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Toward an HIV Cure: Overview and Latest Strategies

November 3, 2012

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How close are we to an HIV cure? What have we learned from the precious few "functional cure" cases out there, and what other interventions are being developed?

To answer these questions, Joseph Eron, M.D., director of the University of North Carolina Center for AIDS Research, provided an overview of HIV cure research at IDWeek 2012. In his presentation, he reviewed the barriers to a cure, while highlighting the current and potential strategies being researched.

Three Patients "Functionally" Cured

Eron started by highlighting the known cases of patients who appear to have been "functionally" cured of their HIV infection. Timothy Brown, whose case has been widely reported, received two stem-cell transplants for leukemia in 2006. His CD4+ cells were replaced by the donor's CD4+ cells, which lacked the CCR5 receptor that HIV primarily attaches to, effectively making him immune to most forms of HIV. He has been off therapy for over five years without the virus rebounding.

Similarly, two other patients show no traces of HIV in their blood after receiving stem-cell transplants. Unlike Timothy Brown, these two patients received donor cells that did not lack the CCR5 receptor. However, because they were on antiretroviral therapy during the transplant period, the donor cells were not infected with HIV. Although the two patients are still on treatment, at 1,300 days post-transplant, no virus can be detected, even with a single-copy assay.

Eron noted that stem-cell transplants are too toxic, too dangerous and too expensive for most individuals living with HIV. However, he suggested that for HIV-infected individuals who need a stem-cell transplant, curing HIV should also be a goal. Regardless, he said, any intervention should be time limited and tolerable, with only moderate risk and a measurable level of success -- it doesn't have to be 100%, Eron said, but we have to start somewhere.


Cure Barriers: Why HIV Persists Despite Treatment

The first and biggest hurdle to achieving a cure for HIV is an infected person's pool of latently infected cells, specifically resting CD4+ cells, Eron pointed out. These cells would be part of hidden HIV "reservoirs" that continue to evade current antiretrovirals. There are different reservoir sites in the body, including the blood, gut, central nervous system and kidneys. They consist of resting CD4+ cells, but could include other cell types. Targeting and eradicating the HIV reservoir remains the number one challenge, Eron said.

Eron also briefly mentioned the role that may be played by long-lived cells, such as macrophages and microglia. "Turns out if you get chemotherapy and radiation, your microglia in your brain actually turn over. That's perhaps one reason why people who get transplants don't relapse in the brain with HIV," he stated. While residual HIV replication may exist in the body, Eron hypothesized that it probably exists in a low level and wouldn't be a major barrier to a cure.

The last barriers Eron listed were HIV-specific immunity loss and generalized immune dysfunction among patients who have been virally suppressed for a long time.

HIV's Evolution in the Body

After patients start treatment, HIV doesn't seem to evolve or diversify for at least six years among those who stay on treatment, Eron said, referencing work done by Mary Kearney, Ph.D., and John Coffin, Ph.D. However, Eron raised a finding he found particularly disturbing: HIV "clone cells" that were showing up five or six years after treatment initiation. "There are things called predominant plasma clones. This is a clone of the virus that's almost identical. There are some cells that are producing identical virus over long periods of time," Eron explained.

"That either means there's one cell producing a giant amount of virus that lives for a long time, or what I think is going on: There's probably a cell that's divided -- maybe it was a stem cell and then it proliferated -- and it continues to produce virus. I think those may be another hurdle we may run into," he continued.

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Reader Comments:

Comment by: MineMan (Texas) Wed., Oct. 1, 2014 at 4:55 pm UTC
It is definitely time to update the articles being archived. There is much new information garnered from more recent clinical trial results.
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Comment by: Jennifer B. (Granite Bay CA. 95746) Sat., Sep. 21, 2013 at 11:37 pm UTC
My brother has been HIV positive for over 25 years and has taken treatments I would think his CD4+cells and CCR5 receptor would be an interesting study. Why has he survived when all his friends that were diagnosed at the same time died. My husband told him to take half the amount of medicine that was prescribed initially .

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Comment by: luis (argentina) Tue., May. 14, 2013 at 6:15 pm UTC
sadly i believe we are far far away from finding a cure if they ever find one
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Comment by: Andrew (UK) Wed., Dec. 12, 2012 at 1:32 pm UTC
Been on treatment for a year now.
Diagnosed very late with cd4 of 121 and masive viral load.
Get told by clinic i have nothing to worry about and i will see old bones.
After reading this it is obvious they are not telling the truth and HIV is going to cut my life to an early grave.
Very dissapointed now.
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Replies to this comment:
Comment by: teddy (sweden) Wed., Jun. 26, 2013 at 5:26 pm UTC
No you have many years to live bellive me. Work out and eat helthy my friend. Dont bellive every thing u read. Trust your clinik

Comment by: Mkunde Mlay (Tanzania) Mon., Nov. 26, 2012 at 8:02 am UTC
Very good overview but in developing world we do have a very long way to go.
Example most of our patients starts treatments while in a very late stage that with CD4+ less than 350. And this is due to the social economical factors that governments can not pay for very high cost of drug denying most of infected population the benefits of early treatment and hence the "cure" in the future.
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Comment by: Ronald T. (South African ) Thu., Nov. 22, 2012 at 2:15 am UTC
I believe one of good days we will win this war and people will leave without fear of HIV. Am young man who is leaving with HIV for a year now i start my treatment early and i believe the coming generation will be free from HIV keep the good work ask God to lead you and He will show u the way
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Comment by: Claudine M G (Lynn, MA) Sat., Nov. 17, 2012 at 2:35 pm UTC
I am Claudine G. a provider case manager, advocate, liaison, Respiratory therapist, Community health Educator to name a few. Working with the HIV population from Florida end up in Boston MA. Thanks for the article I learned so much from the Stem cells to clone. What a is making us run like ants. Bon: I really would like to know what is our plan for the older HIV clients, tenants, in their 60's are we prepared yet to educate the nursing facilities what have we done who is going to do it and when. I am concern about few of the clients that I served and is still serving.... I would like one day to meet my President and seriously talk about this issues. Since college I worked with this population. We are still working hard to adjust what HIV is doing among us. We have a new population the young homosexual and the young lesbian. Don't think the substance abuse is light...don't blame is on divorce family only, we have to bring a health clinic in every high school in the State I am talking for the State of MA. This is serious in MA...We have Heath Centers few places the heavy duty hospitals need to assist in this new development....We need more money and management of that Mula $ My taxes cannot be free for some. We need to take care of the young one or we are going to swim in the ocean deeper than what we had in the 80's because we will have a package and heavy duty package the young one are complex...they have different issues that they can even explain yet the pain is too much to handle
brief examples:
A young female in high school
had a big issue at home with her single mother who is working 3 jobs to pay her rent of couple thousands.
young needs someone to talk to about sex
not too friendly with sister because her best friend lover is a female.
mother not home young girl left for a couple days to try having sex with an older man. Lover did find out exploded...young female went to a clinic near STI. young female drunk before she went home now homeless.
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Replies to this comment:
Comment by: Mathew (Birmingham Alabama) Fri., Dec. 27, 2013 at 4:40 am UTC
You and Ronald T. seem to me to be the same person. Unless you somehow share the exact same manner of speech as someone from South Africa. Or if you originally are from South Africa, and came to Florida later. I say this because you skip the same kind of words that he does. Reading the two comments back to back sounded identical. Unless its just some weird coincidence that you could be educated and raised in America and still make basic speech mistakes, then one of you is a sock puppet. What you would gain from this is beyond me, and it is quitr biizarre.

Comment by: Indian (India) Wed., Nov. 7, 2012 at 11:33 am UTC
Somehow, I was depressed by the article - it did not give hope & was too pragmatic. why can't we come up with mixed cure strategies or cocktail-cure approach that makes life a bit better. That can be an interim approach till a cure is found - isn't it?
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Comment by: marigold b. (guyana south america) Tue., Nov. 6, 2012 at 8:55 am UTC
i want a cure very badly
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