PREFACE:  THIS IS AS SOLID A PAPER I CAN MUSTER IN RAPID FORM.  I BELIEVE I HAVE PROVEN TO MYSELF THAT, "HECK, IT WORKS!"  9801-230 WORKS BECAUSE THERE IS NOTHING TO STOP THE INEVITABLE FUNCTION OF HUMAN IMMUNE CELLS WHICH ARE IMPERVIOUS TO HIV!  BUT LETS REVIEW THE PAPER FIRST, SHALL WE?
MY EXCERPTS COME FROM: (IN THIS ORDER)

http://hivinsite.ucsf.edu/social/nih_reports/2098.22a4.html
http://hivinsite.ucsf.edu/medical/iasusa/2098.3278.html
http://hivinsite.ucsf.edu/topics/basic_science_pathogenesis/2098.4084.html

OK,  you will see this> *** " at the beginning of an excerpt and one of these> "*** at the end.  The excerpt will be bold.  I do use some bold in my comments, so try to stay on the road...This is worth reading, IMO.

HERE WE GO>>>
***"Most scientists think that HIV causes AIDS by directly killing CD4+ T cells and by triggering other events that weaken a person's immune function. For example, the network of signaling molecules that normally regulates a person's immune response is disrupted during HIV disease, impairing a person's ability to fight other infections. The HIV-mediated destruction of the lymph nodes and related immunologic organs also plays a major role in causing the immunosuppression seen in people with AIDS."***
Additional studies indicate clearly, the presence of high concentrations of HIV particles, for prolonged periods of time, lead to several molecularly different disruptions of the immune system, leading to the overall collapse.  The Lymph nodes, Thymus Region and Bone Marrow (Stromal Region) will be discussed later.  An additional indicia of the onset of AIDs (impending collapse of the immune system) includes the production of a high level of naive CD4+ cells, which will also be discussed.  In all cases, the reader needs to think about the successful transduction and subsequent engraftment of a starter colony of true Hematopoietic Stem Cells, diverse in their selection, giving rise to a full spread of three gene antisense+ (ENZO's HGTV-43) immune system components(all immune system cells bearing and transcribing the -43 construct), while the HIV is not yet at the necessary point or "level of effect" to cause collapse of the immune system, or even at that very level.  The pervasive question will be, "What are the parameters for a successful transition within the Patient, from the old immune system HIV+, to the new HGTV-43+?  I will explore this fully, as I believe it is "the" major issue.  Damaged organs involved in the immune system, and those secondary diseases not involved in the immune system (such as a secondary cancer), may mitigate the extent to which a Patient can receive therapeutic value from HGTV-43.  It is not intended to be a cure-all, although the establishment of a competent immune system is actually intended to be as great an overall therapeutic as is known to modern science. However, I believe with a high degree of certainty, those not yet in an impending AIDs condition, or those who exhibit boarderline collapsed to partially collapsed immune systems, may receive enormous benefit from this therapeutic.

***"HIV is a Retrovirus
HIV belongs to a class of viruses called retroviruses, which have genes composed of ribonucleic acid (RNA) molecules. The genes of humans and most other organisms are made of a related molecule, deoxyribonucleic acid (DNA).
Like all viruses, HIV can replicate only inside cells, commandeering the cell's machinery to reproduce. However, only HIV and other retroviruses, once inside a cell, use an enzyme called reverse transcriptase to convert their RNA into DNA, which can be incorporated into the host cell's genes.
Slow viruses. HIV belongs to a subgroup of retroviruses known as lentiviruses, or "slow" viruses. The course of infection with these viruses is characterized by a long interval between initial infection and the onset of serious symptoms.
Other lentiviruses infect nonhuman species. For example, the feline immunodeficiency virus (FIV) infects cats and the simian immunodeficiency virus (SIV) infects monkeys and other nonhuman primates. Like HIV in humans, these animal viruses primarily infect immune system cells, often causing immunodeficiency and AIDS-like symptoms. Scientists use these and other viruses and their animal hosts as models of HIV disease."***

This is good precursory material to keep in mind.  It demonstrates that

1) Mammals are able to fend off retrovirus for an extended period, but eventually, fall prey to the ultimate pathology of the disease.  (Remember Dr. E's comments at the ASM...mortality rate in Africa is 100% for HIV+.  In the end, we lose.)

2) The indication is a small advantage provided by artificial intervention, could prove to be of enormous therapeutic value.  Protease Inhibitors are, unquestionably and taken as a whole, capable of providing such effect.  But they are not the ultimate solution.  The mutation of HIV is key to its survival and proliferation within a single host.  HIV mutates prolifically.

3) Since the body demonstrates quite avidly, it is able to resist the disease, two long term effects of the disease deserve the most attention, in my opinion.  Mutation and Prolific Presence/Expression.

4) Mutation: Since the virus is very capable of mutating, its high replication rate invites the occasional mutation.  The best replicator mutant will always represent the highest population of viral particles, however, some of the mutations underneath are very likely, the actual culprits in causing the major collapse of the immune system.  Mutations are not as random as laypersons are led to believe.  Specific sequences in the polypeptide chains are predictable in their mutations and there are supercomputers and software packages available, capable of predicting those mutations.  As such, the entire class of mutations within HIV are predictable, and HIV repeats its mutation pathway in each and every infected person (Remember, HIV will normally create many billions of virons and viral particles, per day).  The presence of different classifications of HIV in the real world, passing between hosts, represents those mutations that are effective replicators and able to make the jump, from person to person.  They are all closely related, genetically, which opens them up to susceptibility of replication halt and mutation halt, by utilization of genetic antisense.  The sole reason genetic antisense is deadly to the virus vests in the high degree of likelihood that hybridization will occur within an HGTV-43 treated cell, between micRNA and mRNA (antisense product and HIV product) even if the targeted gene region in HIV is mutated from the genetic antisense definitive construct.  This means, the HGTV-43 construct, complements only the HIV gene(s) but is also able to act as a "loose but definitive fitting glove".  The three antisense genes are definitive enough to target only three HIV primary genes, and the hybridization of complementary micRNA and mRNA continues, even when HIV presents a mutation or even several. The glove can still recgonize only the hand it was intended for, despite the warts that may appear.

5) Prolific Presence/Expression: Without any doubt, HIV causes all of the trouble in the human body from its presence and its expressions, not through direct damage to cells and organs.  Indeed, HIV is a brilliant form of evolution, attempting to benefit from its host.  It therefor intends only to proliferate and expand to other hosts.  If it more effectively destroyed the host, the host would not have time or opportunity pass on the virus, as a short period of time would make it reasonably difficult to pass the virus on.  The virus would have disappeared when man was a cave dweller, having wiped out a small colony of people, to the last, but having no opportunity to last long enough to make the jump to another "tribe" (e.g. keep the host alive for two seasons, to allow for travel and contact).  HIV is as ancient as we, and thus deploys nature's ingenuity to travel as we do.  This is a hallmark of its success in our specie.   As you will see, the studies being completed now, show this to be the case.  As HIV advances in an individual, more mass destruction of cells within the HIV+ patient are now believed attributed to the presence of HIV particles on the outside of the cell, rather than infection within the cell.   But there are subtle phases and changes during disease progression.  I will continue to maintain the billions of HIV particles manufactured daily, give rise to each and every predictable mutation on a predictable basis.  Thus, any construct deployed to kill HIV which indeed kills the mass majority of HIV, but favors and leaves behind a mutation, only hastens the mutation's ability to proliferate.  No mass of HIV is left to compete with, allowing the mutant to become the predominant strain.   You will also see that HIV vastly expands and becomes more virulent (chronic veremia) as the immune system finally collapses.  It is as if the HIV is so tuned to Human Cells, it literally feeds on them.  In fact, that is what is happening, per se.  As HIV replicates, its theft of cell membrane for budding, expressions, mRNA and even its amino acid concentrates are foreign and believed lethal to human cells, in concentration.  No CD4+ cells to gather HIV?  No CD8+ cells to liquidate infected cells?  HIV runs rampant through its feeding ground.

***"The viral envelope. HIV has a diameter of 1/10,000 of a millimeter and is spherical in shape. The outer coat of the virus, known as the viral envelope, is composed of two layers of fatty molecules called lipids, taken from the membrane of a human cell when a newly formed virus particle buds from the cell.
Embedded in the viral envelope are proteins from the host cell, as well as 72 copies (on average) of a complex HIV protein that protrudes from the envelope surface. This protein, known as Env, consists of a cap made of three or four molecules called glycoprotein (gp)120, and a stem consisting of three or four gp41 molecules that anchor the structure in the viral envelope. Much of the research to develop a vaccine against HIV has focused on these envelope proteins.
The viral core. Within the envelope of a mature HIV particle is a bullet-shaped core or capsid, made of 2000 copies of another viral protein, p24. The capsid surrounds two single strands of HIV RNA, each of which has a copy of the virus's nine genes. Three of these, gag, pol and env, contain information needed to make structural proteins for new virus particles. The env gene, for example, codes for a protein called gp160 that is broken down by a viral enzyme to form gp120 and gp41, the components of Env.
Three regulatory genes, tat, rev and nef, and three auxiliary genes, vif, vpr and vpu, contain information necessary for the production of proteins that control the ability of HIV to infect a cell, produce new copies of virus or cause disease. The protein encoded by nef, for instance, appears necessary for the virus to replicate efficiently, and the vpu-encoded protein influences the release of new virus particles from infected cells.
The ends of each strand of HIV RNA contain an RNA sequence called the long terminal repeat (LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell.
The core of HIV also includes a protein called p7, the HIV nucleocapsid protein; and three enzymes that carry out later steps in the virus's life cycle: reverse transcriptase, integrase and protease. Another HIV protein called p17, or the HIV matrix protein, lies between the viral core and the viral envelope."***

What is important here?

