THE FAUCI FILES, Vol 3(3): The HIV Clade Hoax
January 10, 1999
Leading AIDS researcher Jaap Goudsmit offers some
rather revealing insights into the junk science that has not
only defined HIV "research", but has defined the agenda of
the National Institutes of Health. It was the NIH ex-Direktor
Harold Varmus who was the junk scientist who
proposed the HIV clade classification nonsense --
it was Harold's brown-nosing minions -- including
NIAID Direktor Dr. Anthony "Mussolini" Fauci, who went
forward with the squandering of BILLIONS of dollars of
taxpayer loot in pursuit of the HIV clade nonsense,
especially for the boondoggle research at the southwestern
headquarters for junk science: Los Alamos.
Naturally, the clade hoax has financial implications for
the HIV gp120 hoax spearheaded by Dr. Death himself,
Dr. Donald Francis, president of Vaxgen, the same murderer
who was responsible for seeding the American HIV "epidemic"
through what he termed the "homosexual vaccine" for
Hepatitis B that was contaminated with HIV and KSV (Kaposi's
sarcoma virus). Recently, it was once again Dr. "Death" Francis
who rushed his company's DANGEROUS experimental vaccine
into the bodies of 5,000 Americans in recent months in order
to maximize the windfall for Vaxgen's initial public offering
(that IPO securities scam resulted in a $25 million dollar
payoff for Vaxgen).
While the NIH and FDA continue their Conspiracy of Silence in
regards to the Vaxgen Scam, UCSF's Jay Levy recently reported
on the FACT that the gp120 HIV vaccine could only INCREASE the
likelihood of HIV infection rather than decrease the chances
of infection with HIV! I will soon be publishing evidence in
THE FAUCI FILES that proves that NIAID Direktor Dr. Anthony
"Mussolini" Fauci and his research minions at NIAID were FULLY
AWARE of these dangers SEVERAL YEARS AGO, yet maintained their
conspiracy of silence while Vaxgen's "Dr. Death" Francis went
about getting rich -- once again at the unneeded cost of
human life.
Perhaps the Securities and Exchange Commission might be interested
in the Donald Francis Vaxgen securities scam, that was aided
and abetted by the conspiracy of silence involving
Toni "The Rat" Fauci and the rest of the government regulators
under the corrupt HHS umbrella?
Crooked Murdering Junk Science Bastards!
fred
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Given the preponderance of junk science in AIDS "research", the
objective science is truly a sight for sore eyes. Here are some
important excerpts from the Jaap Goudsmit Viewpoint on HIV clades,
as published in the 9-10/99 International AIDS Vaccine Initiative
(IAVI) Newsletter:
"So far, to my mind, no studies have firmly linked differences in
transmission rate to intrinsic traits of HIV subtypes."
"For HIV-1, which replicates far better than HIV-2, multiple factors
influence the rate of virus production -- but once again, there is no
clear proof that subtype-specific traits play a meaningful role."
"In summary, there is little convincing evidence that inherent
differences among subtypes underlie the observed differences in viral
load, transmission rates or preferential spread."
"Data from another angle also fail to provide evidence for fundamental
and a priori differences among subtypes. Recently Jan Albert in
Sweden compared the rate of progression to AIDS in people living in
Sweden and infected with different subtypes, and found no evidence
for subtype-specific differences."
"These data suggest that the key issue in vaccine design is how to
generate and test a protective immune response against any subtype,
and argue against the view that shifting from studying subtype B to
subtype C will solve all the problems."
"It may be more important to focus on what all HIV subtypes have in
common rather than on how they differ."
=================================
http://www.iavi.org/newsletter_fall99_view.html
IAVI Report - September - October, 1999
A Newsletter on International AIDS Vaccine Research
Viewpoint: Do HIV Clades Really Matter?
By Jaap Goudsmit
Editor's note: "Viewpoint" columns, an occasional feature of the IAVI
Report, are a forum for researchers to present their opinions on key
questions in AIDS vaccines. In this article, Jaap Goudsmit looks at the
politically charged issue of HIV clades from a scientific perspective.
