ddodell@stjhmc.fidonet.org (David Dodell) (07/16/90)
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TREATMENT ISSUES -- The GMHC Newsletter
of Experimental AIDS Therapies
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Volume 4 no. 4 June 15, 1990
Passive Immunotherapy Update
An Ounce of Prevention: MAI
Expanded Access to ddC
In Brief
Passive Immunotherapy Update
Kevin Armington
Most immune-enhancing treatments in AIDS have focused on T4
cells -- making them function properly, increasing their
numbers, protecting them from HIV infection. About a year ago,
Treatment Issues featured an article on a treatment strategy
called passive immunotherapy, which focuses on another component
of the immune system -- B cells. B cells produce antibodies to
neutralize disease-causing microorganisms and particles.
Treatment with extra doses of antibodies is called "passive
immunotherapy." This technique has been used with some success
as a treatment for cryptosporidium, a parasite that causes severe
diarrhea (1) and is being evaluated as a treatment for CMV (2).
In this article, we review passive immunotherapy as a potential
anti-HIV treatment.
Antibodies to HIV: Why don't they work?
They do. Unfortunately, the antibodies that B cells produce
in response to HIV ultimately do not control the virus. Early on
in HIV infection, B cells produce lots of antibodies. Different
antibodies are produced for each protein that makes up HIV;
therefore, there are many different kinds of antibodies to HIV.
As HIV infection progresses, certain antibody levels drop. It is
not known if this phenomenon is a cause or effect of advancing
HIV infection.
Clinical Update
Encouraging results from an English study of 10 patients
with AIDS or ARC generated some interest about two years ago.
This study began in March 1988 and is still being followed. Five
of six AIDS patients had died by the 17th month, but the ARC
patients are still stabilized (3). A paper published in
Biotherapy concludes that passive immunotherapy is more
efficacious when started early. The study also found that
antibody donors had no disease progression as a result of
frequent donation. (One donor gave five liters of plasma in one
year.)
Unfortunately, only one other clinical study in the U. S.
has actually made any headway since then. A company named
Medicorp holds a patent for use of passive immunotherapy to treat
HIV. Medicorp has been running a trial using antibody-rich
plasma at the Bronx VA Hospital in New York for about a year.
Over 70 patients have been recruited. Participants receive
either passive immunotherapy or placebo, in addition to some
other antiviral (AZT, ddI, etc.) . The results from this trial
will be difficult to evaluate, since participants are taking many
different antivirals. An oversight committee is currently
performing an analysis based on six months of data.
This analysis has dragged on for four months now; and,
according to a spokesperson for Medicorp, no end is in sight.
It is discouraging, to say the least, that research with this
promising treatment is moving along at such a sauntering pace.
According to Elliott Block, President of Medicorp, researchers
reviewing the data are "very encouraged." A difference in
survival is noticeable by the fifth month of the study. If a
clear and significant advantage is seen in the treatment group
after the analysis is finished, Mr. Block has said that the
study will be stopped and all participants will be offered the
plasma.
Medicorp is also underwriting a study that has been planned
in California by a company named HemaCare. This study, which
underwent a laborious approval process through the California
State Food and Drug Board (FDB), will recruit 225 patients.
Two-thirds of the participants will receive passive immunotherapy
and one-third will be given placebo. The trial is scheduled to
begin in July, pending licensing by the FDB of the plasma
treatment facility. The FDB has hinted that they may consider
granting a Treatment-IND (exclusive to California) after six
months if the results are positive.
The New York Blood Center has been gearing up to do a trial
for over a year. Researchers at the Blood Center collected 300
liters of gamma globulin, a component of the blood containing
antibodies. The study recruited donors with high concentrations
of HIV antibodies. According to Dr. Lou Baker, who was involved
with planning the study, bureaucratic delays at NIH have
prevented the study from getting off the ground. Other sources
speculate that NIH was unwilling to make some expensive
modifications at the Center's lab to assure the protection of
health care workers.
The Blood Center is working out an arrangement with Abbott
Laboratories to conduct another clinical trial. Abbott did one
small trial of PWAs with advanced disease. Participants began
the trial with a mean T4 count of 40. Throughout six months of
treatment, patients remained stabilized and there were no deaths
(4).
Are Some Antibodies to HIV More Effective than Others?
