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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