He questions whether they have any real biological meaning, arguing that
there is no evidence for clade-specific genetic differences translating
into differences in how HIV replicates, is transmitted, or causes AIDS.
Nor is it clear whether vaccines will have to be tailored to specific
clades, or whether a "universal" vaccine is possible.
The extensive genetic diversity of HIV is often viewed as a serious
barrier to development of an AIDS vaccine. Far from being a single
virus, HIV is actually a family of related virus types, clades (also
called subtypes) and strains, with the global AIDS epidemic caused by
the eight subtypes of HIV type 1. These subtypes (designated A through
H) differ from one another in about 30% of their total genetic sequence.
Within subtypes, new strains are continuously being generated via HIV's
very high rate of mutation, while genetic recombination -- which
shuffles the genomes of viruses from two different subtypes -- also adds
to the pool of new HIV variants.
Since the discovery of HIV-1 subtypes, there has been fierce debate
about their significance: do their sequence differences translate into
meaningful biological differences (for example, in pathogenicity or rate
of transmission), or is subtype a mostly artificial distinction among
viruses that are biologically much the same? For vaccine development,
the key issue is whether viruses of different subtypes "look" different
to the immune system, which in turn will affect whether a vaccine that
works against one HIV subtype would recognize other subtypes equally
well (or at all). Unfortunately there is too little data to answer these
questions definitively.
The scientific debate on subtypes has also become highly politically
charged. The reason is that the eight HIV-1 subtypes are not evenly
distributed around the world but exist as distinct geographic clusters,
with one or two subtypes dominating particular regions. On top of this,
until very recently AIDS vaccine research has focused almost exclusively
on subtype B, which predominates in Europe, the Americas, Japan and
Australia (although infection rates with this subtype are declining
world-wide), while HIV-1 subtypes A, C, D and the recombinant subtype E
are spreading rapidly in Africa and Asia and cause far more cases of
AIDS globally. This situation has raised concern that current efforts
could yield a vaccine that is effective for industrialized countries but
does not work against the HIV subtypes prevalent in the developing
world. (It is for this reason that IAVI has argued strongly against
concentrating solely on subtype B.) Such an outcome would reinforce the
huge North-South gap that already exists with respect to the
availability of triple drug therapy for HIV-infected people. It would
also be particularly cruel, since lack of access to these effective but
expensive drug treatments gives HIV vaccines an urgency in the
developing world that they do not have in industrial nations. For the
world's poor countries, a vaccine is the only realistic hope for
stopping AIDS.
In asking whether HIV-1 subtypes are biologically distinct entities, the
first issue to consider is their uneven global distribution and unequal
rates of spread. These patterns have sometimes been taken as evidence
for intrinsic biological differences among subtypes. I believe there is
little data to support this notion, and lean strongly towards an
alternative explanation based on what is called a "founder effect."
Once a subtype becomes established in a region (which means it must be
well-adapted to the local host population), a new subtype can infiltrate
the area only if it is transmitted more efficiently in the local risk
population than the already-established subtype. Barring such
differences, the geographic distribution pattern will simply reflect the
HIV subtype(s) that happened to establish first in particular regions.
It is important to realize that a higher transmission rate is not
necessarily due to inherent properties of the virus; a new subtype
can take over simply because it entered a population whose behavior
favors rapid spread (e.g., due to more frequent sexual encounters or
needle-sharing), or whose load of other (non-HIV) infections is higher,
a condition which makes transmission more likely, as discussed below. So
far, to my mind, no studies have firmly linked differences in
transmission rate to intrinsic traits of HIV subtypes.