HIV contains proteins in the core of the virus and in its
outer envelope. The body makes specific antibodies for each
protein. The clinical studies done so far in AIDS have used
fluid containing all HIV antibodies. But some researchers feel
that wholesale infusion of all HIV antibodies may have some
unintended adverse results. Certain antibodies are protective
while others may even be harmful. There is some controversy
about which category specific antibodies fall into.
Antibodies directed at the core protein (p24 antigen) of HIV
are called p24 antibodies. (Please note that p24 antigen levels
are measurements of viral activity; p24 antibodies counteract p24
antigen.) Asymptomatic persons often have lots of p24
antibodies. These levels have been shown to decline as the
individual becomes symptomatic (5). A recent study shows that
individuals progress to ARC and AIDS when the p24 antibody level
falls below a certain level (31 picograms/ml) (6). Another
school of thought suggests that p24 antibodies are not protective
and that high levels of these antibodies are just one indication
of a strong immune response to HIV (7). It is possible that
HIV-infected persons continue to produce p24 antibodies
regardless of disease progression but that they are undetectable
by conventional methods.
There is conflicting evidence about the usefulness of
antibodies to proteins found on the outer envelope of HIV as
well. One study compared antibody levels to gp41, an envelope
protein, with p24 (core) antibody levels (8). A decline in p24
antibody levels was associated with disease progression, while
antibodies to gp41 remained high regardless of patient's
condition. Levels of gp41 antibodies are high in asymptomatic
persons as well as people with full-blown AIDS, which may mean
that they play a minor or insignificant role in fighting HIV.
However, antibodies to gp120, another envelope protein, may
play a role in preventing transmission of HIV from a mother to
her fetus. This protein assists HIV in entering cells (9). A
recently published study demonstrated that HIV-infected mothers
with high levels of antibodies to gp120 were less likely to pass
the virus on to their babies (10). Another study supports the
theory that envelope proteins are protective (11).
Reproducing Individual Antibodies
Dr. Susan Zolla-Pazner, an immunologist affliliated with New
York University, has done extensive laboratory work with B cells
from HIV-positive, asymptomatic donors. Her research has focused
on antibodies to envelope proteins, which she believes to be
protective. B cells which produce these antibodies are isolated
and infected with Epstein-Barr virus (EBV) in the test tube.
EBV-infected B cells then churn out large quantities of
"monoclonal antibodies" which can be used for research or,
eventually, for treatment (12).
For this innovative approach to be effective, the monoclonal
antibodies would have to be capable of neutralizing HIV. Some
monoclonal antibodies do neutralize the virus in the test tube.
Of course, what happens in the test tube is not always duplicated
in the body. Additional research involves attaching a toxin to
the antibodies to kill HIV-infected cells (13). If the second
strategy works, these "guided missiles" would be useful for
killing virus already harbored in cells as well as free-floating
virus.
The next step is gearing up to produce enough of these
monoclonal antibodies to conduct clinical trials. Fortunately, a
corporate sponsor has agreed to fund the research. Dr. Zolla-
Pazner anticipates beginning passive immunotherapy trials with
these antibodies first, then initiating trials of the modified
antibody with the toxin attached. Trials are expected to begin
in about one year.
An advocacy group has formed to help disseminate information
about passive immunotherapy and to encourage research in this
area. The Passive Immunotherapy Foundation has an active chapter
in San Francisco and another chapter is planned in Los Angeles.
For more information, write: PATH Project, 1748 Market St., San
Francisco, CA 94102. They publish a periodic newsletter and a
brochure on passive immunotherapy.
An Ounce of Prevention: MAI
Don Shewey
MAI, which stands for Mycobacterium avium Intracellulare, is
an organism similar to the one that causes tuberculosis (TB).
(M. avium and M. intracellulare are actually two closely related
bacteria. The medical community is increasingly calling this
opportunistic infection MAC or M. avium complex.) The main
symptoms can include fevers, chills, weakness, night sweats, and
diarrhea. It is associated with, and is a major cause of,
"wasting syndrome" in AIDS patients. It is most common in people
who have fewer than 100 T4 cells (14).
One study indicated that MAI occurs less often in patients
with Kaposi's sarcoma than in other AIDS cases. Hispanics had a
lower frequency of MAI than did blacks and non-Hispanic whites
(15).
