Structured Treatment Interruptions 4 to6-month interrupt safe>400-500??

[bimazek]

Structured Treatment Interruptions

Data from SMART, the largest trial of structured treatment interruptions (STI) conducted to date, were reported earlier this year at CROI.[5] The premature discontinuation of this study has been a major obstacle to enthusiasm around further study of STIs in the context of HIV. The results of 2 other trials, Trivacan[6] and DART,[7] have confirmed the SMART results, with an excess of morbidity and mortality in STI arms compared with control arms. In contrast, the results of the Staccato and Windows[8,9] studies have shown significant cost savings using STI without deleterious adverse outcomes, as shown in Table 2.
Table 2. Outcome in Major Studies Assessing Structured Treatment Interruptions (STI)
    


AIDS & Deaths per 100 Patient-Years
           
(5472)   SMART
(326)   rivacan
(813)   DART
(430)   Staccato
(390)  Windows
STI arm      3.1   17.6   8.3   0.2   0.4
Control arm   1.4   6.7   3.2   0.4   0

http://www.medscape.com/viewarticle/549595


These apparent contradictory results could be somewhat reconciled if we consider that short (4- to 6-month) treatment interruptions may be safe only in patients with CD4+ cell counts > 400-500 cells/mcL.[9] Also of note, one of the indirect messages of the SMART trial data is that plasma HIV-RNA does matter clinically, because AIDS/death events in the trial were more frequent in patients off therapy across all different CD4 strata.

my laymans interpretation... short interupts have low danger of adverse effects, long interupts have some danger of adverse effects but haart does such a good job that the some danger is very very low??
please comment on your experiences with treatment interupts??
how many have you had how long?

[hussy_24]

my nurse was talking today again about going on meds, but explained that i would go on meds for about 2 years and if things were ok to come off meds, she says she has other patients who did this and some of them have been off meds for 6 to 7 years. i mentioned the smart study to the nurse. the nurse explained that whilst the smart study generally concluded that there was no benefit for treatment breaks and the virus came back worse, there is a category of persons the study does not fit with. she explained that seroconverters who were only infected recently (say ~1yr) who go on meds quickly can come off them in about 2 years if their bloods are good and as explained above can go for 6-7yrs+ off treatment. i'm in the UK, and my nurse is organising for me to be referred to mortimer market clinic in London as she said they are more experienced in dealing with this particular type of seroconverter (other reasons for referral-> the visiting doctor also is at mortimer, nhs funding problems, ease for me to travel to mortimer clinic).

[bimazek]

hussy thanks for your reply, i do not fall into the 1 year group as you do, but have been exposed 2 years ago, but 500tcells and med vl of 22k.  i wish i could ask your nurse what she thought, i would go on meds now if i thought i could go off of them for 5 years, seems weird because the clinical practice is so different from city to city,
what are your numbers, i am planning to wait till i get to 350tcells or vl spikes up, what are your thoughts

[bimazek]

one big question is, we know that a small to medium pc of hiv are suffering with alcolohism or drug use or even abuse, say up to 20% but did these staccato and other Structured Treatment Interruptions take this into account.

in other words if the adverse effects were seen mostly or only in  those suffering with alcolohism or drug use or even drug abuse perhaps the  Structured Treatment Interruptions are safer than the stats show

it just seems unscientific to group everone together, what about by age, or alcolohism or drug use or even abuse etc

[Ihavehope]

Will there ever be a day in our lives where we can stop taking meds? Is that possible?

[hussy_24]

my numbers are relatively low, 218cd4 viralload 18k~, cd4%19~ fyi. you could always seek a second opinion but i guess most clinics go with whats worked best for their patients (i.e. start meds early or later). if your numbers are fairly high and your feeling ok every day then you may as well wait til u notice a worsening trend.

[gemini20]

I was diagnosed in 1991 and have taken two treatment breaks in the 16 years since I was diagnosed.

I did not start treatment until 8 years after I was infected in 1999 and only then because my cd4 count and % were falling - I had not experienced any illness at all. I lasted only 4 months on treatment due to the severe side effects I experienced.

I stopped all treatment in February 2000 and did not restart again until four years later in April 2004 and only then because my counts were 141 (14%) and v/l at 70,000.

Second time around I stayed on treatment for 18 months until October 2005 when I stopped again due to my lack of compliance. When I stopped my counts had got up to 474 (33%) and v/l undetectable.

So this time around my break has been 15 months and counting. I plan to stay off treatment indefinitely regardless of what my numbers are doing - current cd4 is 245 (15%) and v/l about 13,600.

