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Section 3. General Information on AIDS

Q3.1	Testing Information (please contribute)
Q3.2	AIDS and Opportunistic Infections.
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Question 3.1. Testing Information (please contribute)

All blood products in the U.S. are screened by ELISA assays for several
infectious agents, including: HIV 1/2, HTLV I/II, HBV, HCV, Syphillis,
Hepatitis B core, and a liver enzyme ALT, indicative of hepatic
infections. Some blood donations are also tested for CMV, a more common
virus that has devestating effects in immunocompromised individuals,
such as cancer patients and transplant recipients. 

In addition to these laboratories, all donors are screened through
questionaires that meet or exceed FDA requirements. 

What if a blood-bank finds out you are HIV positive? 

The Red Cross and other blood banks routinely test blood donations for
HIV antibodies.

The Red Cross has specifically asked that people not use blood donation
as a way of finding out if they are HIV+. If you think you might be
infected, go get a blood test. Many cities offer free anonymous HIV
testing. Contact your local public health service office for details. 

This is particularly important if you think you might have been
infected within the last six months, since there's the risk that you
are indeed infected, but do not yet have antibodies to HIV. 

Blood donation is a fine thing to do--but how will you feel if you
donate, then a month later you find out through some other means that
you're HIV+? We're supposed to be making a gift of life, not death. 

The following article discusses how blood banks use the information, if
you have tested positive for HIV antibodies. In addition to your
possible role in killing another person, donating blood to obtain a
free HIV test also risks your anonymity.

From: McCullough J. The nation's changing blood supply system. JAMA.
1993 May;269(17):2239-45.

"The coded identity of potential or actual blood donors who are found
to be unsuitable on the basis of medical history or laboratory testing
is entered into a donor referral registry (DDR). Before each donated
unit of blood is made available for use, the coded identity of the
donor is checked against the DDR to ensure that the donor has not been
found to be unsuitable during a previous donation. Although potentially
infectious donors are so informed and asked not to give blood in the
future, this DDR check is thought to improve the safety of the blood
supply by serving as an additional way of identifying potentially
infectious blood should these donors return. The American Red Cross
operates a single DDR with information from all of its 47 reginal
centers. However, other blood banks' DDRs act only locally since there
is no requirement that different blood banks in the same or neighboring
communities exchange this DDR information. The operation of these DDRs
costs money, consumes experts' time, and has the potential for many
abuses such as failure to obtain informed consent and breeches of
confidentiality. The value of a DDR in improving the safety of the
blood supply has not been established. An analysis of the value of thse
DDRs should be conducted, and based on the results, DDRs should be
either eliminated or refined into an appropriate system."

See also: Grossman BJ. Springer KM. Blood donor deferral registries:
highlights of a conference. Transfusion. 1992;32:868-72. 
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Question 3.2. AIDS and Opportunistic Infections. 

AIDS and Opportunistic Infections

NIAID BACKGROUNDER: Office of Communications, National Institute of
Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, Maryland 20892 - September 1993

Opportunistic infections (OIs) cause most of the illnesses and deaths
among people infected with HIV, the virus that causes AIDS. The
National Institute of Allergy and Infectious Diseases (NIAID) leads the
way in U.S. research on these life-threatening infections. As part of
the NIAID effort, investigators are defining the optimal therapies,
alone and in combination, to prevent and treat OIs. They seek ways to
identify infections earlier and recognize resistance to therapies more
quickly. 

What are OIs?

The immune systems of most people with HIV gradually deteriorate,
leaving them vulnerable to numerous viruses, fungi, bacteria and
protozoa that are held in check in people with healthy immune systems.
These microbes can become active in HIV-infected individuals, causing
frequent and severe disease.

NIAID uses a two-pronged approach to the prevention and treatment of
OIs: basic laboratory research to learn how these microbes cause
disease and clinical research to develop and evaluate promising
therapies. 