A recent study in Texas indicated that mycobacterial
diseases (MAI and TB) are now the leading cause of death in
people with AIDS (16). TB can occur very early in HIV disease,
while MAI usually occurs when someone is severly immunosuppressed
(17). The number of cases appears to be increasing, as the life
expectancy of people with AIDS has been extended through the use
of antivirals such as AZT and prophylaxis for PCP. The Texas
study indicated the following incidence of MAI in the blood:
By the time MAI is diagnosed, patients with AIDS usually
have tremendous amounts of bacteria throughout the organs of the
body (18). Because it is difficult to treat advanced MAI,
attention is being focused on ways to prevent MAI and to provide
early diagnosis, when the disease may be easier to control. The
Antiviral Advisory Committee to the FDA has recommended that
non-placebo trials for treatment of MAI and placebo-controlled
trials for prophylaxis be designed.
Diagnosis
MAI is somewhat difficult to diagnose. Although it
frequently involves the lungs, a chest x-ray is insufficient and
pulmonary symptoms are rare. Positive cultures from sputum or
bronchial fluid are common but are not diagnostic. New
techniques make blood culture an excellent, non-invasive
diagnostic test for disseminated MAI. Other methods include
mycobacterial smear and stool culture as well as tissue biopsy
and culture of lymph node, bone marrow, liver, lung, and
gastrointestinal tract. There is some concern that blood culture
is too slow a method for diagnosing MAI. One study found that
liver biopsy was the fastest method (19). Many clinicians will
make a presumptive diagnosis, after eliminating other
possibilities, in patients with fever of unknown origin and fewer
than 200 T4 cells (20). At the International AIDS Conference in
Montreal in June 1989, one study suggested that, in addition to
such prevalent symptoms as fever, weight loss, and anemia, an
enlarged spleen and abdominal lymphadenopathy -- as shown in a
CT scan -- are highly predictive of disseminated MAI (21).
Lifelong Maintenance Therapy
MAI has historically proved difficult to treat. Because the
organism rapidly develops resistance to antibiotics, treatment
requires an alternating regimen of from three to seven different
drugs, each of which has its own side effects. For
immunocompromised patients, lifelong maintenance drug treatment
is necessary. One Australian study yielded impressive results
treating MAI with a combination of four drugs: rifabutin [300-
600 mg/day], clofazimine [100 mg/day], ethambutol [15 mg/kg/day
to a maximum of one gram] and isoniazid [300 mg/day] (22). Twenty
five patients were included in the study: 18 had complete
resolution of symptoms, and evidence of MAI disappeared from the
blood in 22 patients. Researchers speculate that this unusual
degree of success may be due to higher doses of rifabutin than
are normally used and synergism between rifabutin and ethambutol.
Different strains of MAI respond to different antibiotics.
One study showed that M. intracellulare was more susceptible in
the test tube to streptomycin, ethambutol, and rifampin than was
M. avium, while M. avium was more susceptible to ethionamide.
Also MAI isolates from patients without AIDS were more
susceptible to kanamycin and rifampin, while patients with AIDS
were more susceptible to cycloserine and ethionamide. These
results, however, have not been duplicated in people (23). [For
a detailed discussion of standard drug treatments and profiles of
individual antibiotics, see Treatment Issues Vol. 3, no. 2.]
More recent studies have focused on a handful of newer
treatments that show promise in the early treatment of MAI, such
as a regimen of rifabutin, clofazimine, and macrolides (24). In
a study of mice, azithromycin showed substantial efficacy in
early treatment of MAI infection (25). Another macrolide,
clarithromycin, has proven to be a promising treatment of MAI (in
combination with other drugs) in human studies in Europe.
Another new treatment of MAI under investigation is gamma
interferon, which is not an antibiotic but an immunomodulator.
In a small study of gamma interferon in people with AIDS, the
majority had reduction in MAI levels in the blood, but there was
a bounce back after discontinuation. None of these studies have
been published yet (26). Anecdotal reports of ongoing gamma
interferon trials for MAI have not been encouraging. [See also
"Coping with MAI" by Dr. Larry Waites, Project Inform
Perspective, May 1990, p.12.]
Avoiding Exposure
The precise mode of transmission of MAI remains unclear
(27). MAI is very prevalent in the environment and is acquired
by unpreventable exposure to food, water, dust, soil, poultry,
and other animals. However, there has been some investigation
into possible ways to avoid exposure. Studies have found a high
frequency of mycobacteria in hot tap water in hospitals
suggesting that hot water systems serve as environmental sources
for MAI infection in AIDS patients by creating aerosols. It has
been proposed that the temperature of hot water be raised to
decrease the concentration of mycobacteria and that AIDS patients
take baths rather than showers to avoid exposure to M. avium
through hot water aerosols (28).
