Primary infection with the human immunodeficiency virus (HIV) is generally followed by a burst of viraemia with or without clinical symptoms. This in turn is followed by a prolonged period of clinical latency. During this period there is little, if any, detectable viraemia, the numbers of infected cells in the blood are very low, and it is extremely difficult to demonstrate virus expression in these cells. We have analysed viral burden and levels of virus replication simultaneously in the blood and lymphoid organs of the same individuals at various stages of HIV disease. Here we report that in early-stage disease there is a dichotomy between the levels of viral burden and virus replication in peripheral blood versus lymphoid organs. HIV disease is active in the lymphoid tissue throughout the period of clinical latency, even at times when minimal viral activity is demonstrated in blood.

Follicular T helper cells are the major reservoir for HIV infection and accumulate during chronic HIV infection.

In persons who remain free of disease for many years despite HIV infection the viral load is low, but viral replication persists. Lymph-node architecture and immune function appear to remain intact.

A SIGNIFICANT proportion (up to 70%) of individuals experience an acute clinical syndrome of varying severity associated with primary infection with the human immunodeficiency virus (HIV). We report here studies on six individuals who showed an acute HIV syndrome which generally resolved within four weeks, concomitant with a dramatic downregulation of viraemia. To characterize the T-cell-mediated primary immune response to HIV, we used combined semiquantitative polymerase chain reaction assay and cytofluorometry to analyse the T-cell antigen receptor repertoire in sequential peripheral blood mononuclear cells from the patients. We found major oligoclonal expansions in a restricted set of variable-domain beta-chain (V beta) families. Cells expressing the expanded V beta s predominantly expressed the CD8 T-cell differentiation antigen and mediated HIV-specific cytotoxicity. Major oligoclonal expansions of these CD8+ T lymphocytes may represent an important component of the primary immune response to viral infections and may help to clarify both the immunopathogenic and the protective mechanisms of HIV infection.

The total number of human immunodefi-

A switch from a T helper 1 (TH1) cytokine phenotype to a TH2 phenotype has been proposed as a critical element in the progression of human immunodeficiency virus (HIV) disease. Here, constitutive cytokine expression was analyzed in unfractionated and sorted cell populations isolated from peripheral blood and lymph nodes of HIV-infected individuals at different stages of disease. Expression of interleukin-2 (IL-2) and IL-4 was barely detectable (or undetectable) regardless of the stage of disease. CD8+ cells expressed large amounts of interferon gamma and IL-10, and the levels of these cytokines remained stably high throughout the course of infection. Furthermore, similar patterns of cytokine expression were observed after stimulation in vitro of purified CD4+ T cell populations obtained from HIV-infected individuals at different stages of disease. These results indicate that a switch from the TH1 to the TH2 cytokine phenotype does not occur during the progression of HIV disease.

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Following infection of the host with a virus, the delicate balance between virus replication͞spread and the immune response to the virus determines the outcome of infection, i.e., persistence versus elimination of the virus. It is unclear, however, what relative roles immunologic and virologic factors play during primary viral infection in determining the subsequent clinical outcome. By studying a cohort of subjects with primary HIV infection, it has been demonstrated that qualitative differences in the primary immune response to HIV, but not quantitative differences in the initial levels of viremia are associated with different clinical outcomes.