From: dac@sci.ccny.cuny.edu (David A Cooke)
Subject: Re: AIDS risk/Duesberg
Organization: City College of New York - Science Computing Facility
Date: Sun, 10 Jan 1993 04:10:49 GMT

In article <1993Jan6.012008.1059@genie.slhs.udel.edu> starr@genie.slhs.udel.edu (Tim Starr) writes:
>In article <1993Jan5.030659.11086@sci.ccny.cuny.edu> dac@sci.ccny.cuny.edu (David A Cooke) writes:
>}
>}	Yes, there have been a few individuals with AIDS who have been
>}HIV-.  Several cases of this were brought up at the last international
>}conference on AIDS.  This doesn't really support the arguments of those
>}who argue that HIV doesn not cause AIDS, however.  Most tests for AIDS
>}are indirect, and given the AIDS virus' obscenely high mutation rate,
>}it wouldn't be at all improbable that it will periodically mutate
>}sufficiently that it won't show up on the standard tests.
>
>I'm curious about this mutation rate.  It seems to conflict with the stable
>estimates of the US HIV+ population based upon tests of those entering the
>military.  Will you please elaborate on this?

	HIV has a fairly sloppy reverse transcriptase, which is involved
in translating the virus' RNA into DNA.  As a result, errors are common,
leading to mutations.  There are some constraints on the degree of mutation,
however, since the virus must be sufficiently similar to its progenitor to
function.  
	I'm not entirely sure I understand your question, but I'll go with
what I think you are asking.  The main screening test for AIDS tests for 
the presence of anti-HIV antibodies.  This will catch most HIV-infected
individuals, although there are a small number of people who, for unknown
reasons, don't produce a detectable anti-HIV response despite being HIV
infected.  If an individual tests postive on the antibody test, a second
test, usually a Western blot as far as I know, is performed to verify the
results of the first.  This test checks for the presence of known HIV 
proteins, so it is more definitive than the antibody test.  There is also
a new test out that uses the Polymerase Chain Reaction (PCR) to check
for viral DNA, but I don't know how widely it is being used.  All of these
tests are subject to error because the antibody and Western blot tests
involve particular viral proteins, and the PCR test involves known
sequences of viral DNA.  If the virus from a given individual is sufficiently
mutated that its proteins or DNA no longer resemble those used on the test,
the test won't work.
	This isn't likely to happen often, because of the viability constraints
I mentioned earlier.  Mutations do occur frequently, and a lot of them render
the resultant virus non-viable.  However, since there are thousands of copies
being made and because the replication has a low biologic cost relative to
higher organisms, this is of relatively little consequence.  Others mutations
may produce an altered virus that is still functional, but these are likely to
still be fairly similar to the original, and hence will show up on the tests.
Given enough time and rounds of replication, however, accumulations of 
successive mutations can produce a protein that still fulfils its function,
but is quite different from the starting protein.  This is statistically
unlikely, but can happen eventually.  Most mutations are much less dramatic.
	For this reason, the tests are going to show a fairly constant
HIV+ population because the virus just doesn't achieve this degree of mutation
very often. 
 
>}	If the second possibility is true, it would only disprove the
>}HIV-AIDS link in the strictest sense.  The existence of other viruses
>}that produce syndromes clinically nearly indistinguishable from AIDS
>}does not imply that HIV doesn't cause AIDS.  It simply means that
>}AIDS, like pneumonia, can have more than one causative agent.  The
>}evidence that HIV is far and away the major culprit, if not the only
>}possible one, is overwhelming.  As far as I know, there are less than
>}a hundred known HIV- AIDS cases.  There are hundreds of thousands of
>}HIV+ AIDS cases.  This is a very tight association, and the exceptions,
>}if they are truly exceptions at all, are not sufficient to challenge
>}the rule.
>
>The problem would seem really to be the relatively high number of HIV+
>people without AIDS, which I've heard is about 1.5 million in the USA.  There
>have been predictions that they'd start contracting AIDS in droves, but
>this hasn't happened, leading Gallo of NIH to extend the "dormancy" period
>to between 12 and 30 years.

	I'm not familiar with this particular problem or Gallo's ideas on
the subject, but the current working estimate, at least that given to AIDS
educators, is that the virus has a 8-10 year latency period.  Given that,
people getting sick now were mostly infected around 1982-1984, when the 
infection prevalence was lower.  According to figures on AIDS deaths I
have from the May-June 1992 Michigan HIV Report, 91% of those diagnosed
prior to 1986 nationally have died, and the percentages decrease with
each subsequent year, as would be expected given the latency period.
Unfortunately, I only have a portion of the report available, and the
table doesn't state whether these figures are based on positive HIV
tests, clinical diagnosis of AIDS symptoms, or both, so I can't give 
a more solid answer to your question.  Perhaps someone out there has
more complete data handy?  

		-David Cooke


-- 
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David A. Cooke |First-Year Medical Student| (1) dac@sci.ccny.cuny.edu 
               |  University of Michigan  | (2) David.A.Cooke@um.cc.umich.edu
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