AIDS

acronym of Acquired Immunodeficiency Syndrome, a fatal transmissable disorder of the immune system that is caused by the human immunodeficiency virus (HIV). In most cases HIV slowly attacks and destroys the immune system, the body's defense against disease, leaving the infected individual vulnerable to malignancies and infections that eventually cause death. AIDS is the last stage of HIV infection, during which time these diseases arise. The first cases of AIDS were identified in 1981 in Los Angeles, Calif. Initially most cases of AIDS in the United States were diagnosed in homosexual men, who contracted the virus primarily through sexual contact, and intravenous drug users, who became infected mainly by sharing contaminated hypodermic needles. The agent responsible for the disease, HIV, was isolated in 1983, and by 1985 serologic tests to detect the virus had been developed. HIV is contracted mainly through exposure to blood, semen and other genital secretions, and breast milk. Although it is a transmissable virus, it is not contagious and it cannot be spread through coughing, sneezing, or casual physical contact. The major mode of transmission worldwidethat which accounts for 70 percent of all HIV infectionsis heterosexual intercourse. Other sexually transmitted diseases such as candidiasis and herpes simplex virus increase the risk of contracting AIDS through sexual contact, probably through the genital lesions that they cause. The virus also can be spread from mother to child by transfer across the placenta or through breast milk. Many individuals, including a number of hemophiliacs, were infected from contaminated blood and blood products before screening procedures were introduced in the late 1980s. As of December 1996, there had been more than 8 million cases of AIDS worldwide, resulting in 6 million deaths. It was estimated that approximately 750,000 individuals in the United States and 23 million individuals throughout the world were infected with HIV. AIDS had become pandemic, with more than 90 percent of HIV infections occurring in developing countries. Sub-Saharan Africa accounted for more than 60 percent of all infections, and in some regions of the continent almost one-third of the inhabitants were infected. Another area of high incidence was South and Southeast Asia, where roughly 20 percent of global cases occurred. The course of HIV infection usually involves a number of stages. An average interval of 10 years exists between infection with HIV and development of the conditions typical of AIDS. Within the first few weeks of infection, persons often develop an acute mononucleosis-like illness that usually resolves within two to three weeks. During this time a variety of symptoms may occur; they include general malaise, nausea, joint and muscle soreness, fever, rash, sore throat, diarrhea, stiffness, swollen lymph glands (lymphadenopathy), dementia, and unexplained weight loss. After this stage the infected individual may remain without symptoms for years. As the immune system deteriorates, however, the infected individual becomes susceptible to a variety of diseases. These include opportunistic infections, i.e., infections caused by organisms that do not ordinarily cause disease because they are easily combated by a healthy immune system. The most common of these infections are cytomegalovirus, Pneumocystis carinii pneumonia, toxoplasmosis, candidiasis, herpes simplex virus, herpes zoster, tuberculosis, and atypical Mycobacterium. In addition, HIV-infected individuals have an unusually high incidence of certain cancers, such as Kaposi's sarcoma, tongue and rectal cancers, and non-Hodgkins B cell lymphoma. The development of one or more of these conditions usually marks the onset of AIDS. Pneumocystis carinii pneumonia and Kaposi's sarcoma are two of the most common diseases seen in AIDS patients. Many individuals suffering from AIDS develop a wasting syndrome and become emaciated. Death ultimately results from the relentless attack of opportunistic pathogens or from the body's inability to fight off malignancies. A small proportion of individuals infected with HIV have survived longer than 10 years without developing AIDS. Many of these survivors show no signs that the disease is progressing. It may be that such individuals mount a more vigorous immune response to the virus or that they are infected with a weakened strain of the virus. The main cellular target of HIV is a special class of white blood cells critical to the immune system and known as helper T lymphocytes, or T4 helper cells. These cells play a principal role in normal immune responses by stimulating or activating virtually all the other cells involved in immune protection. These include B lymphocytes, the cells that produce antibodies needed to fight infection; cytotoxic T lymphocytes, which destroy cells infected with virus; and macrophages and other effector cells, which attack invading pathogens. Once HIV has entered the helper T cell, it can cause the cell to function poorly or it can destroy the cell. A hallmark of the onset of AIDS is a drastic reduction in the number of helper T cells in the body. HIV also can infect other cells, including certain monocytes and macrophages, as well as brain cells. Like other viruses, HIV enters a cell in order to multiply. Viruses cannot replicate on their own and instead rely on mechanisms of the host cell to produce new viral particles. HIV is a retrovirus, a unique family of viruses that consist of genetic material in the form of RNA (instead of DNA) surrounded by a protein envelope. HIV infects helper T cells by means of a protein, called gp120, in its envelope. The gp120 protein binds to a molecule called CD4 on the surface of the helper T cell, an event that tricks the cell into letting the virus in. Once inside the T cell, HIV uses the cell's machinery to copy its RNA into DNA by means of the enzyme reverse transcriptase. The newly produced viral DNA is then inserted into the chromosomal DNA of the host cell. It was thought for some time that when HIV integrated into the host DNA it became dormant, a theory that accounted for the long lag time between infection and the development of AIDS. Although this is true of other viruses, it is not the case with HIV. Rather, during the latent period HIV multiplies, usually at breakneck speed. As the virus replicates, many mutations in the RNA arise, a situation that complicates the task of the immune system in combating the virus. Eventually, the large numbers of new virus particles produced are able to debilitate or destroy helper T cells more rapidly than those cells can be produced by the immune system. Physicians used to predict how long a patient infected with the virus would live by measuring the number of T cells in their blood, but they have found the amount of virus in the bloodstreami.e., the viral loadto be a more accurate measure. Two predominant strains of the virus, designated HIV-1 and HIV-2, are known. The genetic material of these two strains is approximately 60 percent identical. Worldwide the most common strain is HIV-1, with HIV-2 more common primarily in western Africa. The two strains act in a similar manner, but HIV-2 causes a form of AIDS that progresses much more slowly than that caused by HIV-1. Each strain contains a number of subtypes, which are slight genetic variations of the virus. This is a result of the high rate at which the genetic material of HIV mutates. Most variations occur in the gene encoding the gp120 protein, and these mutations can alter the protein's structure. By constantly changing the structure of its predominant surface protein, the virus can avoid recognition by the immune system. No vaccine or cure has yet been developed that can prevent HIV infection. Efforts at prevention have been focused primarily on changes in sexual behaviour such as abstinance, monogamy, the use of barrier contraceptives, and other safe sex methods. Attempts to reduce intravenous drug use and to discourage the sharing of hypodermic needles have also led to a reduction in infection rates in some areas. Therapy was initially limited to treatment of the individual opportunistic infections as they arose. However, several drugs, such as azidothymidine (AZT, or zidovudine), 3TC, and dideoxyinosine (ddI), are now used to slow the development of AIDS once an individual has become infected with HIV. These drugs target the reverse transcriptase enzyme, inhibiting its activity and thereby curbing reproduction of the virus. A new class of pharmaceuticals, called protease inhibitors, has been developed that shows promise in combating HIV. These compounds prevent the final processing of a number of important HIV proteins carried out by the enzyme HIV protease. Protease inhibitors, such as ritonavir and indinavir, have been shown to block the development of AIDS, at least temporarily. Protease inhibitors are most effective in stemming the progression of the disease when used in conjunction with two different reverse transcriptase inhibitorsthe so-called triple-drug therapy.