In the 11/1/05 Journal of Clinical Investigation article titled
"HIV-infected individuals receiving effective antiviral therapy for
extended periods of time continually replenish their viral reservoir,"
Chun et al. (Fauci is senior author) state:

"In the present study, we investigate the presence and status of
residual HIV in patients who had received effective antiviral therapy
for up to 9.1 years and examine the underlying mechanisms by which HIV
persists in CD4+ T cells of such individuals. We demonstrate that all
infected subjects studied carried replication-competent HIV in their
CD4+ T cells and the majority of patients harbored considerable levels
of HIV proviral DNA in their activated as well as resting CD4+ T cell
compartments. Finally, we also provide evidence for cross infection
between these 2 compartments, suggesting a possible mechanism by which
HIV persists in patients who are receiving clinically effective
antiretroviral therapy."

"In the present study, we investigated the source(s) and the extent of
residual HIV replication and examined the underlying mechanisms by which
HIV persists in CD4+ T cells of patients who received effective
antiviral therapy for extended periods of time. We demonstrated
that all infected subjects examined carried replication-competent HIV in
their CD4+ T cells despite having received clinically effective
antiviral therapy for extended periods of time (8.3 years on average).
To our knowledge, this is the first study to examine levels of
replication-competent HIV in the CD4+ T cell compartments of patients
who have received effective antiviral therapy for such long periods of
time (up to 9.1 years). We also demonstrated that, contrary to current
dogma, it is the activated CD4+ T cell compartment that harbors the
majority of persisting HIV in infected individuals who have had no
detectable viremia for extended periods of time as a result of effective
antiretroviral therapy. In the years following the first indications of
HIV latency in infected individuals, the vast majority of studies, if
not all, addressing the persistence of HIV in the era of effective
antiviral therapy focused heavily on the latent viral reservoir in the
resting CD4+ T cell compartment as a major impediment to eradication of
HIV. However, the activated CD4+ T cell compartment has not been fully
explored as a potential viral reservoir in infected individuals
receiving clinically successful antiviral therapy mainly because it has
been believed that such cells are short lived and not expected to harbor
virus. By demonstrating the presence of HIV in activated CD4+ T cells of
maximally suppressed individuals, we thus provide compelling evidence
for contribution of this compartment to the continual reseeding of HIV
reservoirs. Although mitotic division of activated CD4+ T cells
harboring defective virus could account for the higher frequency of
cells carrying HIV proviral DNA in activated CD4+ T cell compartments
compared with resting CD4+ T cell compartments, the evidence presented
herein for spontaneous release of virions and viral migration and the
short half-life of activated CD4+ T cells would argue for the
persistence of infectious virus in activated CD4+ T cells."

------------------------------------

This Article FREE, OPEN ACCESS

J. Clin. Invest. 2005 Nov 1;115:3250-3255. doi:10.1172/JCI26197.

HIV-infected individuals receiving effective antiviral therapy for
extended periods of time continually replenish their viral reservoir

Tae-Wook Chun1, David C. Nickle2, J. Shawn Justement1, Danielle Large1,
Alice Semerjian1, Marcel E. Curlin2, M. Angeline O'Shea1, Claire W.
Hallahan3, Marybeth Daucher1, Douglas J. Ward4, Susan Moir1, James I.
Mullins2, Colin Kovacs5 and Anthony S. Fauci1

1Laboratory of Immunoregulation, National Institute of Allergy and
Infectious Diseases, NIH, Bethesda, Maryland, USA.
2Department of Microbiology, University of Washington, Seattle,
Washington, USA.
3Biostatistical Research Branch, National Institute of Allergy and
Infectious Diseases, NIH, Bethesda, Maryland, USA.
4Dupont Circle Physicians Group, Washington, DC, USA.
5Department of Medicine, University of Toronto, Toronto, Ontario,
Canada.