Fortunately I have remained well and healthy since stopping treatment and therefore this makes it easier for me to continue with my decision.

Best wishes,

Emma

[J.R.E.]

Hello,

I know that going on an STI is not in the forecast for me. The doctor informed me of that back in 2003, that an interuption was not likely. But I started treatment at 16 t-cells.

There was also this report. You may have read it ; From 11/30/06 from this site's news section( Smart Study)

http://www.aidsmeds.com/news/am20061130.html


Ray

[bimazek]

scientific papers online about hiv and i did a search on 2007 hiv papers, there are 87 so far.  This one really stands out!
 
*2007
 
*new cd4 cells die in the lymph nodes not in the blood but specifically in the lymph nodes of the gut
 
*but the loss in the gut lymph nodes is not mirrored in the blood or other lymph nodes
 
*which explains why blood cd4 counts do not give a whole picture of the person and what he is facing
 
*also strangely uninfected nearby bystander cd4 cells die --- not the hiv infected ones
 
*FasL anti-body would block this process - sounds like breakthrough to me
 
*only one cd4 cell in 1,000,000 is producing virus, very few of them is infected
 
*hiv is a disease of the homing of the cd4s back to the nodes to be distroyed, the body thinks it has cleared the infecton
after the 2 week initial burst or the chronic fight and then cytokines that home the cds back to the nodes are relesased this tricks the cd4s to go back to nodes and some other molecule switch tells the cd4s to aposisis the un-infected cd4s in the nodes
 
A HOMING RECEPTOR ON OUTSIDE OF UNINFECTED CD4 CELLS GETS TURNED ON BY BEING CLOSE TO OR TOUCHING AN HIV PARTICLE (BUT NOT INFECTED BY IT) THIS CAUSES THE CD4 TO HOME BACK TO THE LYMPH NODE TO KILL ITSELF CALLED APOSISOS...
 
so the disease is actually a disease of the uninfected cells dying
the cd4s that are dying ARE NOT INFECTED
we loose cd4s that are not even infected!!!
this is a huge breakthru if you ask me...
 
sure
 
when you get a flu there is that awful giant wave of immune response and all those terrible chemicals cytokines and bugs being killed off
then the immune system pulls back and says, did i get it all, and then it hits with another wave, then pulls back, and then
says ok i finished and i have to put away all the tanks and big guns and rifles...  thats when the cells get called back to the nodes
that means...
 
that is the period called homing back to the lymph nodes
 
so something wierd is happening in hiv disease because the body thinks the infection has been dealt with then
it calls back the cd4s into the nodes and because they have touched or recieved a signal -=BUT ARE NOT INFECTED OR NOR WILL THEY BE INFECTED-
THEY do aposisos and they die and that is why cd4s deplete
 
it is not the infected ones that die off!!!!
 
also this explains why all those weird alternative therapies though they dont stop it can have some minor effects
 
anything that disrupts the homing of the uninfected cd4s back to the node to aposisos or self die.
 
it all has to do with the FasL --- some chemical in immune system
CD62L is also involved
 
the cool thing is with a anti-FasL monoclonal antibody... which is big time expeimental stuff real complicated to create
they can stop the FasL induced death of the cd4s
 
listen they just figured out which and how the cd4s where dying off a few weeks ago.. before they thought the infected ones were dying
 
now they find out more
 
only the CD62L receptor tells the poor uninfected cd4 cell to go home
but it may be that CD62L and a few other receptor switches get turned on once in the node and the poor cell is told to die off
your job is done
 
 
http://www.jleukbio.org/cgi/rapidpdf/jlb.0506338v1.pdf
 
The hallmark of HIV-1 disease is the
gradual disappearance of CD4
T cells from the
blood. The mechanism of this depletion, however,
is still unclear.
 
Evidence suggests that lymphocytes
die in lymph nodes, not in blood, and that uninfected
bystander cells are the predominant cells
dying. Our and others’ previous studies showed
that the lymph node homing receptor, CD62 ligand
(CD62L), and Fas are up-regulated on resting
CD4
T cells after HIV-1 binding and that these
cells home to lymph nodes at an enhanced rate.
During the homing process, signals are induced
through various homing receptors, which in turn,
induced many of the cells to undergo apoptosis
after they entered the lymph nodes. The purpose of
this study was to determine how the homing process
induces apoptosis in HIV-1-exposed, resting
CD4
T cells. We found that signaling through
CD62L up-regulated FasL. This resulted in apoptosis
of only HIV-1-presignaled, resting CD4
T
cells, not normal CD4
T cells. This homing receptor-
induced apoptosis could be blocked by anti-
FasL antibodies or soluble Fas, demonstrating that
the Fas-FasL interaction caused the apoptotic
event. J. Leukoc. Biol. 81: 000–000; 2007.
 
