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HIV pathogenesis - PERSPECTIVES TIMELINE AIDS pathogenesis...

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© 2003 Nature PublishingGroup PERSPECTIVES reported 3–5 ; we now know this virus as human immunodeficiency virus type 1 ( HIV-1 ). This finding allowed the develop- ment of a reliable test for HIV infection — looking for the presence of circulating immunoglobulin-G antibodies specific for HIV — which provided the basis for screen- ing of donated blood and for large-scale epi- demiological studies. It is worth noting that, in contrast to the analysis of many other infections, HIV-specific antibodies have been widely used for two decades as a marker of persistent infection, rather than as an indica- tor of a past infection that has been cleared. Within a few years, it became clear that the virus was spreading rapidly beyond the ‘risk groups’, with particularly disturbing rates of infection in sub-Saharan Africa 6 . We now know that more than 40 million people are infected with HIV-1 throughout the world, and the epidemic shows no sign of dissipating (FIG.2) . Despite occasional dissenting views, the evidence that HIV causes AIDS is now over- whelming 7 .The tragic infection of a few labo- ratory workers with HIV in the early 1980s, who have now developed the disease 8 , means that HIV has fulfilled Koch’s third postulate as the cause of AIDS,something that has still not been achieved for several other important human infections.However,despite the enor- mous extent of the epidemic and the intensity of the research drive to understand the infec- tion,many questions about HIV remain unan- swered.Is this infection genuinely new to the human population and, if so, how and when did it first occur in humans? What are the main mechanisms responsible for the relentless decline in CD4 + T-cell function and number, 22 years ago, the first cases of an acquired immunodeficiency syndrome afflicting young, homosexual American men were reported, heralding what we now know to be the beginning of the HIV epidemic. Since then, billions of US dollars have been invested in HIV research in the hope of gaining a better understanding of this infection and how to prevent and treat it. What are the landmarks in HIV research over the past two decades, and what questions still remain to be answered? What has the intense study of HIV infection taught us about other virus infections and how our immune system responds to them? In 1981, the attention of physicians in New York and San Francisco was caught by the bizarre phenomenon of young homosexual men dying from infections that a healthy immune system would normally repel with ease 1,2 ( FIG. 1 and TIMELINE ) Within a year, the term ‘acquired immunodeficiency syndrome’ (AIDS) was coined by the United States Centers for Disease Control and Prevention (CDC) to describe this combination of opportunistic infections and tumours occur- ring in the setting of a markedly reduced circu- lating CD4 + T-cell count. Initially, the disease seemed to be confined to a few high-risk groups of people, and speculation at that time implicated a diverse range of possible behavioural and environmental mechanisms.
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