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Since 1984, when it became apparent that the disease that we now know as AIDS was caused by a CD4+ T cell tropic novel human retrovirus, the metaphors used by the research community to describe the pathogenesis of HIV infection have changed at least several times. These shifts in our perception of the effects of HIV on the human T cell system were based on novel experimental evidence that each time changed in a fundamental way the then prevailing ideas.In the early phase of the AIDS pandemic, our picture was dominated by the concept of viral latency that was based on a vast amount of high-profile research in molecular virology. That work was, however, mainly performed in quite artificial in-vitro systems and pointed to critical roles for gene products coded for by several HIV-specific genes in establishing and maintaining latency and regulating re-activation. In those days, the virus was barely detectable in blood or tissues and the loss of CD4 T cells at that time was thought to be largely due to bystander effects, lysis through cytotoxic T cells (CTL) or ingenious autoimmune-related mechanisms.With the introduction of better and more sensitive virological, molecular and immunohistological techniques in the early nineties, such as the polymerase chain reaction (PCR) technique, the idea of viral latency became increasingly challenged. Improved culture methods allowed for virus isolation from nearly all asymptomatic seropositives. Infected cells became readily detectable in blood and appeared to be enriched in lymphoid tissues, even in asymptomatically infected individuals [1,2]. Together with reports on high percentages of apoptotic CD4+ and CD8+ T cells already early in infection in blood and tissues, the scene was gradually set for a more dynamic view of the HIV–T cell interaction from 1990 on . Without any doubt, the idea of viral latency was falsified completely by the seminal papers from the laboratories of Ho and Wei [4,5] that for the first time provided a quantitative view of the truly amazing viral production and decay rates. These papers also proposed the idea of high CD4+ T cell death rates caused directly by infection of high numbers of cells. HIV infection was no longer depicted as initially dormant, waiting for a reactivating event, but all of a sudden was compared to a never ceasing and vigorous battle killing large numbers of T cells every day, eventually exhausting the supplies. In these years, viral latency was replaced by clinical latency, which was depicted as an out-of-control fast train, heading for the abyss.Only 3 years later, based on new experimental findings, the pendulum swung back from high T cell turnover to low-level but chronic activation and insidious interference of HIV with thymic function [6,7]. This generated a host of studies using the newly developed TREC assay to measure thymic output  and more sophisticated in-vivo labeling techniques to estimate T cell production and half-life in relation to T cell depletion and restoration after highly active antiretroviral therapy (HAART). These papers presented compelling evidence that prompted a re-evaluation of the initial idea that increased T cell division was a homeostatic response to the severe T cell loss due to HIV infection. Instead, it appeared that T cell division is part of the systemic immune activation in response to chronic HIV infection – a response that, despite often very low CD4+ T cell numbers, disappears quickly when patients are started on HAART [9,10].