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Nitrite Inhalants: History, Epidemiology, and Possible Links to AIDS

Authors:

Abstract

Nitrite inhalants have been commonly abused substances in the United States. Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use in the USA waned. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in a few laboratory studies, and it remains a candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal.
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Nitrite
Inhalants:
History,
Epidemiology,
and
Possible
Links
to
AIDS
Harry
W
Haverkos,
Andrea
N.
Kopstein,1
Hank
Wilson,
and
Peter
Drotman3
1National
Institute
on
Drug
Abuse,
Rockville,
MD
20857,
USA;
2Committee
to
Monitor
Poppers,
San
Francisco,
CA
94102
USA;
and
3National
Center
for
Infectious
Diseases,
Centers
for
Disease
Control
and
Prevention,
Atlanta,
GA
30333
USA
Nitrite
inhalants
are
commonly
abused
substances
in
the
United
States,
primarily
by
homosexual
men
and
others
who
use
nitrites
to
facilitate
sexual
intercourse
and/or
produce
euphoria
(1-4).
Scientific
interest
in
nitrites
increased
in
the
1980s
due
to
their
possible
links
to
AIDS
(5-11).
In
this
paper
we
review
the
history,
appli-
cations,
and
prevalence
of
use
of
nitrite
inhalants.
We
present
the
hypotheses
link-
ing
their
use
to
AIDS.
We
provide
sugges-
tions
to
physicians,
community
leaders,
policymakers,
and
researchers
on
what
they
can
do
to
limit
the
use
of
nitrites.
History
and
Clinical
Uses
The
alkyl
nitrites
(e.g.,
amyl,
butyl,
iso-
propyl)
are
colorless
or
yellow
liquids
at
room
temperature
and
are
highly
volatile.
They
are
esters
of
nitrous
acid
that
have
a
fruity
odor
(often
described
as
unpleasant)
and
have
been
nicknamed
"poppers"
because
of
the
sound
made
when
glass
capsules
con-
taining
amyl
nitrite
are
crushed
(12).
The
vasodilatory
effect
following
inhalation
of
amyl
nitrite
vapor
was
described
in
1859
and
led
to
the
first
report
of
its
clinical
application
to
provide
relief
for
angina
pectoris
in
1867
(13,14).
In
the
1880s,
butyl
nitrites
were
found
to
have
similar
vasodilatory
qualities,
but
these
compounds
were
never
developed
for
clinical
use
(12).
Amyl
nitrite
was
initially
marketed
as
a
prescription
drug
in
the
United
States
in
1937
and
remained
a
prescription
drug
until
September
1960,
when
the
Food
and
Drug
Administration
(FDA)
eliminated
the
prescription
requirement.
In
the
1960s,
nitroglycerin
sublingual
tablets,
dermally
applied
ointments,
and,
later,
transdermal
patches
began
to
replace
amyl
nitrite
as
the
preferred
treatment
for
angina
pectoris.
In
the
late
1960s,
pharmacists
and
drug
man-
ufacturers
noticed
widespread
purchases
of
amyl
nitrite
by
apparently
healthy
young
men.
These
over-the-counter
purchases
became
the
impetus
for
the
FDA
to
rein-
state
the
prescription
requirement
in
1968.
Since
then
an
underground
market
for
amyl
nitrite
has
emerged
(15).
For
the
last
few
years,
there
has
been
no
medical
adver-
tising
for
pharmaceutical-grade
amyl
nitrite,
and
it
is
no
longer
listed
in
the
Physician's
Desk
Reference
(16).
Amyl
nitrite
remains
available
by
pre-
scription.
The
clinical
indication
listed
in
the
package
insert
is
angina
pectoris
(17).
Amyl
nitrite
is
used
experimentally
to
treat
cyanide
poisoning.
The
drug
produces
methemoglobin,
which
has
a
high
affinity
for
cyanide,
and
leads
to
the
production
of
cyanomethemoglobin,
releasing
cyanide
from
cell
mitochondrial
cytochrome
oxidase
sites,
where
it
is
otherwise
destructive
(18).
When
amyl
nitrite
became
difficult
to
procure
for
nonmedical
or
recreational
pur-
poses
during
the
1970s,
there
was
a
prolif-
eration
of
butyl
nitrite
products
by
non-
pharmaceutical
manufacturers
(15).
Butyl
nitrites
were
marketed
as
"liquid
incense"
or
"room
odorizers."
