Viro-immunological studies in acute HIV-1 infection : AIDS (original) (raw)

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Roos, Marijke Th.L.; de Leeuw, Nicoline A.S.M.; Claessen, Frans A.P.; Huisman, Han G.; Kootstra, Neeltje A.; Meyaard, Linde; Schellekens, Peter Th.A.; Schuitemaker, Hanneke; Miedema, Frank

From the Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam and the Department of Internal Medicine, Academic Hospital of the Free University, Amsterdam, The Netherlands.

Abstract

Objective

To monitor a patient who presented with symptomatic HIV-1 infection for virological and immunological parameters in relation to the clinical course.

Methods

Virological studies included determination of frequency of productively HIV-1-infected peripheral blood mononuclear cells (PBMC) and viral RNA load in plasma and p24 antigenaemia. Immunological studies included the analysis of T-cell subsets, the expression of activation markers, CD45RO and CD45RA antigens, the frequency of cells programmed for death, and T-cell function.

Results

During the first week post onset of primary HIV-1 infection symptoms high plasma titres of p24 and HIV-1 RNA were observed. The number of productively HIV-1-infected PBMC peaked, coinciding with CD4+ T lymphocytopaenia, during week 2 when clinical improvement started. CD8+ T lymphocytosis was observed 10 days post onset of clinical symptoms, the expanded cell population being of the CD8+CD38+, CD8+CD27+ and CD8+CD28-phenotype. 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 of clinical symptoms. Within about 3 weeks, following resolution of clinical 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 rise of activated CD8+ T cells, p24 antigen levels and viral RNA load in serum as well as the number of HIV-producing PBMC steeply declined after 2 weeks.

Conclusion

These findings demonstrate HIV-1-induced abnormalities during severe clinical symptoms of primary HIV-1 infection. The subsequent strong immune response, which is believed to be responsible for efficient control of viral replication, appears to precede clinical improvement.