From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: ATN #160
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6307
Organization: unspecified
Date: Sat, 10 Oct 92 13:56:46 PDT

&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& 
J O H N   J A M E S  writes  on  A I D S 
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Copyright 1992 by John S. James; 
permission granted for non-commercial use. 

AIDS TREATMENT NEWS Issue #160, October 2, 1992 
   phone 800/TREAT-1-2, or 415/255-0588 

CONTENTS:  [items are separated by "*****" for this display] 

International Conference and Clinical Practice:  Interview 
   with Kenneth Mayer, M. D. 
ddI:  FDA Approves Additional Indication 
Rifabutin:  FDA Advisory Committee Recommends Approval for 
   MAC Prophylaxis 
566C80 (Atovaquone):  FDA Advisory Committee Recommends 
   Approval for Pneumocystis Treatment 
Warning:  "Poppers" Return, More Evidence of Harm 
Political Funeral in Washington D. C. October 11; Date, 
   Time, and Route Changed 
ACTG Meeting Starts Election Day; Remember Absentee Ballot 
What to Ask of Clinton:  Call for Information 

***** International Conference and Clinical Practice: 
      Interview with Kenneth Mayer, M. D. 

by John S. James 

     Kenneth H. Mayer, M. D., an infectious disease specialist, 
     is the director of the Brown University AIDS program, and 
     research director at the Fenway Community Health Center in 
     Boston.  We asked Dr. Mayer to outline some of the clinical 
     "bottom lines" of the Eighth International Conference on 
     AIDS (in Amsterdam, July 1992), information that can help 
     physicians today in treating persons with HIV.  [To make 
     this interview easier for non-physicians, AIDS Treatment 
     News added explanatory notes in brackets.] 

     JJ:  Looking back after two months, what do you see as the 
most important information from the International Conference for 
physicians treating HIV disease today? 

     KM:  "What the general media didn't report about Amsterdam 
is that certain clinical questions are closer to being resolved, 
but there are still many questions related to standards of care. 
Two major pragmatic issues are:  combination antiretrovirals, 
given the drugs that are currently approved; and when to 
prophylax specific opportunistic infections. 

     "Much of how you change your practice is nuance.  I function 
as a specialist, I am not doing primary care; I generally see 
patients in consultation and advise their primary care doctors. 
I try to individualize recommendations for each person; some 
patients want to be on as few drugs as possible, and others want 
to pursue all possible leads, depending on how symptomatic the 
persons are and their perception of where they are with their 
infection.  You have to respect these choices and work with 
people on each issue.  Much of the data that informs clinical 
practice is fragmentary and evolving, often more slowly than we 
would like." 

     JJ:  What is most important now in anti-HIV treatments? 

     KM:  "One change will be parallel-track access for 
stavudine, or d4T.  [This program will be for persons without 
approved treatment options; for more information about d4T, see 
AIDS Treatment News #159, September 18, 1992].  Several of us at 
Brown did a phase I trial, and were impressed early on that while 
the neuropathy could be problematic, we could cut back on doses 
and at times restart people after we had to stop. Eventually, we 
are all looking forward to new kinds of drugs, such as protease 
and tat inhibitors, but we can't bank on them yet, given the 
paucity of human trial data.  With later- phase studies of d4T 
looking good, we will have another option for now.  The long-term 
T-helper data that Lisa Dunkle, M. D., presented on this drug 
looks promising for many individuals.  We hope this will be a 
nucleoside analog that is not associated with pancreatitis and 
may have better efficacy than others.  It may be one of the more 
important nucleoside analogs by itself." 

     KM:  "Then we have the concern raised by the presentation of 
David Cooper, M. D., on treating people with much higher T- 
helper counts than when we are accustomed to begin therapy. 
Should we start nucleoside analogs even before the T-helper count 
drops to 500?  Because there weren't many deaths or disease 
progressions in that study, what he reported was time to drop of 
T-helper count.  Those with T-helper counts over 500 who were 
randomized to AZT did have a delay in their T- helper drop. 

     "This one study does not make me start putting everybody 
with T-helper counts over 500 on AZT.  But we should be open to 
the possibility that in the future, standard of care might be 
single-drug treatment initially [at any T-helper count], then 
starting to add drugs as the counts decline.  But that is a leap 
of faith.  Some people have already made that leap; I am not 
there.  But it is hard to reject drug intervention out of hand. 
If a patient came to me and wanted to start AZT at a higher T- 
helper count, at least we have this promising data, but concerns 
about resistance, cost, possible chronic toxicities, and whether 
it really gives any clinical benefit in the long term, have to be 
considered as well. 

