[music]
It's a pleasure to be withyou this evening.
This topic concerning AIDsis an interesting topic to me,
and I might preface my remarks by saying
that it's had a real impact personally
in that in 1981 when I journeyed
to New York City to completemy internal medicine training
in the BigApple is actually when the advent
of the first published articles
on the acquired immunedeficiency were found in the literature.
Are we all set up for slides there?
[?]
Oh.
Let's go back here.
As I mentioned, in 1981,
the first article came out
about June 5th or 8th and described about
five patients who came down withpneumocystis carinii pneumonia.
These patients were homosexuals.
They had no other underlyingimmunodeficiency,
which is what made that occurrence unique.
Some 30 days later,
the second article about the acquiredimmune deficiency appeared in MMWR,
this time describing some 26patients with a rare tumor,
Kaposi sarcoma in a disseminated form,
something which had not been seenexcept in Equatorial Africa.
Also, these patients were uniquein that they were all male homosexuals.
I can remember in grandrounds in 1981 having
various professors come from NYUand presenting their spiel on what later
became known as the acquiredimmune deficiency.
At that point, they were callingit GRID or gay-related immunodeficiency.
However,that definition or characterization
was soon to have to changebecause it became
obvious that another group of people
were at high riskfor the acquisition of AIDs.
These were identified,as you all know, as IV drug abusers.
They have remainedan important part of the acquired
immune deficiency since that discovery.
Also, other risk groups,as you're well aware,
were identified as being at risk for AIDs,
these included hemophiliacs,patients who received,
in particularly, factor VIII concentrate.
There were some other groups identified,in particular,
at that time, Haitians were identified
in New York City area in the Miami area
as being at increased risk for acquiringthis immunodeficiency syndrome.
A lot of water has goneunder the bridge since those first cases,
since defining what acquiredimmune deficiency was, i.e.
an opportunistic infection occurring
in a personin whom there was no underlying
risk for that infection and no antecedent
history of an immuno-compromising disease.
Basically, that boiled down to patients
who were coming up with Kaposi sarcoma,pneumocystis carinii pneumonia.
There are other immuno-compromising
or opportunistic infections that qualify,but most of the patients,
almost 60% to 70%of the patients were presenting
initially with pneumocystis cariniipneumonia and a high percentage
with either pneumocystis cariniipneumonia and Kaposi sarcoma.
I can well rememberthe laundry list of possible
etiologies for the acquiredimmune deficiency,
which were discussedin New York City when I was there.
They included everythingfrom the use of inhaled nitrates,
abuse of nitrates in all kinds of forms,
and I needn't get into all the manner
in which they were abusedby the homosexual population there.
It also include theoriesabout antigenic overload,
ideas that these people
had had so many sexuallytransmitted diseases,
or were exposedto so many infectious disease
processes through sharingneedles and acquiring
that eventually their immunesystems just simply
broke down under the loadof all these infections.
We know that all these patientshad a large laundry list of infections.
They were exposed to CMV infections,
they were exposedto Epstein–Barr virus infections,
they were into numerous--
Hepatitis B becameone of the classic things
that it had seemed that all these riskgroups had in common.
People speculated that a fungus,
I can well remembergoing to an [?] convention,
our biggest conventionin the infectious disease world,
and hearing a very well-presented case
on a fungal toxin that was produced
that caused suppressionof the helper T cell suppression ratio.
As we all know, that didn't pan out.
Due to the efforts of Dr. Galloworking from the NCI
and almost simultaneously,actually reported
a little bit earlier before Gallo did,researchers from the from Paris,
from the Pasteur Institutediscovered or isolated the virus.
In the case of the Parisian researchers,
they isolated the virusfrom a patient who had a prodrome,
what we call ARC or AIDs-related complex.
They later isolated that virus,that same virus, which they called LAV,
or lymphadenopathy-associatedvirus from a full-blown case of AIDs.
The work, I believe,
of Dr. Gallo from the NCIwas a little bit more elegant.
The announcement by the French researcherswent basically unnoticed.
Dr. Gallo, however,
had had a long interest in viruses,in particular,
viruses which caused cancer or leukemias,
and he had been involvedwith a group of retroviruses,
had identified, I believe,what we call HTLV-1 which is associated
with the cause of a certain typeof leukemia a T cell leukemia in certain
Japanese and other third world countries,
and so it was not unnaturalfor him to suspect that a virus,
a retrovirus, that had the propertyof seeking out helper T cells,
in particular,might be associated with the etiology
of the acquired immunedeficiency syndrome.