Because
the
labels
on
bottles
containing
butyl
nitrites
stated
that
they
were
not
to
be
inhaled
and
no
health
claim
was
made,
the
FDA
never
had
juris-
diction
over
this
product
as
it
does
medi-
cine
and
many
foods.
The
legal
status
of
some
key
nitrite
preparations has
changed
in
the
past
few
years.
One
development
prompting
this
change
has
been
the
description
of
several
acute
and
chronic
adverse
effects
attributed
to
the
abuse
of
nitrite
inhalants
(15).
In
response
to
those
reports,
the
U.S.
Congress
enacted
a
ban
on
the
manufac-
ture
and
retail
sale
of
butyl
nitrites
(except
when
used
in
specified
chemical
commer-
cial
processes)
in
the
Anti-Drug
Abuse
Act
of
1988
(Public
Law
100-690,
Section
2404).
The
law
specified
that
the
Con-
sumer
Product
Safety
Commission
(not
the
FDA)
would
enforce
the
ban.
However,
to
circumvent
the
clear
intent
of
the
law,
nitrite
manufacturers
began
to
sell
other
nitrite
alkyl
congeners,
such
as
isopropyl
nitrite,
as
"new
and
improved"
room
odor-
izers.
In
1990,
Congress
outlawed
manu-
facture
and
sale
of
alkyl
nitrites
in
the
Omnibus
Crime
Bill
(Public
Law
101-647,
Section
3202).
Since
then,
at
least
one
manufacturer
has
developed
a
cyclohexyl
nitrite
inhalant
and
marketed
it
diversely.
According
to
chemical
nomenclature,
cyclohexyl
nitrites
are
not
in
the
same
class
as
alkyl
nitrites
and
therefore
may
not
be
banned
under
current
federal
law.
Underground
manufacturers
and
importers
continue
to
market
butyl
and
isopropyl
nitrites
illegally.
The
acute
toxicity
of
inhaled
and
ingested
nitrites
in
humans
includes
skin
irritations
(especially
around
the
nose
and
lips),
tracheobronchial
irritation,
headache,
hypotension,
cyanosis,
methemoglobine-
Nitrite
'in'alat's
have
been
commonly
:
abused
sR
e&
ins
la
the
nIted
tates.
Nitre
ixa
m
s
a
npopular
topic
in
the
early
1980sX
tecu
of
AIDSWas
not
k
Wn.
With
the
discovery
of
HIV,
concern
about
nitrite
use
in
the
USA
waned.
However
nitrite
inhalant
use
is
asoiae
wit
baaiorl
reaaead
HW
t.t.
n.mX.g......
w...`
n
ad.
`HgaZ..
nW
l t
dKcre£'.L''p
te.
cn.
an
natural
killer
cel
activity
in
a
few
labitory
stud-
ies,
d
t:r
a
c
ec
tor
in
the
patdge-nesis
of
AIbS-rele
Kaposi's
sarcomia.
Discourap
g
ir
:continues
to
be
a
wordiwhll&pubiic
health
jI.il
Key
o.rd:
AD5
HI
infection'
Inimunosup-
pressio....
Kpoi's.
sarcoma,
nitrite
;$
ir
behaor.
Envmn
Health
Perspect
102:858-861
(1994)
mia,
intoxication,
and,
rarely,
death
(15).
Other
effects
include
development
of
habitual
use
patterns,
tolerance,
and
burns
resulting
from
inadvertent
ignition
of
the
vapor.
The
National
Toxicology
Program
of
the
National
Institute
of
Environmental
Health
Sciences
evaluated
mice
and
rats
exposed
short
term
(6
hr/day
for
14
days
and
13
weeks)
to
inhaled
isobutyl
nitrite
at
concentrations
ranging
from
0
to
800
ppm
and
noted
several
adverse
effects.
Rats
exposed
to
greater
than
600
ppm
died
dur-
ing
the
14-day
studies.
At
lower
exposure
levels,
the
most
striking
lesion
seen
in
mice
was
hyperplasia
of
the
nasal
mucosa
and
bronchial
and
bronchiolar
tree.
Methemoglobinemia
was
confirmed.
Other
adversely
affected
organs
included
the
liver,
spleen,
thymus,
and
bone
mar-
row
(19).
Prevalence
of
Nonmedical
Nitrite
Use
Alkyl
nitrites
are
among
the
most
com-
monly
used
inhalants
in
the
United
States.
Other
commonly
abused
inhalants
are
nitrous
oxide,
gasoline,
glues,
and
solvents,
such
as
paint
thinners.