 
Steroids, which are known to down-regulate CD62L and retard
lymph node homing, have been shown to stop reduction of CD4
cells in the blood of patients  This may be the consequence
as control of aberrant homing signals for the marked
reduction in apoptosis. Future studies, testing whether inhibition
of lymph node homing or homing receptor induction of
apoptosis would prevent depletion of CD4
cells in patients,
are needed.

One of the
major observations in this study is that apoptosis of HIV-1-
exposed, resting CD4
T cells, in which CD62L was crosslinked,
could be inhibited significantly by blocking anti-FasL
antibodies or sFas (Fig. 4). This indicated that apoptosis of
HIV-1-exposed, resting CD4
T cells, subsequently signaled
through the homing receptor, is Fas-FasL-mediated. It is interesting
that apoptosis was detected in resting CD4
T cells
exposed with X4 virus strain (HIV-1213) or R5 virus (HIV-1BaL)
strain, subsequently signaled by XLCD62L, indicating that this
is a common property of HIV-1 (Fig. 2). Furthermore, such
effect seems to be independent of HIV-1 replication, as UVinactivated,
HIV-1-exposed, resting CD4
T cells, upon
XLCD62L, underwent apoptosis as well (data not shown).
 

Based on
our data, we proposed that in vivo, CD4
T cells are infected
with HIV in Peyer’s patches, where they may get the signals for
homing fast and up-regulated Fas and get the further signals,
such as FasL, through interaction between homing receptors
and their ligand on lamina propria and finally, undergo apoptosis
in lamina propria. We are currently working on the
effects of HIV on gut homing receptor  4
7 and consequence
of cross-linking of  4
7 on the HIV-exposed CD4
T cells
 
 
 
With respect to the in vivo relevance of our findings in the
context of HIV-1 pathogenesis, our data implicate the following
scenario to be operative in vivo and may act as a mechanism for
the death of uninfected CD4
cells. Resting CD4
lymphocytes
in lymphoid tissues (in gut, lymph nodes, etc.), coming
into contact with HIV-1 virions, productively infected cells, or
HIV-1-coated, follicular dendritic cells, result in induction of
a partially activated phenotype, including up-regulation of
homing receptors and Fas. Because of normal lymph node/
blood circulation, in which most lymphocytes in lymphoid
tissues migrate back to the blood within 2 days [56], many of
these cells will end up back in the blood at the time of
maximum-induced expression of homing receptors. These cells
would then home rapidly to peripheral lymph nodes or gutassociated,
lymphatic tissue, dependent on the type of homing
receptors (e.g., CD62L for peripheral lymph nodes;  4
7 for
gut). Following transendothelial migration, these CD4
T cells
receive signals through homing receptors, resulting in induction
of FasL expression on some of the cells and rapid susceptibility
 

Consequently, together
with the increased Fas expression within the same
CD4
T cell population, approximately one-third of them
would be depleted, and they do not produce HIV-1 [18]. In
support of this review, features that are characteristically associated
with HIV-1 infection include the following. As CD4
lymphocytes disappear in the blood, their numbers do not drop,
and the CD4/CD8 ratios do not invert in lymph nodes until late
in disease [57]; there is increased apoptosis of uninfected cells,
mainly localized in lymph nodes or gut-associated lymphatic
tissue [6, 45, 58] but not in the blood [59, 60]; there is
increased FasL-expressing cells with the morphology of macrophages
and lymphocytes, and the degree of FasL in vivo has
been shown to be correlated with the degree of apoptosis [61].
 
Steroids, which are known to down-regulate CD62L and retard
lymph node homing, have been shown to stop reduction of CD4
cells in the blood of patients [62]. This may be the consequence
as control of aberrant homing signals for the marked
reduction in apoptosis. Future studies, testing whether inhibition
of lymph node homing or homing receptor induction of
apoptosis would prevent depletion of CD4
cells in patients,
are needed.
ACKNOWLEDGMENTS
 
Steroids, which are known to down-regulate CD62L and retard
lymph node homing, have been shown to stop reduction of CD4
cells in the blood of patients [
 
Steroids, which are known to down-regulate CD62L and retard
lymph node homing, have been shown to stop reduction of CD4
cells in the blood of patients  This may be the consequence
as control of aberrant homing signals for the marked
reduction in apoptosis. Future studies, testing whether inhibition
of lymph node homing or homing receptor induction of
apoptosis would prevent depletion of CD4
cells in patients,
are needed.

