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Aids
Acquired Immune Deficiency Syndrome (AIDS), suppresses the immune
system related to infection with the human immunodeficiency virus (HIV). A person
infected with HIV gradually loses immune function along with certain immune cells
called CD4 T-lymphocytes or CD4 T-cells, causing the infected person to become
vulnerable to pneumonia, fungus infections, and other common ailments. With the loss
of immune function, a clinical syndrome (a group of various illnesses that together
characterize a disease) develops over time and eventually results in death due to
opportunistic infections (infections by organisms that do not normally cause disease
except in people whose immune systems have been greatly weakened) or cancers.
In the early 1980s deaths by opportunistic infections, previously observed
mainly in organ transplant recipients receiving therapy to suppress their immune
responses, were recognized in otherwise healthy homosexual men. In 1983, French
cancer specialist Luc Montagnier and scientists at the Pasteur Institute in Paris isolated
what appeared to be a new human retrovirus—a special type of virus that reproduces
differently from other viruses—from the lymph node of a man at risk for AIDS. Nearly
simultaneously, scientists working in the laboratory of
American research scientist Robert Gallo at the National Cancer Institute in Bethesda,
Maryland, and a group headed by American virologist Jay Levy at the University of
California at San Francisco isolated a retrovirus from people with AIDS and
individuals having contact with people with AIDS. All three groups of scientists
isolated what is now known as human immunodeficiency virus (HIV), the virus that
causes AIDS.
Infection with HIV does not necessarily mean that a person has AIDS, although
people who are HIV-positive are often mistakenly said to have AIDS. In fact, a person
can remain HIV-positive for more than ten years without developing any of the clinical
illnesses that define and constitute a diagnosis of AIDS. In 1996 an estimated 22.6
million people worldwide were living with HIV or AIDS—21.8 million adults and 830,000 children. The World Health Organization (WHO) estimates that between 1981, when the first AIDS cases were reported, and the end of 1996, more than 8.4 million adults and children had developed AIDS. In this same period there were 6.4 million deaths worldwide from AIDS or HIV. About 360,000 of these deaths occurred in the United States.
Clinical Progression of AIDS
The progression from the point of HIV infection to the clinical diseases that
define AIDS may take six to ten years or more. This progression can be monitored
using surrogate markers (laboratory data that correspond to the various stages of
disease progression) or clinical endpoints (illnesses associated with more advanced
disease). Surrogate markers for the various stages of HIV infection include the
declining number of CD4 T-cells, (the major type of white blood cell lost because of
HIV infection). In general, the lower the infected person’s CD4 T-cell count, the
weaker the person’s immune system and the more advanced the disease state. In 1996, it
became evident that the actual amount of HIV in a person’s blood—the so-called viral
burden—could be used to predict the progression to Aids, regardless of a person’s
CD4 T-cell count. With advancing technology, Viral Burden Determinations are
quickly becoming a standard means of patient testing. An infected person’s immune
response to the virus—that is, the person’s ability to produce antibodies against HIV—
can also be used to determine the progression ofAids; however, this surrogate marker is less precise during more advanced stages of
AIDS because of the overall loss of immune function.
Within one to three weeks after infection with HIV, most people experience
nonspecific flulike symptoms such as fever, headache, skin rash, tender lymph nodes,
and a vague feeling of discomfort. These symptoms last about one to two weeks.
During this phase, known as the acute retroviral syndrome phase, HIV reproduces to
very high concentrations in the blood, mutates (changes its genetic nature) frequently,
circulates through the blood, and establishes infections throughout the body, especially
in the lymphoid organs. The infected person’s CD4 T-cell count falls briefly but then
returns to near normal levels as the person’s immune system responds to the infection.
Individuals are thought to be highly infectious during this phase.
Following the acute retroviral syndrome phase, infected individuals enter a
prolonged asymptomatic phase—a symptom-free phase that can last ten years or more.
