ddodell@stjhmc.fidonet.org (David Dodell) (08/21/90)
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TREATMENT ISSUES -- The GMHC Newsletter
of Experimental AIDS Therapies
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Copyright 1990 Gay Men's Health Crisis, Inc.
All rights reserved.
Permission granted for non-commercial use.
Non-commercial reproduction is encouraged.
Treatment Issues, Volume 4 No. 5
Compound Q
Combination Antiviral Therapy
d4T and AzDU
An Ounce of Prevention: PCP
CD4
In Brief
Notes from San Francisco: Updates from the Sixth
International Conference on AIDS
The articles in this issue are based on data presented at
the Sixth International Conference on AIDS, in June. As was
expected, no single treatment has rendered HIV-infection "chronic
and manageable" yet. But advances in the optimal use of
available antivirals, prevention and treatment of infections and
basic research on how HIV works will all contribute to more
effective treatment strategies for those living with AIDS.
References to data presented at the conference do not follow
the usual footnote format used in Treatment Issues. Instead, we
have printed the abstract number in parentheses within the
article for those who want original sources.
Compound Q
Kevin Armington
Compound Q (GLQ223 or trichosanthin) received a great deal
of attention by the press and conference attendees. Much of the
information presented was already a matter of public record,
however. Two abstracts reported results published late last year
in the Proceedings of the National Academy of Sciences. This
work showed that Compound Q inhibits HIV in acutely (recently)-
infected T4 cells and chronically-infected macrophages (Th.A.
232, Th.A. 233). Three abstracts presented data on absorption,
safety and efficacy (S. B. 464-466). A brief trial at San
Francisco General Hospital led by Dr. James Kahn found the half-
life of Compound Q to be about three hours (i.e., it takes three
hours for half of the drug to leave the bloodstream after
intravenous administration.)
Safety
The phase I, single-dose trial at San Francisco General
Hospital found that Q was fairly well tolerated. The drug caused
no toxicity to red or white blood cells. One participant
experienced a "life-threatening" neurologic complication, from
which he recovered. In addition, researchers noted "a variety of
clinically important side effects" among the 18 participants.
The best known study of Compound Q was conducted
"underground" by Project Inform, in cooperation with the
Community Research Alliance and several community physicians
around the country. Fifty-one patients were evaluated after
receiving one to three injections intravenously or
intramuscularly. Side effects included mild and reversible
muscle pain, delayed fevers and a decrease in serum albumin (a
protein found in the blood and tissues). Six patients developed
dementia 36-60 hours after infusion. Two of these patients
slipped into a coma which reversed after receiving decadron (a
steroid which reduces brain swelling). Changes in mental status
were related to low T4 counts but not to the dose taken.
Efficacy
The Project Inform trial yielded some limited data on the
efficacy of Compound Q. In 10 of 16 patients who had detectable
p24 antigen in their blood, a significant decrease was noted one
month after the first infusion. One person reverted from p24
positive to p24 negative. Patients who began the study with T4
counts above 100 had significant increases in cell numbers after
three infusions.
Project Inform Director Martin Delaney elaborated on these
trial results when he spoke at the morning plenary session on
Friday, June 22. Delaney stated that "We've violated some sacred
cows [in the Q trial] but have covered lots of ground in record
time." Whereas traditional phase I trials would have started with
a tiny dose of the drug, the Project Inform trial began with a
dose that was thought to be therapeutic.
Patients' Histories as Control
Rather than compare Compound Q to placebo or a standard
therapy (AZT), this trial used an unconventional method to judge
the drug's efficacy. Participants' blood values after treatment
with Q were compared with their blood values over the previous
two years. For example, all of the participants who had been
taking AZT (it was not specified for how long) had an average
decline of more than 300 T4 cells over the course of one year
before beginning the trial. After four months of monthly Q
infusions, participants had an average gain in T4 counts of 77.
Although he did not formally present more data, Delaney said that
an additional two months of follow-up showed that this trend
continued. It should be noted that patients continued to take
other drugs while in the trial.
