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Acquired immune deficiency syndrome
(AIDS)
Definition
Acquired immune deficiency syndrome (AIDS) is an infectious disease caused by the human
immunodeficiency virus (HIV). There are two variants of the HIV virus, HIV-1 and HIV-2, both
of which ultimately cause AIDS.
Description
AIDS was first recognized in the United States 1981 in homosexual men. Today is seen in both
homosexual and heterosexual men and women. AIDS is the advanced form of infection with
HIV virus. This virus may not cause recognizable symptoms for a long period after the initial
exposure (latent period). As of early 2009, no vaccine was available to prevent HIV infection.
Until such a vaccine is developed, all forms of HIV/AIDS therapy are focused on improving the
quality and length of life for people who are infected by slowing or halting the replication of the
virus and treating or preventing infections and cancers that often develop in people with AIDS.
AIDS is one of the most devastating worldwide public health problems in recent history. The
United States Centers for Disease Control and Prevention (CDC) estimated that in 2006
944,000 people in the United States had been diagnosed with AIDS since the disease was
identified in 1981. In 2006, an additional 1-1.2 million Americans were diagnosed as infected
with HIV but not yet showing symptoms (HIV positive). However, in early 2009, the CDC
issued a statement that they now thought that earlier the HIV-positive estimates were too low,
as many more people than were originally estimated are living with unreported or undiagnosed
HIV infection.
According to the August 2008 report issued by the Joint United Nations Programme on
HIV/AIDS (UNAIDS), as of 2007, approximately 33 million people worldwide are HIV positive.
Over half of the 33 million are women and this statistic has remained stable for several years.
The highest number of cases is found in sub-Saharan Africa and Southeast Asia.
More than 70% of HIV infections are transmitted through sexual contact. Traditionally in the
United States, the majority of cases were found in homosexual or bisexual men. In 2007, about
half of new HIV cases were acquired by men having sex with other men. Fewer than 20% of
HIV-positive Americans were women. However, this is not the case worldwide, where
transmission by heterosexual individuals is common.
Risk factors
AIDS can be transmitted in several ways. The risk factors for HIV transmission vary according
to the method of transmission.

Sexual contact. People at greatest risk are those who do not practice safer sex by
always using a condom, those who have multiple sexual partners, those who
participate in anal intercourse, and those who have sex with a partner who has HIV
infection and/or other sexually transmitted diseases (STDs). In the United States and
Europe, most cases of sexually transmitted HIV infection result from homosexual
contact, whereas in Africa, the disease is spread primarily through sexual intercourse
among heterosexuals. Most people with AIDS in the United States are between 25 and
44 years of age.

Transmission in pregnancy. High-risk mothers include women sexually active with
bisexual men, 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 HIV transmission as HIV passes into breast milk. The rate of
pediatric HIV transmission in the United States had decreased substantially because
of HIV testing and improved drug treatment for infected mothers, so fewer than 1% of
AIDS cases now occur in children under age 15. In the developing world, mother to
infant transmission remains epidemic. In 2006, AIDS was the single most common
cause of death in children under age 5 in South Africa, while worldwide children
account for about 10% of all AIDS cases.

Exposure to contaminated blood. Risk of HIV transmission among intravenous drug
users increases with the frequency and duration of intravenous use, frequency of
needle sharing, number of people sharing a needle, and the rate of HIV infection in the
local population. In 2006, about 19% of men with AIDS and 25% of women with AIDS
contracted the disease through sharing needles during intravenous drug injection.
With the introduction of new blood product screening in the mid-1980s, HIV
transmission through blood transfusions became rare in the developed world.
However, contaminated blood is still a significant source of infection in the developing
world.

Needle sticks or body fluid splashes among health care professionals. Transmission
through theses sources accounts for fewer than 0.3% of all HIV infections in the
United States. This rate reflects the emphasis on universal safety precautions (e.g.,
use of gloves, face shields, proper disposal of needles) among health care
professionals and first responders.
HIV is not transmitted by handshakes or other casual non-sexual contact, coughing or
sneezing, or by bloodsucking insects such as mosquitoes.
Causes and symptoms
AIDS is a disease that can damage any of the body's major organ systems because HIV
destroys immune system cells. 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. After the virus has attached to the cell's CD4 receptor, the
virus-CD4 complex refolds to uncover another receptor called a chemokine receptor that helps
mediate entry of the virus into the cell. One chemokine receptor in particular, CCR5, has been
the focus of recent research after studies showed that defects in its structure (caused by
genetic mutations) result in a slowing or stopping of the progression of AIDS. 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 immune system cells. Because the immune system
cells are destroyed, a wide variety of infections and cancers can take advantage of a person's
weakened immune system (opportunistic infections/diseases).
The course of AIDS generally progresses through three stages, although not all patients will
follow this progression precisely:
Acute retroviral syndrome
Acute retroviral syndrome describes 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 HIV positive during this phase and may not seek medical
attention. The symptoms are similar to those of many other diseases and may include fever,
fatigue, muscle aches, loss of appetite, digestive disturbances, weight loss, skin rashes,
headache, and chronically swollen lymph nodes (lymphadenopathy). Some 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 HIV virus (viremia) and the appearance of the viral p24 antigen in the
blood.
Latency period
After the virus enters a person's lymph nodes during the acute retroviral syndrome stage, the
disease becomes latent for 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 latent 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 develop low-grade fevers, chronic fatigue, and general weakness. HIV also may
cause a combination of food malabsorption, loss of appetite, and increased metabolism that
contribute to AIDS wasting syndrome.
Other organ systems
At any time during the course of HIV infection, patients may develop 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.
Opportunistic infections
Once the patient's CD4+ lymphocyte count falls below 200 cells/mm 3, 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 mycobacterium avium
complex (MAC) infections. MAC infections are caused by Mycobacterium
avium-intracellulare and occur in about 40% of AIDS patients. This infection rarely
develops until the CD4+ counts falls below 50 cells/mm 3.