Persons with HIV remain in good health during this period, with levels of CD4 T-cells
ranging from low to normal (500 to 750 cells per cubic mm of blood). Nevertheless,
HIV continues to replicate during the asymptomatic phase, causing progressive
destruction of the immune system. Eventually, the immune system weakens to the point
that the person enters the early symptomatic phase. This phase can last from a few
months to several years and is characterized by rapidly falling levels of CD4 T-cells
(500 to 200 cells per cubic mm of blood) and opportunistic infections that are not life
threatening. Following the early symptomatic phase, the infected person experiences the
extensive immune destruction and serious illness that characterize the late symptomatic
phase. This phase can also last from a few months to years, and the affected individual
may have CD4 T-cell levels below 200 per cubic mm of blood along with certain
opportunistic infections that define AIDS. A wasting syndrome of progressive weight
loss and debilitating fatigue occurs in a large proportion of people in this stage. The
immune system is in a state of severe failure. The person eventually enters the
advanced AIDS phase, in which CD4 T-cell numbers are below 50 per cubic mm of
blood. Death due to severe life-threatening opportunistic infections and cancers usually
occurs within one to two years.
Opportunistic Illnesses
Death from AIDS is generally due not to HIV infection itself, but to
opportunistic infections that occur when the immune system can no longer protect the
body against agents normally found in the environment. The appearance of any one of
more than 25 different opportunistic infections, called AIDS-defining illnesses, along
with a CD4 T-cell count of less than 200 cells per cubic millimeter of blood provides
the clinical diagnosis of AIDS in HIV-infected individuals.
The most common opportunistic infection seen in AIDS is Pneumocystis Carinii
Pneumonia (PCP), which is caused by a fungus that normally exists in the airways of all
people. Bacterial Pneumonia and Tuberculosis are also commonly associated with
AIDS. In the late symptomatic phase of AIDS, bacterial infection by Mycobacterium
avium can cause fever, weight loss, anemia, and diarrhea. Additional bacterial
infections of the gastrointestinal tract commonly cause diarrhea, weight loss, anorexia
(loss of appetite), and fever. Also, during advanced AIDS, diseases caused by protozoal
parasites, especially Toxoplasmosis of the nervous system, are common.
In addition to PCP, people with AIDS often develop other fungal infections.
Thrush, an infection of the mouth by the fungus Candida Albicans, is common in the
early symptomatic phase of AIDS. Other infectious fungi include species of the genus
Cryptococcus, a major cause of Meningitis in up to 13 percent of people with AIDS.
Also, infection by the fungus Histoplasma Capsulatum affects up to 10 percent of
people with AIDS, causing general weight loss, fever, and respiratory complications or
severe central nervous system complications if the infection reaches the brain.
Viral opportunistic infections, especially with members of the Herpes virus
family, are common in people with AIDS. One Herpes family member, Cytomegalovirus
(CMV), infects the retina of the eye and can result in blindness. Another herpes virus,
Epstein-Barr virus (EBV), may result in a cancerous transformation of blood cells.
Infections with Herpes Simplex Virus types 1 and 2 are also common and result
in progressive sores around the mouth and anus.
Many people with AIDS develop cancers, the most common types being B-cell
Lymphoma and Kaposi’s Sarcoma. Kaposi’s Sarcoma—a cancer of blood vessels
that results in purple lesions on the skin that can spread to internal organs and cause
death—occurs mainly in homosexual and bisexual men. Although the cause of KS is
unknown, a link between KS and a new type of herpes virus was discovered in 1994.
Human Immunodeficiency Virus (HIV)
The causative agent of AIDS is HIV, a human retrovirus. Researchers have
known since 1984 that HIV enters human cells by binding with a receptor protein known
as CD4, located on human immune-cell surfaces. HIV carries on its surface a viral
protein known as cp120, which specifically recognizes and binds to the CD4 protein
molecules on the outer surface of human immune cells. However, in 1984 researchers
found that CD4 by itself was not sufficient for HIV infection to take place. Some other
unknown factor, found only in human cells, was also required. After much research, in
1996 scientists discovered that HIV must also bind to Chemokine Receptors, small
proteins also found on the surface of human immune cells, to enter the cells. The first
Chemokine Receptor linked to HIV entry was CXCR4 (originally called fusin), which
is bound by HIV strains that dominate during the latter stages of the disease.