     "Regarding combinations, multi-arm studies are now ongoing; 
we are waiting for results of ACTG 155 and ACTG 175 [clinical 
trials conducted by the AIDS Clinical Trials Group of the U. S. 
National Institute of Allergy and Infectious Diseases] to get a 
better feel for how and when to start combining. Robert Yarchoan, 
M. D., presented data comparing combination treatment with AZT 
plus ddI, vs. alternating treatment with those drugs [the 
combination seemed to work better].  I don't think it puts the 
nail in the coffin on alternating these drugs, but it makes me 
feel more comfortable combining them. 

     "I still recommend monotherapy on AZT if people do not want 
to participate in trials and are asymptomatic and have T-helper 
counts less than 500.  If the T-helper count does not stay stable 
over the next few months, I have a lower and lower threshold for 
adding another nucleoside analog. Depending on where their T- 
helper count is at that time and their clinical status, there are 
a number of people I put on ddC per indication, but there are 
times when peoples' counts have dropped rapidly and I put them on 
AZT plus ddI, now that this combination is prescribable.  Their 
rate of change, their clinical history, makes me decide to use 
one drug or the other." 

     JJ:  Do you usually prefer ddC or ddI for combination with 
AZT? 

     KM:  "I feel frustrated that there is not enough data yet to 
make the decision.  If there is any concern with the pancreas, 
the data would push me toward ddC.  On the other hand, if there's 
a fairly rapid drop in T-helper counts, I have extrapolated from 
the data to add ddI instead of ddC at times, since ddI is looking 
so promising as monotherapy. There isn't enough data because 
there have not been adequate studies.  When ACTG and CPCRA [the 
Community Program for Clinical Research on AIDS, which conducts 
community-based trials sponsored by the U. S. National Institute 
of Allergy and Infectious Diseases] results are available, I will 
feel more strongly about using one or the other. 

     JJ:  What about adding acyclovir to HIV treatment?  That 
seems to be continually controversial. 

     KM:  "The acyclovir issue is a tricky one.  The study which 
got so much press at first in the Times of London [in December 
1991] and was reported by Mike Youle, M. D., at the International 
Conference found a survival benefit but not a decrease in CMV 
retinitis.  The question is what is the acyclovir doing?  Perhaps 
it is stopping subclinical reactivation of members of the 
herpesvirus family, and therefore reducing transactivation of 
HIV.  [See "Activation of Human Immunodeficiency Virus by Herpes 
Simplex Virus," The Journal of Infectious Diseases, September 
1992, pages 494-499.] It is also possible that subclinical CMV 
disease may cause organ dysfunction or susceptibility to other 
opportunistic infections; maybe we are not detecting it because 
we are using such an advanced endpoint, CMV retinitis.  There 
have been studies with different doses of acyclovir that have not 
shown clear-cut benefit; here we see survival benefit.  The drug 
continues to impress me; aside from the cost, it is well 
tolerated, and I have not seen it impede peoples' care.  There is 
the issue of how many pills people are willing to take, but now 
that there is an 800-mg acyclovir pill, this is less of a 
problem, taking three or four or even five of those pills a day. 

     "One question that remains is whether the new acyclovir 
prodrug can have a role in CMV prophylaxis; it is going into a 
trial in the ACTG. [A prodrug is a pharmaceutical that turns into 
an effective drug inside the body.  The advantage of the 
acyclovir prodrug, BW 256U87, is that it allows larger doses to 
be given orally than would be possible with acyclovir itself. 
Acyclovir may have a very small anti-CMV effect.] 

     "We still don't understand the biology [of acyclovir's 
benefit with HIV disease], but if something nontoxic has survival 
benefit I am happy to use it, but not entirely clear when to.  If 
somebody's T-helper count is down and they have been on maximal 
antiretroviral therapy, or if acyclovir is something the patient 
requests, I increasingly add it in to the regimen.  But it is 
hard to base a standard of care on one study with a survival 
benefit but not a clear-cut mechanism. There is biological 
plausibility, and we want to maximize quality of life, and how 
well people do over the long haul." 