 
Infection with HIV-1 is usually characterized by a gradual and
inexorable depletion of CD4
T lymphocytes. The importance
of the loss of these cells in the development of AIDS is
unquestioned, as it correlates with the loss of immune capabilities
and the consequent occurrence and severity of opportunistic
infections and HIV-1-associated neoplasms. However,
understanding the mechanisms by which HIV-1 causes CD4

T cell loss remains one of the unanswered questions in the
AIDS field. Many mechanisms have been proposed to explain
how HIV-1 causes depletion of CD4
T cells and the earliest
theorized that virus replication in CD4
T cells resulted in
their death or that virus-specific CTLs killed these infected
cells. However, elimination of productively infected cells could
not explain the significant loss of CD4
T cells [1], as few cells
in vivo are producing virus at any given time (approximately
one in 105 cells) [2, 3]. Recent studies suggest that depletion
of CD4
T cells mainly occurs in lymphoid tissues of the
gastrointestinal tract [4, 5], but the loss of these cells in the gut
is not mirrored in the blood and lymph nodes. In fact, CD4
T
cell depletion occurs in the “effecter area” of gut (lamina
propria) not in the “inductive area” (Peyer’s patches), where
most of the cells producing virus reside. It has also been shown
that increased numbers of CD4
cells are dying in peripheral
lymphoid tissues of HIV-infected subjects, but cells replicating
HIV-1 are not the principal cells dying; uninfected, neighboring
cells are dying [6]. Therefore, most theories about how
HIV-1 depletes CD4
T cells now depict ways uninfected
bystander cells can be eliminated. Some early studies indicated
that HIVgp120 binding to CD4 and CXCR4 receptors
induced apoptosis [7, 8]. All of these studies used transformed
cell lines, and studies using normal CD4 lymphocytes did not
find this phenomenon [7–11]. Also, the apoptosis induced in
cell lines was not Fas/Fas ligand (FasL)-mediated, but other
pathways were [7–9]. Recently, collagen deposition-associated
fibrosis and damaged lymphatic tissues that accompany immune
activation have been shown to be correlated inversely
with blood CD4
T cell count [4, 12]. Some studies suggest
that there is a significant dysregulation of cytokine responses,
which likely, influences T cell susceptibility to apoptosis [13].
Many of these factors may play some roles in CD4
T cell
depletion. However, excessive apoptosis of uninfected CD4
T
cells is thought to be the major reason for depletion of CD4

T cells [13, 14].
Our previous studies showed that HIV-1 binding to resting
CD4
T cells up-regulated the expression of CD62L, the
receptor for homing to lymph nodes, on some cells and enhanced
the homing of these cells from the blood into lymph
nodes [15–17]. Subsequent signaling through various homing
receptors during the homing process on these abortively infected
CD4
T cells induced many of them to undergo apoptosis
[16]. These signaling events occur when the cells transendothelial
migrate into lymph nodes, and it was shown that
CD4
T cells in the blood of HIV-infected people
 
 





Steroids, which are known to down-regulate CD62L and retard
lymph node homing, have been shown to stop reduction of CD4
cells in the blood of patients  This may be the consequence
as control of aberrant homing signals for the marked
reduction in apoptosis. Future studies, testing whether inhibition
of lymph node homing or homing receptor induction of
apoptosis would prevent depletion of CD4
cells in patients,
are needed.

IN THE LATE 80S AND EARLY 90S BEFORE good meds many hiv people seemed to prolong life somewhat
with steroids, perhaps this is the reason it worked

even today many hiv people take steriods for many reason

please comment...

my questions

what kind of steroids are the dr.s talking about?
what is the plan?
how big of a breakthru is this?





 
 
 
also
 
 
2007 hiv vaccines new book
http://books.google.com/books?hl=en&lr=&id=-m6H5kDm1JAC&oi=fnd&pg=PR7&sig=qGajLPO-zwTzLJs4einNA782HWc&dq=hiv#PRA2-PA56,M1

[bimazek]

Administration of vitamin E suppresses CD95L mRNA expression and protects T cells of HIV-1-infected individuals from CD95-mediated apoptosis.