Similar considerations apply to the spread of inter-subtype recombinant
viruses, several of which are causing new local epidemics in West
Africa, Russia and China. Recent data from the groups of Francine
McCutchan at the Henry M. Jackson Foundation in Washington, D.C.,
Martine Peeters of the University of Montpelier and Marion Cornelissen
in our own lab indicate that over 30% of all new infections in certain
West African countries (e.g., Cameroon) come from recombinant viruses,
while A/B recombinants are spreading rapidly in Russia. Recombinants
presumably arise frequently in people infected with two subtypes, but
they become established only if they are transmitted more rapidly than
the already-present HIVs -- again, either because they have an inherent
ability to spread faster or because the right circumstances for
efficient spread arise. More studies are needed to distinguish between
these possibilities.
One factor that clearly does affect transmission efficiency (and
therefore contributes to preferential spread of particular strains or
subtypes) is viral load, a measure of how fast HIV replicates in a given
host. It is generally accepted that the more HIV an infected person's
cells produce, the likelier that this person will transmit virus. HIV-2
provides a good example: it grows poorly, so infected people have
relatively low viral loads; it also spreads slowly and inefficiently,
causing AIDS in only a few percent of infected individuals and only
after an extremely long incubation time.
For HIV-1, which replicates far better than HIV-2, multiple factors
influence the rate of virus production -- but once again, there is no
clear proof that subtype-specific traits play a meaningful role. For
instance, Berkhout in our lab has shown that reduced replication rates
in a particular HIV strain (engineered in the lab to contain genetic
deletions that weaken the virus) can be compensated by sequence changes
in another region (the LTR) without repairing the original gene defects.
This shows that HIV can walk many pathways towards optimizing virus
production. We have noted several fixed but very different LTR sequence
patterns in distinct lineages of the subtypes - a type of observation
that is frequently misinterpreted as evidence for biological differences
among subtypes. But instead, these variations in LTR sequences could
simply reflect different routes to the common goal of all HIVs: to
produce enough virus particles or infected cells for efficient
transmission.
Other ways in which subtype could influence transmission rate include
affecting the efficiency with which HIV enters host cells or via
fundamental differences in co-receptor usage, but the accumulated data
suggest that this is not the case.
In summary, there is little convincing evidence that inherent
differences among subtypes underlie the observed differences in viral
load, transmission rates or preferential spread. But then what explains
these differences? I believe they reside in the host populations. HIV
grows best in proliferating, rather than resting immune cells (immune
cells replicate when they are mobilizing to fight an infection). So
people with other active infections, such as malaria or TB (both
widespread in many developing countries) provide more favorable
conditions for HIV replication, which in turn means higher viral loads
and therefore more efficient transmission. Similarly, HIV-negative
people with other active infections, and hence with replicating immune
cells, tend to be more susceptible to HIV infection upon exposure.
Data from another angle also fail to provide evidence for fundamental
and a priori differences among subtypes. Recently Jan Albert in Sweden
compared the rate of progression to AIDS in people living in Sweden
and infected with different subtypes, and found no evidence for
subtype-specific differences.
Other studies claiming to show such differences have not been done under
well-controlled circumstances. For example, the progression rate of a
subtype B-infected individual in the Netherlands is likely to be much
slower than that of a subtype C-infected person in Ethiopia, even when
the german person is not on triple drug therapy and the two cases
involve equal standards of clinical service and documentation. But there
are other contributing factors that are usually not considered, such as
the African's continuous exposure to virulent pathogens like the
tuberculosis bacterium and the European's treatment with drugs that
prevent PCP disease, both of which can lead to the erroneous conclusion
that subtype C is more virulent than subtype B.
The last issue to address is the relevance of HIV subtypes in the
vaccine context. Most HIV vaccine strategies aim to induce both
antibody-mediated and cellular immunity, which are thought to protect
against incoming viruses and virus-infected cells, respectively. These
two arms of the immune system do not recognize HIV's genetic
(nucleotide) sequence directly, but rather, the protein (amino acid)
sequence it encodes. The distinction is crucial because many of the
nucleotides that differ among subtypes do not result in amino acid
differences, while many stretches of nucleotides and of amino acids in
HIV have strictly conserved sequences, so that the majority of amino
acids are common to all subtypes. This is an important notion.
