                   AIDS INFORMATION NEWSLETTER
                   Michael Howe, MSLS, Editor
                     AIDS Information Center
                VA Medical Center, San Francisco
                     (415) 221-4810 ext 3305
                          June 2, 1995

                Opportunistic Infections (Part I)

                AIDS and Opportunistic Infections

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 treatment and prevention
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 may cause disease in
people 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
die.  During the 1980s, the development of effective therapies led
to more better management of PCP. Drugs for preventing and treating
PCP include aerosolized pentamidine and 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 prevention of PCP because the combination is
effective, tolerated by about half of the patients who take it and
works 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 antimalarial drug, with
clindamycin is an effective oral therapy for PCP.  TMP with Dapson
is an alternative treatment.

The search for new, more effective, less toxic drugs and
combinations of drugs to fight PCP continues.  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 Herpes Virus

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 may
occur in the gastrointestinal tract, lungs, brain, heart and other
organs.

Both intravenous ganciclovir and foscarnet are approved to treat
CMV retinitis.  Life-long 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 herpes viruses have shown that
intravenous foscarnet and ganciclovir are equally effective for CMV
retinitis, although foscarnet was associated with increased
survival for patients.  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 Infection: 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 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, 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 is 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 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 often occurs 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 organism which then becomes 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 for some patients with HIV  and MDR-TB may be only months,
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 are studying other OIs including fungal
infections, herpes simplex virus infections toxoplasmosis and
cryptosporidium infections.

NIAID, a component of the National Institutes of Health, supports
research on AIDS, tuberculosis, allergies, immunology and
infectious diseases.  NIH is an agency of the U.S. Public Health
Service, U.S. Department of Health and Human Services.

[NIAID BACKGROUNDER.  Prepared by: Office of Communications,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, Maryland 20892. April 1994.]


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MORBIDITY AND MORTALITY WEEKLY REPORT 
Centers for Disease Control and Prevention 
1994 November 11; Vol 43, No 44, p 821 
 
                        Notice to Readers

      Draft Recommendations for Prevention of Opportunistic
               Infections in HIV-Infected Persons

     CDC, the National Institutes of Health, and the Infectious
Diseases Society of America have prepared recommendations for
prevention of opportunistic infections (OIs) in human immunode-
ficiency virus-infected persons. The draft document is available
from CDC's Technical Information Activity, Division of HIV/AIDS,
National Center for Infectious Diseases, telephone (404) 639-2076,
fax (404) 639-2007. Comments must be received in writing by
December 16, 1994, and should be mailed to Attention: OI
Recommendations, Technical Information Activity, Division of
HIV/AIDS, National Center for Infectious Diseases, CDC, Mailstop
E-49, 1600 Clifton Road, NE, Atlanta, GA 30333; fax (404) 639-2007.


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              CDC Slides - Opportunistic Infections

     A box of 37 slides for opportunistic infections are available
at no charge from the Centers for Disease Control and Prevention.
Ask for item number L-175 (3).

Contact:  Centers for Disease Control and Prevention, Photographic
Resources, 1600 Clifton Road, N.E., Mail Stop F-02, Atlanta, GA
30333. Telephone: (404) 639-1291.  Toll Free: (800) 418-7246.  FAX:
(404) 639-0050.
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