AIDSAcquired immune deficiency syndrome, or AID
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or AID AIDSAcquired immune deficiency syndrome
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S, is a recently recognized disease entity. It is caused by infection with the human immunodeficiency virus (HIV), which attacks selected cells in the immune system (see IMMUNITY) and produces defects in function. These defects may not be apparent for years. They lead in a relentless fashion, however, to a severe suppression of the immune system's ability to resist harmful organisms. This leaves the body open to an invasion by various infections, which are therefore called opportunistic diseases, and to the development of unusual cancers. The virus also tends to reach certain brain cells. This leads to so-called neuropsychiatric abnormalities, or psychological disturbances caused by physical damage to nerve cells.Since the first AIDS cases were reported in 1981, through mid-1992, more than 190,000 AIDS cases and more than 152,000 deaths had been reported in the United States alone. This is only the tip of the iceberg of HIV infection, however. It is estimated that between 1 million and 1.5 million Americans had been infected with the virus by the early 1990s but had not yet developed clinical symptoms. In addition, although the vast majority of documented cases have occurred in the United States, AIDS cases have been reported in about 162 countries worldwide. Sub-Saharan Africa in particular appears to suffer a heavy burden of this illness.No cure or vaccine now exists for AIDS. Many of those infected with HIV may not even be aware that they carry and can spread the virus. It is evident that HIV infection represents an epidemic of serious proportions. Combating it is a major challenge to biomedical scientists and health-care providers. HIV infection and AIDS represent one of the most pressing public policy and public health problems worldwide.Definition of AIDSThe U. S. CENTERS FOR DISEASE Control has established criteria for defining cases of AIDS that are based on laboratory evidence, the presence of certain opportunistic diseases, and a range of other conditions. The opportunistic diseases are generally the most prominent and life-threatening clinical manifestations of AIDS. It is now recognized, however, that neuropsychiatric manifestations of HIV infection of the brain are also common. Other complications of HIV infection include fever, diarrhea, severe weight loss, and swollen lymph nodes (see LYMPHATIC SYSTEM).When HIV-infected persons experience some of the above symptoms but do not meet full criteria for AIDS, they are given the diagnosis of AIDS-related complex, or ARC. The growing feeling is that asymptomatic HIV infection and ARC should not be viewed as distinct entities but, rather, as stages of an irreversible progression toward AIDS.Historical BackgroundIn the late 1970s, certain rare types of cancer and a variety of serious infections were recognized to be occurring in increasing numbers of previously healthy persons. Strikingly, these were disorders that would hardly ever threaten persons with normally functioning immune systems. First formally described in 1981, the syndrome was observed predominantly to be affecting homosexual and bisexual men. Soon thereafter, intravenous drug users, hemophiliacs, and recipients of blood transfusions were recognized as being at increased risk for disease as well. It was also noted that sexual partners of persons displaying the syndrome could contract the disease.Further study of AIDS patients revealed marked depletion of certain white blood cells, called T4 lymphocytes. These cells play a crucial role in orchestrating the body's immune defenses against invading organisms. It was presumed that this defect in AIDS patients was acquired in a common manner. Then, in 1983, a T-cell lymphotropic virus was separately discovered by Robert Gallo at the U. S. National Institutes of Health and Luc Montagnier at France's Pasteur Institute. The virus was at first given various names: human lymphotropic virus (HTLV) III, lymphadenopathy-associated virus (LAV), and AIDS-associated retrovirus (ARV). It is now officially called human immunodeficiency virus (HIV), and considerable evidence demonstrates that it is indeed the causative agent for AIDS. A second strain that has been identified, HIV-2, is thus far relatively rare outside of Africa.Little is known about the biological and geographical origins of HIV. Apparently, however, this is the first time in modern history that the virus has spread widely among human beings. Related viruses have been observed in animal populations, such as certain African monkeys, but these do not produce disease in humans.The Nature of the VirusHIV is an RNA RETROVIRUS. Viewed in an electron