The
National
Institute
on
Drug
Abuse
has
collected
information
concerning
nitrite
inhalant
use
among
high
school
seniors
since
1979.
Eleven
percent
of
high
school
seniors
interviewed
in
1979
reported
ever
using
nitrites.
Use
has
decreased
consistently
among
seniors
since
1980,
to
1.5%
for
the
class
of
1992
(20).
According
to
national
surveys,
self-
reported
amyl
and
butyl
nitrite
use
varies
by
gender,
region,
and
race.
Male
high
school
seniors
reported
higher
rates
of
Address
correspondence
to
H.
W.
Haverkos,
Room
1OA-38,
NIDA,
5600
Fishers
Lane,
Rockville,
MD
20857
USA.
We
thank
Peter
Delany,
William
Grace,
and
Vincent
Smeriglio
for
reviewing
the
paper
and
providing
helpful
comments.
Received
2
June
1994;
accepted
25
July
1994.
Environmental
Health
Perspectives
858
I
..
. . . . s i
1i
1ifi
S
M
M
Mfi
&
E
F1
diJ
1&-
-
j
f
Il
A
g-.
inhalant
use
and
nitrite
use
than
females.
The
proportion
of
males
who
used
nitrites
at
least
once
was
typically
twice
the
per-
centage
of
females
reporting
lifetime
use
(20).
The
highest
rate
of
nitrite
use
report-
ed
by
high
school
seniors
in
1979
was
in
the
Northeast,
and
the
lowest
rate
was
reported
in
the
West.
Rates
have
decreased
markedly
in
all
regions,
with
the
highest
rates
in
1992
reported
in
the
North-
Central
United
States
and
the
lowest
rates
in
the
Northeast
(21).
Nitrite
use
varies
by
race/ethnicity
as
well
as
geographic
area.
Although
racial/ethnic
data
are
not
available
for
high
school
seniors,
the
Public
Health
Service-
sponsored
National
Household
Survey
provides
limited
population-based
esti-
mates.
Self-reported
nitrite
use
in
1991
was
highest
for
white
males
in
each of
six
selected
metropolitan
areas
for
which
data
were
analyzable.
National
estimates
of
use
by
females
was
1.3%
for
white
females
in
1991,
0.7%
for
black
females,
and
0.8%
for
Hispanic
females
(22).
Nitrite
use
has
been
commonly
reported
among
homosexual
men
for
several
decades,
but
less
so
for
self-identified
het-
erosexual
adolescents
and
adults.
In
1981,
Centers
for
Disease
Control
and
Pre-
vention
(CDC)
investigators
surveyed
420
men
attending
sexually
transmitted
disease
clinics
in
New
York,
San
Francisco,
and
Atlanta
and
found
that
242
of
279
(86%)
homosexual/bisexual
men
compared
with
21
of
141
(15%)
heterosexual
men
report-
ed
any
use
of
nitrite
inhalants
within
the
previous
5
years
(6).
Almost
all
gay
men
enrolled
in
an
AIDS
case-control
study
conducted
by
CDC
in
1981
reported
use
of
nitrites
(23).
Other
studies
of
gay
men
in
the
United
States,
Canada,
and
Europe
found
high
rates
of
nitrite
use
(24-29).
A
multisite
study
demonstrated
a
marked
decrease
of
nitrite
use
among
gay
men
from
66%
to
about
35%
between
1984
and
1989
(L.
Jacobson,
personal
commu-
nication).
Possible
explanations
for
this
trend
include
increased
awareness
of
adverse
effects,
including
concern
about
nitrites'
possible
links
to
AIDS,
and
decreased
availability
after
nitrites
were
banned
as
consumer
products
(30).
Hypotheses
Linking
Nitrites
and
AIDS
At
least
four
separate
hypotheses
have
been
proposed
that
suggest
a
role
for
nitrites
in
the
pathogenesis
of
AIDS.
When
AIDS
cases
were
first
recognized
in
1981,
nitrites
were
proposed
as
a
possible
cause
of
the
new
syndrome
(5,6).
Nitrite
abuse
was
virtually
universal
among
the
gay
men
diagnosed
with
AIDS
in
1980-1983.
However,
this
hypothesis
was
dismissed
when
the
disease
was
recognized
among
drug
injectors,
hemophiliacs,
and
other
heterosexual
men
and
women
who
did
not
consistently
report
using
nitrites.
In
1983
and
1984,
human
immunodeficiency
virus
(HIV)
was
discovered
and
reported
as
the
cause
of
AIDS
(31,32).