1) The viral coating is comprised of human cellular membrane.  A wolf in sheep's clothing. A robber that can cause harm, through budding.

2) Remember the genes and their specific functions.  Simply reference back to this section.  The raw concept of antisense, acting as a regulation means to literally deactivate a target sense gene, is critical to grasp.  Moare particularly, continuing to hybridize when a target gene mutates.  Indeed, ENZO can demonstrate a complementary antisense gene targeted to any of the sense genes cited above, can turn off the sense gene.  (all HIV genes identified above are sense genes, they are genes and they are expressed, each having a named function).  Most critical, even if an HIV gene COULD mutate (which it cannot because it cannot enter into its replication phase, but even if it does replicate here and there, and a mutation does occur), the new gene will still be 99% identical to its original form and the antisense gene will still complement it enough to hybridize with it, shutting it down.  That is key.  Another key to consider is the rare possibility that HIV could mutate around the construct entirely.  Although not believed possible, the HIV which could do this would rapidly present itself to researchers.  They would quickly desequence its targeted genes, acquire the mutation and reform HGTV-43.1 to deal with the mutation.  HIV has to have limits.  I still maintain that HGTV-43 will deal with those limits, but if not, unlike inhibitors and related drugs, the answer is days away, not months or years, as you should see from this aforementioned concept.

3) As complex as HIV or any other virus can appear, clearly there are singular, critical functions, housed within singular genes.  For those of you who can write software, it is like a "PRINTF" command in a C compiler, or for those familiar with baking, lets pretend one of the HIV genes has a function identical to baking powder.

To destroy a program, kill the function that writes to a file.  If there are no secondary functions to thwart your means and the software is not capable or working around your attack, it fails.

In baking, picture muffins that turn out to be cookies and you will see the effect.  Thwart the action of baking powder, and in the absence of any secondary capability, the muffin will not rise.  Not even once.  Never in 10,000,000,000 attempts.

As complex as a virus may be, the key IS to disrupt its replication cycle and to do this in spite of mutation.  To do it every time, no matter how may times the virus tries to enable its normal functions.  This is not at all unlike David slaying Goliath, at the molecular level.  In fact, to do this without disrupting any other function is the very hallmark and ingenuity of genetic antisense.  Antisense must blend in and target only the HIV gene, or any mutation of that gene, but nothing else.  ENZO decided to disrupt more than one gene function.  In fact, three functions.  ENZO used REV, TAT and TAR, I believe.  It is also a slight departure from Cornell, as they used the same genes there, but in the abstract at the 7th annual Retrovirus conference, I believe they switched one HIV gene target.  I have admittedly not followed the labeling conventions for HIV and I believe it could also be the same region, identified later as POL.  Remember the data in HTTP://www.enzo.com. "Stable Human ImmunoDefficiency..."  Well, the regions used at Cornell and the ones used in the Patients are very slightly different, I believe.  It could be that they are not different, but the genomic labeling of a generic HIVmodel was changed.   Regardless, the concept remains the same and ENZO seeks to deliver what it promised.  A single step, genetic product that has no measurable side effect, completely shuts down all viral replication, halts mutation, and if presented with a mutation, still continues to work exactly as intended.  The more you read and study up, the more you see the real battle was already won, in the nucleus of a living human immune cell at Cornell.

***"Steps in Viral Replication
Attachment/Entry
Reverse Transcription and DNA Synthesis
Transport to Nucleus
Integration
Viral Transcription
Viral Protein Synthesis
Assembly of Virus
Release of Virus
 Maturation"***

Observe the life cycle of the virus.  "Attachment".  HIV uses its protein appendages to locate receptors and it "attaches" to the cell wall of its target.  Not one, but two receptors have been identified as targets of HIV.  Logic dictates there will be more and that the various mutations of HIV will also present more variation.  Equally, the receptors HIV targets ARE NECESSARY FOR NORMAL FUNCTION OF THE HUMAN CELL.  Now, just as the virus is nimble, so too is the human cell.  I can probably function around the complete loss of a receptor, however, its function is also probably impeded.  So I maintain that blocking of receptors will not work, such as HGSI's identification of a human gene that gives rise to the primary receptor which HIV utilizes to gain entry into a human cell.  It will not work because HIV will find another receptor, will see its mutations favored IF YOU COULD block a receptor and would find access.  HIV is too well adapted for this technique.  It could well be that genetic antisense is the only way to even begin, logically, to halt such a mutatious and well adapted virus.

Now, read the aforementioned viral replication steps (which are actually life cycle steps).  Do you see what is happening?  HIV is literally rewriting your cells to create copies of HIV, but also, to continue to do all the things that are necessary for your survival.  HIV does not "want to kill its host".  But at some point, its long term presence does kill the host.  The logic I present to you is very clear and convincing.  If HIV can rewrite human DNA to turn living cells into factories producing HIV, why cannot man create the necessary coding to exactly reverse this process, without disruption of other functions?  Now, go back to ENZO.COM STABLE HUMAN IMMUNODEFFICIENCY...and recall something very profound and important.  Remember this very well....Here it is and here is my conclusion>>>

***"Although the U1 antisense was designed to act in the nucleus, the inability to detect provirus sequences in postchallenge cells suggests the possibility that the U1/HIV antisense is capable of acting in the cytoplasm prior to HIV-1 integration. The presence of active antisense in the cytoplasm could result from the natural kinetics of U1 processing (23) wherein the U1/HIV antisense chimeric molecules are present in the cytoplasm prior to reimportation to the nucleus"***

What did ENZO do?  Read the steps above and this paragraph.  What happened?  The three antisense genes have created a barrier to HIV integration into human DNA.  One of the critical functions HIV utilizes to integrate, has been completely disrupted.  ENZO stopped replication, stopped mutation and halted Integration.  The HIV is susceptible to hybridization EARLY IN ITS REPLICATION CYCLE.  This means it has no opportunity to transcribe or express anything because it never even completes Integration.  HIV DNA is not created within human DNA, so HIV RNA byproducts are not produced at all.  HIV cannot imprint upon the cell, because it cannot do anything more than enter into its first few stages of Integration, where it is halted.  Normal cytoplasmic turnover (cycles within human cells) disintegrates everything unused in the cytoplasm. You can see where HIV ends up.  Recycled as food for the cell.  HIV would look like a relatively small ball of yarn particlly unraveled, with a near perfect "yang" ball of yarn (antisense byproduct) attached here and there to the half unwound HIV.  At that point it would freeze up and become seemingly inert.  Motionless.  Perhaps a fair term is "dead", even though in the molecular sense, if you could tugg at it and pull away the antisense, it would reanimate and continue on its preprogrammed pathway to destruction and disruption of normal human cellular molecular functions.

What is a human immune cell, once it is converted in the manner described herein (HGTV-43+)?  AN HIV ROACH MOTEL!  Indeed, the receptors are not impaired or blocked...we want HIV to come in.  COME IN HIV (just like the shorts on the stock).  THE MORE CELLS, THE MORE RECEPTORS.  THE MORE RECEPTORS, THE MORE HIV IS GATHERED.  THE MORE HIV IS GATHERED INTO THE CELLS, THE LESS THERE WILL BE OUTSIDE THE CELLS.  IN FACT, THE LESS HIV THERE WILL BE, PERIOD.  THE CD8 BEARING HGTV-43 MEANWHILE, WORKS IN SPIT OF THE PRESENCE OF HIV AND IDENTIFIES AND DESTROYS INFECTED CELLS, RELEASING HIV PARTICLES, WHIC IS EXACTLY WHAT YOU WANT!  HARBOR BURSTERS.  The vital issue becomes the balance of treated cells growing.  The non-treated cell's fate is already sealed and known.  Will a competent immune system save the Thymus, Marrow, etc...?  Lets find out.  Keep reading. (THEY MAY NOT NEED SAVING, THEY MAY BE INTACT AFTER ALL!)