Not to go through all the laboriousexperiments he did,
but in April of 1983,he announced in conjunction with Margaret
Heckler and James Mason from the CDC,that the cause,
the etiology of AIDs had been isolated,and they termed it HTLV-III
or the human T Lymphotropicvirus number three.
We'd found the virus.
There was good evidencethat it was the virus, i.e.
patients who had prodromal AIDs or ARC
had a very high percentageof antibody to the HTLV-III virus.
Patients who had AIDs had very high, 99%
98% of the patients with full-blownAIDs had antibody to HTLV-III.
In addition, a certain groupwho had only lymphadenopathy,
generalized lymphadenopathy,but who were not ill
as in the age-related complex typeof disease, also were found to have this.
In conjunction with that,
heterosexuals in the communitywho had no risk factors,
had a very, very low incidence of this.
The evidence looked very good
and very convincing that the virus
had been identified and great hopes
arose that this virus would be controlled
and that we would soon have a vaccinewhich would prevent this prevent
its occurrence and that everythingwould be all right with AIDs.
Such as we know [?]was not to be the case,
and AIDs has progresseddespite the identification of this.
If we have time tonight,I would like to talk about
a few of the things that are being done.
I would like to talk to you aboutwhat does positive HTLV-III serology mean
and I'd like to bring you upto date on how many people
are afflicted with this disease
and some of the projectionswe have are making
as to how far this diseaseshould spread in the near future.
This is an updated list.
The columns don't exactly add up.
Every time I would sit down and read
one of the medical journalsor one of the bulletins,
one of these numberswas changing and in fact at the CDC,
over 30 new casesa day are being reported.
That's probably an underreportingof the actual incidents of these cases
and there are probably perhapsdouble that actually occurring,
but this is what we formallyhave and this is official
as of about September the 10th.
As you can see, we had at that point,14,000 total cases, 14,125.
The majority of these patientswere homosexual,
bisexualas that was the identified risk factor
and that constituted about 73%
That percentage has pretty muchheld up over the last year or so.
The next largest group IVdrug users were at about 2,301,
and made up about 17%of those patients who have developed AIDS.
Hemophilias have made up a relatively
small amount of those who have acquiredAIDS at this time compromising
basically about 1% of the total cases.
Transfusionshave not really been a major factor
and only amount to about1.5% of all AIDS cases.
Other category is defined by the CDC
as no specific riskfactors could be identified.
I want to come back
to that particular categorybecause I think
it has some special meaningor may have some special meaning.
Third-world born now was previouslybasically the Haitian group.
CDC recognized that being Haitian,in and of itself,
was not the primary riskfactor for acquiring
AIDS and that indeedpractices within Haiti.
Male homosexual prostitutesand heterosexual men
who prostituted themselves for money,
acting as male homosexual prostitutes,
and also the use of needles and voodoo,
legitimate use of needlesin the medical profession,
not sterilizing needles, reusing needles,
and voodoo practices basically accounted
for what was occurringin this third world country and others.
Now all of the Caribbeanincidences and some of those remotely
from Africa are includedin this category of third-world born.
Other, as I mentioned,no identifiable risks.
Now I bring your attentionto the heterosexual
and what is meant by heterosexual spread.
This perhaps has more meaningto us here is, I think,
we have to watch this categoryvery carefully in the future.
This was defined by CDCas patients who had had sexual contact
with an AIDS personand had acquired disease that way,
had a clear cut history of that.
It would have to now be extended
to include patients who had sexual contact
with a person who is positive for HTLV-IIIserology or for the virus.
Now, I have not listedthe male-female breakdown here,
but suffice it to say,there's only been about,
800, 900 cases of totalfemale cases reported to CDC.
This is not a very high percentageof cases and it has been argued
that that's one evidencethat this disease is primarily,
males are at primarily at risk.
The disease is not transferredwell from females to males.
I don't believe that logic holds up.
These heterosexuals,
the majorityof these are females and about
15 or 18 of those are males of the 137under the heterosexual category.