Researchers then determined that another Chemokine Receptor, CCR5, bound HIV
strains that dominate in the early stages of the disease. Researchers are continuously
discovering more chemokine receptors.
Any human cell that has the correct binding molecules on its surface is a
potential target for HIV infection. However, it is the specific class of human white
blood cells called CD4 T-cells that are most affected by HIV because these cells have
high concentrations of the CD4 molecule on their outer surfaces. HIV replication in
CD4 T-cells can kill the cells directly; however, the cells also may be killed or rendered
dysfunctional by indirect means without ever having been infected with HIV. CD4 T-
cells are critical in the normal immune system because they help other types of immune
cells respond to invading organisms. As CD4 T-cells are specifically killed during HIV
infection, no help is available for immune responses. General immune system failure
results, permitting the opportunistic infections and cancers that characterize clinical
AIDS.
Although it is generally agreed that HIV is the virus that causes AIDS and that
HIV replication can directly kill CD4 T-cells, the large variation among individuals in
the amount of time between infection with HIV and a diagnosis of AIDS has led to
speculation that other co-factors—that is, factors acting along with HIV—may influence
the course of disease. The exact nature of these cofactors is uncertain—it is believed
that they may include genetic, immunologic, and environmental factors or other
diseases. However, it is clear that HIV must be present for the development of AIDS.
Modes of Transmission
HIV is spread through the exchange of body fluids, primarily semen, blood, and blood products. It is most commonly spread by sexual contact with an infected person.
The virus is present in the sexual secretions of infected men and women and gains
access to the bloodstream of the uninfected person by way of small abrasions that may
occur as a consequence of sexual intercourse.
HIV is also spread by any sharing of needles or syringes that results in direct exposure
to the blood of an infected individual. This method of exposure occurs most commonly
among people abusing intravenous (IV) drugs (drugs injected into the veins).HIV
transmission through blood transfusions or use of blood-clotting factors is now extremely
rare because of extensive screening of the blood supply; it is estimated that undetected
HIV is present in fewer than 1 in 450,000 to 600,000 units of blood.
HIV can be transmitted from an infected mother to her baby, either before or
during childbirth, or through breast-feeding. Although only about 25 to 35 percent of
babies born to HIV-infected mothers worldwide actually become infected, this mode of
transmission accounts for 90 percent of all cases of AIDS in children. In addition, even
uninfected children born to HIV-infected mothers have an incidence of heart problems
12 times that of children in the general population.
In the health care setting, workers have been infected with HIV after being
stuck with needles containing HIV-infected blood or, less frequently, after infected
blood contacts the worker’s open cut or splashes into a mucous membrane (for
example, the eyes or the inside of the nose). There has been only one demonstrated
instance of patients being infected by a health-care worker; this involved HIV
transmission from an infected dentist to six patients. In general, infected health-care
workers pose no risk to their patients. There is also no risk of contracting HIV infection
while donating blood.
The routes of HIV transmission are well known, but unfounded fear continues
concerning the potential for transmission by other means, such as casual contact in a
household, school, workplace, or food-service setting. No scientific evidence to support
any of these fears has been found. HIV does not survive well when exposed to the
environment. Drying of HIV-infected human blood or other body fluids reduces the
theoretical risk of environmental transmission to essentially zero. Additionally, HIV is
unable to reproduce outside its living host; therefore, it does not spread or maintain
infectiousness outside its host. No cases of HIV transmission through the air, by casual
contact, or even by kissing an infected individual have been documented. Researchers
have recently identified a protein in saliva, known as secretory leukocyte protease
inhibitor (SLPI), that prevents HIV from infecting white blood cells. However,
practices that increase the likelihood of contact with the blood of an infected individual,
such as open-mouth kissing or sharing toothbrushes or razors, should be avoided. There
is also no known risk of HIV transmission to coworkers, clients, or consumers from
contact in food-service establishments.
Studies have shown no evidence of HIV transmission through insects—even in
areas where there are many cases of AIDS and large popu
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