*** "HIV is Active in the Lymph Nodes
Although HIV-infected individuals often exhibit an extended period of clinical latency with little evidence of disease, the virus is never truly latent. NIAID researchers have shown that even early in disease, HIV actively replicates within the lymph nodes and related organs, where large amounts of virus become trapped in networks of specialized cells with long, tentacle-like extensions. These cells are called follicular dendritic cells (FDCs).
FDCs are located in hot spots of immune activity called germinal centers. They act like flypaper, trapping invading pathogens (including HIV) and holding them until B cells come along to initiate an immune response.
Close on the heels of B cells are CD4+ T cells, which rush into the germinal centers to help B cells fight the invaders. CD4+ T cells, the primary targets of HIV, probably become infected in large numbers as they encounter HIV trapped on FDCs. Research suggests that HIV trapped on FDCs remains infectious, even when coated with antibodies.
Once infected, CD4+ T cells may leave the germinal center and infect other CD4+ cells that congregate in the region of the lymph node surrounding the germinal center.
Over a period of years, even when little virus is readily detectable in the blood, significant amounts of virus accumulate in the germinal centers, both within infected cells and bound to FDCs. In and around the germinal centers, numerous CD4+ T cells are probably activated by the increased production of cytokines such as TNF-alpha and IL-6, possibly secreted by B cells. Activation allows uninfected cells to be more easily infected and increases replication of HIV in already infected cells.
While greater quantities of certain cytokines such as TNF-alpha and IL-6 are secreted during HIV infection, others with key roles in the regulation of normal immune function may be secreted in decreased amounts. For example, CD4+ T cells may lose their capacity to produce interleukin 2 (IL-2), a cytokine that enhances the growth of other T cells and helps to stimulate other cells' response to invaders. Infected cells also have low levels of receptors for IL-2, which may reduce their ability to respond to signals from other cells."***
Now, lets think this through.  B Cells and CD4+ cells arise which are HGTV-43 +.  They are DRAWN NATURALLY to these germinal centers of high activity, where the CD4+ cells collect HIV by way of their receptors and they destroy any HIV that enters.  This is the key.  Read the paragraph(s) above.  Researchers think CD4+ cells tire from over-replication.  Maybe the researchers are wrong and they do not tire, HIV mutates and certain mutations of HIV cause the CD4+ cells to reach their limit of response.  (There is a study coming up that says the Thymus and Bone Marrow does NOT Tire) But in either case, and seemingly ANY CASE, how can HIV create an effect of any kind, if an army of HGTV-43 + B cells, CD4+, CD8, etc, awaits its every trick, which serve only to collect HIV and immediately destroy it as it enters its early stages of replication?  ENZO has every base covered because the means that HIV uses to trick the immune cell, or the organs that react with immune cells or give rise to immune cells, are hereinafter protected.  They are protected by an EVER DECREASING VIRAL LOAD, once the HGTV-43 treated cells reach a certain perigee in their number.  It starts with successful engraftment, which ENZO has already demonstrated.  After that, presuming all things progress according to theory, every immune system component is detectable, bearing the antisense genes.  Where did we hear this?  Mr. Barry Weiner, President of ENZO stated so at the January 2000, Annual Shareholder's Meeting.  Dr. Engelhardt also described the "roach motel" effect of the CD4+, as clearly the receptors found on the CD4+ are the key receptors that HIV is drawn to.  ENZO sought to change not a single thing about the human immune system, rather, ENZO imparted an ability to all immune cells to do three things blindly, in order to create a perfect HIV shield.  All immune cells differentiated from the initial Hematopoietic Stem Cell population transduced with HGTV-43 and engrafted, bear these capabilities and nothing else which was not there already, by nature.  So the progeny of HGTV-43 treated HSC's can unleash their natural mechanisms against HIV and HIV cannot trick them or reduce their number.  Here is another key.  The harder HIV tries to do damage, where it can, the FASTER the treated cells multiply (to a certain limit).  The blood signals remain the same..."MAKE COPIES" and there are less and less untreated cells to respond as a function of time, yet, more HGTV-43 treated cells, as a function of time.  There should eventually be a measurable logarithmic effect with an asymptote to a plateau (read the long form of the reference material, there is a section on reading Log Function Data, in this type of research).  This would be the combined PCR assay for all HGTV-43 immune system components per ml.  Of course, it is also important to look at individual HGTV-43+ discrete immune cell types and their success and growth rates, as well.   Any epicenter of immune activity which calls for CD4+ cells, will see more and more HGTV-43+ CD4+ cells, as a function of time.  And then, lots of HIV goes in, and it does not come out.
One of the items discussed in the papers I cite, involves the fusion of an immune cell with an infected cell.  If an immune cell fuses with an infected cell, the HGTV-43 products will clear the infected cell of HIV.  HIV has lost its grip on the immune system, if HGTV-43 plays out as ENZO planned.  Since the immune system contains components that bear the CD4+ receptors, HIV will be gathered and destroyed at an ever-increasing pace.  Very important, perhaps paramount in the scheme devised by the draftperson(s) of the 9801-230 protocol.  Very, very ingenious, building upon the success of the vector for delivery, the antisense concept, the targeting of the HIV critical process genes, the use of human immune cells that can take advantage of HGTV-43's effect and the means utilized to target a broad spectrum of Hematopoietic Stem Cells, assuring the rise of a diverse immune system.  In a word (or three), MANY TIMES BRILLIANT!
*** "Breakdown of FDC networks. Ultimately, accumulated HIV overwhelms the FDC networks. As these networks break down, their trapping capacity is impaired, and large quantities of virus enter the bloodstream.
Although it remains unclear why FDCs die and the FDC networks dissolve, some scientists think that this process may be as important in HIV pathogenesis as the loss of CD4+ T cells. The destruction of the lymph node structure seen late in HIV disease may preclude a successful immune response against not only HIV but other pathogens as well. This devastation heralds the onset of the opportunistic infections and cancers that characterize AIDS."***
FDC networks do not die unless HIV is present in large quantities.  HIV apparently tricks the immune system into producing largely naive CD4+ cells, while killing the capable CD4+ cells.  Can you see how HGTV-43 treated immune system components of all types, utterly turn the tide against this effect?  Read that last sentence.  When the FDC's collapse, opportunistic infections and cancers arise.  This is not someone's guess.  This is derived from the scientific method.  Reduce and eliminate HIV's presence, turn the tide.  Protect B Cells, CD4+ cells and CD8+ cells, turn the tide.  Many great things happen if HIV cannot replicate within or even successfully fuse to the treated cells.  Using the mind's eye, I am hoping you see that ENZO's approach in protocol 9801-230 is a strong therapeutic and should be a cure.  If not, then time will convince the many unwilling to see the truth.  There are 4 things in balance.  The critical organs that work with the immune system (Thymus, Bone Marrow, etc..), the immature stem cells, the infected immune system and the mature, treated portions of the immune system.  The ultimate formula is>>>Can ENZO create enough treated stem cells, engrafted to a great enough degree, to PERPETUALLY give rise to enough of each type of immune system component, to then turn the tide and deliver a mostly competent immune system, in the constant presence of HIV?  Can this be done in time, to save irreversible damage to the critical immune system organs?  Will HIV then vanish, completely?  Will antivirals help and at which junctures?   It takes a lot of reading and thinking to form an opinion.  I think also, you have to be fair to Dr. Engelhardt, who visibly spoke last to the research community (Dr. Conant spoke last, but in a closed session, and indeed, the stock went up 15 the next trading day with no real news).  Dr. Engelhardt said, at the 7th annual RetroConference>>> ENZO intends to STICK TO THE SAME PROTOCOL during the next Phase.  Does this answer most of the questions I just posed, because if it does not, I am missing something.  It has to.  But there is more evidence.  Lets continue...
*** "Role of CD8+ T Cells
CD8+ T cells are important in the immune response to HIV during the acute infection and the clinically latent stage of disease. These cells attack and kill infected cells that are producing virus.
CD8+ T cells also appear to secrete soluble factors that suppress HIV replication. Three of these molecules -- RANTES, MIP-1alpha and MIP-1beta -- apparently block HIV replication by occupying receptors necessary for the entry of certain strains of HIV into their target cells. Researchers have hypothesized that an abundance of RANTES, MIP-1alpha or MIP-1beta, or a relative lack of receptors for these molecules, may help explain why some individuals have not become infected with HIV, despite repeated exposure to the virus.
CD8+ T cells probably also secrete other soluble factors -- as yet unidentified -- that suppress HIV replication." ***
What have you read in the negative press comments about ENZO(or the whisper comments?)  Lots of criticism about CD4+ cells?  Yet not a soul pointed out that CD8+ would be CRITICAL, if any headway was to be made against the disease.  Well, here is the evidence.  Recall please, that ENZO uses Leukophoresis to extract a SPECTRUM of HSC's so as not to quibble over which subclass gives rise to which immune system component.  Had this not produced all the necessary cell types, ENZO would have already modified their protocol and extracted Bone Marrow so as to transduce every known HSC type in sufficient quantity and return them to the body.  Now some of you have heard that ENZO requires the clinics to have bone marrow specialty equipment?  Correct?  So how do you explain the requirement?  First, Leukophoresis machines are found at advanced centers for SCID therapeutics.  The bone marrow equipment is logically there, already.  Second, the protocol specifically calls for a bone marrow biopsy, making bone marrow work necessary.  Third and critical, ENZO has never been bashful about its intent to treat AIDs patients.  AIDs patients will not be treated with the 9801-230 protocols as they are.  At least, those without a strong remaining colony of HSC's.  In order to help people in advanced cases, I believe aspiration of bone marrow, transduction, and reintroduction back to the marrow areas will be necessary.  Then a reasonable colony size of HGTV-43 transduced Stem Cells will be provided.  Bone Marrow equipment should be present, side by side, with 9801-230 work performed on HIV+ Patients without the need for the equipment.  There is another compelling reason.  ENZO intends to start Bone Marrow Tolerization work, probably quite soon.  Remember Dr. Rabbani's statement at the ASM?  Everything ties together?  These are the superclinics of the future, Ladies and Gentlemen.
Remember the term ABLATION?  CD8+ T Cells bearing the HGTV-43 antisense genes, are HIV IMPERVIOUS SELECTIVE ABLATORS.  What will they selectively ablate?  EVERYTHING INFECTED WITH HIV.  What will they leave alone?  Other HGTV-43 treated cells.  If HIV levels are contained and controlled by the presence of a mostly HGTV-43+ immune system, one major expectation is the halt of any further damage to organs, such as the Thymus, or the Bone Marrow/Stromal Cell.  Why?  Because HIV's prolific replication requires the immune system cell.  Otherwise, I believe that ENZO theorizes the balance achieved will be enough to act as a therapy and a cure.  HIV will replicate here and there, but at so low a pace, the CD8+ HGTV-43+ cells and other cells (CD4+), will find (collect) and destroy HIV.  Evidence?  People who are HIV+ live for years without therapy.  How?  Why?  High levels of HIV ARE NECESSARY to cause the major damage, and there is evidence to attest to this.  Please read on...
*** "Rapid Replication and Mutation of HIV
HIV replicates rapidly; several billion new virus particles may be produced every day. In addition, the HIV reverse transcriptase enzyme makes many mistakes while making DNA copies from HIV RNA. As a consequence, many variants of HIV develop in an individual, some of which may escape destruction by antibodies or killer T cells. Additionally, HIV can recombine with itself to produce a wide range of variants or strains.
During the course of HIV disease, viral strains emerge in an infected individual that differ widely in their ability to infect and kill different cell types, as well as in their rate of replication. Scientists are investigating why strains of HIV from patients with advanced disease appear to be more virulent and infect more cell types than strains obtained earlier from the same individual." ***
This excerpt is equally revealing.  First a quick note, HIV can recombine...hence Recombinant, as a term, takes on more meaning.  Remember the RAC?  Recombinant Advisory Committee?  Ahhh yes!  Virus' which exhibit this trait are termed "RETRO-VIRUS'" and are typically recombinant in nature.
I wish to take issue with the statement above, "the HIV reverse transcriptase makes many mistakes while making DNA copies...".  In fact, it does not.  The sequence of peptides in any polypeptide, represent specific amino acids.  Complex amino acids are prone to certain peptide by peptide complementarity, but there is a degree of probability that different pairings are possible, only less probable.   Nothing would have evolved past a simple chain of peptides, if not for this fact.  Nature survives and Darwin built his model on this basis.  The "fit" survive, the rest fail to adapt and cease to exist.  Because complex single celled organisms adopted a strategy of passing on sequences (replication) and because these sequences MUST vary every now and then, diversity is assured.  Diversity is the key to survival of a specie.  This is an uncontested precept.  HIV reverse transcriptase is not making mistakes.  What is happening is a kind of fuzzy logic.  It is transcribing things, like XXXYYYZZZXXXYYYZZZ with a small probability of producing XXXYYYZZZXXXYYYZZX.  Whatever the probability, the second rare sequence is produced MORE if the HIV reaches an environment with the necessary mechanics to make lots and lots of copies, presenting the rare opportunity to mutate.  The CD4+ cell is the ideal spot.  Take it away and what happens to the replication rate?  And thus the mutation rate?  You see how important it is to get the infected immune system cells OUT, and the HGTV-43 treated system IN and DOMINANT.  Remember SELECTIVE ABLATION, I think it is paramount.  Freeing up viral particles allows CD4+ cells to collect them.  Dr. E was trying to tell us what he was seeing.
