VIRO-IMMUNOLOGICAL STUDIES IN ACUTE HIV-1 INFECTION

Objective: To monitor a patient who presented with symptomatic HIV-1 i nfection for virological and immunological parameters in relation to t he clinical course. Methods: Virological studies included determinatio n of frequency of productively HIV-1-infected peripheral blood mononuc lear cells (PBMC) and viral RNA load in plasma and p24 antigenaemia. I mmunological studies included the analysis of T-cell subsets, the expr ession of activation markers, CD45RO and CD45RA antigens, the frequenc y of cells programmed for death, and T-cell function. Results: During the first week post onset of primary HIV-1 infection symptoms high pla sma titres of p24 and HIV-1 RNA were observed. The number of productiv ely HIV-1-infected PBMC peaked, coinciding with CD4+ T lymphocytopaeni a, during week 2 when clinical improvement started. CD8+ T lymphocytos is was observed 10 days post onset of clinical symptoms, the expanded cell population being of the CD8+CD38+, CD8+CD27+ and CD8+CD28- phenot ype. CD8+ T lymphocytosis was paralleled by a high percentage of cells undergoing programmed cell death on in vitro culture. In vitro T-cell function was severely depressed during the first 10 days post onset o f clinical symptoms. Within about 3 weeks, following resolution of cli nical symptoms, phytohaemagglutinin-induced proliferation was restored to normal levels while responses to the CD3 monoclonal antibody only showed a partial restoration. During follow-up, concomitant with the r ise of activated CD8+ T cells, p24 antigen levels and viral RNA load i n serum as well as the number of HIV-producing PBMC steeply declined a fter 2 weeks. Conclusion: These findings demonstrate HIV-1-induced abn ormalities during severe clinical symptoms of primary HIV-1 infection. The subsequent strong immune response, which is believed to be respon sible for efficient control of viral replication, appears to precede c linical improvement.