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 CDC.
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. Loss of
reasoning ability, loss of memory, inability to concentrate, apathy and loss of initiative, and
unsteadiness or weakness in walking mark AIDS dementia complex. 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 arthritis-like pains in the joints.
Oral symptoms
In addition to thrush and painful ulcers in the mouth, patients may develop a condition called
hairy leukoplakia. The CDC also regards this condition as an indicator of full-blown AIDS.
Hairy leukoplakia is a white area of diseased tissue on the tongue that may be flat or slightly
raised. It is associated with infection 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 people with dark skin) 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 virus-like 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.
While incidence of AIDS-defining cancers such as Kaposi's sarcoma and cervical cancer have
decreased since increase use of antiretroviral therapy, other cancers have increased in AIDS
patients. People with HIV have shown an increased incidence of lung cancer, head and neck
cancers, Hodgkin's lymphoma, melanoma, and anorectal cancer.
Diagnosis
Because HIV infection produces a wide range of symptoms, the CDC has compiled a list of
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.
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. During an
examination, the doctor will look for an overall pattern of symptoms rather than any one
definitive finding.
Laboratory tests for HIV infection
Blood tests (serology)
Diagnostic blood tests for AIDS are given to individuals in high-risk populations, pregnant
women, health care and public service workers who have been exposed to HIV, those who
have symptoms associated with AIDS, or others who fear they may have been exposed to the
virus. The first blood test for AIDS was developed in 1985. 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 bacteria other than HIV and AIDS.
Other laboratory tests
In addition to diagnostic blood tests, other blood tests 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,.
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.
Treatment
Drug treatment guidelines for HIV/AIDS change frequently as new drugs are approved and
new drug regimens developed. Two principles currently guide doctors in developing 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. Current
information on United States Food and Drug Administration-(FDA)approved drugs by class can
be found at the United States Department of Health and Human Services Aids Info Website at
<http://www.aidsinfo.nih.gov/DrugsNew/Default.aspx?MenuItem=Drugs>.
Individuals
interested in participating in a trial of new HIV/AIDS drugs under development can find a list of
clinical trials currently accepting volunteers at <http://www.clinicaltrial.gov>. There is not cost
to volunteers to participate and some medical care and testing is provided.
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. Drugs that may
be given include antibiotics such as trimethoprim-sulfamethoxazole (Bactrim) or pentamidine
(Pentam-300, Pentacarinat) and anti-fungals such as amphotericin B (AmBisome), flucytosine
(Ancobon), and clotrimazole (Lotrim AF, Mycelex, Femizole-7). All these drugs can have
undesirable side effects.
Anti-viral treatments
In recent years researchers have developed drugs that suppress HIV replication, as distinct
from treating its effects on the body. These drugs fall into several classes:

Nucleotide reverse transcriptase inhibitors (also called nucleoside analogues). These
drugs work by interfering with the action of HIV reverse transcriptase inside infected
cells, thus ending the virus's replication process. These drugs include zidovudine
(Retrovir), lamivudine (Epivir), and abacavir (Ziagen) and many others. They are often
used in used in multi-drug combinations.

Non-nucleoside reverse transcriptase inhibitors. This class of drugs binds to an
enzyme that is necessary for the HIV virus to reproduce. Examples of drugs in this
class are viramune, delavirdine (Rescriptor), and efavirenz (Sustiva) and others.

Protease inhibitors. Protease inhibitors work by disabling protease, an enzyme
necessary for HIV reproduction. Protease inhibitors include saquinavir (Invirase),
ritonavir (Norvire), indinavir (Crixivan), nelfinavir (Viracept), amprenavir (Agenerase),
kaletra, and many others.

Integrase inhibitors. Integrase inhibitors prevent the virus from inserting its own
genetic material into the DNA of the infected cell. This stops the virus from replicating.
Integrase was the only FDA-approved drug in this class as of early 2009. Several
investigational drugs in this category were in clinical trials at that time.

