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Meds, Mind, Body & Benefits => Research News & Studies => Topic started by: Tadeys on March 14, 2013, 09:12:03 pm
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14 March 2013 Last updated at 22:50 GMT Share this pageEmailPrint
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Early HIV drugs 'functionally cure about one in 10
They have been analysing 14 people who stopped therapy, but have since shown no signs of the virus resurging.
It follows reports of a baby girl being effectively cured after very early treatment in the US.
However, most people infected with HIV do not find out until the virus has fully infiltrated the body.
The group of patients, known as the Visconti cohort, all started treatment within 10 weeks of being infected.
They stuck to a course of antiretroviral drugs for three years, on average, but then stopped.
Most individuals who follow the same treatment will not control the infection, but there are a few of them who will”
Dr Asier Saez-Cirion
Institute Pasteur
Normally, when the drugs stop, the virus bounces back.
This has not happened in the Visconti patients. Some have been able to control HIV levels for a decade.
Dr Asier Saez-Cirion, from the Institute Pasteur in Paris, said: "Most individuals who follow the same treatment will not control the infection, but there are a few of them who will."
He said 5-15% of patients may be functionally cured, meaning they no longer needed drugs, by attacking the virus soon after infection.
"They still have HIV, it is not eradication of HIV, it is a kind of remission of the infection."
Their latest study, in the journal PLoS Pathogens, analysed what happened to the immune system of the patients.
Early treatment may limit the number of unassailable HIV hideouts that are formed. However, the researchers said it was "unclear" why only some patients were functionally cured.
Dr Andrew Freedman, a reader in infectious diseases at Cardiff University School of Medicine, said the findings were "certainly interesting".
"The presumption is that they've started treatment very early and the virus hasn't spread to so many of the long-term reservoirs and that's why it works.
"Whether they'll control it forever, or whether it'll be for a number of years and subsequently they will progress and the virus will reappear, we don't know."
However, he cautioned that many patients would be diagnosed much later than in this study.
http://www.bbc.co.uk/news/health-21783945
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On the same study.....
'The 10 men and four women have now been off therapy for between 4 and 9.6 years. Their plasma viral loads are below 40 copies of HIV RNA per milliliter in all but three cases, and below five copies in five patients.'
http://www.medpagetoday.com/HIVAIDS/HIVAIDS/37893
Is this the case were these infected individuals have some similarites in their immune system to the elite controlers were HIV is controlled much more efficiantly anyway? Although 1 in 10 makes them a bigger percentage that the Elite controlers we know today.
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Taken at face value, that would suggest that it isn't beyond the realms of possibility that I am functionally cured; but I can't say that I would feel the least bit inclined to stop treatment in order to find out.
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Another link to study:
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003211
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I'm not sure why they're saying 10% - 15% of the patients may have achieved a functional cure, when the article clearly says that 70 people stopped treatment and 14 have no detectable viral load after years of stopping treatment. That comes to exactly 20%. What am I missing? Anyway, it is a significant percentage for the people who started ART early. I'm wondering if the newer generation of more powerful meds may increase this percentage, since a number of these people were taking the cocktails that were available in the late 1990s and early 2000s.
http://abcnews.go.com/Health/14-patients-functional-hiv-cure/story?id=18737570
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Reading this this morning i just wondered what this meant for those of us who live areas where you cant get treatment till ur cd4 is below 350. I for one found out within weeks of infection and it's been 5months now and still not on treatment....
http://www.nytimes.com/2013/03/16/world/europe/french-study-indicates-some-patients-can-control-hiv-after-stopping-treatment.html?_r=0
French researchers have identified 14 adults who have been able to control their H.I.V. infection for years after stopping treatment with antiviral drugs, a finding that suggests that some patients might be able to achieve a so-called functional cure.
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The report comes only two weeks after doctors in the United States announced that a baby born in Mississippi had apparently been cured of infection with the virus that causes AIDS.
In both cases, scientists said, a crucial element appears to be initiating drug treatment shortly after the infection occurs, though that is not always practical. In the case of the French patients, treatment began within several months of infection, faster than is the case for most adults.
The researchers, who reported their findings this week in the journal PLOS Pathogens, estimated that as many as 15 percent of people who start treatment early and continue for at least a year might then be able to control the virus without treatment, relieving them of a lifelong daily drug regimen.
Asier Sáez-Cirión, the lead author of the study, said that the French patients were in a sort of “remission” rather than being cured, because the virus was still present in their bodies, though at low levels.
Still, he said, figuring out why some people seem to be able to control the virus could point the way toward a functional cure by which people might live healthily without drugs even if their infection was not eradicated.
