High Titers of Cytopathic Virus in Plasma of Patients with Symptomatic Primary HIV-1 Infection

作者：Stephen J. Clark, Michael S. Saag, W. Don Decker, Sherri Campbell-Hill, Joseph L. Roberson, Peter J. Veldkamp, John C. Kappes, Beatrice H. Hahn, George M. Shaw · 发表于：New England Journal of Medicine · 年份：1991 · DOI：10.1056/nejm199104043241404 · 被引用次数：694 · 研究领域：HIV Research and Treatment、Viral-associated cancers and disorders、HIV-related health complications and treatments

BACKGROUND: Primary infection with the human immunodeficiency virus (HIV-1) frequently causes an acute, self-limited viral syndrome. To examine the relations among viral replication, the immune response of the host, and clinical illness during this initial phase of infection, we undertook a quantitative, molecular, and biologic analysis of infectious HIV-1 in the blood and plasma of three patients with symptomatic primary infection and of a sexual partner of one of them. METHODS: During an eight-week period of primary infection, HIV-1 was cultured frequently in dilutions of plasma and peripheral-blood mononuclear cells (PBMC), and levels of HIV-1 antigen and antibody were determined sequentially by enzyme-linked immunosorbent assay and immunoblotting. Replication-competent HIV-1 proviruses were cloned and characterized biologically. RESULTS: Six to 15 days after the onset of symptoms, high titers of infectious HIV-1 (from 10 to 10(3) tissue-culture-infective doses per milliliter of plasma) and viral p24 antigen were detected in the plasma of all three patients. These titers fell precipitously by day 27, and the decline coincided with an increase in the levels of antiviral antibodies and the resolution of symptoms. Sequential isolates of virus from plasma and PBMC obtained throughout the period of primary infection, as well as virus derived from two molecular proviral clones, were highly cytopathic for normal-donor PBMC and immortalized T cells, despite the marked reduction in...