I am hoping that what helps HIV may be what helps us as well. The HIV folks have had 30 years and billions of dollars spent on research so let's hope that their research and medications can be used for us - and quickly too.
Sadly I do believe that when both HIV and the XMRV or other Retrovirus hit, the CDC and Federal health orgs picked HIV/AIDS to put money into - meaning we got nothing. How very stupid given that both viruses were in the Retrovirus group and research in one area could probably bleed over into the other area. But the CDC and others did not think about that. And so here we are, with XMRV out there for 30 years doing its damage all because of stupid, short-sighted people not understanding cross-polination between/among these two Retroviruses. I do believe this situation is going to make the poor Tuskegee people and that huge, long so unethical period look not so bad (as what has gone on with XMRV out in the public/blood supply/products/lungs/etc. And THAT is pretty bad!
I fear that real research for us and a real cure may well take 20 years or more. By then, I should be pushing up Daisys, if those numbers of "average age of death is 55" or "we die on average 25 years earlier than normal" - Where did those numbers come from that I and many others quote?
Have to see what HTLV1 is all about. Isn't there an HTLV2? Just woke up as you can see!
New humic acid derivative as potent inhibitors of HIV-1 replication.
Kornilaeva G, Bercovich A, Pavlova T, Karamov E; International Conference on AIDS (15th : 2004 : Bangkok, Thailand).
Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. A10360.
Ivanovsky institute of virology, RAMS, Moscow, Russian Federation
Background: The anti-HIV-1 activity of the new humic acid derivative has been determined in vitro, and the serial passages at low concentrations have been performed to investigate the emergence of resistance to this drug candidate.
Methods: The antiviral efficiency of the humic acid derivative was tested against HIV-1 T-tropic laboratory strain and HIV-1 M-tropic AZT-resistant wild-type strain. CEM cells were infected and cultivated in the presence of compound at the concentrations 250-0.0025 mug/ml. The level of virus reproduction in infected cells was detected with p24 HIV-1 antigen ELISA detection system. The serial virus passages were performed at the concentration - 0.0025 mug/ml of compound. The virus generation of each passage was analyzed for HIV-1 p24 antigen and the infectious activity.
Results: The IC50 values of the humic acid derivative against HIV-1 T-tropic laboratory strain and HIV-1 M-tropic AZT-resistant wild-type strain were 0.85 and 3.5 mug/ml respectively. The combination of humic acid derivative and AZT intensifies their anti virus activity in 30-100 times. The determined p24 HIV-1 antigen value of the first passage virus generation at the presence of 0.0025 mug/ml of compound was identical to that of the control while the infectious activity approached to zero. The virus generations of second and third passages possessed the low values of p24 HIV-1 antigen and the undetectable infectious activity.
Conclusions: The new acid humic derivative is an effective inhibitor of various HIV-1 variants with high selectivity indexes (5500-3000). According to our date this compound disorder HIV-1 replication and yield the defective unifectious virions.
Hi; about those 55 years--Jason wrote in his piece on what kills us CFSers that 20% die of heart failure, at an average age of I think 56 years, compared to the average age at which other folks die of HF, which if I recall is about 83. Not sure if that is what you were thinking of, and in any case it does not apply to the whole cohort of CFSers--only those who die of HF, and only those that Jason included in his count. Noone should give up hope just now! Best, Chris
HIV Reservoir in the Brain Doesn’t Respond to Treatment Intensification
Adding a new antiretroviral (ARV) drug with the ability to penetrate into the brain to an existing regimen doesn’t reduce residual HIV in the brain or brain inflammation in people who have good suppression of HIV elsewhere in the body, according to a study published in the December 15 issue of the Journal of Acquired Immune Deficiency Syndromes. These data suggest that the brain does serve as a protected reservoir of HIV infected cells, and that simply adding ARVs that penetrate into the central nervous system (CNS) may not shut down residual virus or reduce brain cell inflammation.