“This is proof of concept that we can induce this status in individuals who were not going to do so naturally or spontaneously,” said Dr. Sáez-Cirión, an assistant professor at the Pasteur Institute in Paris.
Some AIDS experts agreed. “These people are not cured, but they have some advantages that would be good to understand,” said Dr. Myron S. Cohen of the University of North Carolina.
One implication of the French study is that many people now taking antiviral medications might be able to safely stop. But doctors said the study did not provide enough information to predict which patients that might be, and that patients should not stop on their own.
Previous clinical trials have shown that, in general, interruption of treatments leads to worse outcomes.
Dr. Max Essex, chairman of the Harvard School of Public Health AIDS Initiative, said that new tests measuring viral loads in the body are so sensitive that it “might not be a huge risk to take people off treatment for a month” — and quickly put them back on if H.I.V. was to begin multiplying rapidly.
Another implication of the study is that treatment should be started earlier for most people. But that cannot always be done.
“We and others have difficulty identifying and treating such adults so early after infection,” said Dr. Douglas D. Richman, director of the Center for AIDS Research at the University of California, San Diego.
Many people are infected for months or years without knowing it. Even if they know it, some do not want to start treatment immediately because of the cost of the drugs or concerns about side effects. The patients in the French study started treatment soon after infection because many had symptoms that sent them to the doctors early, allowing their infection to be detected.
Dr. Sáez-Cirión said that most of the patients stopped treatment because they were in studies testing whether patients could take drug holidays. But some just stopped on their own, he said.
The patients were on therapy for one year to seven and a half years. They have been off treatment for 4 to nearly 10 years.
Since stopping treatment, most have had viral blood levels below 50 copies per milliliter, which is considered undetectable. But some have had measurements of up to a few hundred copies.
A small number of people infected with H.I.V. — 1 percent or less — are so-called elite controllers, meaning their bodies keep the virus in check without antiviral drugs. It is possible that some of the French patients might never have needed drugs, but that will never be known because they started treatment so soon after infection.
But the French researchers say the patients, whom they termed “post-treatment controllers,” were different from elite controllers.
Post-treatment controllers tended to have very high viral loads soon after infection, while elite controllers are more likely to keep virus levels down, even at the start, the researchers said. The immune systems of the post-treatment controllers also tended to differ in certain ways from those of elite controllers.
The chief barrier to an AIDS cure is that even when drugs sharply reduce the levels of H.I.V. in the blood, the virus can hide out in so-called reservoirs in the body. Dr. Sáez-Cirión said that the viral reservoirs in post-treatment controllers were smaller than those of a typical infected person and had a smaller proportion of long-lived immune cells.
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Reading this this morning i just wondered what this meant for those of us who live areas where you cant get treatment till ur cd4 is below 350. I for one found out within weeks of infection and it's been 5months now and still not on treatment....
Sigh, woe is us.
Although, I'm curious to know if there are biomarkers or metrics that would be useful in determining a functional cure. Lower antibody levels? Presence of broadly neutralising antibodies?
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I'm not sure why they're saying 10% - 15% of the patients may have achieved a functional cure, when the article clearly says that 70 people stopped treatment and 14 have no detectable viral load after years of stopping treatment. That comes to exactly 20%. What am I missing?
It is an estimate based on a relatively small sample (the smaller the sample, the larger the margin of error), so I am guessing it is a mixture of healthy caution and margin of error.
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I'm glad they put 'functionally cured' in quotation marks. It seems that as of late, this term is being thrown around quite a lot. That may not be helpful.
As for those patients, to me it seems that thanks to the early-on treatment they have turned into something like an elite controller. That's not exactly any kind of cure, is it? As we know elite controllers/longterm non-progressors might live with the virus very well for many years but the viral load may come back at some point in time.
To avoid confusion between the different termini, I hereby suggest the introduction of the term "temporary functional cure" ;D
That should describe those patients in the study well enough and make the distinction between this and cases like Timothy Brown, who is actually functionally cured as far as we know.
(I'm just imagining an situation where that's being applied. You go on a date, there is some chemistry and you end up in bedroom. Your date asks: "Do you have HIV?" and you reply "You have absolutely nothing to worry about as temporarily I am functionally cured!" :P)
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Taken at face value, that would suggest that it isn't beyond the realms of possibility that I am functionally cured; but I can't say that I would feel the least bit inclined to stop treatment in order to find out.
Larsen, you could stop treatment and monitor your viral load closely. If it shows an increase then go back onto the same medication you were on previously. There was a trial done recently to see how long people would stay undetectable after treatment stops. From memory the average was about a week before there was a detectable viral load and then when returned to treatment immediately it took about 2 weeks to return to being undetectable. All of the people in the trial returned to be undetectable and had no resistance issues.