Fusion inhibitors and entry inhibitors. Fusion inhibitors block specific proteins on the
surface of the virus or the CD4+ cell. These proteins help the virus gain entry into the
cell. The only FDA-approved fusion inhibitor as of early 2009 was enfuvirtide (Fuzeon).
Entry inhibitors block HIV from entering cells. The only FDA-approved fusion inhibitor
as of early 2009 was maraviroc (Selzentry). Several drugs in this class are, as of 2009,
in pre-approval clinical trials.
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 also can
be used to help with side effects of the medications used in the treatment of AIDS.
Prognosis
As of early 2009, there was no cure for AIDS and no vaccine to prevent infection. 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 improved and prolonged the life of HIV/AIDS patients in the United States.
Researchers are actively working on producing preventative and therapeutic vaccines for HIV.
Preventative vaccines immunize an individual against a disease, so that he or she does not
become infected. A therapeutic vaccine, also called a treatment vaccine, does not keep
someone from getting a disease the way a preventative vaccine does. Instead, therapeutic
vaccines are used to boost the body's immune system in order to help control infection. The
potential exists to 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.
Prevention
As there is no cure for AIDS, prevention of HIV infection becomes extremely important in
controlling the disease. Efforts to prevent the spread of AIDS include:

Restricting sexual activity to a single partner and practicing safer sex (i.e., always
using a condom). Besides avoiding the risk of HIV infection, condoms are successful
in reducing other sexually transmitted diseases and unwanted pregnancies. Before
engaging in a sexual relationship with someone, getting tested for HIV infection is
recommended.

Avoiding needle sharing among intravenous drug users.

Donating one's own blood before planned major surgery to prevent risk of infection
from a blood transfusion, although blood supplies are extremely safe in the developed
world.

Practicing universal safety precautions when handling body fluids or needles.
Healthcare professionals, first responders, and teachers, for example, are now trained
in these precautions.

Testing for HIV infection by anyone how suspects infection. If treated aggressively and
early, the development of AIDS may be postponed. If HIV infection is confirmed, it is
also vital to let past sexual partners know so that they can be tested and receive
medical attention.
名词解释：
Key Terms
Acute retroviral syndrome
A group of symptoms resembling mononucleosis that often are the first sign of HIV
infection.
A condition in which the body's immune system produces antibodies in response to its
own tissues or blood components instead of foreign particles or microorganisms.
CCR5
A chemokine receptor; defects in its structure caused by genetic mutation cause the
progression of AIDS to be prevented or slowed.
CD4
A type of protein molecule in human blood, sometimes called the T4 antigen, that is
present on the surface of 65% of immune cells. The HIV virus infects cells with CD4
surface proteins, and as a result, depletes the number of immune system cells (T cells,
B cells, natural killer cells, monocytes) in the individual's blood. Most of the damage to
an AIDS patient's immune system is done by the virus' destruction of CD4+
lymphocytes.
Chemokine receptor
A receptor on the surface of some types of immune cells that helps to mediate entry of
HIV into the cell.
Hairy leukoplakia of the tongue
A white area of diseased tissue on the tongue that may be flat or slightly raised. It is
caused by the Epstein-Barr virus and is an important diagnostic sign of AIDS.
Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans. Two forms of HIV are now
recognized: HIV-1, which causes most cases of AIDS in Europe, North and South
America, and most parts of Africa; and HIV-2, which is chiefly found in West African
patients. HIV-2, discovered in 1986, appears to be less virulent than HIV-1 and may
also have a longer latency period.
Immunodeficient
A condition in which the body's immune response is damaged, weakened, or is not
functioning properly.
Kaposi's sarcoma
A cancer of the connective tissue that produces painless purplish red (in people with
light skin) or brown (in people with dark skin) blotches on the skin. It is a major
diagnostic marker of AIDS.
Latent period
Also called incubation period, the time between infection with a disease-causing agent
and the development of disease.
Lymphoma
A cancerous tumor in the lymphatic system that is associated with a poor prognosis in
AIDS patients.
(MAC) infection
A type of opportunistic infection that occurs in about 40% of AIDS patients and is
regarded as an AIDS-defining disease.
Non-nucleoside reverse transcriptase inhibitors
The newest class of antiretroviral drugs that work by inhibiting the reverse
transcriptase enzyme necessary for HIV replication.
Nucleoside analogues
The first group of effective anti-retroviral medications. They work by interfering with the
AIDS virus' synthesis of DNA.
Opportunistic infection
An infection by organisms that usually do not cause infection in people whose immune
systems are working normally.
pneumonia (PCP)
An opportunistic infection caused by a fungus that is a major cause of death in patients
with late-stage AIDS.
Progressive multifocal leukoencephalopathy (PML)
A disease caused by a virus that destroys white matter in localized areas of the brain.
It is regarded as an AIDS-defining illness.
Protease inhibitors
The second major category of drug used to treat AIDS that works by suppressing the
replication of the HIV virus.
Protozoan
A single-celled, usually microscopic organism that is eukaryotic and, therefore,
different from bacteria (prokaryotic).
Retrovirus
A virus that contains a unique enzyme called reverse transcriptase that allows it to
replicate within new host cells.
Thrush
A yeast infection of the mouth characterized by white patches on the inside of the
mouth and cheeks.
Wasting syndrome
A progressive loss of weight and muscle tissue caused by the AIDS virus.