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AIDS The Disease
Sunday, February 1, 2009/ 12:36 AM
AIDS, the Disease
With time the immune system is overwhelmed, with the result that the replication of HIV escalates, opportunistic fungal, protozoal, bacterial, and viral infection occur, characteristic cancers appear, and neurological symptoms become apparent. The time to progression to AIDS following infection by HIV is variable but average about 10 years.
Symptoms occur much sooner in infants infected at birth, perhaps because the immune system is not as well developed. In adults infected by the virus, the time to appearance of the symptoms of AIDS is correlated with the level of viral replication during the latent period. In individual in which viral replication is high, the CD4+ T-cell count declines faster and the time to appearance of AIDS is shorter. The rate of virus replication is probably a function of the strength of the immune response against the virus, especially the CD8+ CTL response. Individuals with a better immune response control virus replication better and longer. Once the symptoms of AIDS appear, the time to death is usually 1-2 years unless antiviral treatment is administered.
CD4+ T cells, most of which function as T helper cells, are a critical part of the immune system. They are necessary for an immune response to an antigen, whether the response is to produce CD8+ CTLs or to produce circulating antibodies. AIDS results when so few CD4+ t cells are present that the body is unable to mount an effective immune response. The first symptoms usually occur when the CD4 T-cell concentration falls below 500/ul and may include reactivation of viruses such as Herpes Zoster, reactivation of bacteria such as Mycobacteria tuberculosis, oral lesions caused by fungi, or lymph node pathology. These first symptoms are sometimes referred to as AIDS-related complex or ARC. Full-blown AIDS is normally signalled by a drop in the CD4+ T-cell concentration below 200/ul. At this point the infected individual becomes susceptible to numerous opportunistic infections, including those of microorganisms such as Pneumocystis carinii, bacteria such as Mycobacterium, and fungi such as yeast.
Viruses that are normally controlled by the immune system become a problem, such as cytomegalovirus and Herpes Simplex virus. Several virus-induced cancers become common, such as lymphoma caused by Epstein-Barr virus, Kaposi’s sarcoma caused by human Herpesvirus-8, or anogenital carcinoma caused by Human Papilloma virus. Many of these opportunistic diseases, such as P. Carinii pneumonia or Kaposi’s sarcoma, are rarely seen in non-HIV-infected people. Others are regularly seen in the general population but HIV-infected individuals have a much higher incidence of the disease, 100-fold higher in the case of lymphoma, for example. Other symptoms of AIDS include a wasting syndrome and neurological abnormalities, described below. The symptoms of AIDS become progressively worse as the CD4+ count continues to drop until virtually no CD4+ cells are present. The decline in numbers of CD4+ cells is accelerated by the increased replication of HIV during this terminal phase, when the immune system can no longer control viral infection.
The lymph nodes are organs that trap invading pathogens and present them to immune cells. Large numbers of macrophages and CD4+ T cells are present in lymph nodes, and the nodes are sites of active HIV replication. During the progression of disease following HIV infection, the lymph nodes deteriorate. During the final stages of disease, the architecture of the nodes is completely destroyed and this loss of lymph node function contributions to the loss of immune function.
A wasting syndrome is characteristic of late-stage HIV infection. Bowel involvement results in diarrhea and malabsorption. The wasting syndrome is thought to be a symptom of HIV infection itself, but opportunistic infections of the gut probably the symptoms in many individuals.
Most HIV-infected individuals suffer, sooner or later, from neurological disease. Some disease is caused by opportunistic pathogens, such as progressive multifocal leukoencephalopathy caused by JC virus. However, two-thirds of infected individuals develop an encephalopathy induced by HIV infection itself that produces symptoms including dementia, motor and behavioural abnormalities, and seizures. These symptoms are referred to as AIDS dementia complex. HIV is present in the brains of infected individuals in macrophages and microglia, but does not infect neurons. The cause of the neuronal loss induced by HIV infection is unknown.
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