It is believed that these femaleshaving had sexual contact
with a male, received the disease.
Now, we know that the acquiredimmune deficiency,
virus, HTLV-III is found in the blood.
We know that it's foundin high concentrations in the semen.
We know that it's found in the salivaat low concentrations and we know
that has been isolated from tearsalso in low concentrations.
Most body fluids it's believed,
eventually provedto have HTLV-III virus in them.
It's a matter of how easily
those particular bodyfluids spread the disease,
but blood is an effective transmitterof the disease,
as is semen, for sure.
Now, this is just a reviewof the modes of transmission of HTLV-III.
Homosexual contact is a very effectivemeans of spreading the disease.
It's been felt that anal intercourseis a particularly effective method
for spreading the disease.
We do not know the risks of other forms
of sexual contact or homosexual activity,
but we suspect that they also are at risk
of exchanges of body fluids are involved.
We know by historythat parenteral blood products
are an effective means of deliveringthe virus and causing infection.
IV drug abuse,
basically needle sharing is the meanswhereby the virus can be spread.
Knowing this causeda great deal of concern
about needlestick injuriesin hospital personnel
and what would happento them and would they become
infected with the HTLV-III virus.
Blood transfusion products we know
are an effective meansif you're giving large quantities
of blood with a blood transfusion
and it's an effective meansof transmitting the virus.
Factor VIII concentratesalso a blood product,
and we know as an effective means.
We now know that, for example,
in homosexualswithin New York City are running
between 70% and 80%seropositivity as a group.
This basically holds upin other large metropolitan
areas where there's a significanthomosexual population.
There's a great dealof virus around there.
We know that hemophiliacsare running about at 80% seropositivity,
as a group and we knowthat IV drug abusers
in large cities are also runningabout the same level,
between 70% and 80% seropositivity.
Now, we don't know,unfortunately, how long,
in most cases,that has taken this group to become
seropositive because we don't have bankedsera back years
in the past for some of these risk groups.
There was a cohort,however, in San Francisco,
that studied male homosexual patientsin whom they had sera from 1978,
and that sera in 1978of that cohort ran about
4.5% seropositivityfor the HTLV-III virus.
In 1985, that changed, went up to 73%
We know that the evidence for exposure
to the virusis very good in that population
and that's a very effective meansof apparently spreading the virus.
I have assumedand not have told you is that,
what did seropositivityfor the HTLV-III virus mean?
Well, I think we all hoped
that we would findthat it meant protection.
If someone had antibodylevels against HTLV-III,
like rubella, in most instances,
antibody of surfaceantigen in Hepatitis B,
but it meant that an individual
would be protectedand it appears to be unfolding
that seropositivity for HTLV-IIIin man now is a marker for infectivity.
In a study of normal,healthy male homosexuals,
it was found that 80%
who were healthy and had no generalizedlymphadenopathy but were at risk.
Of those positive,virus was isolated in 80% of those.
Additional studies are going on to seeif that's going to hold up,
but it involved a spectrum of patients
who had been seropositivefor varying lengths of time,
and it appeared that the virusremains in the blood
of the seropositiveindividuals for long times.
This may just simplybe a marker for viral positivity
and that's the way most peoplehave chosen to look at the meaning
of the true positive HTLV-III serology.
Now, how do we measure HTLV-IIIserologies and how is it done?
There are two methods.
Some of you may be familiar with that.
We have a very sensitive,test called the ELISA test.
This doesn't missmany of the seropositive patients and does
not miss many of the patientswho have the virus in their blood,
but unfortunately, has a high degreeof sero false positivity.
We have the Western blottest which is very specific.
The combination of those two testsused together is fairly
accurate for identifyingthe true seropositive to HTLV-III.
The American Red Cross currently,as I understand it,
has been using a repeatof the ELISA to identify patients.
Repeat it once. Do it once.
If it's positive, repeat it again.
If it's positive, that person is excluded.
I think they have plansto go ahead and also employ
the Western blot in those patientswho turn up seropositive.
Right now, I think we have to interpret
HTLV-III seropositivityas meaning infectivity.
I think it's important for usas physicians and people employed
in hospitals to recognizehow the AIDS virus is not transmitted.
It is not transmittedthrough household non-sexual contact.