Prevention and treatment of one such disease, Pneumocystis carinii
pneumonia or PCP, has been a major thrust of the NIAID program. Other
NIAID investigations include cytomegalovirus (CMV) infection,
Mycobacterium avium complex (MAC) and tuberculosis (TB). Institute
research focuses on these infections because, although they occur
repeatedly among HIV-infected people, they are rare in the general
population and few drugs are available now to prevent and treat them. 

PCP: The Most Common OI

PCP remains the most common, life-threatening opportunistic infection
in people with HIV, occurring in up to 80 percent of individuals who do
not take preventive therapy.

The PCP organism, a microscopic parasite, appears to infect most people
during childhood. In people with healthy immune systems, the parasite
normally remains dormant, but it may cause disease in those with
damaged immune systems.

PCP infection is characterized by a dry cough and shortness of breath.
Individuals may experience other, less specific symptoms such as fever,
fatigue and weight loss for weeks or even months before respiratory
problems appear. As PCP infection progresses, the functioning lung
tissue becomes clogged, which decreases the transport of oxygen from
the inhaled air into the blood. At this point, the oxygen in the blood
may be lowered to dangerous or even fatal levels.

Without treatment, close to 100 percent of HIV-infected patients with
PCP die. During the 1980s, the development of effective therapies led
to better management of PCP. Drugs for preventing and treating PCP
include aerosolized pentamidine and oral trimethoprim-sulfamethoxazole
(TMP/SMX), but both can result in serious side effects that prevent
some patients from taking the drugs.

TMP/SMX is recommended more often than aerosolized pentamidine for
treating and preventing PCP because the combination is effective,
tolerated by about half of the patients who take it and may work
against other disease-causing organisms as well. In 1992, an
NIAID-supported trial proved that TMP/SMX is better than aerosolized
pentamidine at preventing a second episode of PCP in people with AIDS
who can tolerate either therapy.

Although definitive research data are lacking, other agents may be
considered in situations in which neither TMP/SMX nor aerosolized
pentamidine can be given. The drug atovaquone is approved for patients
with mild to moderate PCP who cannot tolerate TMP/SMX. One NIAID study
showed that primaquine, an antimalaria drug, with clindamycin is an
effective oral therapy for PCP. TMP with dapsone is an alternative
treatment.

The search for new, more effective, less toxic drugs and combinations
of drugs to fight PCP continues. NIAID studies play an important role
in this effort. One trial compares three drug regimens--TMP/dapsone,
primaquine/clindamycin and TMP/SMX--for oral treatment of mild to
moderate PCP. Another protocol looks at an 8-aminoquinoline, an
antimalaria drug, while a third trial considers two regimens of TMP/SMX
to prevent PCP. 

CMV: A Herpesvirus

Infection with CMV, a virus in the herpes family, may occur throughout
life. By age 50, about half of the general population has been exposed
to this virus, yet most people do not become ill. After the original
infection, the virus may lie dormant and reactivate itself if the
immune system becomes suppressed.

For people with HIV infection, CMV is one of the most frequent and
serious OIs they face. CMV retinitis, an inflammation of the
light-sensitive inner layer of the eye, is the most common CMV
infection and leads to blindness if left untreated. Infections also may
occur in the gastrointestinal tract, lungs, brain, heart and other
organs. 

Both intravenous ganciclovir and foscarnet are approved to treat CMV
retinitis. Lifelong maintenance on either treatment is required because
the drugs do not kill CMV, they merely slow down its ability to grow.
Even with therapy, the rate of relapse is high. 

NIAID studies of CMV and other herpesviruses have shown that
intravenous foscarnet and ganciclovir are equally effective for CMV
retinitis, although foscarnet was associated with increased survival
for patients in the study. An ongoing trial is testing an oral form of
ganciclovir to prevent CMV disease. The oral form of the drug would be
much easier and safer for patients to take.

MAC: A Bacterial OI

Infection with MAC is diagnosed in up to 40 percent of people with AIDS
in the United States, making it the most common bacterial OI. Usually,
it affects people in advanced stages of HIV disease when the immune
system is severely suppressed.