     JJ:  What are the most important conference results on 
opportunistic infections? 

     KM:  "Some of the most useful information at the 
International Conference was on macrolide antibiotics and MAC. 
Also, Lowell Young, M. D., and colleagues had a paper in The 
Lancet [November 2, 1991] on azithromycin and MAC.  R. E. 
Chaisson, M. D., and colleagues had particularly interesting data 
on clarithromycin at 500, 1000, and 2000 mg twice a day.  The 
decrease in MAC bacteremia [in the blood] was impressive, and it 
happened quickly.  The sobering data is that resistance did 
develop fairly quickly, so I do not think that single-drug 
therapy with either of the newer macrolides [clarithromycin or 
azithromycin] is a good idea.  It is certainly important to treat 
this infection; data from Stephen Nightingale, M. D., showed that 
there are very many MAC cases.  People with low T-helper counts 
are living longer, and therefore this disease is a major source 
of illness and death.  Aggressive treatment with macrolides is 
clearly indicated.  The question is, is it macrolide plus one 
drug?  Chaisson said ethambutol; many of us would also use other 
oral agents.  One thing the macrolides have done is to make it 
less likely for clinicians to use amikacin or other injectable 
aminoglycosides. 

     "You can easily give a four-drug regimen with azithromycin 
or clarithromycin, ethambutol, ciprofloxacin, and then either 
rifampin or clofazimine.  One of the issues on which drugs to use 
is whether to hold some in reserve because of the emergence of 
multidrug resistant MAC; that will be a hard one to sort out. 
There is also the issue of cross-resistance when people are at 
risk of getting tuberculosis; there is concern about using any 
rifamycin in that situation. 

     "Concerning MAC prophylaxis [as opposed to treatment], one 
of the concerns of the FDA and its advisory committee has been 
that rifabutin might increase the probability of developing 
rifampin-resistant TB. The data is not at all clear; it is a 
theoretical concern."  [Note:  the Antiviral Drug Products 
Advisory Committee recommended approval of rifabutin for MAC 
prophylaxis on September 24, 1992, the day before this interview 
was conducted; the FDA will almost certainly approve the drug.] 

     JJ:  What is your practice now when somebody needs to start 
clarithromycin or azithromycin for MAC?  What other drugs do you 
use? 

     KM:  "I would always add ethambutol and ciprofloxacin; when 
it was hard to get clofazimine I was adding rifampin, now I am 
adding clofazimine.  At least those four.  With five or more 
drugs, it gets onerous in cost and toxicity.  Many physicians 
feel three would be enough; I would be happy to cut back. Studies 
of optimum combinations are underway.  The other things you have 
to consider are which other drugs the patient has used or is 
currently using. 

     "One important value of the data from Adria Laboratories 
[which conducted trials on rifabutin for MAC prophylaxis] is the 
good epidemiological information, showing, for example, at which 
T-helper counts people are likely to get MAC bacteremia.  Very 
few above 100 developed it.  But people with T-helper counts 
below 100 were also likely to be on multiple other medications, 
or to have other complications.  If somebody has abnormal liver- 
function tests, for example, I certainly will not give them 
rifampin.  And I do not think it would be wise to give full-dose 
ethambutol to somebody who had CMV retinitis, because the drug 
can cause ocular toxicity; even though it is a different kind of 
toxicity [than the damage CMV retinitis causes], one would not 
want to take any chance of impairing somebody's vision.  You 
balance the regimen according to these kinds of considerations." 

     JJ:  What about rifabutin, which will probably be approved 
for prophylaxis soon? 

     KM:  "I put a couple people on the treatment IND [for early 
access to rifabutin before its marketing approval] in the past, 
and will use the drug when it is approved.  I have been concerned 
that some physicians, even without a positive blood culture for 
MAC, have put people on clarithromycin or azithromycin because of 
the low T-helper count and the ease of writing a prescription. 
These are broad-spectrum and very useful drugs, but resistance 
can develop rapidly. 

     "In the rifabutin trials, for ethical reasons, people were 
not kept on placebo after they developed MAC bacteremia. Because 
they were offered rifabutin and could also use other drugs, these 
trials would not show differences in survival. And unless you 
have autopsies, you may not be able to prove that MAC was the 
cause of death.  But MAC bacteremia often indicates that people 
are severely ill, so I do not feel that I would be treating a 
laboratory value [meaning that people should start treatment for 
MAC (with more than one drug) if a positive blood culture is 
found, even if there are no MAC symptoms yet]. 