In 1996, researchers dramatically pronounced that they believed they could eradicate HIV in a person’s body within two to three years with combination ARV therapy including protease inhibitors (PIs). That same year, the first batch of PIs was approved.
Within a few years, however, this optimistic eradication hypothesis was laid to rest because researchers discovered that reservoirs of virus go unscathed by ARV therapy. And in recent years, these reservoirs have been tied to ongoing cellular inflammation, responsible for all kinds of harmful effects, including cardiovascular disease, cognitive problems and certain cancers.
This has led to the question of whether the virus is actively replicating within the reservoir or if the cells are simply releasing virus that is trapped within the cells. Answering this question is important. If ongoing replication is occurring, then simply adding more potent drugs could shut it down. If there is no active replication, and infected cells are simply releasing intact virus, then the only way to get rid of it will be to purge these infected cells entirely.
One of the suspected reservoirs is the CNS, where virus has been found despite undetectable levels in the blood. To better understand what is happening in the brain, Aylin Yilmaz, MD, PhD, from the University of Gothenburg in Sweden, and his colleagues tested the strategy of treatment intensification in 20 people living with HIV who had undetectable levels of HIV in the blood, but detectable levels in their brains.
The study involved adding one of two types of intensified ARV drugs for six weeks, and then switching over to the other type for an additional six weeks. One type of ARV, Fuzeon (enfuvirtide), doesn’t penetrate well into the brain. It’s chemical structure is too large. The other type of ARV—in this case either Selzentry (maraviroc) or Kaletra (lopinavir plus ritonavir)—does penetrate well into the brain.
The research team’s theory was that if active replication were occurring in the brain, then intensifying treatment would shut it down. If intensification didn’t work, then the experiment would prove that active reproduction was not the cause of residual virus.
Yilmaz’s team found that the latter was true. Intensifying treatment did not reduce the level of HIV present in the brain, nor did it reduce the level of cellular inflammation. The use of a drug for six weeks that did not cross over into the brain was necessary to ensure that whatever effect they found was not a result of virus reduction in other parts of the body, but what was actually occurring only in the CNS.
The authors argue that their results have two implications. First, the data indicate that the tiny bit of detectable HIV in the brain is not due to active reproduction, and that new strategies will be needed to get rid of it. Further, the data suggest that a trend toward seeking and using ARV regimens with good brain penetration might not have the intended effect of lowering HIV and reducing cellular inflammation there.
do you think that our brain inflammation is caused mainly by XMRV reservoirs? if that is the case, i am doomed! like in HIV, some people have small reservoir and some have large ones. maybe i have large ones in the CNS for whatever reason. and if RNase L and elastase is any indication, it looks like i may have shut down viral production but the inflammation still remains.
dr. lombardi told me a few times that the inflammation might have to be treated also - that viral reproduction will be only 1 part of the problem.
this is also in keeping with MLV's in mice, where AZT only helps if its taken within a week after infection...after that, maybe the reservoir inflammation is too great to stop the disease process.
maybe jamie deckoff-jones, snyderman, and others who responded quickly to ARV's just had very small viral reservoirs.
same with HTLV-1...the latent reservoirs are indicators of whether disease will develop.
not lookin good....
plus gammaretroviruses are very stable in the latent state...they dont cause cell distress like HIV does
Have you ever looked at Nexavir? I know some of the well-known ME/CFS docs give it both as an anti-viral and as an anti-inflammatory. Don't know about the blood brain barrier, but since you have access to researchers, it might be worth asking.
Here is a quote about it:
Nexavir Is believed to have anti-inflammatory and anti-viral properties. Nexavir is a prescription drug produced from pig livers. Favorable responses to NEXAVIR in patients with skin diseases (acne vulgaris, herpes zoster, "poison ivy" dermatitis, pityriasis rosea, seborrheic dermatitis, urticaria and eczema) and severe sunburn have been reported. One study suggested in-vitro effectiveness against the HHV-6 virus. Nexavir, formerly kutapressin, is available from www.bellevuepharmacy.com
Few studies have examined the use of this drug in disease and information on it is scanty. The PubMed data base lists two Nexavir studies in the last forty years.