The MAC organism is found widely in the environment and is thought to
be acquired most commonly through the mouth or gastrointestinal tract.
It can spread to the lungs, liver, spleen, lymph nodes, bone marrow,
intestines and blood. MAC causes chronic debilitating symptoms--fever,
night sweats, weight loss, fatigue, chronic diarrhea, abdominal pain,
liver dysfunction and severe anemia.

Rifabutin is the first drug to be approved for preventing MAC disease
in people with advanced HIV infection. The Food and Drug administration
based this approval on clinical studies showing that patients who
received rifabutin were one-third to one-half as likely to develop MAC
as were patients who received placebo.

To prevent MAC disease, a U.S. Public Health Service Task Force on
Prophylaxis and Therapy for MAC suggests that patients with HIV
infection and fewer than 100 CD4 + T cells receive oral rifabutin for
the rest of their lives unless disease develops. In the latter case,
multiple drug treatment is needed. CD4+ T cells are immune system cells
targeted and killed by HIV. No other drug regimen is recommended
currently to prevent MAC. Azithromycin and clarithromycin are promising
agents for prophylaxis, but studies of these agents have not been
completed. 

Increasing evidence suggests that treatment can benefit patients with
disseminated MAC, especially multiple-drug regimens including either
clarithromycin or azithromycin. Therefore, the PHS task force suggests
that all regimens, outside of a clinical trial, should consist of at
least two drugs, including clarithromycin or azithromycin plus one
other agent such as clofazimine, rifabutin, rifampin, ciprofloxacin
and, in certain situations, amikacin. They recommend continued therapy
for the patient's lifetime, as long as clinical benefit and reduction
of mycobacteria are observed.

NIAID has several studies under way looking at the roles of
clarithromycin and azithromycin, and other drugs such as sparfloxacin,
alone and in combination, to prevent and treat this serious disease. 

TB: An Airborne Disease

TB, a chronic bacterial infection, causes more deaths worldwide than
any other infectious disease. About one-third of the world's population
harbors the predominant TB organism, Mycobacterium tuberculosis, and is
at risk for developing the disease.	The World Health Organization (WHO)
estimates that 4.4 million people worldwide are coinfected with TB and
HIV. WHO predicts that by the year 2000, TB will take one million lives
annually among the HIV-infected.

Because of their weakened immune systems, people with HIV are
vulnerable to reactivation of latent TB infections, as well as to new
TB infections. Transmission of this disease occurs most commonly in
crowded environments such as hospitals, prisons and shelters--where
HIV-infected individuals make up a growing proportion of the
population. 

Active TB may occur early in the course of HIV infection, often months
or years before other OIs. TB most often affects the lungs, but it also
can cause disease in other parts of the body, particularly in people
with advanced HIV disease.

Of particular concern for people with AIDS is multi-drug-resistant TB
(MDR-TB). MDR-TB can occur when patients fail to take their TB medicine
for the prolonged periods necessary to destroy all TB organisms, which
then become resistant to the drugs. These resistant organisms can be
spread to other people. Even with treatment, for individuals coinfected
with HIV and MDR-TB, the death rate may be as high as 80 percent, as
opposed to 40 to 60 percent for people with MDR-TB alone. The time from
diagnosis to death may be only months for some patients with HIV and
MDR-TB, as they are sometimes left without adequate treatment options. 

The initial site of TB infection is in the balloon-like sacs at the
ends of the small air passages in the lungs. In these sacs, white blood
cells called macrophages ingest the inhaled TB organism. Some of the
organisms are killed immediately, while others remain and multiply
within the macrophages. If the organism breaks out of the sacs, TB can
become active disease. This spreading sometimes results in
life-threatening meningitis and other problems.

NIAID launched the first large U.S. study to assess TB treatment
strategies for people coinfected with HIV and TB. The study is aimed at
finding state-of-the-art treatment. NIAID is the lead institute for TB
research at the National Institutes of Health, supporting more than 50
research projects related to TB.

Other OIs

NIAID-supported scientists also study other OIs including fungal
infections, herpes simplex virus infections, toxoplasmosis and
cryptosporidium infections.