     "The idea of MAC prophylaxis is that you would like to start 
early [before a positive blood culture].  In my mind, early 
enough is when the T-helper count is close to 100.  I tend not to 
put many people on rifabutin with T-helper counts between 150 and 
200.  Again it would depend on the individual case, e.g. the 
presence of otherwise unexplained constitutional symptoms or 
laboratory abnormalities [which might justify rifabutin 
prophylaxis at higher T-helper counts]." 

     JJ:  What about other opportunistic infections? 

     KM:  "One concern is the intestinal parasites.  There was 
data at the International Conference about better diagnostic 
techniques for microsporidiosis.  One question is how much of the 
AIDS-related intestinal disease may be caused by undiagnosed 
infectious agents. 

     "For cryptosporidiosis, there was some promising data on 
albendazole.  And for patients with higher T-helper counts, many 
have had good experience with paromomycin [Humatin, a readily 
available prescription drug].  But not everybody responds to this 
drug; we clearly need better ones. Macrolides may be helpful 
here. 

     "On toxoplasmosis, there was data suggesting that 
sulfonamide drugs used for pneumocystis prophylaxis or for other 
purposes seemed to have some protective effect against toxo.  A 
European study looked at dapsone plus weekly pyrimethamine, an 
interesting approach.  The pyrimethamine issue is still 
confusing, because there are people who are sulfonamide or 
sulfone intolerant and cannot be desensitized, so we want to know 
how effective pyrimethamine could be alone or in combination. 
There was a CPCRA study which suggested that pyrimethamine for 
toxo prophylaxis could be detrimental, but the mechanism was not 
clear.  Perhaps use of folinic acid (leucovorin) might be helpful 
there.  We need more information on toxoplasmosis prophylaxis; 
trials are looking at it both in the U. S. and in Europe. 

     "The big issue in opportunistic infections is that we need 
large-scale multi-site trials of multiple OI prophylaxis 
regimens.  Which ones give the broadest spectrum of prevention 
with the best tolerance, also considering drug interactions, and 
real-world issues of ease of administration and cost? 

     "The other group of infections that need much more study are 
fungi.  At what T-helper count should one consider fluconazole 
prophylaxis?  Should the recommendation be gender-specific? 

     "We are studying fluconazole prophylaxis of mucosal fungal 
infections in HIV-infected women.  The CPCRA network is also 
doing a study; they are looking at a once-weekly dose, and we are 
trying smaller doses three times a week, 50 mg Monday, Wednesday, 
and Friday.  It might be that antifungal prophylaxis should begin 
when T-helper counts are low, but the optimal starting point is 
unclear.  This issue needs to be sorted out.  Also, when should 
fluconazole be used to prevent cryptococcal disease -- or other 
disseminated mycoses?" 

     JJ:  Such as histoplasmosis, in some areas?  In San 
Francisco we seldom see it. 

     KM:  "We rarely see cases in Boston, but in the South, and 
parts of the Midwest, it is a big problem.  And in Arizona and 
some parts of California, coccidioidomycosis [valley fever] is a 
big issue as well." 

     JJ:  What else from the international conference comes to 
mind? 

     KM:  "The therapeutic vaccine data looked promising to me, 
as an adjunctive therapy in keeping peoples' T-helper counts 
higher.  There were several good presentations.  The followup [on 
people using some of the vaccines] is getting to be long enough 
that I am looking forward to expanded-access trials. We are very 
eager to participate in community-based therapeutic vaccine 
studies, based on the Amsterdam data. 

     "The other treatment I thought was very promising -- I have 
prescribed it occasionally on an individual basis -- is 
pentoxifylline.  Bruce Dezube, M. D., and colleagues did show 
reduction in viral load.  That was impressive.  I think quality 
of life measurements are important.  We want people to feel 
better, even if we are only palliating them, as long as we are 
not causing any detriment immunologically.  That pentoxifylline 
made a difference in HIV replication was important; I am looking 
forward to seeing more intensive studies and a better definition 
of the population where it will be beneficial.  [For more 
information on pentoxifylline and the report at the conference, 
see AIDS Treatment News #156, August 7, 1992, pages 4-5.] 

     "I think ICAAC will be a good conference for information on 
followup to Amsterdam."  [For information on ICAAC, the 
Interscience Conference on Antimicrobial Agents and Chemotherapy, 
which will be held October 11-14 in Anaheim, California, see AIDS 
Treatment News #159, September 18, 1992]. 

     "Progress has been incremental -- slower than we would like, 
but there were more practical developments at the conference than 
were generally reported.  Hopefully a new U. S. administration 
will be able to mobilize the resources and cooperation needed for 
a more efficient process to get treatments from the lab to the 
patient." 

***** ddI:  FDA Approves Additional Indication 

     On September 28 the U. S. Food and Drug Administration 
officially approved an additional indication (use) for ddI -- for 
treatment of patients who had already received prolonged prior 
treatment with AZT.  Previously, ddI had only been officially 
approved for persons who could not tolerate AZT or had 
significantly worsened while using it.  While the new approval 
does not give physicians any power which they did not already 
have, it will in practice encourage wider use of ddI. 
[Physicians can prescribe an approved drug for other than its 
approved indications, but many are reluctant to do so.  Also, 
some third-party payers refuse to reimburse for expensive drugs 
which are used "off label" (for conditions other than the FDA- 
approved indications) -- despite the fact that FDA indications 
were never intended to be used in this way, since the standard of 
care in medicine often includes unlabeled use of approved drugs, 
especially for serious diseases such as cancer and AIDS.] 

     The new ddI approval is based on results of a major study by 
the AIDS Clinical Trials Group of the U. S. National Institute of 
Allergy and Infectious Diseases (James O. Kahn, Stephen W. 
Lagakos, Douglas D. Richman and other, "A Controlled Trial 
Comparing Continued Zidovudine with Didanosine in Human 
Immunodeficiency Virus Infection," New England Journal of 
Medicine, August 27, 1992, pages 581-587.)  This study enrolled 
913 volunteers who had successfully tolerated AZT for at least 16 
weeks; they were randomly assigned to either continue AZT, switch 
to low-dose ddI, or switch to high-dose ddI.  The low-dose ddI 
group did best, with significantly fewer deaths and AIDS-defining 
events than the group assigned to AZT.  The researchers were 
surprized that it did not matter how long the patients had been 
on AZT before switching. 

     Another major study (ACTG 116A) has compared first-line use 
of ddI vs AZT, but the results are not known yet.  They are 
expected later this year. 

***** Rifabutin:  FDA Advisory Committee Recommends for 
      MAC Prophylaxis 

     On September 24 the FDA's Antiviral Drug Products Advisory 
Committee recommended the approval of rifabutin (brand name 
Mycobutin) for prevention of MAC.  Two studies conducted by the 
drug's sponsor, Adria Laboratories, found that volunteers with 
T-helper counts less than or equal to 200 developed MAC 
bacteremia (shown by positive blood cultures) about half as often 
in the group given rifabutin, compared to the group given a 
placebo. 

     The FDA is not required to follow the recommendations of its 
advisory committees, but it almost always does so.  Official 
approval of rifabutin is expected in the coming weeks or months. 

     For more information about rifabutin, see the interview with 
Kenneth Mayer, M. D., in this issue. 

***** 566C80 (Atovaquone):  FDA Advisory Committee Recommends 
      Approval for Pneumocystis Treatment 

     On September 24 the FDA Antiviral Drug Products Advisory 
Committee also recommended approval of 566C80 (also called 
atovaquone), a drug developed by Burroughs Wellcome Company, for 
treating pneumocystis.  The committee recommended that the drug 
be used as second-line treatment, if 
trimethoprim/sulfamethoxazole (TMP/SMX, commonly known as Septra, 
or Bactrim) could not be tolerated or failed to work. Trials had 
shown that TMP/SMX was more likely than 566C80 to be effective 
against pneumocystis, but also more likely to be discontinued 
because of side effects.  The importance of 566C80 is to offer 
another pneumocystis treatment option for those times when it is 
needed. 

     566C80 might also be useful in treating toxoplasmosis. 

     FDA approval of 566C80 is expected in the next several weeks 
or months.  Meanwhile, a Burroughs Wellcome "treatment IND" 
program which started in November 1991 will continue to be 
available for those who need the drug now; there is also a 
similar "compassionate release" system for use outside North 
America.  More than 800 patients have been treated in these 
programs.  To enroll a patient in the treatment IND, physicians 
can call 800/755-2020, 7 days a week 24 hours a day. 

****** Warning:  "Poppers" Return, More Evidence of Harm 

by John S. James 

     "Poppers" are nitrite inhalants which have been used in the 
gay community as a sexual aid.  Following research reports that 
these chemicals might be contributing to immune problems in AIDS 
or to the development of Kaposi's sarcoma, they were banned in 
the United States in 1988.  But now they are coming back, being 
sold allegedly for such purposes as removing fingernail polish, 
in sex clubs, bars, through the mail, and by advertisements in 
gay publications.  One concern is that promoters of new 
preparations, in an effort to get around the law, could replace 
banned chemicals with substitute ones, with completely unknown 
effects when deliberately inhaled; one unlucky choice of 
ingredient could cause widespread damage.  Efforts are under way 
to analyze inhalants now being sold to determine what they 
contain. 

     [The 1988 law, section 8 of the Consumer Product Safety Act, 
banned the manufacture for sale, distribution in commerce, or 
importation of various forms of "butyl nitrite." Manufacturers 
then substituted isopropyl nitrite, and in 1990 Congress amended 
the law to also ban "volatile alkyl nitrites that can be used for 
inhaling or otherwise introducing volatile alkyl nitrites into 
the human body for euphoric or physical effects."  We do not know 
if the current products have substituted other chemicals in order 
to evade this language.] 

     In most of the world poppers are not illegal or regulated, 
and they have remained in widespread use in some countries. 

     According to Hank Wilson, a well-known AIDS activist with 
ACT UP/Golden Gate who fought poppers years ago and recently 
brought the current resurgence to our attention, one problem in 
alerting the gay community to the dangers is that some gay 
newspapers are reluctant to report negative news about poppers 
because they carry advertisements for these preparations.  As a 
result, young people now entering the gay community often do not 
know that there ever was a health issue or controversy about the 
use of these drugs.  (A San Francisco law requiring a warning 
sign where poppers are sold took effect in January 1984.  But 
today the traffic is underground, so this warning law isn't 
working.) 

     The issue of poppers in the gay community first surfaced in 
1981, and some observers suspected that poppers themselves might 
cause AIDS.  Later, those theories were largely dismissed, but 
confusion occurred because some people thought the issue was 
finished.  The remaining concerns are that poppers might be a 
cofactor in the development of AIDS, or could lead to relapse to 
unsafe sex, or make HIV infection more likely by causing changes 
in blood vessels(1), or possibly cause poisoning if unknown 
chemicals are substituted in an effort to evade the law.  And 
some of the chemicals are known to degrade over time, so there 
could be harmful byproducts as well.  Some researchers also 
suspect that the body may metabolize the nitrites to 
nitrosamines, which are strongly carcinogenic(1). 

     Because of the high profit margin -- it costs about 25 cents 
for the chemical which sells for about $10 retail -- this issue 
is expected to remain with us for some time. 

Recent Studies of Popper Use 

     Poppers have not been conclusively proven to be harmful; 
absolute proof would require a large clinical trial with people 
randomly assigned to take a placebo or  each of the various 
chemicals in use, clearly an ethical impossibility. One recent 
study(2), however, gave repeated doses of amyl nitrite to 
volunteers and found suppression of immune functions, especially 
of natural killer cells, following moderate inhalation.  The 
number of these cells did not decrease, but their activity 
decreased about 30 percent, and remained low until several days 
after the use of the drug was stopped.  (The volunteers were 
HIV-negative men who had used poppers previously.  The 
researchers' institutional review board would not allow the test 
to be repeated on HIV-positive volunteers, because of the risk of 
harm their health.) 

     An epidemiological study in Vancouver published in May 
1992(3) followed a cohort of 353 gay men and found that those who 
used nitrite inhalants were 2.3 times more likely to develop 
Kaposi's sarcoma than those who did not.  Because such an 
association could be caused by factors other than the chemical 
effect of the nitrites (for example, those who used poppers might 
also have had more unsafe sexual contacts), the data was 
statistically adjusted for known HIV risk factors. Poppers use 
was still associated with increased risk of KS. 

     However, an English study of 65 gay men(4) failed to find an 
association between poppers use and KS. 