It might be difficult to have a doctor do this 'trial' on you however. It would required daily VL tests and a rapid turn around on the results. It wouldn't be the cheapest trial to do either. My guess is that soon a standard test process will be developed to determine functionally cured people. It is probably easier to just stay on meds for another few years.
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Larsen, you could stop treatment and monitor your viral load closely.
Littleprince, yes, I could; but as far as I can see, both the SMART and DART studies showed pretty conclusively that the risks of even relatively short treatment breaks, where there isn't a clinical need, by far outweigh the benefits for what is, at the end of the day, still a very long odds chance of something that would still leave me looking over my shoulder for the rest of my life.
I've taken part in a fair few trials over the years, but this would just have too many negatives.
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Huffpost Healthy Living
14 Adults 'Functionally Cured' Of HIV, Study Says
http://www.huffingtonpost.com/2013/03/15/14-adults-cured-of-hiv-functionally-cure-_n_2884201.html?utm_hp_ref=mostpopular
And we're off...
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To avoid confusion between the different termini, I hereby suggest the introduction of the term "temporary functional cure" ;D
That should describe those patients in the study well enough and make the distinction between this and cases like Timothy Brown, who is actually functionally cured as far as we know.
It is still debated whether Tim Brown was functionally cured or sterilizingly cured.
The terms themselves are pretty standard: one means the ability to control the virus inside your body without the use of ART and another the absence of ALL traces of the virus.
From my perspective, the VISCONTI cohort and long term non progressors are in the same group. They are able to control the virus inside their bodies without lifelong use of meds.
I'm not sure if those 'long term non-progressors' who eventually experience immune damage at some distant point in the future would be called as such. They would be more accurately named as slow progressors.
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Do the articles say which medication these people were on?
Did the type of medication (ie PI, NNRTI, II) affect the "cure rate?"
(I haven't had a chance to read all the articles, been traveling a lot)
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My ID doctor told me the other day she is curious how many people are still taking meds and might be functionally cured. This is indeed very interesting and should blossom into something exciting within the next decade.
Best
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Post-treatment controllers tended to have very high viral loads soon after infection, while elite controllers are more likely to keep virus levels down, even at the start, the researchers said. The immune systems of the post-treatment controllers also tended to differ in certain ways from those of elite controllers.
Maybe I'll end up as a post controller? I actually have a potential situation where I'll be able to find out in several months. (I'll post my results if/when it happens)
Details.........
I was diagnosed early 2012. I had a pretty bad flu for 3 weeks so I got tested. They told me I had a VL of 2 million, but still tested negative for antibodies. (they have a dual HIV test at the clinic I went to) So that means I caught it about as early as it gets.
I did research and I jumped into a clinical trial of a new CC5 blocking med:
http://www.aidsmeds.com/archive/cenicriviroc_2656.shtml (with Truvada)
(when I started, I felt normal, and VL was pretty low naturally)
I became undetectable in several weeks. (and zero side effects)
I just completed the cenicriviroc trial and switched to complera a month ago. (again zero side effects)
The next trial I'm on the top of the list to participate in Arm 2 or 3 of the Calimmune Gene transfer trial.
http://forums.poz.com/index.php?topic=46455.0
Here's the interesting part.........
I need to STOP taking my meds several weeks before I get treated via Calimmune. I never imagined that I might remain undetectable after I stop ART. I'll have been on ART nearly 2 years by the time they would want me. The fact I was on the CCR5 blocking cenicriviroc for so long and started so early gives me a decent chance at least. I was told I was the healthiest patient in every program they have across the board too. So pending my qualification for Calimmune, and they call me, I'll consider it a double experiment!
I'm pretty sure I was told the Calimmune trial requires you to actually have a detectable VL before they'll treat you. What if I remain UD month after month? I would imagine they want test groups to be detectable so they can rule out the potential Post-treatment controller anomalies
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My ID doctor told me the other day she is curious how many people are still taking meds and might be functionally cured. This is indeed very interesting and should blossom into something exciting within the next decade.
there's another thread going right now where the topic of a drug holiday is being discussed. Oddly enough instead of hearing from all these functionally cured people, we're hearing all the tales of people whose health plummeted back to AIDS levels and hospitalizations all within 3 -12 months.
Personally I've never heard of someone that quit meds permanently or took a drug holiday whose health didn't fail and didn't die or return to medications to save their lives.
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I started taking meds while still in the window period -- positive on the VL, neg on the antibodies. But I sure wouldn't stop taking meds unless I had a very good reason (such as participating in a trial that I thought had a real shot at a cure).