Nexavir May Work in Chronic Fatigue Syndrome (ME/CFS) Because it has anti-inflammatory effects and it may inhibit two viruses HHV-6 and EBV that may be reactivated in some patients.
Chronic Fatigue Syndrome (ME/CFS) Studies - no studies have examined this drugs effectiveness in ME/CFS.
Chronic Fatigue Syndrome (ME/CFS) Doctors Report: Dr. DeMeirleir uses Nexavir in combination with injections of Vit. B-12 (10 mg./twice weekly) to reduce pain and improve sleep. From 60-70% of his and Dr. Enlander's patients reportedly responded positively to the drug. (Dr. Enlander uses a brand called Hepapressin +B-12). Dr. Cheney uses Nexavir as an immunomodulator and broad spectrum antiviral. Dr. Teitelbaum has seen 'dramatic improvement' with regular use of the drug but notes that regular treatment can be difficult given its expense. He also notes that symptoms may return after the drug is discontinued. Dr. Lapp calls it a 'wonderful alternative' with the proviso that its expensive.
Chronic Fatigue Syndrome (ME/CFS) Patient's Report: Click here for ME/CFS patients reports of their experiences with Nexavir.http://whitneygabhartnd.com/nexavir.aspx
Well I think it is certainly possible that the reservoirs cause the inflammation and not the "free floating virus". That does not mean that arv's are useless; many of our other symptoms such as pem etc may be very well be helped by it. I guess for the neuroinflammation we may have to consider other treatments.
It is not neccesarily a very bad thing, it just means that we have to think about which other things may help us.
By Kate Kelland
updated 52 minutes ago 2010-12-22T19:20:05
Share Print Font: +-LONDON — A new kind of experimental HIV medicine can halt one of the earliest stages of HIV infection and may eventually lead to a novel class of drugs to fight other dangerous viruses, German scientists said on Wednesday.
The drug, being developed by small privately held Hannover-based firm VIRO Pharmaceuticals, is called VIR-576 and reduced the amount of HIV infection in the blood by as much 95 percent in an early-stage trial of 18 patients.
It works by preventing the virus from being able to anchor itself in human immune cells, according to the researchers, who published a study in the Science Translational Medicine journal.
.."What the virus does is a bit like throwing an anchor to get hooked up to the cell," Frank Kirchhoff, of the University Hospital of Ulm in Germany, said in a telephone interview. "This drug occupies the anchor — which is called the fusion peptide — and prevents its insertion into the cell membrane. So then the virus cannot get into the cell."
Kirchhoff said VIR-576 is similar to other fusion inhibitors such as Fuzeon, sold by Trimeris and Roche, but is designed block the infection process at an earlier stage.
According to latest figures from the United Nations, an estimated 33.3 million people worldwide are infected with the human immunodeficiency virus that causes AIDS.
The virus can be controlled with cocktails of drugs, but there is no cure and nearly 30 million people have died of HIV-related causes since the disease first emerged in the 1980s.
HIV belongs to a group of viruses known as "enveloped" viruses, which also includes influenza, mumps, measles, hepatitis B, hepatitis C, Ebola and SARS.
Kirchhoff also said the discovery that VIR-576 can fight early HIV infection suggests it may be possible in future to develop similar blockers for these other viruses.
"It's more wishful thinking than hard evidence at the moment," he said. "It proves the principle, but now there is a lot more work to be done."
In this trial in HIV, Kirchhoff's team studied 18 HIV-infected volunteers who were treated for 10 days with one of three different doses of VIR-576, which is given via injection. None of the patients was taking any other type of HIV drug and VIR-576 was the first antiretroviral drug they had received.
The results showed that at the highest dose of 5 grams per day there was a 95 percent reduction in the patients' viral load — a measurement of the amount of HIV in the blood. Side effects were minimal and mainly involved soreness around the injection sites, Kirchhoff said.