In a lively exchange of letters in The Journal of the
American Medical Association, this recommendation was disputed as
premature by investigators who pointed out that MAI in people
with AIDS mostly attacks the gastrointestinal tract rather than
the lungs. Elderly patients infected with MAI more frequently
have pulmonary disease. The response suggested that, in
immunosuppressed patients, aerosol-borne microorganisms may well
originate in the respiratory tract and proceed to the bloodstream
(29). A tempest in a shower stall? Perhaps, but at least one
long-term study is underway in San Francisco to determine the
effect of drinking distilled water to avoid exposure to M. avium
(30). More studies need to be done on this issue, investigating,
for instance, the possibility of respiratory transmission through
casual contact with infected individuals.
Prevention
After the clear success researchers have had in preventing
PCP, the FDA is very interested in the movement afoot to find a
similar method to stop the incidence of MAI (31). Several
clinical trials are or will soon be enrolling participants for
studies of drugs for MAI prophylaxis. The two drugs being
focused on are rifabutin and clofazimine, because they have been
shown to be the most effective anti-MAI drugs in the test tube.
Although standard therapy for MAI uses a combination of
antibiotics, rifabutin and clofazimine are being studied alone
for prophylaxis since there may be fewer organisms present at
earlier stages of infection. This seems to be the case with TB,
for which isoniazid (INH) has proved to be an effective
prophylactic agent. On the other hand, MAI authority Dr. Lowell
Young points out that single-drug prophylaxis in TB was shown to
work in patients with intact immune systems. [A comprehensive
article on TB prophylaxis appeared in Treatment Issues, Vol 4,
no. 3.]
Planned Clinical Trials
Community Research Initiative (CRI) in New York is beginning
a multi-site trial of rifabutin, which not yet licensed in the U.
S, in people with AIDS who have fewer than 200 T4 cells and do
not already have MAI or TB. Its effectiveness as prophylaxis for
MAI was suggested by accident in a study of the antiviral effects
of rifabutin (also known as ansamycin). The study showed no
antiviral properties, but investigators noticed that participants
in the study did not get MAI. In contrast with patients at
Memorial Sloan- Kettering Cancer Center with a similar profile,
the patients taking rifabutin delayed the onset of MAI for a
year. This finding encouraged the manufacturer (Adria
Pharmaceuticals), to pursue its merits as a prophylactic
treatment for MAI (32).
Studies have shown that rifabutin is generally well
tolerated, but it does have side effects, most commonly nausea,
vomiting, and diarrhea. Rash, fever, and allergic reactions have
also been reported. At high doses, some patients have developed
arthritis. Decreased numbers of white and red blood cells have
occurred in some cases. Research on laboratory animals has also
indicated the possibility of birth defects in babies caused by
the use of rifabutin by either parent (33). Clofazimine for
prevention of MAI will be studied in two clinical trials: one at
San Francisco General Hospital and another at Rush Presbyterian
in Chicago. Clofazimine is an FDA-approved drug for leprosy,
which is also caused by a mycobacterium. It is available by
prescription. The side effects may include abdominal pain or
cramps, diarrhea, loss of appetite, and weight loss. Since one
of the side effects is a change in skin pigment (which ranges
from what looks like a healthy tan to an orange or purple tint),
the San Francisco study is not placebo-controlled but operates on
a treatment/no-treatment basis. When it was originally designed,
the study was to focus on subjects recently diagnosed with PCP,
assuming that they were at high risk for MAI. Since the incidence
of PCP has been reduced, the rules of the study have changed to
include any participant with fewer than 125 T4 cells (34).
Conclusion
Despite the pessimistic attitude regarding treatment of
mycobacterial infections in patients with AIDS, clinical responses
to new therapies for MAI suggest that the prognosis for this
infection will improve. Earlier diagnosis and treatment as well
as preventive therapy may prolong survival or improve quality of
life.
Expanded (? ) Access to ddC
Kevin Armington
Hoffman LaRoche announced last week that the company would
allow certain patients access to ddC, a powerful antiviral,
outside of clinical trials. While this is good news for the small
group of people who qualify, it is a limited gesture that is about
two years overdue.