Last note, "Scientists are investigating why strains of HIV from patients with advanced disease appear to be more virulent and infect more cell types than strains obtained earlier from the same individual".  My comment here is that the answer  should be obvious to those skilled in the art.  So I take issue, again.  Ths Scientists know why, they just want to confirm it.  First, there is no such thing as spontaneous evolution.  This excerpt makes it sound as if HIV has a brain.  What is happening is two-fold.  First, the immune system and the Patient's other related systems (Thymus, Bone Marrow, Lymphoid) must collapse to lead to the Patients indicia of late stage secondary infection and high HIV veremia.  Every person resists with tens of thousands of molecular processes not yet known to modern scientists.  The second effect of HIV becoming apparently more virulent in late stage infection is the emergence of the natural adaptation of HIV, according to Darwin.  HIV may not be making copies (viral particles) at the rate of  multi-billions per day, as earlier in its timeline, because the CD4+ cells and many other immune cells are mostly gone.  The high volume factory is extinct and so too, a certain clade of the virus falls to inactivity.  But the MUTATED viral particles from earlier are seeded here and there.  As HIV "PRIME" winds out of the system, no longer able to make its prolific copies, the more subtle mutations come to the surface.  It is not a surprise, it is not an unknown.   If you can excuse a crass and horrific illustration, it is like watching a piece of meat rot and saying "look at all the different kinds of bacterium that are present".  No kidding, there are several systems down, surrounding and including the immune system.  HIV has its mutants and they "appear" as the more CD4+ affinitized HIV clades, run their course, destroy the mature portion of the immune system and fall to invisibility.  HIV works its human host down, through many layers of resistance.  We are remarkable in our ability to adapt and to survive, but HIV is a potent match, ultimately.  Unless earlier in the timeline, when it can make a difference, a tiny advantage is given to the immune system.  That is the theory, and it will also apply late in the progression of the disease, but to a point.  In the case of HGTV-43, we are really talking about a triple advantage.  And the complex and systematic series of occurrences related to the presence of HIV is believed halted, because the immune system not only stays, it holds on to its CD4+ cells, which bear the receptors necessary to absorb HIV and its CD8+ Cells, which go about their business of SELECTIVE ABLATION.  And there is more to consider.  What about the 10,000 processes not yet discovered?  The CD4.9+ Cell, or CD8 3/4+ cell?  F Cells? Etc... Ahhh the wisdom of using the raw output of a Leukophoresis machine, transducing everything "Hematopoietic" and putting it all back in.  The diversity of the returned product is key.  Again, forgive my illustration (above), but I do think I am right.  I also believe ENZO will be successful, and thus many of these subprocesses will remain, undiscovered.  Upon ENZO's achievement of total success, I hope research continues unabated in this area, because several of these sub-processes are key to understanding other unrelated forms of immune dysfunction or over-function. Tolerization is a broad concept which ENZO also pioneered.  They would seek to shut down or to promote singular sub-processes that could down regulate or upregulate a targeted process.  The more known processes, the better the options for other diseases.
*** "Theories of Immune System Cell Loss in HIV Infection
Researchers around the world are studying how HIV destroys or disables CD4+ T cells, and many think that a number of mechanisms may occur simultaneously in an HIV-infected individual. Recent data suggest that billions of CD4+ T cells may be destroyed every day, eventually overwhelming the immune system's regenerative capacity.
Direct cell killing. Infected CD4+ T cells may be killed directly when large amounts of virus are produced and bud off from the cell surface, disrupting the cell membrane, or when viral proteins and nucleic acids collect inside the cell, interfering with cellular machinery.
Syncytia formation. Infected cells also may fuse with nearby uninfected cells, forming balloon-like giant cells called syncytia. In test-tube experiments at NIAID and elsewhere, these giant cells have been associated with the death of uninfected cells. The presence of so-called syncytia-inducing variants of HIV has been correlated with rapid disease progression in HIV-infected individuals.
Apoptosis. Infected CD4+ T cells may be killed when cellular regulation is distorted by HIV proteins, probably leading to their suicide by a process known as programmed cell death or apoptosis. Recent reports indicate that apoptosis occurs to a greater extent in HIV-infected individuals, both in the bloodstream and lymph nodes.
Uninfected cells also may undergo apoptosis. Normally, when CD4+ T cells mature in the thymus gland, a small proportion of these cells are unable to distinguish self from non-self. Because these cells would otherwise attack the body's own tissues, they receive a biochemical signal from other cells that results in apoptosis. Investigators have shown in cell cultures that gp120 alone or bound to gp120 antibodies sends a similar but inappropriate signal to CD4+ T cells causing them to die even if not infected by HIV.
Innocent bystanders. Uninfected cells may die in an innocent bystander scenario: HIV particles may bind to the cell surface, giving them the appearance of an infected cell and marking them for destruction by killer T cells.
Killer T cells also may mistakenly destroy uninfected CD4+ T cells that have consumed HIV particles and that display HIV fragments on their surfaces. Alternatively, because HIV envelope proteins bear some resemblance to certain molecules that may appear on CD4+ T cells, the body's immune responses may mistakenly damage such cells as well.
Anergy. Researchers have shown in cell cultures that CD4+ T cells can be turned off by a signal from HIV that leaves them unable to respond to further immune stimulation. This inactivated state is known as anergy.
Superantigens. Other investigators have proposed that a molecule known as a superantigen, either made by HIV or an unrelated agent, may stimulate massive quantities of CD4+ T cells at once, rendering them highly susceptible to HIV infection and subsequent cell death.
*****
Damage to Precursor Cells. Studies suggest that HIV also destroys precursor cells that mature to have special immune functions, as well as the parts of the bone marrow and the thymus needed for the development of such cells. These organs probably lose the ability to regenerate, further compounding the suppression of the immune system.
*****" ***
This is a complex excerpt.  I want to address the last paragraph with the 5*'s first.  "Damage to percursor cells".  This is important because reaching a Patient too late, serves no purpose.  HGTV-43 cannot fix pre-existing, catastrophic damage.  It can only help build an immune system that can stop HIV, thus halting any further progression of the true source of damage.  There is a recent study I will address later on, which hits this on point.  In fact, the Stromal Cells (parts of the bone marrow) and the Thymus, do survive in-tact, until very late in the progression of the disease, perhaps later than first imagined by researchers.  This adds credence and gives hope to the concept of arriving late to the party, but not too late, with something profound and meaningful.  HGTV-43!!!
Other paragraphs in this excerpt support all of my comments made in this document.  Just read each one and ask yourself each of these questions>>>
1) If HIV was not around, would this be happening?
2) What happens if the precursor cells and the entire immune system are impervious to the effects of HIV as a direct result of ENZO's HGTV-43 therapeutic?
I will try my own questions on for size, to each paragraph above.
Direct cell killing. Infected CD4+ T cells may be killed directly when large amounts of virus are produced and bud off from the cell surface, disrupting the cell membrane, or when viral proteins and nucleic acids collect inside the cell, interfering with cellular machinery.
Answer Q1) If HIV levels are low>>>then there are not large amounts of virus present, less budding, less viral protein and viral nucleic acid. Since HGTV-43 intends to halt all viral production in CD4+ cells, treated cells would have no virus inside, no viral proteins and no nucleic acids, so according to this theory, HGTV-43 would fix this problem.  CD4+ cells which are treated would survive and function normally.  The normal function is not imagined on my part, because of the given theory> "no viral proteins, no viral nucleic acids present, normal function".  Correct?
Answer Q2) The viral levels necessary to fulfill this theory are never reached.  Protease inhibitors provide the initial control, but as HGTV-43 treated precursor cells and their progeny become a measurable component, eventually, they "become the immune system", in its entirety.  As such, HGTV-43 seems to conquer the issue posed by this excerpt.
LETS TRY THE NEXT ONE, SAME TWO QUESTIONS
Syncytia formation. Infected cells also may fuse with nearby uninfected cells, forming balloon-like giant cells called syncytia. In test-tube experiments at NIAID and elsewhere, these giant cells have been associated with the death of uninfected cells. The presence of so-called syncytia-inducing variants of HIV has been correlated with rapid disease progression in HIV-infected individuals.
Answer Q1) Reading the last sentence first, a viable answer becomes clearer.  Syncytia formations only appear at the late stage of disease progression.  Since this condition is marked by high viral load, it holds logically that elimination of the virus, would eliminate any Syncytia formation.  Also, the presence of viable CD8+ cells would seek and kill infected cells more efficiently, as CD4+ cells, bearing normal receptors, continue to sweep up and destroy HIV particles (Viral particles...Virons, etc...).  You get a double edged effect of no free virus and CD8+ cells killing the cells that lead to Syncytia formations.  You also have a normal function, concentration of CD4+ in lymphatic regions, placing more "roach motels" in proximity to "more viral particles" and the CD8+ cells destroy the infected cells and release even more HIV particles.
Answer Q2) As addressed in the answer to Q1) HGTV-43 allows CD4+ and CD8+ to exactly reverse the conditions for Syncytia Formations.  Additionally, the salvation of the lymphoid system has to make an enormous difference.  Since CD4+, CD8+, pre-Synctia or Synctia Formations and singular infected cells are naturally drawn to the lymphoid sites into points of high infectious concentration, HGTV-43 treated immune components will magnify the effects described in my answer to Q1), they will ALL be concentrated in proximity, CD4+ will gather HIV and destroy it, CD8+ will selectively kill (ablate) the infected cells and pre-Syncytia Formations.  The Lymphoid system will be able to fulfill its normal function, concentrating infected cells and immune system components in close proximity, to get the effect nature intended with ENZO's shield in place, to assist.
I can go on and on, but I think you can see the information presented to this point, and the data or logic which backs it up.  It leads me to the conclusion that ENZO has conceived of touching the human immune system, at its PRECURSOR cell level, and its mature level, to create the necessary "seed" to literally displace the failing immune system and in all cases, give rise to conditions which perfectly reverse these observed conditions associated with HIV disease progression.  The only remaining issue, once the trial results become known to all, is the issue of pre-existing damage within the individual.  Reaching the Patient too late, will cause secondary issues to emerge, even if the immune system can be restored.  How late is too late?  I think it will vary per Patient.  In most cases, I think there is evidence showing that you can reach a Patient and transduce HGTV-43 into their remaining stem cells at a very late stage, and still find the Thymus and Bone marrow receptive and functional, even if damaged.  There is a study coming up which amplifies this thought.
I will do one more, then move on.
Apoptosis. Infected CD4+ T cells may be killed when cellular regulation is distorted by HIV proteins, probably leading to their suicide by a process known as programmed cell death or apoptosis. Recent reports indicate that apoptosis occurs to a greater extent in HIV-infected individuals, both in the bloodstream and lymph nodes.
Uninfected cells also may undergo apoptosis. Normally, when CD4+ T cells mature in the thymus gland, a small proportion of these cells are unable to distinguish self from non-self. Because these cells would otherwise attack the body's own tissues, they receive a biochemical signal from other cells that results in apoptosis. Investigators have shown in cell cultures that gp120 alone or bound to gp120 antibodies sends a similar but inappropriate signal to CD4+ T cells causing them to die even if not infected by HIV.
Answer to Q1) As before, with HIV absorbed by CD4+ HGTV-43+ cells and CD8+ HGTV-43+ cells killing infected cells, HIV levels will theoretically drop, and in my Question, I pose no further virus present.  With no virus present, the HIV proteins theorized are eliminated, thus the apoptosis or spontaneous apoptosis effect is halted.  I agree that extensive damage to the Thymus could cause a replacement of the immune system to be for naught, IF THE DAMAGE IS GREAT ENOUGH.  But if the damage is caught in time, through down regulation of HIV to "0", I believe the CD4+ maturation will be sufficient to completely restore the immune system to its normal function.  Here is an important link>
http://rex.nci.nih.gov/PATIENTS/INFO_TEACHER/bookshelf/NIH_immune/html/imm04.html