Using the patient's history as his/her own control is an
intriguing idea. However, the Project Inform trial was able to
take advantage of extensive patient histories that will not be
available to some people infected with HIV, especially those who
are newly-diagnosed or who do not have access to quality health
care.
What Next?
Project Inform has received a large grant from Geneslab, the
pharmaceutical company holding the Compound Q patent, to conduct
a Phase II trial, which has already begun. In addition, the FDA
has granted formal permission to Project Inform to continue its
clinical research. Only people who have already been treated
with Q in this trial will be retreated.
It is truly remarkable that we have any efficacy results for
a drug one year after it showed promise in the test tube. The
Project Inform trial is a commendable example of how to conduct
clinical research in an expedient manner.
Combination Antiviral Therapy
Kevin Armington
When the phrase "combination therapy" was first applied to
AIDS, the intent was to combine (a) antiviral (anti-HIV) drugs
with (b) drugs that would restore the immune system to proper
functioning (immunomodulators) and (c) drugs that cure and
prevent infections (anti-infectives). In San Francisco, a new
dimension to combination therapy seemed to have "come of age":
taking more than one antiviral together or in alternating
regimens. It has become clear that none of the candidate drugs
for "magic bullet" (AZT, ddI, ddC, alpha interferon, etc.) will
be sufficient alone to control HIV. Certain combinations might
have significant advantages, such as delayed development of
resistance, reduced toxicity and greater efficacy.
Hoffman-La Roche, makers of ddC, sponsored a half-day
symposium devoted to this topic. The only presenter who actually
discussed her experience combining antivirals was Dr. Margaret
Fischl, a researcher from the University of Miami who has been on
the forefront of AIDS research for many years. She presented
results from a trial of AZT plus alpha interferon in people with
KS.
AZT plus Alpha Interferon
The trial reported on by Dr. Fischl (ACTG 013) studied doses
of alpha interferon ranging from 9 million units (MU) to 18 MU
with AZT doses ranging from 400 mg to 800 mg. Many adverse
reactions were seen. Dr. Fischl hypothesized that the toxicities
of the two drugs were additive, especially in terms of liver
damage. Six participants receiving 800 mg AZT with 9 MU
interferon died, possibly as a result of severe depletion in
white blood cells. Dr. Fischl noted that this may be the first
time that drug-related neutropenia in a clinical trial has led to
a fatal opportunistic infection. The maximum tolerated dose of
these two drugs together was stated to be 600 mg AZT (although
Dr. Fischl said that 400 mg might be just as effective) with 9-18
MU alpha interferon.
The efficacy of these two antivirals appears to be
synergistic as well. T4 count rises were more sustained at
higher doses, as was suppression of viral activity. After six
months of treatment no drug resistance was seen, another positive
sign. In addition, many participants had complete or partial KS
tumor regression after three or four months of treatment.
A small study done at the National Institutes of Health
found that the synergistic effects of AZT with alpha interferon
are maintained when a third drug, GM-CSF, is added (S. B. 420).
GM-CSF boosts neutrophil counts, the white blood cell that both
AZT and alpha interferon suppress. It will be interesting to see
if these results are sustained longer than the 16 weeks that this
trial lasted. These results were underscored by a shorter study
at Memorial Sloan-Kettering Cancer Center, demonstrating that
GM-CSF permitted better tolerance of AZT with alpha interferon
(S. B. 513).
AZT plus ddC
Two approaches are being tried with this combination:
taking the two drugs together in low doses or alternating AZT
with ddC so that only one drug is taken at a time.
The low-dose combination trial is being conducted in Miami
and San Diego (S. B. 426). The trial has six arms:
ddC-AZT
1. .005 mg/kg100 mg
2. .005 mg/kg200 mg
3. .01 mg/kg 100 mg
4. .01 mg/kg 200 mg
5. .005 mg/kg50 mg
6. 0 50 mg
[All doses are three times per day.]