Address correspondence to: Tae-Wook Chun, Laboratory of
Immunoregulation, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Building 10, Room 6A32, 9000 Rockville
Pike, Bethesda, Maryland 20892, USA. Phone: (301) 496-0890; Fax: (301)
402-5920; E-mail: twchun{at}nih.gov.

Received for publication July 7, 2005, and accepted in revised form
August 23, 2005.

Abstract: The persistence of latently infected, resting CD4+ T cells is
considered to be a major obstacle in preventing the eradication of HIV-1
even in patients who have received effective antiviral therapy for an
average duration of 5 years. Although previous studies have suggested
that the latent HIV reservoir in the resting CD4+ T cell compartment is
virologically quiescent in the absence of activating stimuli, evidence
has been mounting to suggest that low levels of ongoing viral
replication persist and in turn, prolong the overall half-life of HIV in
patients receiving antiviral therapy. Here, we demonstrate the
persistence of replication-competent virus in CD4+ T cells in a cohort
of patients who had received uninterrupted antiviral therapy for up to
9.1 years that rendered them consistently aviremic throughout that time.
Surprisingly, substantially higher levels of HIV proviral DNA were found
in activated CD4+ T cells when compared with resting CD4+ T cells in the
majority of patients we studied. Phylogenetic analyses revealed evidence
for cross infection between the resting and activated CD4+ T cell
compartments, suggesting that ongoing reactivation of latently infected,
resting CD4+ T cells and spread of virus by activated CD4+ T cells may
occur in these patients. Such events may allow continual replenishment
of the CD4+ T cell reservoir and resetting of the half-life of the
latently infected, resting CD4+ T cells despite prolonged periods of
aviremia.

We heard you the first time.

Clinically effective treatment does not eradicate HIV from the viral
reservoirs.
It would be wonderful if it did, but as Fauci states - this therapy IS
clinically effective, so its the next best thing to a cure, and not a
cause to imply there are problems with HAART

"DavidT" <david199@volcanomail.com> wrote in message
news:1132069142.119592.43220@g43g2000cwa.googlegro ups.com...
No, you merely cringed twice.

Gee, imagine that. Anti-viral "treatment" that doesn't remove the virus
is somehow "clinically effective"!

Strange how you seemed to miss the point. Religious fervor
tends to do that among its gullible victims.

But what about the FACT that the HAART promise of
"undetectable" virus is a BIG LIE? Or that "undetectable"
virus has NOTHING to do with ANYTHING?

Or hasn't it dawned on you yet that they are only looking in the
most convient place for "viremia" - in the bloodstream?

Convenient, that is, for the drug companies...

Insulin doesn't cure type 1 diabetes either, but its a hell of a lot
better than the alternative...

"DavidT" <david199@volcanomail.com> wrote in message
news:1132077751.595487.198610@g49g2000cwa.googlegr oups.com...
Gee, what a wonderfully defective leap of illogic!!!

There is ONE difference between the efficacy of diabetes
treatment and the scurrilous claims of "antiviral cures":

P R O O F

but nice try, dear.

Gee, what a wonderfully defective leap of illogic!!!

"There is ONE difference between the efficacy of diabetes
treatment and the scurrilous claims of "antiviral cures":

P R O O F

but nice try, dear."


Susie,
what they're doing is quite simple. No matter WHAT, they don't want
ANYBODY to EVER think there is a way OUT of their nightmare. It's just
too damned profitable. Easy as that.

"Gee, imagine that. Anti-viral "treatment" that doesn't remove the virus
is somehow 'clinically effective'!"


Ssshhhh, Susie!

Don't point out the obvious contradictions. They HATE that!

wilyretrovirus wrote:
What contradiction?

Antiviral drugs do not remove HSV from reservoirs in the CNS but it
does control active replication. It is effective in treating HSV but it
is not a cure.

Ignorance is curable.

Chris Noble

Chris,

you're right. You're right in your make-believe, fairy-tale land of the
one retrovirus that can do just about any trick it's asked to perform.