This link provides some basics about the human immune system.  I believe CD4+ cells emerging from the HGTV-43 treated stem cells can mature in the Thymus but also, can mature in other back-up organs.  There is also a study I will cite later, which backs up this critical point, because it proves that the thymus and other organs are still very active, late in the HIV/AIDs progressive stages.
Answer to Q2) Here the answer is different than before.  The precursor cells and immune system component cells need to become dominant and thus numerous, as quickly as possible, in order to preserve what is still functional in the Thymus, Stromal and Lymphoid systems.  It is fair to say that these systems would have been normal, if not for the presence of the HIV in the first place.  Disruption of the high rate of replication and down regulation to "0" must halt the damage.  The key is likely SELECTIVE ABLATION.  CD8+ HGTV-43+ cells which are capable of hunting down infected cells and selectively destroying them.  HIV proteins and amino acids cannot reach any measurable level and thus are no longer a threat.  Since no one has ever cleared a human Patient of HIV, completely, restorative effects of HIV elimination are unknown.  ENZO is in uncharted waters on that count, but then, there is another issue at stake.  The immune system is indeed capable of billions of espressions and recognitions.  As such, an immune system which is impervious to HIV could well take actions against HIV more effectively, perhaps reversing the effects the HIV had from its presence in, for example, a Thymus gland cell.
Lets keep plowing ahead.
*** "HIV PATHOGENESIS
HIV pathogenesis was discussed at the Los Angeles and Atlanta courses by H. Clifford Lane, MD, from the National Institutes of Health, Bethesda, Maryland.
Recent studies in viral dynamics, host immune response, and the regenerative ability of the immune system have yielded a substantial amount of information on pathogenesis of HIV infection. Studies of HIV replication and survival dynamics, detailed investigation of the architecture of lymphoid tissue in infection, and studies of CD4+ lymphocyte dynamics have demonstrated that HIV infection is a dynamic process of continuous viral replication (see accompanying article). Disparate lines of investigation have merged in the discovery of coreceptors to HIV and research has characterized a progressive decrease in the size and diversity of the CD4+ lymphocyte pool." ***
Ahhh, what have we here?  I think they are saying HIV and AIDs have created so huge a push to learn how to stop the virus, we are learning about the various immune sub-systems, their interaction and relationship of damage to HIV levels, CD4+ levels or the lack thereof, etc....
*** "The identification of coreceptors in part explains why some people, despite multiple high-risk behaviors, do not become infected with HIV. Genotypic analyses identified that some of these high-risk uninfected individuals are homozygous for deleted alleles of the CCR5 gene. The frequency of this mutation, a 32 base-pair deletion, is estimated at 11% in the Caucasian population and 1.7% in the African-American population. The homozygous genotype appears to confer resistance to HIV-1 infection. In a cohort of 1343 HIV-positive and 612 HIV-negative patients, none of the HIV-positive patients were homozygous for the D32 CCR5 mutation compared with 3% of the HIV-negative patients.
The heterozygous genotype does not appear to have an effect on resistance to infection; several studies have shown a consistent, but minor difference in the rate of disease progression between patients with the heterozygous D32 mutation and those with no mutation." ***
Time for a test.  How big is this discovery?  I bet everyone undervalues this HUGE discovery?  Ok, lets chew it up.  I did not pull the entire article, it is too big.  But this is the conclusory part.  Scientists have identified 2 receptors HIV uses to get into living human cells.  Common sense dictates there are probably 3, 4 or even more.  But look at the discovery.  According to genotype (the natural definitive sequence of genes your ancestors gave to you), certain individuals are less likely to contract HIV, even though their "practices" are prone to contraction of the disease.  WHY?  The sneaky word is HOMOZYGOUS versus HETROZYGOUS.  In understandable terms, 11% of Caucasians and 1.7% of African Americans ARE MISSING a 32 pair set of polypeptides within their CCR5 gene.  This study may not prove that you cannot contract HIV permanently, if you are one who expresses this mutation, but it does show very strongly, that HIV has a much, much harder time infecting those with this receptor mutation.  Does the living cell not have the receptor, or is the receptor molecularly different?  I think it is the latter, the receptor is molecularly different in people with this mutation.  If you are ever offended by the term mutation, remember, WE ARE ALL MUTANTS.  There is no definitive, perfect genome.  Hence the ENZO MuUutant takes no offense to any ribbing.  He has no ribs.  Back to the importance.  According to this study, 1343 HIV positive patients were checked and their genomes did not once express the 32 base pair mutation.  This means, if you take it literally, the mutation renders the individual completely immune.  I will not jump that far, but I will say that the discovery demonstrates HIV is highly susceptible to singular, relatively simple GENETIC advantages.  HIV can be defeated and it appears that the balance which it takes advantage of, can be only modestly tipped in favor of the Patient, and wondrous results can be achieved.  Note also that HIV uses 2 receptors and I will continue to point out, that even more receptors are used but remain to be discovered.  (Remember HGSI's recent discovery of a gene which gives rise to a receptor which HIV uses?  Important, but probably not a viable therapeutic, IMO.  You cannot block the receptor in its entirety, but genetic antisense can possibly be fashioned to modify the in-place gene's product to mimic the mutation?) Remember how CD4+ cells can fuse to a target, to destroy it?  Upon fusion, HIV passes if the CD4+ was infected.  Sometimes, a CD4+ will fuse and disengage.  If it does this, the "touched" cell is infected and NO receptor was involved.  The other thing to remember, is that individuals with this mutation may be hard to infect, e.g not through mucous membranes, but not impossible, e.g. accidental stick, contamination, etc...  But the hope is raised and the scientific point is clear.  Something seemingly small can tip the scales.  And in this case, it was a GENETIC difference.  HGTV-43 is far more specific as an antiHIV effect, than a mutation of only one receptor.  The lack of any patients bearing the receptor mutation, could simply signal that HIV has a harder time getting a foothold, if it is introduced through conventional contact, but if introduced through high concentration, would gain the necessary foothold through the secondary and tertiary receptors.  Once extablished, HIV mutates, possibly achieving a form that BEATS THE RECEPTOR MUTATION.  It is not a simple issue, but genetic antisense is indeed, a simple concept.  Anti-Virus to the virus in question, but gene by gene, instead of a whole organism.  That is the concept, where the desired antigenes are produced by the cells most harmed by HIV.
*** "Disease Progression
The strength of the immune response to acute HIV infection appears to have a long-term impact on the course of the disease. Those patients who are able to control the virus well, as evidenced by low plasma HIV RNA levels and diverse T-cell responses, advance to clinical disease much more slowly than do those with high plasma HIV RNA levels (eg, >100,000 copies/mL) and a more restricted immune response. Nevertheless, the majority of patients eventually exhibit disease progression. A small proportion of patients— estimated by Dr. Lane at probably less than 5%—do not appear to progress. "Longterm nonprogressors" have been the focus of much recent study that has attempted to characterize the immune effector mechanisms of such an apparently potent and enduring response to infection.
Much of the work done in the area of nonprogression has been descriptive and has thus far failed to adequately characterize the mechanisms underlying the phenomenon. In general, those persons categorized as long-term nonprogressors have lower levels of plasma HIV RNA and broader T-cell immune responses, ie, more CD8+ T-cell clones, than do persons who progress more rapidly. In fact, long-term nonprogressors do not constitute a discrete subset of patients; Dr. Lane maintained that it is more likely that "nonprogression" is part of a continuum of responses ranging from very rapid to very slow progression. He cited data from a study in Multicenter AIDS Cohort Study (MACS) patients that showed that those who maintained relatively stable CD4+ cell counts over the first several years of HIV disease still exhibited a characteristic decline in counts in subsequent years. In that study, a cohort of 56 patients who had been identified as longterm nonprogressors on the basis of follow-up over the first 7 years, during which they exhibited a mean CD4+ Iymphocyte count increase of 18 cells/mL per year, were found to have a mean decrease of 67 cells/mL per year over the following 5 years—a rate of decline comparable to that observed in patients exhibiting a more typical infection course." ***
This large block of information does confirm two things.  Maintaining a high T cell count (of what must be mature T cells, and not naive), leads to a slowing of the progression of the disease.  Even on the non-progressors, those who are likely better defenders (genetic or otherwise), ultimately, they too face the collapse.  The point is to concentrate on discovering the differences.  A note that high, sustained CD8+ T cell counts parallels slower disease progression is important to keep in mind.  What is ENZO trying to do, exclusively?  Re-establish a competent immune system and presume that this re-establishment will take care of all secondary issues and eventually, HIV itself.  Is there evidence to support this theory?  So far, plenty and this excerpt adds quite an important facet.  CD8+ matter in the long run, just as much as CD4+.  If ENZO's HGTV-43 construct produces all immune system cell types, what can one expect as those cells become the predominant cell and encompass lets say more than 50% of the immune system?  I think a sudden and sustained drop in HIV load will then present, and the CD8+ will clear the remainder or expose the remainder, harbored inside infected macrophages, the Lymphatic system, etc.
*** "CD4+ Lymphocyte Dynamics
Studies of CD4+ Iymphocyte dynamics in HIV infection have shown that the immune system is in a state of constant turnover far greater than under normal conditions. This phenomenon is readily demonstrated by the rapid increases in CD4+ cell counts following initiation of effective antiretroviral therapy and by measuring the fractions of CD4+ cells that are in the S phase (actively preparing to divide) at any given time. Despite the increased production of CD4+ cells during HIV infection, there is a steady decline in the number of CD4+ cells over time. Along with this quantitative change, there are qualitative changes that have profound implications for treatment. Studies of changes in "naive" and "memory" CD4+ Iymphocyte populations, analyses of the survival and distribution of genetically marked CD4+ Iymphocytes, and analyses of specificity-mapping of the CD4+ Iymphocyte receptor repertoire all support the conclusions that (1) elements of the T-cell repertoire are lost during progressive infection, and (2) increases in cell counts observed during treatment represent expansion of the remaining elements of the repertoire rather than addition of new or reacquisition of lost elements." ***
This paragraph says it all.  The body tries to compensate.  HIV has a means through which it "destroys" the most potent CD4+ cellular subtypes early on, leaving only those which have no effect on HIV.  (Read 1) and 2) carefully in the final conclusory sentences).  "Elements within the T Cell repertoire are lost early, they do not return".  Now, ENZO has proposed to transduce precursor cells, giving rise to ALL types of immune system cell, including CD4+ and more particularly, at least some of those CD4+ cells which are naturally effective against HIV.  Here is another point.  CD4+ cell subtypes that have no "natural" weapon against HIV, still bear the receptor which HIV desires, or they would not be called "CD4+".  This classification is assigned to a cell specifically because the cell exhibits a certain receptor.  Guess what?  There may not be any naive CD4+ cells, if they are transduced with HGTV-43.  HIV will still collect and inside these cells, micRNA awaits the HIV to destroy it.  Or another observation would be that even in a case where most of the progeny of the HSC's are naive CD4+ cells, if only some are the right type, THEY ARE STILL ALL IMPERVIOUS TO HIV.  Some may be enough.  Some will be enough at a certain level.  The level will vary slightly per individual, but a level of perhaps 50% of normal, should demonstrate a huge impact on the HIV levels in the blood.  Eventually, it is key to see normalcy in CD4+, CD8+ levels and all measurable immune system components, bearing the HGTV-43 antisense genes.   And at that point, an equal opposite effect waged against HIV.  HIV should be GONE.    All this, provided one additional function, the CD8+ bearing HGTV-43 must continue its normal role and seek out infected cells, destroy them and eliminate harbors for the virus.  Think long and hard about the genetic differences between people, ever so slight, perhaps as close as 32 base pairs, yet this is enough to seemingly impart immunity, or at least an encouraging inability to contract, despite behavior which is "at risk".  1300 people is quite a lot of people to find that none bear the 32 base pair mutation, yet all are HIV+.  This is compelling.  Lets move on...
***"The finding that some patients exhibit an increase in naive cell populations suggested that new cells may be entering the system from the thymus, and thus that the system might be able to regain elements of the repertoire deleted through quantitative loss.
However, a number of findings suggest that in fact this is not the case*****. High resolution CT scanning of the thymus during treatment-associated increases in CD4+ cell counts has shown increases in both naive- and memory-cell populations despite involution of the thymus. In one example presented by Dr. Lane, an increase in CD4+ cell counts from approximately 50/pL to more than 500/mL was not accompanied by thymic hyperplasia or other evidence that the cells originated from the thymus ( Figure 3). Labeling of existing cells with a genetic marker has shown that the proportion of marked cells remains constant throughout the expansion of the population, indicating that the increase in cell numbers can be explained by expansion of existing circulating cells, not entry of new cells from the thymus*****."***
Here is a cut down excerpt.  Essentially, the presence of HIV causes CD4+ cells to deteriorate in their total Naive and Memory Cell counts.  Although the prior studies argue that as a function of time, the Memory CD4+ cells deteriorate first and Naive CD4+ cells increase their count, this study determined that both deteriorate.  But with therapeutics applied (protease inhibitors), there is a rebound.  The argument then ensued as to where the rebound came from.  Thymus, Stromal or free form replication.  The last sentence suggests spontaneous replication of mature cells, OR, we can accept the obvious, that precursor cells provided the needed boost. I believe anyone skilled in the art would accept that CD4+ cells emerge from both precursor cells and pre-existing CD4+ cells, as is normally the case in the absence of HIV.  HIV/AIDs is a disease of the immune system , primarily, which eventually wears down these and other defenses of the body.  More and more, the evidence is mounting that the simple seeding of the Bone Marrow, with precursor cells (true Hematopoietic Stem Cells, or HSC's) transduced with HGTV-43, will be the answer.  Remember, ENZO HAS SEEN THE PRESENCE OF ALL CELL TYPES, 120 DAYS, POST INFUSION OF THE TRANSDUCED HSC's, MATURED AND BEARING THE HGTV-43 ANTISENSE GENES, AND THEIR POPULATION IS GROWING .  This should spark more and more meaning as time progresses.  Keep reading!

