AIDS

Acquired immune deficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). It was first recognized in the United States in 1981. AIDS is the advanced form of infection with the HIV virus, which may not cause recognizable disease for a long period after the initial exposure (latency). No vaccine is currently available to prevent HIV infection. At present, all forms of AIDS therapy are focused on improving the quality and length of life for AIDS patients by slowing or halting the replication of the virus and treating or preventing infections and cancers that take advantage of a person's weakened immune system.

Description

AIDS is considered one of the most devastating public health problems in recent history. In June 2000, the Centers

Risk of acquiring HIV infection by entry site
	Entry site	Risk virus reaches entry site	Risk virus enters	Risk inoculated
	Conjuntiva	Moderate	Moderate Very low
	Oral mucosa	Moderate	Moderate	Low
	Nasal mucosa	Low	Low	Very low
	Lower respiratory	Very low	Very low	Very low
	Anus	Very high	Very high	Very high
	Skin, intact	Very low	Very low	Very low
	Skin, broken	Low	High	High
Sexual:
	Vagina	Low	High	High
	Penis	Low	Low	High
	Ulcers (STD)	Medium	Low	Very high
Blood:
	Products	High	High	Low
	Shared needles	High	High	High
	Accidental needle	High	Very High	Low
	Traumatic wound	Modest	High	High
	Perinatal	High	High	High

for Disease Control and Prevention (CDC) reported that 120,223 (includes only those cases in areas that have confidential HIV reporting) in the United States are HIV-positive, and 311,701 are living with AIDS (includes only those cases where vital status is known). Of these patients, 44% are gay or bisexual men, 20% are heterosexual intravenous drug users, and 17% are women. In addition, approximately 1,000-2,000 children are born each year with HIV infection. The World Health Organization (WHO) estimates that 33 million adults and 1.3 million children worldwide were living with HIV/AIDS as of 1999 with 5.4 million being newly infected that year. Most of these cases are in the developing countries of Asia and Africa.

Risk factors

AIDS can be transmitted in several ways. The risk factors for HIV transmission vary according to category:

• Sexual contact. Persons at greatest risk are those who do not practice safe sex, those who are not monogamous, those who participate in anal intercourse, and those who have sex with a partner with symptoms of advanced HIV infection and/or other sexually transmitted diseases (STDs). In the United States and Europe, most cases of sexually transmitted HIV infection have resulted from homosexual contact, whereas in Africa, the disease is spread primarily through sexual intercourse among heterosexuals.
• Transmission in pregnancy. High-risk mothers include women married to bisexual men or men who have an abnormal blood condition called hemophilia and require blood transfusions, intravenous drug users, and women living in neighborhoods with a high rate of HIV infection among heterosexuals. The chances of transmitting the disease to the child are higher in women in advanced stages of the disease. Breast feeding increases the risk of transmission by 10-20%. The use of zidovudine (AZT) during pregnancy, however, can decrease the risk of transmission to the baby.
• Exposure to contaminated blood or blood products. With the introduction of blood product screening in the mid-1980s, the incidence of HIV transmission in blood transfusions has dropped to one in every 100,000 transfused. With respect to HIV transmission among drug abusers, risk increases with the duration of using injections, the frequency of needle sharing, the number of persons who share a needle, and the number of AIDS cases in the local population.
• Needle sticks among health care professionals. Present studies indicate that the risk of HIV transmission by a needle stick is about one in 250. This rate can be decreased if the injured worker is given AZT, an anti-retroviral medication, in combination with other medication.

HIV is not transmitted by handshakes or other casual non-sexual contact, coughing or sneezing, or by blood-sucking insects such as mosquitoes.

AIDS in women

AIDS in women is a serious public health concern. Women exposed to HIV infection through heterosexual contact are the most rapidly growing risk group in the United States population. The percentage of AIDS cases diagnosed in women has risen from 7% in 1985 to 23% in 1999. Women diagnosed with AIDS may not live as long as men, although the reasons for this finding are unclear.

Mature HIV-1 viruses (above) and the lymphocyte from which they emerged (below). Two immature viruses can be seen budding on the surface of the lymphocyte (right of center). (Photograph by Scott Camazir, Photo Researchers, Inc. Reproduced by permission.)

AIDS in children

Since AIDS can be transmitted from an infected mother to the child during pregnancy, during the birth process, or through breast milk, all infants born to HIV-positive mothers are a high-risk group. As of 2000, it was estimated that 87% of HIV-positive women are of childbearing age; 41% of them are drug abusers. Between 15-30% of children born to HIV-positive women will be infected with the virus.