Background -- Excessive Toxicity
Early trials of ddC, using doses now considered to be too
high, resulted in irreversible toxicity (peripheral neuropathies)
for some patients. ddC got a bad reputation, and its future in
AIDS seemed dim. Additional trials of much lower doses produced
a more favorable toxicity profile while maintaining significant
anti-HIV activity (35). Other innovative approaches are being
tried, like switching back and forth between AZT and ddC or
taking them together in very low doses. AZT and ddC cause
different toxicities, so it was theorized that alternating them
would decrease side effects usually seen with constant use of
either. In addition, when ddC and AZT are combined in the test
tube, they have a much greater anti-HIV effect together than
either does alone.
Expanded Access Program
The expanded access program will start out very cautiously.
Only 50 patients will be allowed to try ddC outside of trials,
and they must meet all of the following criteria: a diagnosis of
AIDS or ARC, serious toxicity from AZT or failure to respond to
AZT and serious toxicity from ddI. In addition, patients may not
have had peripheral neuropathies, the most common side effect
associated with ddI. [Neuropathies can also be caused by other
factors, like vitamin deficiencies (esp. vitamin B12) or nerve
damage by HIV itself.] Finally, only physicians who have
experience with ddC will be allowed to administer it during the
first month of the program. Hoffman La Roche has estimated that
between 1000-2000 patients will be eligible for ddC. However,
only 250 patients will be enrolled during the first five months
of expanded access. Given the rigid exclusion criteria, it is
hard to believe that thousands of patients will meet all of the
eligilibity requirements. In particular, it seems absurd to
include only patients who have experienced serious toxicity from
ddI, not including peripheral neuropathy. The two other common
toxicities associated with ddI are pancreatitis and severe
diarrhea. Fewer than 200 people have had to discontinue ddI at
doses of 750 mg/day or less as a result of either of these
conditions. Where will the 2000 patients come from? Limiting
the program in its first phase to physicians who have already
used ddC withholds the drug from the vast majority of people who
might benefit from it.
Ongoing Trials and Combination Therapy
The American Journal of Medicine published a special
supplemental section in the May 21, 1990 issue, describing
several ddC trials, but results are not being made available
yet. By the time this issue of Treatment Issues went to press,
researchers were very concerned about saving results for the VIth
International Conference in San Francisco later this month.
One trial is using alternating doses of AZT and ddC in
people who have had serious bone marrow toxicity on AZT alone.
This trial will have four arms including alternating weeks of AZT
and ddC and alternating months of AZT and ddC. By the beginning
of June, 109 patients had been recruited. Preliminary results
hint that alternating AZT and ddC on a monthly basis is less
toxic than on a weekly basis (36). No conclusions can be drawn
yet about efficacy. Researchers have also noted that patients
who experience serious toxicity with ddC tend to have adverse
reactions after six or seven months of treatment, suggesting that
there may be a subset of patients who are more susceptable to ddC
toxicity. Skin reactions were noted during the first four to six
weeks of treatment, but tended to subside with time.
Another trial for people who have been on long-term AZT will
compare continued AZT alone versus ddC alone or very low doses of
the two together. A third phase I trial is recruiting people with
AIDS or ARC who have had no prior AZT or ddC. This is a dose-
escalation trial of low-dose AZT plus low-dose ddC. Investigators
will closely examine any synergism between AZT and ddC. To date,
only minimal toxicity has been seen (37). For further
information about any of these trials, call 1-800-TRIALS-A.
In Brief
Warning on ddI with other drugs: Three deaths have been
reported in England among patients taking ddI in combination with
anti-MAI drugs 36 Personal communication, D. Richman. 37
Personal communication, M. Fischl. [clofazamine or rifabutin
(ansamycin)]. One patient died during a convulsion of unknown
origin. The other two experienced cardiac complications. It is
possible that the drug combination played a role in the deaths.
Bristol-Myers recommends that any patients taking ddI and
rifabutin be promptly evaluated for electrolyte imbalance,
electrocardiographic and radiographic abnormalities. They also
recommend that treatment with the combination be discontinued
until the drug interaction is better understood.
Bristol-Myers has warned physicians that ddI should not be
given to patients taking intravenous pentamidine (not aerosolized
pentamidine). Both of these drugs can cause pancreatitis, an
inflammation of the pancreas that can be fatal. The first
symptom of pancreatitis is usually abdominal pain. Anyone taking
ddI who develops abdominal pain should notify his/her doctor
immediately. Physicians can monitor amylase levels to detect
possible pancreatitis early.