*** "Polymerase Chain Reaction (PCR) Studies of T-cell Receptor Families
Other data demonstrating that loss of elements of the T-cell repertoire occurs during HIV infection come from PCR studies of T-cell receptor repertoires. A number of different subsets of T cells are produced by rearrangement of the T-cell receptor gene after stem cells enter the thymus. Some of these subsets can be recognized by distinctive T-cell receptor variable region b (Vb) chains. A total of 24 different types of Vb chains has been identified, each of which gives rise to T-cell receptors of 8 different sizes, producing a total of 192 different T-cell receptor families. Selective PCR amplification of the Vb chains allows mapping of the distribution of the different T-cell receptor types.Figure 4 shows the results of such studies in syngeneic twins discordant for HIV infection. Such results indicate that HIV infection is associated with a severe disruption of CD4+ lymphocyte repertoire. This disruption does not appear to be reversed, at least over the short term, by effective antiretroviral treatment. Figure 5 shows the distribution of receptor families for 3 Vb chains before and after treatment with a protease inhibitor and interleukin-2, which resulted in an increase in CD4+ cell counts from 238/mL to 1102/mL.
The determinants of the quality of the CD4+ lymphocyte pool in the context of HIV infection can be understood schematically (see Figure 6). Cells leave the pool both through death as part of the natural remodeling of the immune system and through HIV-induced death. Cells can enter the pool by *****stem-cell differentiation and processing in the thymus in early life or by somatic cell division. In adults, regardless of whether HIV infection is present, the entry of new cells appears to play little, if any, role; the division of cells already existing in the pool accounts for all replenishment of cells lost through natural or other death. Thus, it appears that if diversity within the existing pool is lost in the adult, it is not likely to be replaced, at least during the short term. According to Dr.. Lane, the T cells of the immune system can be viewed as the tiles in a game of Scrabble. In the normal aging process, a memory pool is generated of the letters that are commonly needed; the crucial part of the immune system resides in the memory pool. Some of the naive pool is retained, analogous to the letters that are not used as often. As HIV progresses, there are fewer letters and fewer different letters. As Dr.. Lane noted, it is still possible to communicate with these fewer letters, but far more difficult." ***
Well, well, well, what do we have here?  More evidence?  This is a huge piece of the puzzle.  I am reading the part that says "after stem cells enter the Thymus" and the Thymus is responsible for "programming" 24 chains, 8 sizes, 192 possibilities, etc... The discussion also suggests that in adults, the division of cells in the existing pool act as the source of replenishment for lost cells.  This poses an interesting puzzle.  What is ENZO seeing?  Well, I still need to point out another study, that claims the thymus is still functional late in the progression of disease.  But notwithstanding that point, ENZO transduces the entire output of the leukophoresis machine.  The stem cells (and everything else transduced), are replaced into the body.  ENZO HAS SEEN THE DIFFERENTIATED CELLS COMPRISING ALL COMPONENTS OF A NORMAL IMMUNE SYSTEM.  So is the Thymus processing, or is this even initially needed?  Other organs can process T-Cells in place of the Thymus.  Remember, immune cells are not made into CD4+ cells in the Thymus, they are "processed" or "programmed" and this seems to be an ongoing process.  A tweaking mechanism.  So assuming ENZO has seen these cells (and they stated so at the ASM) at day 120, the HSC's are engrafting.  CD4+ ARE being produced.  If the Thymus processed these OR NOT, would it matter?  here is one interesting point.  CD4+ cells bear the CD4+ receptors and will gather HIV effectively.  The Thymus is NOT needed to make the cell utterly destroy any HIV or HIV mutant which enters the progeny of the HGTV-43 treated HSC's.  These cells will kill all HIV and resist all mutation.  But the Thymus is needed to make the CD4+ cells mature and effective against all other diseases and to restore any natural anti-HIV defenses these cells can be endowed with, as described above (192 net configurations).  So it would seem fair to state that the Thymus needs to be functional to the extent that it can continue to program some of the CD4+ cells bearing the HGTV-43 antisense genes.  But it is equally fair to note that other glands in the body, replicate the Thymus function.  As HIV levels drop, would the Thymus regain function?  Perhaps yes?  Other damaged glands?  Same.  It also seems that the application of Il-II could assist in boosting T Cell production, but the real need for a boost in production is in the CD8+ cells which are HGTV-43 +, so long as there are some CD4+ cells that are also HGTV-43 +.  CD8+ cells will target and destroy all infected cells, causing a void.  The void causes natural signals to command replication of CD4+ cells, wherever they are in the body.  The CD4+ cells that are HGTV-43+ are favored because HIV has killed the untreated CD4+ cells.  It is almost a CD8+ first strategy.  But in any case, ENZO's observations are becoming more and more revealing, once you read and grasp these data.  Has ENZO created an army of Naive CD4+ cells that, despite their Naivity, bear the CD4+ receptors and HGTV-43, gather and destroy HIV, but last only 25 days instead of 90 days?  Would this matter, if CD4+ cells which are HGTV-43+, replicate in response to hormonal signals, replenishing the naive CD4+ HGTV43+ cells?  WILL THEY CLEAR HIV?  WILL THE CLEARING OF HIV RESTORE THE THYMUS?  IS THE THYMUS AND BACKUP ORGAN SYSTEMS DAMAGED IN THE FIRST PLACE?  Again, because ENZO is pioneering into uncharted territory, only they know the secret of post HGTV-43 Patient glandular condition.  But then, there is this other study re: The Thymus coming up...
*** "Summary
Current understanding of viral and immune system dynamics can be summarized as follows: (1) HIV infection is characterized by ongoing viral replication that leads to progressive depletion of CD4+ lymphocytes with preferential loss of "naive" cells. (2) This viral replication is Dr.iven by the number of productively infected cells and is associated with an increased turnover of CD4+ lymphocyte. (3) As the CD4+ lymphocyte pool is quantitatively reduced, there is a progressive and irreversible loss in immunologic diversity. Dr. Lane emphasized that these data all point to the importance of early therapeutic intervention in patients with HIV infection.