microscope, it has a dense cylindrical core that encases two molecules of viral RNA genetic material. A spherical outer envelope surrounds the core.Like all retroviruses, HIV possesses a special enzyme, called reverse transcriptase, that is able to make a DNA copy of the viral DNA. This enables the virus to reverse the normal flow of genetic information (see GENETIC CO?E) and to incorporate its viral genes into the genetic material of its host. The virus may then remain in a latent form for a variable and often lengthy period of time until it is reactivated. Further knowledge of the mechanisms and triggers of the activation process is important to the efforts being made to Control HIV infection.A critical step in HIV infection is the binding of the virus to a host-cell receptor, enabling it to gain entrance into the cell. Studies have demonstrated that a molecule called CD4, expressed predominantly on the surface of the T4 cell, serves as this receptor. Although the T4 cell is a major HIV target, virtually any other cell also expressing the CD4 surface molecule is able to become infected with HIV. Thus cells of the monocyte and macrophage type are very important additional targets.Modes of TransmissionResearchers have isolated HIV from a number of body fluids, including blood, semen, saliva, tears, urine, cerebrospinal fluid, breast milk, and certain cervical and vaginal secretions. Strong evidence indicates, however, that HIV is transmitted only through three primary routes: sexual intercourse, whether vaginal or anal, with an infected individual; nondigestive exposure to infected blood or blood products; and from an infected mother to her child before or during birth.At least 97 percent of U.S. AIDS cases have been transmitted through one of these routes, with transmission between homosexual men accounting for about 60 percent of the cases. Heterosexual transmission in the United States accounts for only about 5 percent of cases but is a significant mode of transmission in Africa and Asia. About 21 percent of AIDS cases occur in intravenous drug abusers exposed to HIV-infected blood through shared needles. Current practices of screening blood donors and testing all donated blood and plasma for HIV antibodies have reduced the number of cumulative cases due to transfusion to about 1 percent.The number of new cases of AIDS in women of reproductive age is increasing at an alarming rate. AIDS has become the leading cause of death for women between the ages of 20 and 40 in the major cities of North and South America, Western Europe, and sub-Saharan Africa. In the United States, AIDS has hit hardest among black and Hispanic women. These women represent 17 percent of the female population but make up 73 percent of women with AIDS. AIDS is also having a devastating impact on infant mortality, since over 80 percent of HIV-infected children under the age of 13 acquired HIV from their infected mothers. Between 24 and 33 percent of children born to infected women will develop the disease.No scientific evidence supports transmission of AIDS through ordinary nonsexual conduct. Careful studies demonstrate that despite prolonged household contact with infected individuals, family members have not become infected--except through the routes described above. Health-care workers have been infected with HIV from exposure to contaminated blood or by accidentally sticking themselves with contaminated needles.Clinical SignsFollowing infection with HIV, an individual may show no symptoms at all, or may develop an acute but transient mononucleosis-like illness. The period between initial infection and the development of AIDS can vary greatly, apparently from about 6 months to 11 years. Various estimates indicate that somewhere between 26 to 46 percent of infected individuals will go on to develop full-blown AIDS within a little more than 7 years following infection. Once AIDS sets in, the clinical course generally follows a rapid decline; and most people with AIDS die within 3 years.Opportunistic Infections and CancersBecause the T4 cell is involved in almost all immune responses, its depletion renders the body highly susceptible to opportunistic infections and tumorous growths. The most predominant and threatening is Pneumocystic carinii pneumonia, which is frequently the first infection to occur and is the most common cause of death. Other infections include the parasites Toxoplasm? gondii (see TOXOPLASMOSIS) and Cryptosporidiosis; fungi such as Candida (see CANDIDIASIS) and Cryptococcus (see fungus diseases); mycobacteria such as Mycobacterium avium, intracellulare, and tuberculosis (see tuberculosis); and viruses such as cytomegalovirus and herpes simplex and zoster (see HERPES). Increased susceptibility to bacterial infection is noted particularly among children with AIDS.