AIDS is one of the 10 leading causes of death in children between one and four years of age. The interval between exposure to HIV and the development of AIDS is shorter in children than in adults. Infants infected with HIV have a 20-30% chance of developing AIDS within a year and dying before age three. In the remainder, AIDS progresses more slowly; the average child patient survives to seven years of age. Some survive into early adolescence.

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.

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.

OPPORTUNISTIC INFECTIONS. 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.
• Protozoa. Toxoplasmosis is a common opportunistic infection in AIDS patients that is caused by a protozoan. Other diseases in this category include isoporiasis and cryptosporidiosis.
• Mycobacteria. 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/mm³.
• Bacteria. AIDS patients are likely to develop bacterial infections of the skin and digestive tract.
• Viruses. 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.

Because the immune system cells are destroyed by the AIDS virus, many different types of infections and cancers can develop, taking advantage of a person's weakened immune system. (Illustration by Electronic Illustrators Group.)

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.

MUSCULOSKELETAL COMPLICATIONS. Patients in late-stage AIDS may develop inflammations of the muscles, particularly in the hip area, and may have arthritislike pains in the joints.

ORAL SYMPTOMS. 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.

AIDS-RELATED CANCERS. 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.

Diagnosis

Because HIV infection produces such a wide range of symptoms, the CDC has drawn up a list of 34 conditions regarded as defining AIDS. The physician will use the CDC list to decide whether the patient falls into one of these three groups:

• definitive diagnoses with or without laboratory evidence of HIV infection
• definitive diagnoses with laboratory evidence of HIV infection
• presumptive diagnoses with laboratory evidence of HIV infection

Physical findings

Almost all the symptoms of AIDS can occur with other diseases. The general physical examination may range from normal findings to symptoms that are closely associated with AIDS. These symptoms are hairy leukoplakia of the tongue and Kaposi's sarcoma. When the doctor examines the patient, he or she will look for the overall pattern of symptoms rather than any one finding.

Laboratory tests for HIV infection

BLOOD TESTS (SEROLOGY). The first blood test for AIDS was developed in 1985. At present, patients who are being tested for HIV infection are usually given an enzyme-linked immunosorbent assay (ELISA) test for the presence of HIV antibody in their blood. Positive ELISA results are then tested with a Western blot or immunofluorescence (IFA) assay for confirmation. The combination of the ELISA and Western blot tests is more than 99.9% accurate in detecting HIV infection within four to eight weeks following exposure. The polymerase chain reaction (PCR) test can be used to detect the presence of viral nucleic acids in the very small number of HIV patients who have false-negative results on the ELISA and Western blot tests. These tests are also used to detect viruses and bacterium other than HIV and AIDS.

OTHER LABORATORY TESTS. In addition to diagnostic blood tests, there are other blood tests that are used to track the course of AIDS in patients that have already been diagnosed. These include blood counts, viral load tests, p24 antigen assays, and measurements of β₂-microglobulin (β₂M).

Doctors will use a wide variety of tests to diagnose the presence of opportunistic infections, cancers, or other disease conditions in AIDS patients. Tissue biopsies, samples of cerebrospinal fluid, and sophisticated imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography scans (CT) are used to diagnose AIDS-related cancers, some opportunistic infections, damage to the central nervous system, and wasting of the muscles. Urine and stool samples are used to diagnose infections caused by parasites. AIDS patients are also given blood tests for syphilis and other sexually transmitted diseases.

Diagnosis in children

Diagnostic blood testing in children older than 18 months is similar to adult testing, with ELISA screening confirmed by Western blot. Younger infants can be diagnosed by direct culture of the HIV virus, PCR testing, and p24 antigen testing.

In terms of symptoms, children are less likely than adults to have an early acute syndrome. They are, however, likely to have delayed growth, a history of frequent illness, recurrent ear infections, a low blood cell count, failure to gain weight, and unexplained fevers. Children with AIDS are more likely to develop bacterial infections, inflammation of the lungs, and AIDS-related brain disorders than are HIV-positive adults.

Treatment

Treatment for AIDS covers four considerations:

TREATMENT OF OPPORTUNISTIC INFECTIONS AND MALIGNANCIES. Most AIDS patients require complex long-term treatment with medications for infectious diseases. This treatment is often complicated by the development of resistance in the disease organisms. AIDS-related malignancies in the central nervous system are usually treated with radiation therapy. Cancers elsewhere in the body are treated with chemotherapy.