The researchers said the results were encouraging but stressed that the experimental drug has some drawbacks which would need further work. Because VIR-576 is a peptide and must be given through injections, it will be costly and inconvenient to use, they said, and the high dose of 5 grams a day would also make it relatively expensive.
The team's focus now is to hunt for a small molecule that works just like just like VIR-576 but that could be made cheaply and given orally in the form of a pill
Unexpected Find Opens Up New Front in Effort to Stop HIV
ScienceDaily (Jan. 24, 2011) — HIV adapts in a surprising way to survive and thrive in its hiding spot within the human immune system, scientists have learned. While the finding helps explain why HIV remains such a formidable foe after three decades of research -- more than 30 million people worldwide are infected with HIV -- it also offers scientists a new, unexpected way to try to stop the virus.
The work by researchers at the University of Rochester Medical Center and Emory University was published Dec. 10 in the Journal of Biological Chemistry.
It's thanks largely to its ability to hide out in the body that HIV is able to survive for decades and ultimately win out against the body's relentless immune assault. One of the virus's favorite hiding spots is an immune cell called a macrophage, whose job is to chew up and destroy foreign invaders and cellular debris.
For more than 15 years, Baek Kim, Ph.D., has been fascinated by HIV's ability to take cover in a cell whose very job is to kill foreign cells. In the last couple of years Kim, professor of Microbiology and Immunology at the University of Rochester Medical Center, has teamed with Emory scientist Raymond F. Schinazi, Ph.D., D.Sc., director of the Laboratory of Biochemical Pharmacology at Emory's Center for AIDS Research, to test whether the virus is somehow able to sidestep its usual way of replicating when it's in the macrophage.
The pair found that when HIV faces a shortage of the molecular machinery needed to copy itself within the macrophage, the virus adapts by bypassing one of the molecules it usually uses and instead tapping another molecule that is available.
Normally, the virus uses dNTP (deoxynucleoside triphosphate, the building blocks for making the viral genetic machinery) to get the job done, but dNTP is hardly present in macrophages -- macrophages don't need it, since they don't replicate. But macrophages do have high levels of a closely related molecule called rNTP (ribonucleoside triphosphate), which is more versatile and is used in cells in a variety of ways. The team found that HIV uses primarily rNTP instead of dNTP to replicate inside macrophages.
"The virus would normally just use dNTP, but it's simply not available in great quantities in the macrophage. So HIV begins to use rNTP, which is quite similar from a chemical perspective. This is a surprise," said Kim. "The virus just wants to finish replicating, and it will utilize any resource it can to do so." When the team blocked the ability of the virus to interact with rNTP, HIV's ability to replicate in macrophages was slashed by more than 90 percent.
The work opens up a new front in the battle against HIV. Current drugs generally target dNTP, not rNTP, and take aim at the infection in immune cells known at CD4+ T cells. The new research opens up the possibility of targeting the virus in macrophages -- where the virus is out of reach of most of today's drugs.
"The first cells that HIV infects in the genital tract are non-dividing target cell types such as macrophages and resting T cells" said Kim. "Current drugs were developed to be effective only when the infection has already moved beyond these cells. Perhaps we can use this information to help create a microbicide to stop the virus or limit its activity much earlier." Kim notes that a compound that targets rNTP already exists. Cordycepin in an experimental compound, derived from wild mushrooms, that is currently being tested as an anti-cancer drug. The team plans to test similar compounds for anti-HIV activity.
"This significant breakthrough was unappreciated prior to our paper. We are now exploiting new anti-HIV drugs jointly based on this novel approach that are essentially not toxic and that can be used to treat and prevent HIV infections," said Schinazi, who has developed several of the drugs currently used to treat HIV patients.
The first authors of the paper, who contributed equally to the project, are graduate students Edward Kennedy of Rochester and Christina Gavegnano of Emory. Other authors include, from Rochester, graduate students Laura Nguyen, Rebecca Slater and Amanda Lucas; and from Emory, post-doctoral associate Emilie Fromentin.