title: Identification of human immunodeficiency virus primary isolates resistant to interferon-alpha and correlation of prevalence to disease progression.
abstract: Human immunodeficiency virus (HIV) primary isolates, derived from donors at various stages of HIV infection, were assayed for their sensitivity to interferon (IFN)-alpha 2 in vitro. These isolates displayed a broad range of sensitivity to IFN-alpha 2. The prevalence of IFN-alpha 2 resistance was low in the absence of AIDS but dramatically increased once HIV infection progressed to AIDS. Although there was no linear correlation between the percentage of IFN-alpha 2 inhibition in vitro and the CD4 cell number in vivo or the level of endogenous IFN-alpha, serum IFN-alpha levels were higher in donors with AIDS and were associated with low CD4 cell numbers. Thus, circulating IFN-alpha appeared to either promote resistance or favor survival of IFN-alpha resistant variants. IFN-alpha 2 resistance was neither limited to a particular cell tropism nor enhanced by therapy with zidovudine. Sequential analysis indicated that reversion to IFN-alpha 2 sensitivity could occur during the course of infection.
authors.affiliation: Oncology Center, Johns Hopkins University, Baltimore, Maryland.
authors.forename: M S
authors.initials: MS
authors.lastname: Künzi
authors.forename: H
authors.initials: H
authors.lastname: Farzadegan
authors.forename: J B
authors.initials: JB
authors.lastname: Margolick
authors.forename: D
authors.initials: D
authors.lastname: Vlahov
authors.forename: P M
authors.initials: PM
authors.lastname: Pitha
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D004352:Drug Resistance, Microbial; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology; D008297:Male; D011994:Recombinant Proteins; D014779:Virus Replication / Q000187:drug effects
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins