HIV IN HIDING: Researchers target HIV's hideaway in long-lived immune cells, opening up the possibility of eradicating, rather than just controlling, the virus.
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Rousing the human immunodeficiency virus (HIV) from slumber may not sound like a good idea. But just as it is next to impossible to lure and trap a hibernating animal, catching a virus on the move is far easier than snaring one lying dormant.
That's the thinking behind some strategies to effectively eradicate latent reservoirs of HIV—thought to be the virus's last stand when under attack from increasingly effective drug cocktails. Researchers are uncovering multiple methods for awakening and subsequently destroying the virus, which hides out in "resting" immune cells. But they are far from agreeing on which approach offers the most realistic hope—or just how much hope to have in the seemingly unattainable goal to cure AIDS. "This is a very optimistic and maybe even impossible objective," says Douglas Richman, the director of the Center for AIDS Research at the University of California, San Diego. "But it is our number-one objective now."
Drug cocktails—or more technically, highly active antiretroviral treatment (HAART)—have turned what used to be a death sentence into more of a chronic disease in recent years. But an HIV-positive diagnosis still generally means a shorter, sicker life and one that necessitates a continuous supply of expensive therapies; no therapy today can completely eliminate the virus from the body.
"Whenever anybody stops HAART, the virus comes back," says Robert Siliciano, who studies the dynamics of HIV replication at the Howard Hughes Medical Institute and Johns Hopkins University School of Medicine.
Hiding out in CD4 cells
HIV's resting place is the immune system's memory CD4 T cells, which have the ability to recognize foreign bacteria and viruses from previous encounters. (From the second meeting on, they replicate and mount an attack.) In these cells, the virus can sit quietly for years, even decades, remaining unseen by the immune system and antiretrovirals. "Since immunologic memory is for life," says Richman, "then so is maintenance for latent HIV."
But once CD4 cells awaken to an invader, HIV rears its head, too, and begins to replicate with its host. So researchers are now on the hunt for a way either to ensure that deactivation is permanent for any CD4 cell harboring HIV, or to spark activation for all infected CD4 cells—with anti-HIV drugs ready and waiting to attack.
Most experts favor the second strategy, aiming to awaken and attack the virus repeatedly. "If you do this enough times, and deplete the pool of latently infected cells, you could potentially cure patients from infection," says Eric Verdin, a senior investigator at the Gladstone Institute of Virology and Immunology at the University of California, San Francisco.
Chemical wake-up call
Many factors appear to restrict replication of the HIV virus in latent cells, and Verdin's team described last month in PLoS Pathogens one such mechanism: methylation, a chemical modification of DNA that reduces gene activity. They also identified a drug, 5-aza-2'deoxycytidine, that inhibited this restriction process and caused HIV to reactivate and replicate. Alternatively, researchers can target histone deacetylases (HDACs), key enzymes that work with DNA methylation; blocking HDACs also ultimately wakes HIV.
But inhibiting methylation or HDACs alone may not be enough, according to Verdin. A major problem is toxicity: impeding either may not only activate latent virus, but also a whole lot of other cellular genes leading to symptoms like those seen in the side effects of cancer chemotherapy. Another big obstacle is that just one viral recluse is enough to refill the reservoir.
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19 Comments
Add CommentTrying to find more drugs to cure aids is ridiculous. There's already a current procedure that has removed all traces of the virus from an american gentleman. Pursuing more research into this procedure would be more promising that 'taking years before trials could begin...'
Reply | Report Abuse | Link to thisThe american gentleman suffered from leukemia. His doctor specifically chose a donor that was naturally immune to the aids virus. 2 years after the bone marrow transplant the patient still has no signs of the virus. Doesn't that sound more interesting the waiting for more toxic drugs?
Here's the story:
http://www.thezimbabwetimes.com/?p=7210
Trying to find more drugs to cure aids is ridiculous. There's already a current procedure that has removed all traces of the virus from an american gentleman. Pursuing more research into this procedure would be more promising that 'taking years before trials could begin...'
Reply | Report Abuse | Link to thisThe american gentleman suffered from leukemia. His doctor specifically chose a donor that was naturally immune to the aids virus. 2 years after the bone marrow transplant the patient still has no signs of the virus. Doesn't that sound more interesting the waiting for more toxic drugs?
Here's the story:
http://www.thezimbabwetimes.com/?p=7210
Trying to find more drugs to cure aids is ridiculous. There's already a current procedure that has removed all traces of the virus from an american gentleman. Pursuing more research into this procedure would be more promising that 'taking years before trials could begin...'
Reply | Report Abuse | Link to thisThe american gentleman suffered from leukemia. His doctor specifically chose a donor that was naturally immune to the aids virus. 2 years after the bone marrow transplant the patient still has no signs of the virus. Doesn't that sound more interesting the waiting for more toxic drugs?
Here's the story:
http://www.thezimbabwetimes.com/?p=7210
Trying to find more drugs to cure aids is ridiculous. There's already a current procedure that has removed all traces of the virus from an american gentleman. Pursuing more research into this procedure would be more promising that 'taking years before trials could begin...'
Reply | Report Abuse | Link to thisThe american gentleman suffered from leukemia. His doctor specifically chose a donor that was naturally immune to the aids virus. 2 years after the bone marrow transplant the patient still has no signs of the virus. Doesn't that sound more interesting the waiting for more toxic drugs?
Here's the story:
http://www.thezimbabwetimes.com/?p=7210
So does that mean they're going to add more spicy ingredients in drug cocktail? if so, it would make any difference further but giving sufferings to the body.
Reply | Report Abuse | Link to thisWhy not try some alternate therapies, since some of their theories and strategies sound similar,like arousing the disease and pathogens before getting rid of it and annihilation,through drug therapies. So Chinese and Indian herbal medicines which are good in treating chronic diseases due to what they term as low vitality may hopefully do the trick-any way there is no harm in trying
Reply | Report Abuse | Link to thisKatsielyonz - anything reported in the Zimbabwe Times is automatically suspect. Under the Mugabe regime that country has gone from a shining light to a festering cesspool.
Reply | Report Abuse | Link to thisIt is however an interesting idea that a marrow transplant from an HIV immune person (if such really do exist) to a sufferer may affect a cure. As far as I understand it, and I could easily be wrong, immunity to HIV can't be proven completely due to the long periods of dormancy after infection. People that appear to be immune may simple be experiencing a delayed onset of symptoms. Then again, if the onset is delayed decades I would consider that as good as a cure.
I have an intermediary understanding of HIV Immunology and think that this is the CLOSEST we have ever been to a complete cure/eradication for HIV-1. Thank god the Canadians are continuing this research.
Reply | Report Abuse | Link to thisIn this article scientists are merely saying "we know HOW to cure it - we just haven't found/synthesised the right substance to trigger these sleeping latently infected CD4 cells to awaken" Once chemically activated these cd4 cells allow HIV gene expression inside them, thus releasing the virus latent virus into the plasma where upon it is stopped cold by hi-levels of Antiretrovirals, quickly dies and is disposed of by the body.
They points they are trying to make are: 1) we haven't found the awakening chemical yet that has LITTLE HUMAN TOXICITY.
And 2) we still don't know how we'll tell if we have found and destroyed ALL the reservoirs of the virus. Therefore I believe this kind of cure therapy would not be an acute 'shot' or simply one pill.
I suspect it would mean an extended period of time undergoing repeated 'hits' with this awakening chemical, while in the presence of high levels of non-contraindicating HAART, with close viral load blood-monitoring, so as to be sure that *ALL* reservoirs have been found, awoken, released, suppressed from replicating long enough to die, and destroyed.
This chemical treatment is surely only a matter of time & money away, as many sleeper cells have already been isolated from patients and are currently being exposed to a veritable known library of related drugs to begin the search.
I am simply a 29 year old layman who happens to be an avid reader of scientific/medical journals. I was only 96 hours ago diagnosed HIV+, much to my abject horror initially. I'm still going through a bit of a roller-coaster of emotions, but as I reach rationality I thank God I contracted it in 2009 and not in 1983.
-We KNOW how to Kill it. (it is essentially a very weak organism)
-We KNOW how to stop it replicating.
-We just haven't, by way of time & trial, figured out how to kill it where it hides dormant.
I think we are 2 out of 3 steps done towards perfecting total eradication (CURE) and 2 out of 4 steps towards stimulating human immuno response for any future encounters (Vaccine/prevention). I suspect the latter will require more genetic research and less chemical, as the reason the human autoimmune response to HIV slowly fails is that the HIV targeted cells the body produces to destroy the virus unfortunately look like enemies to the other generic CD4 cells and our own body destroys them.
Im excited -C.Ma
oh and yes, there are some lucky people who are completely immune to almost all forms of HIV. They mainly occur in Scandinavian genetic descendants where there is a mutation affecting a cell wall protein called CCR5 Delta-32. People who have inherited this mutation from 1 parent are partially immune, people who have inherited it from both parents are completely immune. It should also be noted that the patient with the bone marrow transplant deliberately chose a donor that WASN'T the best match for him in order to obtain bone marrow from someone with this mutation, putting his life at risk, as it really was his last chance of survival in any case.
Reply | Report Abuse | Link to thisWhile this procedure worked and allowed him to create the impervious antibodies to kill the virus, anyone who has ever had HIV infection and then been cured would hypothetically always test positive on antibody tests. That and we would never know if all of the reservoirs had been eradicated, noting that latently infected sleeping T-cells can remain that way for decades with immunologic memory waiting to be trigger by whatever pathogen it was that it first encountered.
also, the high mortality rate of grafting non matching bone marrow into a patient, currently makes it farily unreasonable to consider as a cure option, i feel.
But it definitely calls for more research.!!!
the following is of great interest and encouragement to me. particularly the latter.
http://www.emaxhealth.com/2/53/31980/hiv-sanctuary-cell-treatment-signals-possible-cure.html
http://www.thebody.com/content/art48190.html
I have read the article entitled "Rise 'n Die, HIV: Strategies for a Cure Based on Waking the AIDS Virus" with great interest. One thing scientists have to bear in mind that they are dealing with a virus, which can create not only long-term reservoirs, but also transitory reservoirs. HIV has to use this strategy to shuttle between diverse cellular and anatomical compartments when the immune system is slowly collapsing. Immune system not only collapses with the virus, but also with the long-term use of currently prescribed therapies for HIV. Immune reconstitution disease is the main manifestation of HAART treatment given to HIV patients. Thus, more therapeutic strategies will not lead to viral eradication because HIV can conceal itself in cellular and diverse tissue reservoirs. Also, the biggest impediment is that there is not one reservoirs, there are many reservoirs and attacking them with one strategy will never be successful. On the contrary, it will be the basic understanding of how HIV moves between cells and tissues at different stages of HIV disease and also during anti-HIV therapy will provide clues to better and solid strategies to deal with viral reservoirs.
Reply | Report Abuse | Link to thisNitin Saksena
Head, Retroviral Genetics Division
Westmead Millennium Institute
Westmead, Sydney. Australia
I think this article poses an interesting approach, though it may indicate high levels of risk that may not be potentially identified.
Reply | Report Abuse | Link to thisI wouldn't hurt to still give it a try.
The "Berlin patient" who has been functionally cured of HIV, as described by katielyonz, had to undergo complete ablation of his own immune cells, meaning that before the bone marrow transplant, doctors effectively had to kill all of the patient's own immune cells in order to replace them with the HIV-immune donor tissue. This is an extremely dangerous procedure, and many patients die from it. I think most HIV positive persons would still prefer to take daily pills with toxicities that accumulate over the long term than to undergo a procedure that has a 30% mortality rate.
Reply | Report Abuse | Link to thisis it possible someone is infected with hiv ten years ago has not passit on to is children,other women,babymother and wife negitive,how can that be
Reply | Report Abuse | Link to thiswant to know if is possible for someone can be infected and dont pass it on to his children,babymother,wife over a fifteen year period,still looks the same,no sickness
Reply | Report Abuse | Link to thisThere is many other ways to help your body rid of the hiv virus.coconut oil has shown to reduce lipid coated viruses,ozone therapy destroys hiv. Selenium slows down repliation of the virus....check out this page for more info.......http://pushgood-nomorehiv.blogspot.com/
Reply | Report Abuse | Link to thisThere are many natural ways to rid your body of HIV. In contrast with the traditional antiviral cocktails of medicine today, which cost thousands, have severe side effects, and comes with the double edged sword delema,meaning if the virus doesn’t kill you the cocktails will, this medicine is all natural.Please visit this site for the full information about this subject……http://pushgood-nomorehiv.blogspot.com/
Reply | Report Abuse | Link to thisI just received an article by John Elder which showed some FIV cats had developed autoantibodies CD134 against the disease. This creates longer survival from the disease. I wonder if that will lead to some ideas an a cure? Maybe just living with the virus.
Reply | Report Abuse | Link to thisHIV is the most dangerous sexually transmitted infection, and it affects people of all ages. It is now the 5th leading cause of death for American women and men between the ages of 25 and 44 years old. HIV destroys the CD4 cells of the body which are part of the immune system (our defense system against infection). As HIV destroys these cells it weakens the immune system allowing infections to make the person sick. HIV-positive people who pick up scabies are at increased risk for a particularly aggressive scabies infestation (referred to as "crusted scabies"), and therefore may need to work with a specialist in order to properly rid themselves of an infestation.
Reply | Report Abuse | Link to thissource: http://simplestdtesting.com/resources/2009/07/are-you-at-risk-of-hiv-infection/
HIV is spreading around the world. check STDRomance site and you will know how many HIV singles there are
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