Subsequently,
three
other
hypotheses
suggesting
nitrites
as
promoting
factors
in
AIDS
have
been
proposed.
First,
nitrites
have
been
pro-
posed
to
enhance
HIV
transmission
by
their
association
with
risky
sexual
behaviors
and
HIV
infection
among
gay
men.
Second,
nitrite
use
has
been
associated
with
immune
suppression
and
thus
might
hasten
the
onset
of
symptomatic
disease.
Third,
nitrite
inhalant
use
has
been
associ-
ated
with
the
development
of
AIDS-related
Kaposi's
sarcoma.
Nitrites
and
Sexual
Behavior/HIV
Transmission.
Several
studies
have
linked
nitrite
use
with
risky
sexual
behavior
and/or
HIV
infection
among
gay
men.
Ostrow
et
al.
found
these
associations
in
the
Multicenter
AIDS
Cohort
Study
(29,30).
A
similar
correlation
was
not
found
for
other
substances
of
abuse,
including
alcohol
(30).
Stall
et
al.
(33)
linked
nitrite,
alcohol,
marijuana,
and
other
drug
use
during
sex
with
increased
likelihood
of
"risky"
sexual
behavior
for
HIV
infection
among
gay
men
in
San
Francisco.
They
did
not
identify
a
unique
risk
for
nitrites
independent
of
several
other
drugs
studied
(33).
In
a
longitudinal
study
of
249
gay
men
in
Toronto,
Calzavara
et
al.
(28)
found
a
significant
decline
in
sexual
activities
associated
with
HIV
infection
and
that
nitrites
and
other
drug
use
during
sex
are
strong
predictors
of
continuation
of
high-risk
behaviors
for
HIV
infection.
Among
all
the
variables
tested,
Penkower
et
al.
(34)
found
that
nitrite
inhalant
use
was
the
most
strongly
associated
with
HIV
seropositivity
among
a
cohort
of
1045
gay
men.
Nitrites
and
the
Immune
System.
The
hypothesis
that
nitrite
inhalants
might
induce
immune
suppression
was
first
advanced
by
Goedert
et
al.
in
1982
(8).
T-
lymphocyte
abnormalities
were
reported
in
9
of
10
gay
men
who
reported
regular
nitrite
use
compared
to
1
of
7
who
did
not
use
nitrites
(8).
This
study
came
under
criticism
because
of
its
small
numbers
and
lack
of
evaluation
for
many
potentially
confounding
variables,
including
HIV
infection.
Several
other
investigators
have
evaluat-
ed
the
effects
of
nitrites
on
human
immune
function.
Hersh
et
al.
(35)
cul-
tured
venous
blood
with
up
to
1%
isobutyl
nitrite
in
alcohol
and,
after
24
hr,
observed
irreversible
effects
on
various
lymphocyte
functions,
including
blastogenesis,
cell-
mediated
cytotoxicity,
and
monocyte
adherence.
Dax
et
al.
(36)
at
the
Addiction
Research
Center
studied
the
effects
of
three
inhalations
at
various
concentrations
per
day
for
3
or
18
days
on
the
immune
sys-
tems
of
18
male
volunteers.
One
inhala-
tion
of
amyl
nitrite
(0.18,
0.36,
or
0.48
ml)
was
administered
from
a
closed
4-1
flask
at
3-hr
intervals
each
day
of
study.
After
full
exhalation,
the
subject
inhaled
from
the
flask
through
the
mouthpiece
with
the
nose
"clipped"
and
held
at
full
inspiration
for
5
sec
before
exhalation.
Blood
was
drawn
for
immune
profile
immediately
after
the
last
inhalation
and
1,
4,
and
7
days
later.
Modest
depression
of
T-lymphocyte
counts
and
natural
killer
cell
activity
were
noted
with
a
rebound
to
at
least
baseline
levels
several
days
after
the
last
inhalations.
Cell
proliferation
respons-
es
to
phytohemagglutinin
(PHA),
con-
canavalin
A
(Con
A),
and
pokeweed
mito-
gen
(PWM)
were
unaffected
by
amyl
nitrite
inhalation
(36).
Ross
and
Drew
(37)
interviewed
97
gay
men
in
Australia
and
measured
T-cell
counts
and
mitogenesis
responses
to
PHA,
Con
A,
and
PWM.
T-lymphocyte
counts
did
not
differ
between
nitrite
users
and
nonusers.