PROPHYLACTIC TREATMENT FOR OPPORTUNISTIC INFECTIONS. Prophylactic treatment is treatment that is given to prevent disease. AIDS patients with a history of Pneumocystis pneumonia; with CD4+ counts below 200 cells/mm³ or 14% of lymphocytes; weight loss; or thrush should be given prophylactic medications. The three drugs given are trimethoprim-sulfamethoxazole, dapsone, or pentamidine in aerosol form.

ANTI-RETROVIRAL TREATMENT. In recent years researchers have developed drugs that suppress HIV replication, as distinct from treating its effects on the body. These drugs fall into three classes:

• Nucleoside analogues. These drugs work by interfering with the action of HIV reverse transcriptase inside infected cells, thus ending the virus' replication process. These drugs include zidovudine (sometimes called azidothymidine or AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir (ABC).
• Protease inhibitors. Protease inhibitors can be effective against HIV strains that have developed resistance to nucleoside analogues, and are often used in combination with them. These compounds include saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, and lopinavir.
• Non-nucleoside reverse transcriptase inhibitors. This is a new class of antiretroviral agents. Three are available, nevirapine, which was approved first, delavirdine and efavirin.

Treatment guidelines for these agents are in constant change as new medications are developed and introduced. Two principles currently guide doctors in working out drug regimens for AIDS patients: using combinations of drugs rather than one medication alone; and basing treatment decisions on the results of the patient's viral load tests.

STIMULATION OF BLOOD CELL PRODUCTION. Because many patients with AIDS suffer from abnormally low levels of both red and white blood cells, they may be given medications to stimulate blood cell production. Epoetin alfa (erythropoietin) may be given to anemic patients. Patients with low white blood cell counts may be given filgrastim or sargramostim.

Treatment in women

Treatment of pregnant women with HIV is particularly important in that anti-retroviral therapy has been shown to reduce transmission to the infant by 65%.

Alternative treatment

Alternative treatments for AIDS can be grouped into two categories: those intended to help the immune system and those aimed at pain control. Treatments that may enhance the function of the immune system include Chinese herbal medicine and western herbal medicine, macrobiotic and other special diets, guided imagery and creative visualization, homeopathy, and vitamin therapy. Pain control therapies include hydrotherapy, reiki, acupuncture, meditation, chiropractic treatments, and therapeutic massage. Alternative therapies can also be used to help with side effects of the medications used in the treatment of AIDS.

Prognosis

At the present time, there is no cure for AIDS.

Treatment stresses aggressive combination drug therapy for those patients with access to the expensive medications and who tolerate them adequately. The use of these multi-drug therapies has significantly reduced the numbers of deaths, in this country, resulting from AIDS. The data is still inconclusive, but the potential exists to possibly prolong life indefinitely using these and other drug therapies to boost the immune system, keep the virus from replicating, and ward off opportunistic infections and malignancies.

Prognosis after the latency period depends on the patient's specific symptoms and the organ systems affected by the disease. Patients with AIDS-related lymphomas of the central nervous system die within two to three months of diagnosis; those with systemic lymphomas may survive for eight to ten months.

Prevention

As of 2001, there is no vaccine effective against AIDS. Several vaccines are currently being investigated, however, both to prevent initial HIV infection and as a therapeutic treatment to prevent HIV from progressing to full-blown AIDS.

In the meantime, there are many things that can be done to prevent the spread of AIDS:

• Be monogamous and practice safe sex. Individuals must be instructed in the proper use of condoms and urged to practice safe sex. Besides avoiding the risk of HIV infection, condoms are successful in preventing other sexually transmitted diseases and unwanted pregnancies. Before engaging in a sexual relationship with someone, get tested for HIV infection.
• Avoid needle sharing among intravenous drug users.
• Although blood and blood products are carefully monitored, those individuals who are planning to undergo major surgery may wish to donate blood ahead of time to prevent a risk of infection from a blood transfusion.
• Healthcare professionals must taken all necessary precautions by wearing gloves and masks when handling body fluids and preventing needle-stick injuries.
• If you suspect that you may have become infected, get tested for HIV infection. If treated aggressively early on, the development of AIDS may be postponed indefinitely. If HIV infection is confirmed, it is also vital to let your sexual partners know so that they can be tested and, if necessary, receive medical attention.