Our data suggest that the survival and differentiation of HIV-specific CD8(+) T cells may be compromised by CD95/Fas apoptosis induced by FasL-expressing HIV-infected cells.   

[gordonh28]

I have been poz now for almost 12 years. I was diagnosed with 530 tcells and a low viral load, about 12000.00. I was on DDI and zerit from the beginning, then switched over to multiple random treatment of drugs that were in the 1st line of treatment. ( No P>I>'S )
My first drug holiday was 3 years in to treatment, and with the doctors approval I went on a 9 month drug holiday, because of the small hump in the back of my neck. I did not fit in to any of the protocols that would be causing a buffalo hump, but I did indeed have one.
I do believe at this time that Zerit was the culprit drug. Well, it went away in 9 months, and though I had never had a viral load below 500, my t-cells and CD% were always in the 700-1200 range, and 33%-39% range. Go figure? I was very active with biking and roller blading, in addition to waiting tables 55 hours a week as well, so it was not due to a lack of exercise or diet. My BIA was 11%..........................................
I went back to meds again and still was on 1st defense drugs, and we tried to stay clear of the zerit, but that was not easy, I started developing neuropathy to the point that I could not keep up my exercise routine, and had to stop working so many long hours on my feet.
My joints also ached to a pain level of about 6. Using a 1-10 scale.
Still keep in mind that I still had a viral load of more than 500, but high t-cells and %'s.
We did daily injections of b-12 for a while and that gave some relief.
I was in Dade County at the time and then moved up here to St Pete. I has also at the same time been drafted in a study at the NIH which was of no benefit to me, except for the paid expenses. My joint pain continued to worsen and my nerve endings were on fire.
The only way I could explain what was going on in my feet was that it felt like there was a AA battery compartment in my foot that would not stop vibrating, it was driving me nuts, and ARNP would not even try to understand what I was feeling, so after having a discussion with an HIV specialist in th NIH, and against my ARNP's approval, I took another drug holiday. She moved me to another nurse who was even more skeptical than the 1st, and thus I decided to find another clinic, even though I had to drive to another county to do so. I have never regretted that decision. I went to a orthopaedic doctor and he discovered burrs on my hips, and also some extra space within both hip joints as well. My knees were also grinding away at each other. After I went to a new primary doctor, because at this time I had applied for disability, for those reasons and a few i don't feel relate to this, social services gave me that access and he diagnosed me with neuropathy in one visit. He wasn't even a HIV doctor, but a good primary. He tried several drugs and nothing seemed to help. The longer I stayed off the HIV meds the better the neuropathy got. Meanwhile, I had a right hip replacement done, and recovered, no it was not a pleasant experience. Turns out I had a high sensitivity to morphine, so during my whole recovery time in the hospital was spent tripping out on this drug, physical therapy??? Right...did not happen, I was to spaced out. Then to make things worse, the hospital would not dispense me the zanax i was on for my panic attacks, because they could not get it from their pharmacy. So, I was also going through severe withdrawl symptoms. Well, I ended up in a nursing home for almost three months, and got the physical therapy I needed and finally got back on the anxiety medicine, even than i had to do everything but the Irish Jig to get the doctor to release me. I was 44 and the youngest person there. it was a rare eye opening life experience.Oh, and I still was not taking any HIV drugs.
After 3 years of no drugs my viral load went up to 878,000.00 Yep, but still had 700 T-cells, and 25%. My buffalo hump never went away, and I got a bump on my belly as well. No more biking, no real exercise, and no more roller blading. Oh, and no work. I lost 33 pounds but only because of the surgery, I gained every single pound back.
At this point after a 3 year drug hoilday we all decided that I had to go back on drugs and this time in the PI group. Well, I had near death episodes with the 1st two they tried on me, then we had to wait two months and got geno typing done and it came back with 2 trios that I could take. I picked the 1st and I am still on it. I take Norvir, Combivir, and Lexiva. My Viral load went undetectable with 3 months. My t-cells have worked there way back up to 954 and my % is 33. Guess what?? I had a nother hip replacement within that time and my #'s stayed true. never missed a dose of meds, not even once, and I got released to my own care and physical therapy, with 5 days of surgery. Go figure, it had to be that i was given something other than morphine for the pain this time. Though I did catch them giving me the wrong meds once and blacked out for a day, but that did not happen again because I think I went psycho on them when I snapped out of it. LOL!!!!
So there goes my story about drug holidays. Sorry it took so many words to tell. Yes, I still have neuropathy very bad, and I finally got approved to get shots of b-12 again, and it has given me considerable relief.
The End!!!!!