Mitogenesis
in
response
to
the
three
antigens
was
significantly
higher
in
users
compared
with
nonusers
after
cells
were
incubated
for
72
hr,
but
the
differences
disappeared
for
PHA
and
Con
A
by
96
hr
(37).
Studies
of
the
immune
system
of
mice
following
nitrite
challenge
are
even
less
consistent
than
those
among
humans.
Studies
evaluating
nitrites'
effects
on
immune
parameters
have
been
hampered
because
formulations
and
dosages
vary
greatly,
and
routes
of
administration
and
immunologic
outcome
measures
have
not
been
standardized.
CDC
investigators
evaluated
the
effects
of
isobutyl
nitrite
on
the
immune
system
of
BALB/c
mice
(38,39).
The
mice
were
exposed
to
either
50
or
300
ppm
isobutyl
nitrite
for
6.5
hr/day,
5
days/week
for
up
to
18
weeks.
Mice
were
sacrificed
at
vari-
ous
times
and
antibody-producing
cells
were
enumerated;
mitogenesis
responses
were
evaluated
to
PHA,
Con
A,
PWM,
and
lipopolysaccharide
and
skin
test
reac-
tions
to
purified
protein
derivative
of
immunized
mice
were
observed.
No
immunotoxic
effects
were
discerned,
although
decreased
thymic
weights
were
noted
for
female
mice
at
the
highest
dose
levels
(38,39).
Other
investigators
have
noted
decreases
in
natural
killer
cell
activity,
helper
lymphocyte
counts,
and/or
body
weight
in
mice
exposed
to
nitrites.
Lotzova
et
al.
(40)
injected
mice
with
0.50
ml
isobutyl
nitrite
and
noted
significant
depression
of
natural
killer
cell
activity
in
female
C57BL/6
x
DBA/2
mice.
Administration
of
isobutyl
nitrite
by
inhalation
(2-
to
3-
min
exposures
twice
daily)
also
suppressed
natural
killer
cell
function
in
mice
(40).
Volume
102,
Number
10,
October
1994
859
-
-
-
-
- e
Ortiz
and
Rivera
(41)
exposed
CD-I
mice
to
increasing
amounts
of
amyl
nitrite
by
nasal
administration
for
up
to
21
weeks.
The
total
T-cell
and
suppressor
cell
counts
did
not
differ
from
mice
exposed
to
saline
solutions.
However,
helper
cell
counts,
body
weight,
and
weight
gain
rates
were
significantly
decreased
in
nitrite-exposed
versus
control
mice
(41).
Soderberg
and
Barnett
(42)
exposed
female
C57BL/6N
mice
to
900
ppm
isobutyl
nitrite
by
inhala-
tion
chamber
for
45
min
per
day
for
14
days.
Body
weight
was
reduced
4%,
mixed-lymphocyte
reaction
(MLR)
was
reduced
50-60%,
and
mitogen
response
to
Con
A
was
reduced
was
reduced
33%
(42).
Although
much
laboratory
work
has
been
done
to
evaluate
nitrites
and
the
immune
system,
it
remains
unclear
whether
continued
nitrite
use
by
HIV-
infected
or
uninfected
individuals
is
immunotoxic.
Nitrites
and
AIDS-related
Kaposi's
Sarcoma.
The
epidemiology
of
Kaposi's
sarcoma
(KS),
the
most
commonly
report-
ed
cancer
among
AIDS
patients,
differs
markedly
from
the
other
opportunistic
dis-
eases
that
have
characterized
the
AIDS
epi-
demic.
KS
has
occurred
much
more
fre-
quently
among
gay
men
with
AIDS
and
much
less
frequently
among
other
AIDS
patients.
Furthermore,
the
rate
of
increase
in
KS
cases
has
been
lower
than
that
of
other
AIDS
indicator
diseases
(43-46).
KS
was
almost
never
seen
in
HIV-infected
blood-transfusion
recipients,
even
when
the
presumed
HIV
donor
developed
KS
(47,48).
KS
was
reported
about
twice
as
often
among
white
gay
men
with
AIDS
than
among
black
gay
men
with
AIDS,
suggesting
an
association
with
increased
socioeconomic
status
or
some
other
factor
(49).
Women
linked
sexually
to
gay
men
were
reported
with
AIDS-related
KS
more
often
than
women
infected
with
HIV
by
heterosexual
contact
with
intravenous
drug
users
(50).
Wide
geographic
variations
of
KS
rates
were
reported
among
gay
men
with
AIDS
in
the
United
States
(50).