Let's do a thought-experiment. Cytotoxic T-cells (CTLs), the main actors
in cellular immunity, recognize their prey via very short amino acid
"target" sequences called epitopes. Many such epitopes have been
identified for HIV and are common to many subtypes. Other epitopes vary
among subtypes, but is this relevant? If the HIV epitopes relevant for a
protective CTL response are common to different subtypes, who cares
about subtypes in vaccine design? Unfortunately we do not yet know which
epitopes on which HIV proteins are most important for vaccine
protection, or whether they will turn out to be shared among subtypes.
To me, resolving this issue should be a top priority for AIDS vaccine
developers. (However, until we have clear answers, vaccine development
efforts must be based on the "worst case scenario" that shared,
protective epitopes may not exist, and therefore candidate vaccines
should be matched to circulating subtype).
Antibodies are also considered crucial for effective protection against
HIV. Yet not one of the many vaccine approaches tested so far in Phase I
human trials has induced antibodies that can neutralize primary HIV
isolates. On the other hand, Guido van der Groen at the University of
Antwerp in Belgium showed that sera from about 10% of HIV-infected
individuals neutralizes primary isolates from all HIV-1 clades and even
the "outlier" group O strains, clearly demonstrating that broadly
neutralizing antibodies can be elicited by virus of a single subtype.
What is not known is how to mimic this property in a vaccine. Recently,
however, Jack Nunberg's group at the University of Montana obtained
promising results on this front when they immunized mice with the HIV
envelope protein complexed to the surface of a host cell, in an attempt
to capture the "transition state" molecular structures that exist
fleetingly at the moment when HIV enters a cell. Another relevant point
is that human monoclonal antibodies (against envelope) which neutralize
primary isolates do so by recognizing the twisted, folded shapes of
protein epitopes (i.e., their 2D and 3D structures), not simply their
linear nucleotide sequences, and it is entirely possible that these
shapes remain the same even if the underlying sequences do not; in other
words, subtype-specific sequence variation may not alter these epitopes
in any meaningful way. This idea is supported by the fact that these
envelope epitopes are involved in essential functions of the virus
(i.e., entry into host cells), increasing the likelihood that they are
preserved across subtypes.
These data suggest that the key issue in vaccine design is how to
generate and test a protective immune response against any subtype, and
argue against the view that shifting from studying subtype B to subtype
C will solve all the problems. However, as stated above, this is not to
suggest that subtype should be ignored. On the contrary, it remains
crucial to include non-B subtypes in all HIV vaccine development
efforts; it would be a tragic mistake if we finally generated an AIDS
vaccine and found that it protects against subtype B but not other
subtypes or recombinants. Therefore, a priority should be to produce the
viruses and other reagents needed for more research across clades. These
include stocks of pathogenic and nonpathogenic SHIVs with envelope
sequences from subtypes A, C and D and perhaps from intra-envelope
recombinants and stocks of nonpathogenic subtypes (A, C and D for
chimpanzee experiments, to evaluate immune responses that cannot be
tested in the monkey/SHIV model). In addition, as many parallel human
Phase I trials as possible should be initiated to test for ways of
inducing cross-clade immune responses, and the appropriate non-B
laboratory reagents produced (such as tetramers and peptides).
In conclusion, I caution against overemphasizing the importance of HIV
subtypes for vaccine design and getting distracted from the most crucial
challenges: optimizing the immunogenicity of different vaccine
approaches in a series of human Phase I trials and then making the hard
choices as to which candidates are most promising and should be moved
forward into Phase II and Phase III trials in areas of the world most in
need of a vaccine. It may be more important to focus on what all HIV
subtypes have in common rather than on how they differ.
Jaap Goudsmit is head of the Department of Human Retrovirology at the
University of Amsterdam and chair of IAVI's Scientific Advisory
Committee. He is the author of Viral Sex (1997: Oxford University Press)
and the upcoming Viral Fitness.
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