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A New Disease

In the summer of 1981, clinicians in New York and California observed among young, previously healthy, homosexual men an unusual clustering of cases of rare diseases, notably Kaposi sarcoma and opportunistic infections such as Pneumocystis carinii pneumonia, as well as cases of unexplained, persistent lymphadenopathy.[2,3] It soon became evident that these individuals had a common immunological deficit in cell-mediated immunity, resulting predominantly from a significant diminution of circulating CD4+ T cells.[11,12] Early suggestions that AIDS resulted from behavior specific to gay men were largely dismissed when the syndrome was observed in distinctly different groups in the United States.

After several false leads, many investigators concluded that the clustering of AIDS cases and their occurrence in diverse risk groups could be explained only if AIDS were caused by an infectious microorganism transmitted by intimate contact, for example through sexual activity or blood.[13] As with many emerging infectious diseases, the initial and most powerful tool to illuminate the etiology of the disease was classic epidemiology. Initial observations regarding the immunopathogenesis of AIDS, together with a growing understanding of human and animal retroviruses, suggested that the disease might have a retroviral etiology.[9,10] Two retroviruses, human T-lymphotrophic virus (HTLV)-I and HTLV-II, which had been recently recognized at that time, were the only viruses known to preferentially infect CD4+ T cells. The transmission pattern of HTLV was similar to that seen among individuals with AIDS; in addition, HTLV-I and related retroviruses were known to cause varying degrees of immune deficiency in humans and animals.[14] Thus, the search for a new retrovirus was undertaken in earnest.

In 1983, experimental data indicating an association between a retrovirus and AIDS were published by a research team in France led by Luc Montagnier.[15] In 1984, the French group and researchers at the US National Institutes of Health, led by Robert C. Gallo, published seminal papers that established, with virological and epidemiological evidence, that the virus now known as HIV was the cause of AIDS.[9,10] The virus was also isolated independently by Jay Levy in California from both individuals affected with AIDS and asymptomatic individuals from groups at high risk for AIDS.[16]

As is very often the case in science, the identification of HIV drew heavily on many previous advances, in particular the discovery in the 1970s of the reverse transcriptase enzyme used in the replication cycle of retroviruses[17] and the cytokine interleukin-2, which is required for the robust growth of cultured T cells essential to the propagation of large quantities of HIV in the laboratory.[18]

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