovudine