GMHC Treatment Issues 1991 Oct 1; 5(7): 4
Since initial reports in September, 1989, that the drug n-
acetylcysteine (NAC) exhibited strong anti-HIV properties in
laboratory experiments, new information has come to light
confirming and expanding these findings. To date, all published
work in this are is from test tube studies. Human drug trials
have only just begun. Naturally, the nearly two-year delay in
initiating a federally sponsored human study is hard to
understand and enormously frustrating, especially since the
drug looks so promising and is readily available through
buyers' groups and elsewhere.
In September, 1989, two Stanford University microbiologists,
Drs. Leonard and Leonore Herzenberg, announced at a conference
in Switzerland that NAC inhibits HIV activity in test tube
studies. NAC, currently prescribed to treat bronchitis and
Tylenol overdoses, works by raising blood levels of a substance
called glutathione. This substance has been found in levels
well below the average in many HIV-infected individuals. It
is thought that glutathione is necessary to moderate the
effects of tumor necrosis factor (TNF), a naturally-occurring
protein which may trigger HIV activity in the body. TNF has
been found in elevated levels in people with AIDS.
The Herzenbergs published other findings in June, 1990, showing
that TNF stimulation of HIV activity can be inhibited by adding
NAC to HIV-infected cells. These results were later confirmed
in another study. In fact, low levels of glutathione appear
to correlate with over-sensitivity to TNF, implying that
keeping glutathione at a normal level may prevent HIV
activation. In February, 1991, work by NIAID scientists,
including Dr. Anthony Fauci, who has conducted much research
with TNF and HIV, revealed that NAC suppresses TNG-triggered
Additional test tube work published in June, 1991, indicates
that NAC works in both recently-infected and
chronically-infected T-cells and monocyte cells. This is a
potentially important finding, considering the immune function
of T-cells and the fact that monocytes are reservoirs for HIV
in the body.
The first of a total of twelve HIV-infected participants have
enrolled in a NIAID study of NAC in Bethesda, Maryland in May,
1991. This phase I study is designed to last approximately one
year and will test the safety and pharmacokinetics of the drug.
Patients with T4 cells under 500 will be divided into three
four-person groups. Both oral NAC (administered at home) and
intravenous (IV) NAC (administered three times weekly at a
clinic) will be given for a period of six weeks. Oral doses are
150 mg, 300 mg or 600 mg every 6 hours in the form of an
effervescent tablet dissolved in water. The first of the three
groups is now being completed, and so far no changes in
surrogate markers (T4 cells, etc.) have been noted. Patient
recruitment is currently in progress for the second group but
cost constraints limit it to people living within a 100-mile
radius of Bethesda. Recruitment is still open, and more
information can be obtained by contacting Chris Boenning, RN at
1-800-772-5464 ext. 401.
Additional results of NAC are, for the most part, anecdotal and
can lead to widely divergent conclusions. One patient featured
in a December 10, 1989 New York Newsday article who had been
taking NAC since January, 1989, died recently of lymphoma.
However, another long-term NAC recipient, taking the drug for
almost three years, has seen T4 cells increase from 300 to 450
and p24 levels drop sharply to near zero. NAC is available
through various buyers' groups that import different brands
One common brand, Fluimucil, is available in a 600 mg tablet.
In general, Fluimucil is taken two or three times daily by many
PWAs experimenting with the drug. Treatment Issues has also
heard that some people are taking doses as low as 90 mg per
day. It is unclear whether this dosing will result in levels
comparable to those which were necessary to inhibit HIV in the
test tube. The number of people taking NAC remains fairly high.
The PWA Health Group in New York indicates that the drug is
their second-highest seller (after ddC), with about 150
customers monthly. The approximate cost of taking NAC three
times daily is approximately $2.25-$3.50 per day. To buy the
drug or get more information, call the PWA Health Group at
Side effects and toxicity of NAC appear to be low but may
involve infrequent allergic reactions, nausea, vomiting and
fevers. There have been reports that NAC is also available
through certain health food companies. However, it is likely
that drugs produced under supervision at a pharmaceutical
company may result in better quality control. It is believed
NAC must be wrapped in foil (as Fluimucil is) to prevent
potentially damaging exposure to air.
NAC has a relatively brief half-life of 5-6 hours in the body,
implying frequent dosing to maintain appropriate levels of drug
in the blood. Twenty to 25% of oral and intravenous NAC is
eliminated unchanged in urine, raising questions about the
degree to which the drug is absorbed in the body.
Trials of another TNF-inhibiting drug, pentoxifylline, are in
development at the NIH. A recent report has emerged that the
FDA has granted the go-ahead to Clintec Nutrition Co. for a
phase I trial of a glutathione-raising substance called
Procysteine. Clintec reports that this trial will begin
1. Eck, HP et al. Low concentrations of acid soluble thiol
(cysteine) in the blood plasma of HIV-1 infected patients. Biol
Chem Hoppe-Seyler 370:101-108, Feb 1989.
2. Lahdevirta J et al. Am J Med 85:289-291, 1988.
3. Roederer M et al. Cytokine-stimulated human
innumodeficiency virus is inhibited by N-acetyl-L-cysteine.
Proc of Nat Acad of Sciences 87 (12):4884-8, 1990; and Staal et
al. Intracellular thiols regulate activation of nuclear factor
kappa B and transcription of human innumodeficiency virus. Proc
Nat Acad of Sciences 87(24):9943-7, 1991.
4. Kalebic et al. Suppression of human immunodeficiency
virus expression in chronically infected monocytic cells by
glutathione, glutathione ester, and N-acetylcysteine. Proc of
Nat Acad of Sciences 88(3):986-990, 1991.
5. Roederer at al. N-acetylcysteine inhibits latent HIV
expression in chronically infected cells. AIDS Research and
Human Retroviruses 7(6):563-567, 1991.
6. Personal communication, Dr. R. Walker.
7. Personal communication, Dr. Leonore Herzenberg.
Copyright (c) 1991 - Gay Men's Health Crisis. Non-commercial
reproduction encouraged. Distributed by AEGIS, your online
gateway to a world of people, knowledge, and resources. Direct
Dial: v.34+: 714.248.2836; v.120/ISDN: 714.248.0433 Internet:
telnet:aegis.com www: www.aegis.com