Identification of Human Immunodeficiency Virus Primary Isolates Resistant to Interferon-  and Correlation of Prevalence to Disease Progression

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.