Do the functionally cured people have normal level of CD8 cells? Mine have always been elevated (as I imagine all of ours are) in response to the infection. Seems to me that number should be in the normal range for the functionally cured people. Does anyone know about CD8 levels with this lucky group of people?
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I'm in this "early" treatment group as well. Based on my recollection, I started what I'd describe as the worse fever of my life about a week after the likely infection date. But I didn't think much of it until the red spots appeared and a couple lymph nodes swelled a few days later. At that point I rushed to the doc and didn't leave there until they gave me a viral load test. I was so sure the antibody test would be pointless. At first the doc resisted doing it but what else could they do after seeing all the other basic tests come back neg and my high suspicions of what it was, along with my knowing when I thought I might have got infected. At that point, the doc wanted to know for sure as much as I did, at least to rule it out. But sure enough I was right, my RNA VL came back about 700k. Then a week later when I started meds, they gave me another VL test and it pegged the result out at >10million. lol So I actually had the unique opportunity to see the early upper side of the seroconversion curve with mine.
But even starting meds that early, I would never consider stopping until at least 3 years. Based on what I read so far from the various research, perhaps up to 20% of HIV infected people eventually start producing antibodies broadly enough to kill over 55% or so of all HIV strains after around 3 years of being infected. However, since most don't start treatment early, the virus in most has a chance to mutate diversely so much so that by the time their immune system does finally start homing in robustly on it, it is too late. This is why rarely can anyone's immune system control it, except perhaps if you do starting meds as soon after infection.. The key is that ARV treatment pretty much immediately stops the mass mutation and subsequent viral diversity and gives you a better chance to control it when, and IF, your immune system does start responding better over time.
What I'm wondering is, what if one who started meds early waits longer than 3 years before stopping the meds, would their chance to control it go higher than 20%? Who knows. That's why I wouldn't think about stopping and testing this until 5 years at least had gone by.
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My unqualified advice would be to wait for at least 7 years. After this time most of the latent cells are dead, except the cells in the bone marrow. I can't recommend a treatment break, You should talk with an expert. May be You can take part in a clinical study.
Anyway, I read this abstract:
http://www.retroconference.org/2012b/Abstracts/44329.htm (http://www.retroconference.org/2012b/Abstracts/44329.htm)
Does it mean that DLG can be active against latent macrophages and lymphozytes, or did I misunterstand it?
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Odd how none, and I mean none of the people I have encountered on this forum or in real life have been among the "functionally cured."
We've had, what, a dozen or so people who are long term slow progressors, and perhaps half a dozen long term non-progressors, so you'd think at least ONE person would have come through here with thatr situation.
I HAVE encountered several hundred (or more) people who, for whatever reasons, have stopped taking meds, and have been hospalized with opportunistic infections. Or died.
Frankly, if anyone is considering stopping meds to see what happens, my advice is go for it!
We need periodic object lessons on this forum, after all.
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Odd how none, and I mean none of the people I have encountered on this forum or in real life have been among the "functionally cured."
We've had, what, a dozen or so people who are long term slow progressors, and perhaps half a dozen long term non-progressors, so you'd think at least ONE person would have come through here with thatr situation.
I HAVE encountered several hundred (or more) people who, for whatever reasons, have stopped taking meds, and have been hospalized with opportunistic infections. Or died.
Frankly, if anyone is considering stopping meds to see what happens, my advice is go for it!
We need periodic object lessons on this forum, after all.
This is because no one has been "functionally cured" except for the Burlin patient and perhaps a baby, if you want to call that a curing.. I more call it giving someone meds early enough (within days) after infection that hadn't taken hold, which anyone could have done (baby or not) and gotten "cured".
The discussion here is whether someone is "functionally cured" who had been taking meds early after infection and then stops having a maintained very low or undetectable VL. We don't know the answer to that because no one knows what the baseline for these patients would have been had they never started meds to begin with. That's why you never hear of anyone being classified as "functionally cured" in this category. Since such people are so rare to begin with, when encountered they are just passed off as possibly could have been long-term non or slow progressors to begin with.
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This is because no one has been "functionally cured" except for the Burlin patient and perhaps a baby, if you want to call that a curing.. I more call it giving someone meds early enough (within days) after infection that hadn't taken hold, which anyone could have done (baby or not) and gotten "cured".
The discussion here is whether someone is "functionally cured" who had been taking meds early after infection and then stops having a maintained very low or undetectable VL. We don't know the answer to that because no one knows what the baseline for these patients would have been had they never started meds to begin with. That's why you never hear of anyone being classified as "functionally cured" in this category. Since such people are so rare to begin with, when encountered they are just passed off as possibly could have been long-term non or slow progressors to begin with.
While I agree in theory, you have to understand that the criteria for slow/non progressors specifically rules out treatment experience.