Causes and Symptoms
Because HIV destroys immune system cells, AIDS is a disease that can affect any of the body’s major organ systems. HIV attacks the body through three disease processes: immunodeficiency, autoimmunity, and nervous system dysfunction.
Immunodeficiency describes the condition in which the body’s immune response is damaged, weakened, or is not functioning properly. In AIDS, immunodeficiency results from the way that the virus binds to a protein called CD4, which is primarily found on the surface of certain subtypes of white blood cells called helper T cells or CD4 cells. After the virus has attached to the CD4 receptor, the virus-CD4 complex refolds to uncover another receptor called a chemokine receptor that helps to mediate entry of the virus into the cell. One chemokine receptor in particular, CCR5, has gotten recent attention after studies showed that defects in its structure (caused by genetic mutations) cause the progression of AIDS to be prevented or slowed. Scientists hope that this discovery will lead to the development of drugs that trigger an artificial mutation of the CCR5 gene or target the CCR5 receptor.
Once HIV has entered the cell, it can replicate intracellularly and kill the cell in ways that are still not completely understood. In addition to killing some lymphocytes directly, the AIDS virus disrupts the functioning of the remaining CD4 cells. Because the immune system cells are destroyed, many different types of infections and cancers that take advantage of a person’s weakened immune system (opportunistic) can develop.
Autoimmunity is a condition in which the body’s immune system produces antibodies that work against its own cells. Antibodies are specific proteins produced in response to exposure to a specific, usually foreign, protein or particle called an antigen. In this case, the body produces antibodies that bind to blood platelets that are necessary for proper blood clotting and tissue repair. Once bound, the antibodies mark the platelets for removal from the body, and they are filtered out by the spleen. Some AIDS patients develop a disorder, called immune-related thrombocytopenia purpura (ITP), in which the number of blood platelets drops to abnormally low levels.
As of 2000, researchers do not know precisely how HIV attacks the nervous system since the virus can cause damage without infecting nerve cells directly. One theory is that, once infected with HIV, one type of immune system cell, called a macrophage, begins to release a toxin that harms the nervous system.
The course of AIDS generally progresses through three stages, although not all patients will follow this progression precisely:
- Acute retroviral syndrome
Acute retroviral syndrome is a term used to describe a group of symptoms that can resemble mononucleosis and that may be the first sign of HIV infection in 50-70% of all patients and 45-90% of women. Most patients are not recognized as infected during this phase and may not seek medical attention. The symptoms may include fever, fatigue, muscle aches, loss of appetite, digestive disturbances, weight loss, skin rashes, headache, and chronically swollen lymph nodes (lymphadenopathy).
Approximately 25-33% of patients will experience a form of meningitis during this phase in which the membranes that cover the brain and spinal cord become inflamed. Acute retroviral syndrome develops between one and six weeks after infection and lasts for two to three weeks. Blood tests during this period will indicate the presence of virus (viremia) and the appearance of the
viral p24 antigen in the blood.
- Latency period
After the HIV virus enters a patient’s lymph nodes during the acute retroviral syndrome stage, the disease becomes latent for as many as 10 years or more before symptoms of advanced disease develop. During latency, the virus continues to replicate in the lymph nodes, where it may cause one or more of the following conditions:
- PERSISTENT GENERALIZED LYMPHADENOPATHY (PGL).
Persistent generalized lymphadenopathy, or PGL, is a condition in which HIV continues to produce chronic painless swellings in the lymph nodes during the latency period. The lymph nodes that are most frequently affected by PGL are those in the areas of the neck, jaw, groin, and armpits. PGL affects between 50-70% of patients during latency.
- CONSTITUTIONAL SYMPTOMS.
Many patients will develop low-grade fevers, chronic fatigue, and general weakness. HIV may also cause a combination of food malabsorption, loss of appetite, and increased metabolism that contribute to the so-called AIDS wasting or wasting syndrome.
- OTHER ORGAN SYSTEMS.