By June, 43 participants (of 55 recruited) were still
participating in the study. Five participants developed
opportunistic infections and three developed serious toxicity
(one bone marrow toxicity and two neuropathies). T4 cell counts
rose in all arms and peaked between one and three months of
treatment, before beginning a gradual decline. Although the
number of participants is small, it appears that rises in T4
counts were more sustained in the groups receiving 600 mg AZT
daily. Viral activity, measured by p24 antigen levels, was
significantly decreased in all arms, even in both participants
taking just 150 mg AZT alone. The authors conclude that the
combination of AZT and ddC is safe and that beneficial effects
are seen. This group had fairly advanced disease, with an
average T4 count of below 100 at the beginning of the trial.
This is a small study that was not followed for long, but early
results are encouraging. The study is ongoing.
Alternating AZT with ddC
A multicenter study using AZT and ddC in alternating
regimens currently has 90 participants (Th.B. 23). Forty-one
others have dropped out; eight due to ddC toxicity, two due to
AZT toxicity. There are seven arms to the study. Four compare
alternating weeks or alternating months of AZT (1200 mg daily)
and high-dose (.01 mg/kg six times a day) ddC or low-dose (.03
mg/kg six times a day) ddC. Two arms of the trial give
intermittent dosing, i.e. a week of AZT followed by a week of no
treatment or a week of high-dose ddC followed by a week of no
treatment. In the last arm, participants receive continuous AZT
(1200 mg daily). Peripheral neuropathies occurred in all arms,
but were more frequent in the arms using high-dose ddC. Early
results suggest that alternating the two drugs is better than
intermittent dosing (week-on/week-off drug). The group receiving
high-dose ddC had more sustained rises in T4 counts and
suppression of p24 antigen. A similar study is being done with
people who have become intolerant to AZT (S. B. 425). One
hundred nine patients with AIDS or ARC have been recruited, of
whom only 38 remain on the study. The primary purpose of this
trial is to determine the least toxic regimen. Preliminary
analysis by the authors states that peripheral neuropathies were
more common in the weekly alternating AZT/ddC regimens and that
bone marrow toxicity was more common in the monthly alternating
regimens.
According to another paper, drug resistance did not develop
in two people who had taken ddC and AZT in alternating regimens
for one year (Th.A. 263). In contrast, the same researchers
found that HIV from two other people who had taken AZT
continuously for six months had reduced sensitivity to AZT.
AZT plus Acyclovir
For years now, it has been suspected that this combination
would enhance AZT's activity, which it does in the test tube.
Many conflicting reports have been made about the antiviral
effect of AZT and acyclovir (Zovirax), but most of them have been
small, short-term studies. The only reports given in San
Francisco were both from studies so small that they cannot really
be considered conclusive. One was conducted at the University of
Washington in Seattle (Th.B. 24). Twenty-two participants
received 300 mg AZT or 600 mg AZT with or without 4800 mg
acyclovir daily. Roughly three-quarters of participants had
detectable viral activity at the beginning of the study. After
six months, there was no significant difference between those on
AZT alone or AZT with acyclovir in terms of viral activity (the
amount of virus in plasma [plasma viremia] and p24 antigen levels
were monitored). Interestingly, however, this small study found
no advantage to taking 600 mg AZT over 300 mg daily. The authors
also note that suppression of plasma viremia was sustained for
only eight weeks, while p24 antigen levels remained depressed for
24 weeks.
Another small Dutch study gave 3200 mg acyclovir and 1000 mg
AZT to 24 participants over two years (S. B. 449). The numbers
in this study are too small to draw any final conclusions, but
the authors claim that acyclovir appeared to provide no
additional benefit.
New Antivirals: d4T and AzDU
Wayne Kawadler
Two antivirals that showed promise in the test tube last
year have now been used in small human studies. Both are
nucleoside analogues chemically similar to AZT. Dr. Robert
Yarchoan of the National Institutes of Health gave an oral
presentation on both of these drugs which have shown some
efficacy against HIV in phase I studies.
d4T
This agent was studied at Brown University to evaluate its
safety and efficacy. Participants were given one of four daily
doses ranging from 2 mg/kg to 12 mg/kg given in 3 doses (S. B.