Parallel Track: After long delays by the FDA, the proposed
regulations for "parallel track" access to experimental drugs
have finally been published in the Federal Register. A parallel
track is a mechanism that would allow early access to some
experimental drugs in phase II clinical trials, for people who
are ineligible for trials. The regulations also mandate the
establishment of a committee to decide which drugs to recommend
for early release. This body, called the AIDS Research Advisory
Committee (ARAC), will include representatives from the National
Institute of Allergy and Infectious Diseases, other scientists,
AIDS activists and HIV-infected individuals. Participation in
the parallel track program by pharmaceutical companies is
voluntary. These regulations are now open for public review and
comment until July 20, 1990. Comments about the proposal can be
sent to: Parallel Track Policy, National AIDS Program Office,
200 Independence Avenue SW, Room 738-G, Washington DC 20201.
Hyperthermia: Much has been made in the media lately about
a new "cure" for KS involving a process called hyperthermia.
This is a process by which the blood temperature is artificially
raised to 114 degrees fahrenheit. Blood is withdrawn from the
body, heated with a heat exchanger and then returned to the
bloodstream. This treatment has previously been use for treating
some infections and may be useful in treating some cancers.
Hyperthermia has been tried in only two people with KS.
According to reports, the first person's KS lesions started to
improve in 48 hours, and his T4 cell count rose dramatically.
His doctors claim that his blood cultures seroreverted from HIV-
positive to HIV-negative.
This case report has been submitted to medical journals (and
rejected from at least one). It is crucial that these results be
evaluated by objective doctors. Media reports have been
sensational and have aroused a lot of premature excitement. And,
of course, the $35,000 price tag is very suspicious.
Hyperthermia can be dangerous if done improperly by a physician
who is not knowledgeable in the procedure. In short, this
treatment cannot be evaluated until we have more information on
larger numbers of patients who are followed for longer than three
months.
Other Resources
The AIDS Treatment Registry provides up-to-date information on
clinical trials of antivirals, immunomodulators, and drugs for
HIV-related infections and cancers in New York and New Jersey.
Their easily readable guide can be obtained by calling (212)
268-4196.
American Foundation for AIDS Research (AmFAR)also publishes a
catalog of trials involving experimental drugs. To order the
"AIDS/HIV Experimental Treatment Directory", write to AmFAR at
1515 Broadway, Suite 3601, New York, N. Y. 10036, or call (212)
719-0033.
The National Institutes of Health operate a toll-free hotline to
provide information on HIV-related clinical trials run by the
federal government. Callers may request a Spanish speaking
operator. The lines are open Mon.- Fri. 9:00 am to 7:00 pm
eastern time. The number is 1-800-TRIALS-A.
"AIDS Treatment News" is a biweekly report which chronicles
current developments in experimental and alternative treatments
and deals with public policy issues. Contact John S. James at P.
O. Box 411256, San Francisco,CA 94141 or call (415) 255-0588.
Project Inform publishes a newsletter called "PI Perspective"
which deals with experimental treatments.
Another resource is their drug hotline: 1-800-822-7422.
"PWA Coalition Newsline", published "by and for people with AIDS
and AIDS Related Conditions," is a grass-roots news magazine that
appears monthly. Write PWA Coalition Inc., 31 West 26th St., New
York, N. Y. 10010, or call (212) 532-0290.
"ATIN" (AIDS Targeted Information Newsletter) performs a monthly
search of hundreds of medical journals worldwide. Definitely
aimed at doctors and researchers, it is the best ongoing
literature search available. It has an impressive cast of
editors who comment on the significance of the studies cited.
Published by Williams & Wilkins, P. O. Box 23291, Baltimore, MD
21203 or phone 1-800-638-6423.
"Healing AIDS" is a monthly magazine which focuses on holostic
approaches to AIDS and ARC including diet and nutrition,
relaxation and visualization techniques, and stress reduction.
It regularly lists other resources. Subscriptions are $10/year
for people with AIDS/ARC/low income, and $15 for others. Write:
3835 20th Street, San Francisco, CA 94114 or Phone: (415) 821-
7646.
Body Positive is a organization for people who are HIV-positive.
They publish a monthly newsletter called "The Body Positive."
Write to: 208 West 13th St., New York, NY 10011 or call 212-
633-1782. Also providing services to seropositives is an
organization called "Positive Action". For more information,
call (212) 727-7768.
Treatment Issues is GMHC's newsletter devoted to providing
reliable information on experimental AIDS therapies. Describing
an experimental therapy should not be construed as recommending
it. All new treatments should be done under a physician's care.