     An epidemiological study in Boston(1) found that poppers use 
increased the risk of HIV infection, especially during unsafe 
sex.  And the same Vancouver research group mentioned above 
reported, at the 1991 International Conference on AIDS in 
Florence, that gay men who practiced unsafe sex were more likely 
to use poppers than those who did not(5). 

     Two 1990 articles from the U. S. National Institute of Drug 
Abuse(6,7) called nitrite inhalants a leading candidate as a 
cofactor for the development of KS in persons with AIDS, and 
urged physicians to encourage patients to avoid their use. 

     However, a report from the San Francisco City Clinic Cohort 
Study(8) did not find differences in nitrite use among AIDS 
patients with KS vs those who did not have KS. 

     A study of gay men in the Paris area found that poppers use 
was associated with increased risk of being HIV positive, even 
after the data was adjusted for known risk factors(9). 

     In an animal study, mice exposed to isobutyl nitrite 45 
minutes a day for 14 days showed several kinds of immune 
suppression(10). 

     This list is far from complete; there are many other 
medical-journal articles on poppers, most of them reporting 
evidence of health risks.  We only included the ones which were 
published in 1990 or later, and which seemed most important. 
Therefore our list entirely omits the earlier medical-journal 
warnings about poppers which led to the law against them in the 
United States. 

Comment 

     We may never have final answers to the questions about 
health hazards of poppers; some of the articles cited here did 
not find evidence of harm.  But the weight of the evidence 
strongly suggests that poppers are certainly not safe and 
probably do cause damage to health, especially to persons with 
HIV.  Since these drugs are coming back into use despite the U. 
S. law against them, people will have to make their own 
decisions.  It is important that the available information be 
widely circulated in the gay community and among other users of 
such inhalants. 

     Note:  Anyone who wants to work on the poppers issue can 
call Hank Wilson at 415/441-4188, or write to him at 55 Mason 
Street, San Francisco, California 94102. 

References 

(1) Seage GR 3rd, Mayer KH, Horsburgh CR Jr, Holmberg SD, Moon 
MW, and Lamb GA.  The relation between nitrite inhalants, 
unprotected receptive anal intercourse, and the risk of human 
immunodeficiency virus infection.  American Journal of 
Epidemiology.  January 1, 1992:  volume 135, number 1, pages 1- 
11. 

(2) Dax EM, Adler WH, Nagels JE, Lange WR, and Jaffe JH.  Amyl 
nitrite alters human in vitro immune function. Immunopharmacology 
and Immunotoxicology.  1991:  volume 13, number 4, pages 577-587. 

(3) Archibald CP, Schechter MT, Le TN, Craib KJ, Montaner JS, and 
O'Shaughnessy MV.  Evidence for a sexually transmitted cofactor 
for AIDS-related Kaposi's sarcoma in a cohort of homosexual men. 
Epidemiology.  May 1992:  volume 3, number 3, pages 203-209. 

(4) Beral V, Bull D, Darby S, and others.  Risk of Kaposi's 
sarcoma and sexual practices associated with faecal contact in 
homosexual or bisexual men with AIDS.  Lancet.  March 14, 1992: 
volume 339, pages 632-635. 

(5) Willoughby BC, Schechter MT, Craib KJ, and others. 
Characteristics of risk takers among seronegative men in a gay 
cohort.  VII International Conference on AIDS, Florence, June 
16-21, 1991 [abstract # W. C. 3003]. 

(6) Haverkos HW.  The search for cofactors in AIDS, including an 
analysis of the association of nitrite inhalant abuse and 
Kaposi's sarcoma.  Progress in Clinical and Biological Research. 
1990:  volume 325, pages 93-102. 

(7) Haverkos HW.  Nitrite inhalant abuse and AIDS-related Kaposi's 
sarcoma.  Journal of Acquired Immune Deficiency Syndromes.  1990: 
volume 3, supplement 1, pages S47-S50. 

(8) Lifson AR, Darrow WW, Hessol NA, and others.  Kaposi's 
sarcoma among homosexual and bisexual men enrolled in the San 
Francisco City Clinic Cohort Study.  Journal of Acquired Immune 
Deficiency Syndromes.  1990:  volume 3, supplement 1, pages S32- 
S37. 

