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.