At any time during the course of HIV infection, patients may suffer from a yeast infection in the mouth called thrush, open sores or ulcers, or other infections of the mouth; diarrhea and other gastrointestinal symptoms that cause malnutrition and weight loss; diseases of the lungs and kidneys; and degeneration of the nerve fibers in the arms and legs. HIV infection of the nervous system leads to general loss of strength, loss of reflexes, and feelings of numbness or burning sensations in the feet or lower legs.
- PERSISTENT GENERALIZED LYMPHADENOPATHY (PGL).
- Late-stage disease (AIDS)
AIDS is usually marked by a very low number of CD4+ lymphocytes, followed by a rise in the frequency of opportunistic infections and cancers. Doctors monitor the number and proportion of CD4+ lymphocytes in the patient’s blood in order to assess the progression of the disease and the effectiveness of different medications. About 10% of infected individuals never progress to this overt stage of the disease and are referred to as nonprogressors.
Once the patient’s CD4+ lymphocyte count falls below 200 cells/mm3, he or she is at risk for a variety of opportunistic infections. The infectious organisms may include the following:
Fungi. The most common fungal disease associated with AIDS is Pneumocystis carinii pneumonia (PCP). PCP is the immediate cause of death in 15-20% of AIDS patients. It is an important measure of a patient’s prognosis. Other fungal infections include a yeast infection of the mouth (candidiasis or thrush) and cryptococcal meningitis.
Toxoplasmosis is a common opportunistic infection in AIDS patients that is caused by a protozoan. Other diseases in this category include isoporiasis and cryptosporidiosis.
AIDS patients may develop tuberculosis or MAC infections. MAC infections are caused by Mycobacterium avium-intracellulare, and occur in about 40% of AIDS patients. It is rare until CD4+ counts falls below 50 cells/mm^3.
AIDS patients are likely to develop bacterial infections of the skin and digestive tract.
AIDS patients are highly vulnerable to cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), and Epstein-Barr virus (EBV) infections. Another virus, JC virus, causes progressive destruction of brain tissue in the brain stem, cerebrum, and cerebellum (multifocal leukoencephalopathy or PML), which is regarded as an AIDS-defining illness by the Centers for Disease Control and Prevention.
AIDS DEMENTIA COMPLEX AND NEUROLOGIC COMPLICATIONS.
AIDS dementia complex is usually a late complication of the disease. It is unclear whether it is caused by the direct effects of the virus on the brain or by intermediate causes. AIDS dementia complex is marked by loss of reasoning ability, loss of memory, inability to concentrate, apathy and loss of initiative, and unsteadiness or weakness in walking. Some patients also develop seizures. There are no specific treatments for AIDS dementia complex.
Patients in late-stage AIDS may develop inflammations of the muscles, particularly in the hip area, and may have arthritislike pains in the joints.
In addition to thrush and painful ulcers in the mouth, patients may develop a condition called hairy leukoplakia of the tongue. This condition is also regarded by the CDC as an indicator of AIDS. Hairy leukoplakia is a white area of diseased tissue on the
tongue that may be flat or slightly raised. It is caused by the Epstein-Barr virus.
Patients with late-stage AIDS may develop Kaposi’s sarcoma (KS), a skin tumor that primarily affects homosexual men. KS is the most common AIDS-related malignancy. It is characterized by reddish-purple blotches or patches (brownish in african-Americans) on the skin or in the mouth. About 40% of patients with KS develop symptoms in the digestive tract or lungs. KS may be caused by a herpes viruslike sexually transmitted disease agent rather than HIV.
The second most common form of cancer in AIDS patients is a tumor of the lymphatic system (lymphoma). AIDS-related lymphomas often affect the central nervous system and develop very aggressively.
Invasive cancer of the cervix (related to certain types of human papilloma virus [HPV]) is an important diagnostic marker of AIDS in women.
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No Hiv, No Aids on January 26th 2007