456). Of 20 participants, 44% developed peripheral neuropathies
(nerve damage in the hands or feet). Neuropathies occurred
mostly at the higher doses. At the onset of neuropathy, the drug
was stopped, but some participants were later put back on half-
dose with no recurring side effects to date. However on a more
positive note, everyone experienced a decline in p24 antigen
levels, and had an early rise in T4 counts. The next step in
this trial is assessing whether the efficacy of d4T at lower
doses (below 2 mg/kg/day) is sustained.
Another dose-escalating study of d4T is being done by Dr.
Kathleen Squires at Cornell Medical College. In this study,
participants received 2, 4, 8, or 12 mg/kg/day of d4T (Th.A.
241). Sixteen participants completed greater than 10 weeks of
the study. Of nine participants enrolled with detectable p24
antigen levels before the trial, eight had undetectable antigen
within two to five weeks of treatment. However this trial showed
some serious toxicities at higher dose levels, including chemical
hepatitis (abnormal liver function tests), neuropathy, nausea and
anemia. The protocol for this trial has been altered to one of
dose de-escalation. The new trial will start at 4 mg/kg/day
(which was determined to be the maximum tolerated dose) and go
down to 2 mg/kg/day and 1 mg/kg/day to further determine
tolerance and effect of d4T on HIV. In both of these trials,
anecdotal reports are that participants feel an increased sense
of well being while on the drug. Trial participants also seem to
have more energy.
AzDU
This substance is very closely related to AZT, but to date
has shown none of the bone marrow toxicity that is commonly
caused by high doses of AZT. AzDU and AZT are so similar that
strains of HIV that are resistant to AZT are also resistant to
AzDU, so this drug will probably not be useful for people are AZT
resistant. One trial is being done at UCLA by Drs. Mitsuyasu and
Miles. To date the drug has been well tolerated up to 30
mg/kg/day (S. B. 482). The next group of participants will be
started at 20 mg/kg twice per day. For those with no prior use
of AZT, decline in p24 antigen levels and a rise in T4 counts
were seen. The only significant side effect to date has been low
white cell counts, which rebounded when the dose was halved. No
bone marrow toxicity has been seen (1).
The second phase 1 study of AzDU is being done by Dr.
Michael Polis at the National Institutes of Health (S. B. 483).
This study is also a dose-escalating study with patients getting
up to 12 mg/kg 4 times per day. No significant signs of toxicity
or efficacy have been seen to date.
An Ounce of Prevention: PCP Prophylaxis Update
Gabriel Torres, M. D.
In spite of the advances made over the last few years in PCP
prophylaxis, we still don't know the best method for preventing
this infection. Since the advent of using aerosolized
pentamidine (AP) to prevent PCP, some of the drug's shortcomings
have become apparent. Recently there has been concern about
incidents of PCP in people taking AP. In addition, some unusual
cases of the infection have been seen in individuals receiving
AP. Reports on these issues and more data on oral medications to
prevent PCP were presented in San Francisco.
AP Efficacy Update
The efficacy of AP was initially demonstrated by the San
Francisco County Consortium study, which showed that inhaling
pentamidine at a dose of 300 mg once a month was superior to a
dose of 30 mg every two weeks, using the Respigard II nebulizer
(2). In San Francisco one controversial Swiss study was
presented which compared inhaled pentamidine (300 mg once
monthly) to placebo in patients who had not had PCP and found no
difference in cases of PCP. Four patients in each group developed
PCP, although the follow-up time was short and the study
continues to enroll patients (Th.B. 406). A large Canadian study
reported the results of an AP treatment program in Toronto where
550 HIV positive patients have received AP at a dose of 60 mg
every two weeks using the Fisoneb nebulizer. Only six cases have
occurred one to six months after initiation of prophylaxis (Th.B.
