Treating HIV without drugs

A new method for the treatment of HIV, without using drugs, This new approach was announced yesterday in a paper published in the New England Journal of Medicine.

Very early results look promising but, as with almost all new techniques, additional time, money and research are needed.

I read through the paper, and wanted to walk you through the findings.

One of the people involved in the research is Dr. Carl June of the University of Pennsylvania, who has done other work on HIV and cancer. I covered some of his earlier research looking at using HIV to cure leukemia.  He and numerous colleagues participated in the research that was funded by the National Institutes of Health.

This research uses genetically re-engineered cells taken from HIV+ patients to help make their cells immune to infection by HIV.

First, a simplified explanation of how HIV enters cells

When HIV enters the body it has to enter cells in order to replicate.

HIV virus attacking cell. 3D render, via Shutterstock.

HIV virus attacking cell. 3D render, via Shutterstock.

HIV enters by binding to a receptor on the surface of cells known as the CCR5 receptor. There are many CCR5 receptors on CD4+ cells. An HIV particle touches a CCR5 receptor and binds to it. The HIV particle then undergoes a structural change that allows it to come into close contact, and then merge, with the CD4+ cell. The viral RNA enters the cell. Infection occurs and viral RNA replication begins. After replication, the virus particles leave the CD4+ cell and go off to infect other cells.

Eventually, the infected CD4+ cell dies. As more CD4+ cells are infected, and subsequently die, the CD4+ count declines. Decreasing counts can lead to increased opportunistic infections in patients. These may cause serious illness or death.

Here’s a short video on how HIV enters cells:

What the researchers did

Most people have a gene from each parent that causes CCR5 to be formed on cell membranes. Heterozygotes (people having only one copy of the gene that causes CCR5 to be formed) produce substantially fewer copies of CCR5 receptors per cell. This makes it much more difficult for HIV to infect those cells. In the (rare) homozygote, who has no genes that code for the production of CCR5, no CCR5 receptors are produced. Therefore, HIV can’t attach to these cells, can’t enter, can’t cause an infection, can’t replicate and can’t kill the cell.

Researchers removed some CD4+ cells from the patients in the study and used an enzyme to make the genes that code for CCR5 inactive. These cells then lost their ability to display CCR5 receptors on their membranes, just like the homozygote in the above description. Billions of these cells were then reinfused into the patient that they were initially harvested from. The study showed that these cells lived in the patient and functioned like CD4+ cells. They were more resistant to infection by HIV. Only one patient had moderately serious temporary side effects.

While these are interesting and promising results, remember that they are still early results and that there were only a few patients in the study. Further work is needed.

What this study showed was that the cells could be genetically engineered to cause them to lose their CCR5 receptors. And that the cells could be returned to their hosts safely and continue to function.

The potential for this research in treating HIV

Timothy Ray Brown, a patient in Berlin, had HIV and was on antiretrovirals. He developed leukemia and was given a stem cell transplant from someone who lacked the ability to produce CCR5. After transplant, his viral load decreased and CD4+ count continued to rise. He was taken off of antiretrovirals. Gradually his CD4+ cells that were HIV infected died off. But the new donor cells, lacking CCR5, couldn’t get infected. His viral load is now undetectable, and his CD4+ cell count remains near normal. Today, about 5 years after the transplant, he is considered to be cured of HIV.

What researchers hope is that, since they can produce cells that lack the ability to produce CCR5, they can engineer these cells, infuse them into HIV patients and, perhaps get the same results as with the Berlin patient: getting him to a point where he’s got undetectable HIV levels and has enough functioning CD4+ cells to consider him cured and get him off antiretrovirals.

One possible drawback is that the bioengineered CD4+ cells may not be all that long-lived. That is, the cell harvesting, engineering, infusion, etc., may need to be repeated every few years. That is just one of the future studies that will need to be carried out before this technique could be put into routing practice. Of course, those studies will be dependent on additional funding from the government through the NIH.

We can only hope that the research budget will not be limited as it has been in the past. This work, and many other studies, not just on HIV/AIDS, but on many other diseases and treatments is dependent on enough money to keep the researchers working.


Mark Thoma, MD, is a physician who did his residency in internal medicine. Mark has a long history of social activism, and was an early technogeek, and science junkie, after evolving through his nerd phase. Favorite quote: “The most exciting phrase to hear in science... is not 'Eureka!' (I found it!) but 'That's funny.'” - Isaac Asimov

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  • Indigo

    That’s good to know.

  • docsterx

    Sorry, I should have defined which BM I was talking about.

    Ever since fecal transplantation started, I’ve avoided chocolate milkshakes in hospital cafeterias. ;-(

  • docsterx

    No. When you do large scale research, you may have to rely on the honesty of the research subjects. In one of the studies I mentioned, hundreds of people took part. The data gathered is based on lab testing, physical exams and what the subjects reported. Even though researchers try to keep everything as honest and straightforward as possible, that isn’t always possible. So the data generated is somewhat dependent on whether the human subjects told the truth. That makes it extremely difficult to ever state anything with 100% certainty when you’re dealing with subjectively reported information.

    Now, at CROI (Conference on Retroviruses and Opportunistic Infections) a major meting of the minds on HIV/AIDS, Alsion Rodger presented on:
    HIV Transmission Risk Through Condomless Sex if HIV+ Partner on Suppressive ART: PARTNER Study

    Her interpretation of the data was essentially that it is impossible for someone with an undetectable viral load on antiretroviral therapy to transmit HIV to an uninfected partner.
    .

  • Indigo

    In less evasive terms, it’s not certain.

  • When I read ‘BM transplant’, bone marrow was not the first thing to come to mind, despite reading your whole post. Maybe I shouldn’t have read that article on fecal transplantation earlier. :)

  • docsterx
  • docsterx

    Please see above. Studies have shown that the lower the viral load, tthe lower the risk of transmitting HIV to an uninfected partner. http://www.nejm.org/doi/full/10.1056/NEJMoa1105243

  • docsterx

    The Berlin patient had his entire immune system essentially wiped out with medication AND total body irradiation. And that process was repeated twice, The Boston patients did not have that exact same treatment. Also, the bone marrow donor for the Boston patient was a close immunological match and the donor had the gene for CCR5 with the delta 32 mutation. The Boston donors did not have that exact same genetic profile. The Boston patients were maintained on ART for quite some time after they were transplanted. Timothy Brown wasn’t maintained on ART for long after the transplant.

    Yes, there are a few types of HIV (and other viruses) that can use other receptors to enter CD4+ cells. These patients could, theoretically, catch those rarer subtypes of HIV. But that has nothing to do with the results in the Berlin patient. These techniques aren’t being researched to make people immune to all forms of HIV, they are being researched get information that may allow for development of strategies and techniques to treat HIV. Also, they’re not being promoted as treatments that can be offered to the average HIV patient. Timothy Brown and the Boston patients all had cancer and were only able to undergo transplants based on having that additional diagnosis along with having HIV.

    Both the second Berlin patient, Timothy Brown (there was a first Berlin patient, who survived after treatment and is not on ART. He did NOT have a BM transplant) and Boston patients had BM transplants from unrelated donors. The BM transplants from unrelated donors is not being suggested as a method to cure people of HIV infection. Additionally, in the patient described above, he did NOT have his immune system destroyed and his own marrow cells (an autologous transplant) were used. That process is quite different from what was done in the Berlin and Boston patients.

    The only patient that has been called “cured” is Tim Brown who has been off of antiretrovirals for about 7 years now and still shows no trace of virus. Even the Boston patients’ doctors didn’t say that they were cured, only that they may have been cured.

  • nicho

    Over the last 30 years, I’ve seen an awful lot of treatments that were successful in the “early tests.” However, as we’re finding out, this is a very crafty virus with an remarkable ability to reinvent itself on the fly.

  • Rrhain

    How is this different from the two Boston patients that received bone marrow transplants? They, too, were seemingly HIV-free for months only to have the virus return. None of the articles that I see about them indicate what it was about the bone marrow that was received that would have conferred immunity.

    On top of that, there is a variant of HIV that doesn’t use CCR5. The articles I read say that this strain tends to not present itself in patients with a functioning immune system, but they also caution that this is by no means a guarantee.

    Plus, the treatment for the Berlin patients required a bone marrow transplant which is extremely risky. Essentially, they have to destroy your current bone marrow (which makes you highly susceptible to disease) in order to prep your body for the transplant. And there is always the chance for rejection.

    Keep working at it. This is promising research, but we need to be extremely careful about calling this a “cure” by any stretch.

  • Indigo

    “Cured” or “in remission”? It’s a crucial distinction. The basic issue becomes that of whether this “cured” person could inadvertently infect someone else. On the whole, that’s fascinating stuff and excellent news for those who are infected. The question remains, is a trace HIV transmittable?

  • Henry Owen

    Thank you for the imbedded videoclip. I teach a Genetics course, and I’ll be talking about genetic variations of the CCR5 strain of HIV in a couple of weeks. This will add some good visuals of the overall process of infection.

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