(9) Messiah A, Bucquet D, Mettetal JF, and Rouzioux C.  Sexual 
practices associated with increased risk of HIV infection: the 
danger of self-defined safer-sex?  VI International Conference on 
AIDS, San Francisco June 20-23, 1990 [abstract # S. C. 686]. 

(10) Soderberg LSF and Barnett JB.  Exposure to inhaled isobutyl 
nitrite reduces T cell blastogenesis and antibody responsiveness. 
Fundamental and Applied Toxicology.  1991: volume 17, pages 821- 
824. 

***** Political Funeral in Washington D. C. October 11; Date, 
      Time, Route Changed 

     The political funeral in Washington D. C. (announced in AIDS 
Treatment News #158) has been moved up one day, to Sunday, 
October 11 (which is the last day of the display of the Names 
Project AIDS Memorial Quilt on the Washington Monument grounds). 
The new plan is to meet at the steps of the Capitol building at 
1:00 p. m., and march from there to the White House.  Bring ashes 
of someone who has died, or a picture, or an obituary. 

     For more information, call Shane in New York, 212/866-7967, 
or call David in San Francisco, 415/252-7401. 

***** ACTG Meeting Election Day; Remember Absentee Ballot 

     On November 3-6, in Washington, D. C., several hundred AIDS 
researchers and assistants, and some AIDS activists, will attend 
the thrice-yearly meeting of the AIDS Clinical Trials Group of 
the U. S. National Institute of Allergy and Infectious Diseases. 
Since many of those attending will be traveling to the meeting 
and unable to reach their polling place on November 3, they will 
need to apply for an absentee ballot before the deadline to avoid 
missing the national election.  (In California your application 
for an absentee ballot must reach the elections official by 5:00 
p. m. on October 27; the deadline and rules may vary in other 
states.) For information call your registrar of voters, or a 
local political organization. 

     Anyone who may be unable to get to the polling place due to 
illness or for any other reason should also consider absentee 
voting. 

***** What to Ask of Clinton:  Call for Information 

by John S. James 

     If Clinton wins the presidential election on November 3, his 
transition team will have two months to prepare for the change of 
administrations.  It will be a time of frantic political 
activities, mostly behind the scenes, as thousands of different 
interests try to influence planning and policy decisions and the 
appointment of hundreds of top officials throughout the Federal 
government.  This transition work will mostly wait until after 
November 3, since until then the candidates will be preoccupied 
with the election. 

     How well the AIDS community does in relating, for the first 
time, to a White House which is potentially responsive instead of 
fundamentally hostile, will depend greatly on how well this 
community knows what it wants to ask for -- and when and how to 
best ask for it.  Government cannot come up with successful 
policies by itself; instead, its success will depend on relating 
with the people and organizations who have been working with the 
issues for years.  But the AIDS community has never known a 
responsive White House, and has much to learn about its end of 
the relationship.  There is no time to waste. 

     To promote early discussion and planning, AIDS Treatment 
News will be covering the issues around a potential transition to 
a Clinton administration.  If you have government or political 
experience or have thought much about this matter, you can help 
us by sharing your knowledge and ideas.  What would we want from 
the White House?  Do we want an "AIDS czar," or would it be 
better to focus on getting good people throughout the government? 
Who should (or should not) be appointed or re-appointed to the 
health-related offices that Clinton's team will fill?  What kind 
of system do we want for providing access to health care?  What 
should we ask for during the transition, and during the first 
hundred days of a new Administration?  How could a president 
signal that it is time to change the widespread denial, 
hostility, and indifference toward AIDS in government, in the 
corporate world, and elsewhere in the national life?  And is 
there any danger that the Democrats might backtrack on one thing 
Bush has done well -- supporting faster FDA action on treatments 
for life-threatening conditions? 

     Send information and comments on these and other White House 
issues to:  attn:  Transition, AIDS Treatment News, P. O. Box 
411256, San Francisco, CA 94114. 

***** 

AIDS TREATMENT NEWS 
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Editor and Publisher: 
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AIDS Treatment News reports on experimental and 
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survivors have usually tried many different treatments, 
and found combinations which work for them.  AIDS 
Treatment News does not recommend particular 
therapies, but seeks to increase the options available. 

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ISSN # 1052-4207 

Copyright 1992 by John S. James.  Permission granted for 
noncommercial reproduction, provided that our address 
and phone number are included if more than short 
quotations are used. 

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Newsgroups: sci.med