408). Another study compared pentamidine distribution throughout
the lung using different nebulizers and found the Respigard II
and Fisoneb similar in terms of the average amount of drug
deposited in the lungs (6.4 and 7.3 mg, respectively); the System
22 Mizer nebulizer was the most efficient, depositing an average
of 16.2 mg of pentamidine (Th.B. 415).
Problems with Aerosol Administration
As early as 1988 in Stockholm, Leoung et al. had reported
patients relapsing with PCP in the upper lung zones who had
received AP in the original San Francisco County Community
Consortium study (3). They hypothesize that less aerosol is
delivered to the upper lung zones, allowing the organism to
infect areas where the aerosol is not delivered. Studies at
Memorial Sloan-Kettering Cancer Center (MSKCC) using radioactive
aerosols with particle sizes similar to those of AP show unequal
distribution, with the upper lung zones receiving less drug.
Methods to correct this uneven distribution have been suggested,
including breathing from residual volume, or while lying down, or
using higher doses of pentamidine. PCP in the upper lung zones
often looks like active tuberculosis. Jules et al. reported a
study of 52 patients who developed PCP at MSKCC between June 1987
and August 1988 (4). 38% of the patients on AP had mostly upper
lung involvement compared to 7% of the controls not receiving AP.
Of 21 patients who had received AP, the diagnosis was made by a
method called bronchoalveolar lavage (BAL) in only 63%. BAL is a
procedure where the air passages are washed with saline solution
and the resulting fluid is examined under the microscope for the
presence of the PCP organisms. In patients who had not received
AP, BAL detected 100% of PCP cases. In patients with pneumonia
who have received AP for prophylaxis, it may be necessary to do a
biopsy in addition to BAL to determine if PCP is the cause. A
biopsy poses more of a risk of bleeding and lung collapse
(pneumothorax).
Another concern related to the use of AP has been the
occurrence of spontaneous pneumothoraces. A pneumothorax is
defined as collapse of a portion of the lung by entry of air into
the chest cavity either from a wound or a defect in the lining of
the lung (pleura); it is a life-threatening condition requiring
immediate placement of a chest tube in most cases, to reexpand
the lung. Pneumothoraces have been reported in patients with
active PCP, whether they have received AP or not. It is
theorized that AP is suppressing a smoldering PCP infection, and
is unable to affect the outer and upper lung zones, allowing for
formation of cysts, cavities and eventually lung collapse or
pneumothorax. In Montreal, Leoung et al. reported
pneumothoraces in only 13 of 408 patients receiving AP,
suggesting that PCP itself was related to the occurrence of the
pneumothoraces, and not the drug (5). A group at Cabrini
Hospital has reported 24 cases of pneumothorax among patients
receiving AP regardless of the type of nebulizer, including
Respigard II, Aerotech II and the DeVilbiss ultrasonic nebulizer.
Others have suggested that the ultrasonic nebulizers may cause
more cough and bronchospasm, which may be related to the lung
collapse (6). One study presented in San Francisco showed that
in a series of 17 patients who developed lung collapse, 11 (65%)
had received AP prophylaxis, 82% had active PCP at the time of
the collapse and 38% died during the hospitalization (S. B. 415).
The issue of whether AP is related to spontaneous pneumothoraces
is still not settled and will require further investigation.
One of the major side effects of AP is "wheezing" or
bronchospasm; several posters in San Francisco describe how this
can occur in up to 30% of patients, regardless of a previous
history of cigarette smoking, asthma or prior PCP. It is
alleviated by pretreatment with a bronchodilator such as
terbutaline or albuterol (Th.B. 420, Th.B. 421).
