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Scientist Cure HIV in a Second Patient

  • by Fehbe Meza
  • Mar 06, 2019
  • MCAT Blog

A team of London virologists has just announced that an anonymous patient, termed “the London patient”, has been HIV-free for a year and a half since he received an experimental bone marrow transplant. This is the second time in history that someone has been “cured” of HIV.

In the United States, HIV was first clinically described in 1981. Los Angeles doctors observed several isolated cases of rare infections, like pneumocystis pneumonia and Kaposi’s sarcoma, in otherwise healthy young men. These opportunistic diseases had previously been seen only in patients with compromised immune systems. And then, apparently out of nowhere, similar cases began popping up across the country and around the world. But it would be several years until two research groups, working independently, would simultaneously identify the virus responsible for this new epidemic.

Race to an HIV Cure

But if HIV was discovered nearly forty years ago, why hasn’t a cure been found? To answer this question, we need to take a look at the virus’ pathology. HIV is a retrovirus that infects specialized cells of the immune system called helper T cells and dendritic cells. Once inside a host cell, the virus copies its single-stranded RNA genome into double-stranded DNA, which enters the nucleus to be integrated into the host cell’s genome. After integration, the virus can lay dormant inside the cell for an indeterminate length of time. In fact, many HIV patients do not show symptoms of infection until many years later, when latent HIV genes inside their cells are inexplicably activated. By this point, the virus is essentially unstoppable because the cells that were initially infected have given rise to an entire population of cells with dormant viral genes.

To add another layer of complexity, HIV infects and destroys the very same cells that are responsible for killing it. After the viruses’ genes are activated inside host cells, viral proteins are produced and assembled into progeny viruses, which burst from the cell membrane, killing the host cell in the process. In other cases, the infected cell notices the virus first and destroys itself to prevent the spread of infection. Either way, the immune system’s population of helper T cells and dendritic cells slowly begins to decline. After they fall below a critical threshold, the patient becomes vulnerable to other infections. These viruses are normally harmless, but they begin to cause deadly diseases in the absence of immune protection. At this point, an HIV patient is diagnosed with AIDS and will likely die within several years without treatment. In short, HIV is incredibly difficult to cure because the virus can escape immune detection by hiding inside the immune system itself and slowly destroying it.

Many attempts have been made to find a cure but to no avail. Instead, anti-retroviral drugs have been the standard of care for HIV patients for decades now. These drugs act on different viral targets to decrease the patient’s total viral load, preventing the onset of AIDS symptoms and reducing their infectivity.

Bone marrow transplants are a totally different strategy. During a transplant procedure, HIV-resistant stem cells are introduced into the infected recipient’s bone marrow. These cells differentiate into healthy helper T cells and dendritic cells. The old infected cells eventually die out, leaving the patient with a brand-new HIV-resistant immune system, thereby curing them of the virus—in theory. This is essentially the procedure the London patient underwent.

Why is the London Patient so Special?

The London patient was not the first to be “cured” of HIV with a bone marrow transplant. In 2007, an HIV-positive leukemia patient named Timothy Ray Brown received two bone marrow transplants from a donor who had a specific mutation that prevents HIV from entering host cells. Since his transplant, Mr. Brown has remained HIV-free without help from anti-retroviral drugs. But this radical procedure came at a cost: Mr. Brown nearly died from complications related to the transplant and the harsh post-operative treatment regimen.

Since that initial success, researchers have been trying to cure other HIV-positive patients using marrow transplants, but all attempts have met with failure. Every time, the patient has either died or returned to HIV-positive status within a year of discontinuing anti-retroviral treatment. Not surprisingly, scientists began to think that Mr. Brown’s case was a just lucky break, and that bone marrow transplants might never be viable as a cure for HIV.

The London patient changes this outlook. He recovered from his operation without incident and has remained off anti-retroviral treatment for over a year with no sign of HIV. Doctors are cautiously optimistic about both patients, given HIV’s resilience and ability to hide within the body. However, the virus hasn’t returned in either patient.

A Brighter Outlook

What does this mean for the future of HIV treatment? Are bone marrow transplants the ultimate cure that patients across the world have been hoping for? Well, probably not. These procedures are incredibly difficult, costly, and dangerous. They come with potentially life-threatening complications, including graft failure, organ damage, and the onset of new cancers. The most notable is probably graft vs. host disease, in which the transplanted stem cells treat the recipient’s body as foreign and begin to attack and destroy healthy cells.

Needless to say, bone marrow transplants are typically reserved for patients that will otherwise die of acute disease. All of the HIV-positive patients that have undergone this procedure were selected because they also suffered from deadly bone and blood cancers. But thanks to modern advances in anti-retroviral therapy, HIV is no longer a death sentence. The vast majority of HIV patients can live nearly normal lives with the right drug regimen, so a dangerous and expensive experimental cure is not a great option for them. A cure for HIV may never be as broadly effective as continuous treatment and careful monitoring, but doctors and scientists will never stop searching for a cure.

Written by Next Step Test Prep MCAT Tutor Kelsey Roman

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