There have been four or five studies,even more perhaps now,
that have identifiedno seropositivity conversions
in household members of AIDS patients
where they've lived with the family
and they have not had sexual contactor have not shared IV needles.
We know that babies bornvertical transmission is possible.
Again, that involvesthe exchange of blood, and hence,
that's the mechanismby which that is transmitted.
Casual contact, householdcontact do not transmit the virus.
A peck on the cheek, a kiss on the cheek,
perhaps a light kiss on the lipsis not known to transmit the virus.
Handshake does not transmit the virus.
Doing a physical examinationdoes not transmit the virus.
You have to have a parenteral exchange
of fluid and that has to be significant.
General nursing care doesnot transmit the virus and routine
lab specimen handlingalso does not transmit the virus.
Even careful autopsyexamination has not been shown.
There's not been a pathologistknown to become seropositive
for HTLV-III or didnot belong to a high-risk group.
I have to mention the study conductedby CDC of 1,758 needle sticks.
In that study, 26 patients turnedup seropositive for HTLV-III.
Of those 26, all but 3 had risk factors,
belonged to one of these majorrisk groups, and hence,
we could account for their seropositivity.
In the remaining three,
one was anonymous and we don't knowanything more about that.
Bruce, are you talkingabout inadvertent accidental
needle stick medicalcenter type of [?] [crosstalk]?
I hope they weren't purposeful. [chuckles]
[?] type of thing?
Yes. These are needlesticks in a healthcare setting
that we're awareof and they included house staff,
physicians, attending physicians,they included nurses,
anybody who was stuck with a needlewhile dealing with an AIDS patient.
Needle goes into the AIDSpatient comes out and is injected,
the needle goesinto the particular healthcare worker.
Of this, only three of themwere positive without risk fast group,
and in two of those, one was anonymous.
We really don't know what was going on.
Two of them,these people were sexually active.
As I hope to point out my closing remarks,
that may have been the means whereby
they actually acquired the HTLV-III virus.
I think, at some point,
somebody's going to sticka needle in themselves
and they're going to get a high enough
inoculum that indeedthe virus will be transmitted
and indeed they will become seropositive.
This is a very unlikely event.
If you're a betting person,you've got the odds in your favor.
Basically, the answeris good for healthcare professionals,
is extremely difficult to acquire
the viral infectionthrough normal healthcare
and even through some of these accidents.
The one case that was suspicious
was a person who'ddealt in the blood bank,
who inoculated himselfon two occasions with units
that unbeknown to himwere actually positive for HTLV-III.
He indeed may have converted on that basis
but 1 out of 1,758 is not bad odds.
Basically, the answeras I mentioned for healthcare people
is that it looks good for us.
Now, there's one erroron this slide that I want to point out.
The spectrum of HTLV-III diseasewhich has now been estimated
now that we have the serologyfor HTLV-III.
Asymptomatic should read 1 million.
It is now estimated that we have
between 500,000 and 1 million asymptomaticpatients
who are positive for HTLV-III serology
and hence probably infective.
It is estimated basedon what we know about the occurrence
of lymphadenopathy and the asymptomaticand the number of AIDS patients
that there are 200,000 or more patientswho have the lymphadenopathy
syndrome and naturallywould be positive for HTLV-III.
It is estimated that there are 100,000patients within the United States
who have the AIDS-related complexand it is also estimated and we know,
as I mentioned,that we have 14,000 plus patients.
Actually,we have 15,500 based on the CDC records
as about three days ago.
It is growing at a fast rate.
Now, what would we predictof these people who are asymptomatic?
How many of them would we predictbased on what we know
about the disease would comedown with a disease?
If there are 1 million asymptomaticpatients,
we know that between 5%and 10% of asymptomatic patients
during a period of about three years,come down with a disease.
We would predictin the next three years that we'll see,
of these asymptomatic patients,
probably 100,000 of themwill come down with AIDS.
Of the lymphadenopathy patients,we suspect that about
15% of those will come down with AIDS.
Of the AIDS-related complex,
between 20% and 25%of those patients should come
down with AIDS in the next three years.
Our skimpy 15,000 patients
is bound to multiply dramatically
in the next few yearsand we have a real problem on our hands.
Now, everyone has takengreat comfort in the fact
that or most everyonehas taken great comfort in the fact
that this diseasehas seemed to only involve
the IV drug abusersand the homosexual population.