These
observations
suggested
that
some
cofactor
highly
associated
with
gay
lifestyle
was
operating
in
conjunction
with
HIV
in
the
pathogenesis
of
AIDS-related
KS.
Nitrite
inhalants
were
suggested
as
one
possible
factor
(10,11,51-56).
There
are
several
reasons
to
consider
nitrite
inhalants
as
a
KS
cofactor.
First,
the
epidemiology
of
nitrite
use
in
the
United
States
parallels
that
of
HIV-related
KS.
Nitrite
inhalants
are
used
more
commonly
by
gay
men
than
others
(6);
use
has
been
declining
since
AIDS
was
first
reported
(30)
and
has
roughly
paralleled
the
pattern
of
reported
KS
cases,
and
use
among
whites
is
greater
than
among
blacks,
as
is
the
incidence
of
KS
(22).
Second,
some,
but
not
all,
epidemiologic
studies
have
shown
a
statistical
association
between
the
development
of
KS
among
gay
men
with
AIDS
and
the
use
of
large
quantities
of
nitrite
inhalants
when
compared
with
gay
men
with
AIDS,
but
without
KS
(11,51-56).
Third,
anecdotal
reports
of
increased
frequency
of
AIDS-related
KS
on
the
chest
and
face,
especially
the
nose,
and
in
the
lungs
are
consistent
with
the
body
areas
most
heavily
exposed
to
nitrite
vapors
when
inhaled.
Finally,
plausible
mecha-
nisms
of
action
have
been
proposed
for
nitrites
and
their
metabolites,
such
as
cho-
lesteryl
nitrite
and
nitrosamines,
to
be
car-
cinogenic,
and
mutagenesis
has
been
demonstrated
in
the
Ames
test
(7,57,58).
Nitrites
are
known
to
affect
small
blood
vessels,
the
anatomic
site
presumed
to
give
rise
to
KS
(12).
Nitrite
inhalants
are
one
of
several
fac-
tors
proposed
as
KS
promoters
in
HIV-
infected
individuals.
Other
KS
cofactors
proposed
include
a
second
sexually
trans-
mitted
agent
and/or
genetic
factors
(48,59465).
Conclusions
In
summary,
nitrite
inhalants
are
common-
ly
abused
substances
in
the
United
States.
Nitrite
inhalants
are
associated
with
behav-
ioral
relapse
and
HIV
transmission
among
gay
men,
with
decreased
lymphocyte
counts
and
natural
killer
cell
activity
in
a
few
laboratory
studies,
and
they
remain
a
candidate
cofactor
in
the
pathogenesis
of
AIDS-related
KS.
Encouraging
the
decline
in
nitrite
abuse
appears
to
be
a
worthwhile
public
health
goal.
The
most
effective
ways
to
accomplish
this
goal
are
not
clear.
In
the
United
States,
laws
banning
nitrite
manu-
facture
and
sale
were
enacted
in
1988
and
1990.
However,
use
of
nitrite
inhalants
had
started
to
decrease
even
before
the
laws
were
implemented.
What
impact
did
dis-
cussions
of
scientific
findings
suggesting
a
link
between
nitrites
and
AIDS,
particular-
ly
as
reported
in
the
predominantly
gay
press,
have
on
nitrite
sales
and
use?
What
impact
did
grass-roots
organizations
dis-
couraging
nitrite
use
have?
What
alterna-
tive
drugs
of
abuse
will
take
the
place
of
nitrites
by
those
who
discontinue
use?
The
search
for
cofactors
in
AIDS-relat-
ed
KS
remains
an
important
scientific
chal-
lenge.
If
the
KS
cofactor(s)
can
be
identi-
fied,
it
may
provide
important
insights
into
the
pathogenesis
of
AIDS
and
possibly
some
forms
of
cancer.
Nitrite
use
is
consis-
tent
with
much
of
the
epidemiology
of
AIDS-related
KS.
Further
studies
of
nitrite
use
and
other
potential
cofactors
among
gay
men
with
KS
as
well
as
women
and
others
with
KS
should
be
encouraged.
Animal
models
exposed
to
retroviruses
and
nitrite
inhalants
should be
pursued.
The
possible
links
of
nitrites
with
AIDS
and
the
other
known
adverse
effects
of
these
inhaled
substances
suggest
that
more
attention
to
these
products
by
clini-
cians
and
researchers
is
warranted.
Clinicians
and
community
leaders
should
discourage
the
use
of
nitrite
inhalants.
Researchers
should
study
further
the
asso-
ciations
between
nitrite
use
and
HIV
infec-
tion
and
AIDS.
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