Local vs. Systemic Prophylaxis: PCP outside of the Lungs
Cases of PCP occurring outside of the lungs continue to be
reported. PCP has now been found in the lymph nodes, the bone
marrow, liver, spleen, retina, bones, skin, thyroid gland,
adrenal glands, intestines, kidneys and hearts of patients with
AIDS (7). Systemic prophylaxis with trimethoprim-
sulfamethoxazole (Bactrim or Septra) or Dapsone prevents
disseminated PCP infections, but AP will not. It must be
emphasized that PCP outside of the lungs still remains a rarity
and it is unclear whether it has become more common in patients
since the advent of AP. CT scans and ultrasounds of the abdomen
may be useful in finding PCP outside of the lungs, especially in
the spleen and liver (8) (Th.B. 424). In San Francisco several
posters compared Dapsone (an oral drug) with AP and found equal
efficacy and few side effects. Doses of Dapsone as low as 200 mg
once weekly or 100 mg twice weekly were effective; in two studies
Dapsone was combined with pyrimethamine, which may also prevent
toxoplasmosis (Th.B. 407, Th.B. 411, Th.B. 414).
Two posters describe the use of Bactrim for prophylaxis; a
Danish study of 122 patients who had a previous history of PCP
showed a relapse rate of 6.1% per year using one double-strength
Bactrim tablet per day, with only 5.7% of patients having to
discontinue treatment due to allergic reactions (Th.B. 412).
Another retrospective study from the Community Health Project in
New York found that Bactrim once daily did not lower the white
blood cell counts and was 100% effective in preventing PCP (Th.B.
413). This study also found significantly fewer patients had to
discontinue Bactrim due to side effects when the drug is
administered once daily (2086). Some physicians have
successfully "desensitized" patients to Bactrim by starting them
on extremely low doses and escalating the dose.
Conclusion
The most effective and safe method of PCP prophylaxis is
still an open question. The long-term experience with AP is
disappointing, with higher than expected breakthroughs (cases of
PCP) and complications, which make it more difficult to diagnose
PCP. Oral prophylaxis may be more effective and will prevent
dissemination outside of the lungs. Combinations of AP and
Bactrim or Dapsone have been proposed as alternative regimens for
those who have developed PCP while on AP, as well as higher doses
and more frequent inhalations of pentamidine. Further studies on
PCP prophylaxis are needed to determine the optimal and most
effective regimens that will be nontoxic, tolerable over long
periods of time and will not lead to development of resistance.
CD4 -- Time for a Reassessment?
Mike Barr
For years now, CD4 has enjoyed the high profile of hope-
sustaining wonder drug at the expense of more "mundane" drugs
that are equally promising in the test tube. A toxic dose has
yet to be observed; neither has evidence of efficacy. Since the
drug appears to be safe, the argument goes, it makes sense to
continue dose escalation studies until some sort of clinical
benefit -- or development of toxicity -- is seen.
In both Stockholm, at the Fourth International AIDS
Conference, and last year in Montreal, at the Fifth International
AIDS Conference, the status reports were essentially the same:
no observable toxicity, no consistently beneficial effect in
patients. This past month, in San Francisco, UCLA researcher Dr.
David Ho showed that much of the early work with CD4 was
scientifically flawed due to the use of only one rare viral
strain of HIV in test tube studies (Dr. Robert Gallo's HIV-IIIB
strain). Dr. Ho demonstrated that CD4's effect against other
strains of HIV is minimal. CD4 works (in theory, at least) by
blocking the passageway (called the CD4 receptor) by which HIV
enters cells. Using strains taken directly from patients' blood,
Dr. Ho showed that the attraction between the CD4 receptor and
the protein on HIV's outer coat that facilitates entry of the
virus into cells (gp120) is much less than previously reported
(S. B. 88). He expressed dismay that more extensive preclinical
work had not been done before the drug was used in clinical
experiments. Dr. Ho estimates that blood concentrations of CD4
100 times greater than what are currently being tested may be
needed to neutralize various HIV strains in the blood. If this
dose was shown to be effective, the cost to patients would be
hundreds of thousands of dollars.
Even if CD4 is a failure as a single agent, some evidence
has shown that it might augment the potency of other antivirals.