Treatment Issues is published ten times yearly. Copyright 1990
Gay Men's Health Crisis, Inc. All rights reserved. Non-
commercial reproduction is encouraged. Subscription lists are
kept confidential.
Editor: Kevin Armington
Medical Consultant: Gabriel Torres, M. D.
Technical Assistance: Wayne Kawadler
Writers: Don Shewey
Kevin Armington
Proofreader: Roger Cottingham
GMHC, Department of Medical Information, 129 West 20th Street, New York, NY
10011.
Footnotes:
1 Vth Int Conf on AIDS abstract # WBP. 45, Montreal, June, 1989.
2 Phase I study of anti-CMV monoclonal antibodies in patients
at risk for disseminated CMV infection, Eskild Petersen M. D.,
Principal Investigator, Univ. of Arizona Health Sciences Center.
3 Karpas A et al. Passive immunotherapy in ARC and AIDS.
Biotherapy 2:159-72, 1990.
4 Personal Communication, K. Gordon.
5 Weber JN et al. HIV infection in two cohorts of
homosexual men: neutralising sera and association of anti-
gag antibody with prognosis. Lancet Jan 17, 1987.
6 Croxsan TS et al. Prognostic significance of quantitative
levels of HIV: p24 ginding capacity in HIV infection.
AIDS Research and Human Retroviruses 6:455, 1990.
7 Personal communication, S. Zolla-Pazner.
8 Allain JP et al. Long-term evaluation of HIV antigen and
antibodies to p24 and gp41 in patients with hemophilia. NEJM
317(18):1114-21, 1987.
9 Pert CB et al. Octapeptides deduced from the neuropeptide
receptor-like pattern of antigen T4 in brain potently inhibit
HIV receptor binding and T-cell infectivity. Proc Natl Acad Sci
83:9254-58, 1986.
10 Goedort JJ et al. Mother to infant transmission of HIV
association with prematurity or low gp120. Lancet, Dec. 9, 1989,
p. 1351.
11 Bernard J et al. Discrimination between protective and
enhancing HIV antibodies. AIDS Research and Human Retroviruses
6(2):243-49, 1990.
12 Gorny MK et al. Generation of human monoclonal antibodies
to HIV. Proc Natl Acad Sci, 86:1624, 1989.
13 Till M et al. HIV infected T cells and monocytes are
killed by monoclonal anti-gp41 antibodies coupled to Ricin A
chain. Proc Natl Acad Sci, 86:1987, 1989.
14 Community Research Initiative Research Subject Informed
Consent Form.
15 Horsburgh CR Jr. and Selik RM. The epidemiology of
disseminated nontuberculous mycobacterial infection in AIDS. Am
Rev Respir Dis 139:4-7, January 1989.
16 Nightingale S. Presentation at a meeting of the Antiviral
Advisory Committee to the FDA.
17 Pitchenik AE. The treament and prevention of mycobacterial
disease in patients with HIV infection. AIDS 2 (suppl 1):S177-
S182, 1988.
18 Armstrong D., comment on Inderlied CB, et al. In vitro
and in vivo activity of azithromycin against the Mycobacterium
avium complex, in AIDS Scan 1(2), 1989.
19 Prego V et al. Comparative yield of blood culture for
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20 Personal communication K. Squires.
21 Vth Int Conf on AIDS, abstract #ThBP 53, Montreal 1989.
22 Hoy J et al. Quadruple drug therapy for MAI bacteremia in
AIDS patients. J Infec Dis 161(4):801 -- 5, 1990.
23 Guthertz LS et al. Mycobacterium avium and Mycobacterium
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24 Vth Int Conf on AIDS, abstract #ThBP 54, Montreal, 1989.
25 Personal communication L. Young.
26 Personal communication K. Squires.
27 Prince DS et al. Infection with Mycobacterium avium complex
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28 Du Moulin CG et al. concentration of Mycobacteruim avium
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29 Waterborne Mycobacterium avium infection. JAMA 261:994,1989.
3020 Personal communication L. Young.
31 Personal communication D. Abrams.
32 Personal communication B. Bihari.
33 CRI Research Subject Infromed Consent Form.
34 Personal communication D. Abrams.
35 Merigan TC et al. Safety and tolerance of ddC as a single
agent. Am J Med 88(suppl 5B):11S-15S, May 21, 1990.
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