H. Clifford Lane is Clinical Director at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, in Bethesda, Maryland.
Suggested Readings
Chou CC, Gudeman V, O'Rourke S. et al. Phenotypically defined memory CD4+ cells are not selectively decreased in chronic HIV disease. J Acquir Immune Defic Syndr.1994;7:665-675.
Cocchi F. DeVico AL, Garzino-Demo A, et al. Identification of RANTES, MIP-1a and MIP-1b as the major HlV-suppressive factors produced by CD8+ T cells. Science.1995;270:1811-1815.
Embretson J. Zupancic M, Ribas JL, et al. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature.1993;362:359-362.
Graziosi C, Pantaleo G. Gantt KR, et al. Lack of evidence for the dichotomy of TH1 and TH2 predominance in HlV-infected individuals. Science.1994;265:248-252.
Roederer M, Dubs JG, Anderson MT, et al. CD8 naive T-cell counts decrease progressively in HlV-infected adults. J Clin Invest.1995;95:2061-2066.
Rowland-Jones S. Sutton J. Ariyoshi K, et al. HlV-specific cytotoxic T cells in HlV-exposed but uninfected Gambian women. Nat Med.1995;1:59-64." ***
I included the suggested reading, so you can see where the information is derived.  Lets think about the summary, because it is a summary of data derived from these aforementioned references and has been updated as of 02/2000. The current understanding of viral and immune system dynamics is summarized as follows: (1) HIV infection progresses through ongoing viral replication that leads to progressive depletion of CD4+ lymphocytes with preferential loss of "naive" cells. (2) This viral replication is Driven by the number of productively infected cells and is associated with an increased turnover of CD4+ lymphocyte. (3) As the CD4+ lymphocyte pool is quantitatively reduced, there is a progressive and irreversible loss in immunologic diversity.  ENZO steps in and transduces HSCs with HGTV-43, replaces them into the bloodstream.  Two things happen.  CD4+ cells appear which attract HIV because they are CD4+ and bear the necessary receptors.  HIV goes in and it does not come out.  Meanwhile, CD8+ are also produced, bearing HGTV-43.  These target and destroy only INFECTED cells.  Sounds like a winner and a PERFECT COMPLIMENT to the SUMMARY of WHAT IS TRULY GOING ON IN AN HIV+ PATIENT, taken from the VERY LATEST RESEARCH IN AIDS.  Moving on...
*** "Several studies have now demonstrated the correlation between higher viral load and more-rapid disease progression and death in HIV-infected adults and children. The risk of progression and death grows steadily with increasing viral load." ***
Would you look at this gem.  Where does all the HIV come from?  INFECTED CELLS.  We know this.  HIV cannot replicate outside of a living, human cell.  So I stand by my observation just above this one, ...ENZO has the perfect compliment to the  known problem.  ENZO has created an immune system that is impervious to the effects of HIV.  If in fact, the CD4+ and CD8+ cells have been observed, differentiated from the immature stem cells originally inserted and bearing the -43 antisense gene package, THE CD4+ WILL COLLECT AND DESTROY HIV AND THE CD8+ WILL TARGET AND DESTROY HIV INFECTED CELLS, CAUSING THE CD4+ HGTV-43+ CELLS TO GROW AND BECOME PREDOMINANT.
*** "Newer generation bDNA and RT PCR research assays, which can detect as little as 20 to 50 copies of HIV RNA/mL of plasma have confirmed that "undetectable" does not necessarily indicate "no viral replication." Further, while the virus may be undetectable in the plasma, it may be present in the central nervous system, the lymph nodes, the bone marrow, and other body compartments." ***
No surprises here.  We kind of suspected this all along.  Guess what cell can penetrate these tissues and collect HIV?  T-CELLS!  CD4+ CD8+ with HGTV-43 internally along for the ride.  Do you see where this leads?  HIV can be collected by an immune system that is internally immune to HIV's presence.  HIV is able to be repelled by individuals with a missing set of alleles, 22 to be precise, giving rise to a key receptor in the CD4+ cell.  THEY DO NOT APPEAR TO CONTRACT THE VIRUS.  Why would the addition of HGTV-43 be any different?  lets not be short sighted.  ANY HUMAN WHO ENGAGES IN UNSAFE PRACTICES WILL CONTRACT THE VIRUS IF EXPOSED.  It is the reaction of the body than mitigates if the virus will ever become entrenched, and thus, eventually, chronic.  HGTV-43 is still finding support in these data and observations.  It is hard to kill or even ding.  I see a strong suggestion of success.  What was it ENZO said besides "they work"?  They are more and more encouraged as time progresses.  THEY SHOULD BE.  Everything is pointing in the right direction.  More?  OK!
*** "What are the implications of this study, and what questions were not answered?
Some firm conclusions can be drawn from these results:
CD4 lymphopenia in advanced HIV infection is due to both a shortened survival time and a failure to increase the production of circulating CD4+ T cells.
The increase in CD4 counts after short-term HAART is not due to simple redistribution of T cells from tissue into blood (there were more newly produced cells present).
The increase in CD4 counts after short-term HAART was related to higher production rate (greater inflow of new cells into the bloodstream), not longer survival of cells in the bloodstream.
 Thus, these results make the (optimistic) suggestion that T cell producing systems are impaired but not irreversibly damaged or exhausted in advanced HIV disease. If HIV itself suppresses T cell generation (e.g., in the thymus ***** or peripheral lymphoid tissues) this is a very different scenario than if the system were terminally damaged or "burned out," due to a long-standing strain on proliferative reserves.
This model, if it proves true, would have some therapeutic implications. Adjunctive immunostimulatory therapies might prove effective in addition to antiretroviral therapy, if T cell production capacity is a key factor determining CD4 counts. Patients may also differ in their ability to produce new T cells; kinetic measurements may identify those individuals with T cell production that is HAART-unresponsive and might help select the patients who are most likely to benefit from adjunctive therapies. Preservation of T cell proliferative reserve might be a goal in its own right that will need to be considered in designing therapeutic strategies in the future." ***
Was I happy to find this? OHHHHH YEAHHHH!  This is a recent study.  I had to cut out a lot so you could read it.  But the long version (link to) is listed in the Preface.  What does it conclude?  Well, as you read the long version, these folks got creative with their labeling techniques, so they could answer some unanswered questions.  Lets tackle the big one. T cell producing systems are impaired but not irreversibly damaged or exhausted in advanced HIV disease.  And all ENZO proposes to do is take a reasonable and diverse set of precursor cells (HSC's), modify them to be impervious to HIV, expect them to retain this trait as it is a genetic, embedded capability, and not a learned capability, and engraft these puppies into the Patient's UNDAMAGED, STILL FUNCTIONAL SYSTEMS.  IF IT GIVES RISE TO A COMPLETE COMPLIMENT OF HGTV-43 + IMMUNE CELLS, THIS SHOULD WORK AS A VIABLE THERAPEUTIC.  IN FACT, IT WILL WORK AS A VIABLE THERAPEUTIC, but that is just my opinion.  And I did very little research to reach this opinion...:)