There has not been very muchserious consideration
of this being a significant problemamongst the active heterosexual
or the promiscuousheterosexual population.
I think we need to takeanother look at that.
The African AIDS, particularly in Zaire,does not support that.
In fact, in Zaire, studies
that have been donereveal a one-to-one ratio
of male-to-femaleacquisition of the disease.
It is very highly associatedwith prostitution in Zaire.
Hence,it appears that it is very effectively
spread by the prostitutes.
I think we're beingnaive in the United States
to think that this disease only affectsmale homosexuals predominantly
and that they're the only groupthat are at risk.
Every other sexually transmitteddisease we know is basically transmitted
50-50 in terms of risk factorsand may be a few percentages off of that.
We have started to seeand have the first cases
of documented heterosexualspread of the disease.
Walter Reed has reported40 patients of AIDS,
16 of those patients were strictlyheterosexual and their only
risk factors were promiscuityamongst heterosexuals.
As far as they knew,none of this promiscuity
amongst other patients was associated
with any homosexual activityor was associated with homosexuals.
We know that the incubationof this disease can last
from about anywherefrom six months to five plus years.
Some patients in New York
when I was there gave a history
of not having used drugsfor perhaps 7 to 10 years.
We don't knowhow long it takes before the virus
gets in and before it gets going.
I think there's a significant riskthat we have to at least contemplate
for heterosexualtransmission of this disease.
I think the Zaire experience,
the African experiencetells us that once the virus
gets in the heterosexual population.
It has the possibilityof becoming a real plague
amongst the heterosexual population.
My time is running out.
Let me say about therapy,
that a vaccine is not in sightfor at least five years.
There are problems with antigenic drift.
The outer code of this viruschanges dramatically.
Our only hope, we think,is that the core proteins
which are basically 70% stablemight provide an ultimate vaccine.
We don't even knowthat if you get antibody
to that, that is protective.
We do not know how the humanbody effectively deals with this virus.
Is it actually antibody?
Is it some other aspectof the immune system?
There's a great dealwe do not know about that.
A vaccine will probably not be available
for at least five years and onlyunder optimal conditions.
All of the antiviral agentsthe reverse transcriptase inhibitors
so far the three or three majorones that have been employed,
I'm not going to get into names,have not panned out.
At the very best, they have stoppedthe replication of the virus
but have not alteredthe clinical course in one degree.
Hopes for reconstituting the immune system
are basically dependenton finding an agent that stops
at least arreststhe multiplication of the virus
within the human beingand hopefully would cure it.
We have recently found out that HTLV-III
virus infects the central nervous system.
Hence, in order to cure it,you're going to have to get an agent,
which penetratesinto the central nervous system.
it's neurotropicand accounts for the dementia
that we've been seeing in these patients
what was one of the most significantthings I saw
in New York that amazedme is what I call brain [?],
These patients literally became demented,
had brain atrophy, had myelitis,all kinds of neurologic problems,
and brain atrophy and dementia,as I mentioned.
We now know that these virusis also neurotropic.
We have a great many things to do in terms
of getting this particular plagueunder control.
We do know how to stop it.
I'm skeptical that we can't stop it.
Basically,as was mentioned before celibacy,
offers the ultimate solutionthat not being acceptable.
Certainly, monogamous relationships,
which if everyone practicedmonogamous sexual relationships,
that certainly would stop the virus cold.
The only group that would be at risk then
would be the IV drug abusers, basically.
This disease boils down to being a disease
that is practically a sexual disease.
There is a 17%that's transmitted via needles,
in the IV drug abuser, but basically,it's a sexually transmitted disease.
It is preventable.
I think we have to useour education wisely now.
I think it's imperative that we have much
freer use of HTLV-IIIserology amongst health
professionalsand the public health service
to keep track of how fastthis virus is spreading.
I think we've got to getover some of these ridiculous notions
of we have to protect peoplewho have the tests so they can't be used
against them but we needto have access as a medical community
in monitoring this in order to stopwhat could be a very serious plague.
I thank you for your attention and I think
I'll stop with this last slide.
In the words of [?] [chuckles]
I think we have some concernabout heterosexual transmission.
I think that's where to lookfor the new wave
of this disease to take place at.
Thank you very much.
[?] too late.
[applause]