Susie was correct in pointing out the misleading language. I would expect
that a "clinically effective" drug regime would be um...effective. But lo
and behold, the "viral reservoir is continually being replenished".
Doesn't sound "effective" to me. I suppose "effective" is a rather broad
term, and in "AIDS-land" could mean whatever the researchers at the moment
want it to mean. So, yes, you're "right", Chris.

You have absolutely no understanding of the words "clinically
effective".
I think you have made that fact completely clear.

Not in your case, Mr. Noble. How you have the nerve to compare HSV with
"HIV" is beyond me.
But anyhow: Happy Thanksgiving.

Which virus we talk about is immaterial. The point is that there are
many viruses which persist in the host despite there being clinically
effective treatment which can ameliorate or eliminate symptoms of the
disease.
The fact that they can do so does not make the treatments any less
effective at what they do.

It appears there are many things which are "beyond you", not only an
understanding of HIV pathogenesis.

David,
I understand the words "clinically effective" quite well. Unfortunately,
most folks out there don't know that the words *effective* and *clinically
effective* may have absolutely nothing to do with each other. Take Immune
Reconstitution Disease, for example. Those wonder drugs might be taking
credit for the patient's high CD4 counts and low viral load, but, oops,
they got PCP and died anyway. Oh well...tra la la...at least the
"treatment" was "clinically effective".

You have no concept of the term "clinically effective", quite clearly.
If there is clinical improvment, there is clinical efficacy. If there
is deterioration, there is not. So a patient dying will not be regarded
as an outcome showing clinical effectiveness.

You also have no grasp of the Immune reconstitution. PCP is not one of
the diseases that characterises this type of syndrome. You have just
plucked out a disese name at random, obviously. If you knew the first
bit about the syndrome you would have given any one of several other
well-recognised infections as an example.

You have no concept of the term "clinically effective", quite clearly.
If there is clinical improvement, there is clinical efficacy. If there
is deterioration, there is not. So a patient dying will not be regarded
as an outcome showing clinical effectiveness.

You also have no grasp of the Immune reconstitution. PCP is not one of
the diseases that characterises this type of syndrome. You have just
plucked out a disease name at random, obviously. If you knew the first
bit about the syndrome you would have given any one of several other
well-recognised infections as an example.

You have no concept of the term "clinically effective", quite clearly.
If there is clinical improvement, there is clinical efficacy. If there
is deterioration, there is not. So a patient dying will not be regarded
as an outcome showing clinical effectiveness.

You also have no grasp of immune reconstitution. PCP is not one of the
diseases that characterises this type of syndrome. You have just
plucked out a disease name at random, obviously. If you knew the first
bit about the syndrome you would have given any one of several other
well-recognised infections as an example.

For you that may be so. That's just because you live in a ridiculous
inverted world in which high levels of lymphocytes are a sign of good
health, and antibodies against a virus are a sign of persistent infection
by that same virus.
The nitwits who taught you your trade are the same people who tried in
vain for 20 years to find a virus that causes cancer, and just when
everybody could see clearly how incompetent they were, invented a new
disease to apply their bankrupt virus theory for yet another 20 years.

is deterioration, there is not"

Well, I do. This "clinical effectiveness you're talking about is very
short-lived. The patient has a brief feeling of well-being (because ARV's
are killing off bacteria and fungi, along with body cells). Then the
patient dies - of liver failure.
This "clinical effectiveness" has been known since 1895 as the Herxheimer
effect. Even cancer patients on chemotherapy show this phenomenon. They
seem to get better, to the delight of close relatives, then they die
suddenly.
For all I care you can stick this kind of "clinical effectiveness" up a
warm and dark place.

You must have thought your comment was very valuable, Master David, to post
it 3 times

No- "clinically effective" implies a beneficial clinical outcome, and
not deterioration/death.
Stop being obtuse.

Also, please look up the Immune reconstitution syndrome before you
start shooting your mouth off about PCP.
There are several OIs that are characteristic of this syndrome, but PCP
is not one of them. Bad guess.