MY SUMMARY:
ENZO SCIENTISTS WORKED VERY HARD TO DETERMINE THEIR COURSE OF ACTION IN DEVELOPING 9801-230 AND HGTV-43.  IT IS NOT A LARK, A WASTE OF THE SHAREHOLDER'S TRUST OR A POORLY DEVISED SCHEME TO MAKE IT LOOK LIKE ENZO MIGHT BE PROGRESSING.  IT IS BOLD, CUNNING, CALCULATED AND PERFECT.  HIV IS A DISEASE OF THE IMMUNE SYSTEM.  THE STUDIES CITED ABOVE DO PROVE THAT THE HIV+ PATIENT'S SYSTEMS ARE IN FACT, IN-TACT UP TO THE FINAL STAGES OF DISEASE PROGRESSION.  WHAT IS LACKING IS A SERIES OF IMMUNE CELLS PERFECTLY COMPATIBLE WITH THE PATIENT, WHICH DO NOT MAKE COPIES OF HIV, DO PERFORM ALL NECESSARY IMMUNE SYSTEM FUNCTIONS AND WILL SELECTIVELY ABLATE THE INFECTED CELLS, RELEASING ALL VIRAL PARTICLES.  HGTV-43 PRODUCES A LINE OF CELLS THAT SHOULD PERFORM THIS FUNCTION.  THE CHILDREN OF AN HGTV-43 TRANSDUCED HEMATOPOIETIC STEM CELL CAN REPLICATE, AND THE ENGRAFTED STEM CELLS CAN ALSO REPLICATE AND DIFFERENTIATE, UPON RECEIPT OF A SIGNAL FROM THE BODY.  THE SIGNALS ARE THERE NOW.  BUT THE CELLS PRODUCED BY THE PATIENT'S NATURAL SYSTEMS, SERVE TO FEED THE HIV.  HGTV-43 CELLS WILL NOT FEED HIV.  THE CD8+ WILL DESTROY HIV INFECTED CELLS.  THE CD4+ WILL COLLECT VIRAL PARTICLES AND DESTROY THEM.  THESE ARE FACTS.  WHAT IS NOT A FACT YET IS THE REMAINING FUNCTIONS OF THESE NEW IMMUNE SYSTEM CELLS.  ARE THEY, IN FACT, NORMAL IN ALL OTHER RESPECTS AND WILL THEY, IN FACT, RESPOND TO THYMUS PROGRAMMING AND OTHER PROGRAMMING, MANDATED BY THE BODY?  THEY SHOULD.  BECAUSE THE CHANGES MADE GENETICALLY, DO NOT SEEM BROAD ENOUGH TO INTERFERE WITH ANY OTHER NATURAL FUNCTION.  IF I AM CORRECT, THE IMMUNE SYSTEM "ORGANS" ARE IN-TACT. THYMUS FUNCTION CAN EVEN BE OFF LINE AND COME ON LINE AS HIV IS REDUCED.  CD8+ CELLS CAN ABLATE INFECTED CELLS AT SOME REASONABLE PACE, AND THE INFECTED CELLS WILL ALSO EVENTUALLY SELF DESTRUCT, AS EVIDENCE SUGGESTS THE HIGH PRODUCTION OF HIV PROTEINS AND AMINO ACIDS KILLS THE CELL FROM THE INSIDE.  THIS IS GOOD, IN THE 9801-230 SCENARIO.
I HOPE EVERYONE READS THIS COMPLETELY.  OVER AND OVER.  DRS>>> FIND SOME FAULTS WILL YOU?  PLEASE?  I WILL NOT LEARN OR PROGRESS UNLESS YOU HELP.
ICPOSSE
TRP TRAP
CUTIS
SURFSURGEON
DHARAF
PEDPRO
PAUL (YOU KNOW WHO YOU ARE !!!)
HELP ME LEARN.  OR TOAST ME.  BUT DO NOT REMAIN SILENT. PLEASE COMMENT.