A recently published test tube study showed that AZT, alpha
interferon and CD4 used together inhibited HIV in the test tube
longer than AZT alone or AZT in combination with alpha interferon
(9) (F. A. 66). Unfortunately, the lab work was conducted using
only Gallo's IIIB strain of the virus, leaving this work open to
the criticisms raised by Dr. Ho.
Altered Versions
One of the earliest concerns about CD4 was that it did not
remain in the bloodstream long enough to be useful
therapeutically. To address this concern, the CD4 molecule was
altered and attached to immune globulin (IgG), which extends
CD4's life in blood. Genentech, one of the pharmaceutical
companies engaged in the race to bring CD4 to market,
collaborated in four phase I trials of this hybrid, CD4-IgG. All
of these trials reached the same conclusion: CD4-IgG is well-
tolerated and its half-life is significantly longer in people
than CD4 alone (S. B. 478-S. B. 481). Keeping the drug in the
bloodstream for longer periods, however, does not seem to have
improved CD4's performance as an antiviral. Another approach
being investigated is attachment of a toxin to the CD4 molecule,
to kill HIV-infected cells. One study done at the National
Institutes of Health found CD4 plus a bacterial toxin to be a
"highly potent and selective agent for killing HIV-infected
lymphocytes and macrophages" and that it is synergistic with ddI
or AZT in protecting uninfected cells in the test tube (Th.A.
248). However, a study sponsored by Biogen, another
pharmaceutical company pursuing FDA licensing for CD4, found
somewhat less optimistic results. In their study, CD4 plus a
toxin was only able to partially inhibit viral reproduction (F.
A. 70). The drug was not able to protect uninfected human T
cells when exposed to HIV-infected T cells in the test tube. CD4
is classified as a high priority drug at the National Institutes
of Health. In light of the most recent data on CD4, this status
may need to be reassessed. Further preclinical research using
strains of HIV isolated from patients will be needed to establish
the potential antiviral effect of this agent. Concern about the
production of enhancing antibodies in response to CD4, which may
actually promote HIV infection, has also led to skepticism about
the drug's potential usefulness in human trials.
In Brief
Cigarette Smoking: One important study linked cigarette
smoking with disease progression. Analysis of data from the San
Francisco Men's Health Study suggests that smokers' T4 counts
fall faster than non-smokers' (Th.C. 39).
Another paper reported smoking data from the Multicenter
AIDS Cohort Study (MACS). In this study, 285 men were followed
from one year before they became positive for HIV antibodies
(Th.C. 675). Before seroconversion, a significantly higher
number of T4 cells was noted in those who smoked. However, T4
levels were roughly equivalent at one year after seroconversion
in smokers and non-smokers.
Two other papers showed an association between cigarette
smoking and high risk behavior (Th.C. 555) and incidence of
sexually transmitted diseases (F. C. 736).
Footnotes:
1 Personal communication, Cindy Scarborough, R. N.
2 Nebupent Monograph, Lyphomed, Inc., 1989.
3 IV Int Conf on AIDS, abstract # 7166, Stockholm, June, 1988.
4 Jules-Elysee. Aerosolized pentamidine: effect on diagnosis
and presentation of PCP. Ann Intern Med 112: 750, 1990.
5 V Int Conf on AIDS, abstract # TBP. 76, Montreal, June 1989.
6 Lee M et al. Aerosolized pentamidine and spontaneous
pneumothoraces in AIDS. Chest 97: 510, 1990.
7 Northfelt DW. Extrapulmonary pneumocytoses in patients
taking aerosolized pentamidine. Lancet, p. 1454, 1989.
8 Lubat E et al. Extrapulmonary pneumocystis carinii infection
in AIDS: CT findings. Radiology 174: 157, 1990.
9 Johnson VA et al. Three-drug synergistic inhibition of HIV-1
replication in vitro by zidovudine, recombinant soluble CD4 and
recombinant interferon-alpha A. J Infect Dis 161: 1059-67,
1990.
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 NY 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: Wayne Kawadler
Gabriel Torres, M. D.
Mike Barr
GMHC, Department of Medical Information,
129 West 20th Street, New York, NY 10011.
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