At the April meeting of the Miami Men who have Sex with Men Collaborative, Dr. Mario Stevenson discussed “Obstacles to the Cure of HIV Infection.” Stevenson identified the major obstacle to an HIV cure as those “resting,” HIV-infected cells that fail to express signs of infection.
This makes them invisible to the healthy parts of the immune system and unable to infect other cells. These “resting,” but infected, cells form a reservoir of HIV. According to the AIDS Vaccine Advocacy Coalition (AVAC), this reservoir forms prior to antiretroviral treatment. It is believed to drive increases in viral load when people stop antiretroviral treatment. Any HIV cure will have to target these cells.
HIV cures differ from HIV disease management in that once cured, people could stop antiretroviral treatment. Stevenson described two cures. A sterilizing cure would eliminate HIV from the body. A functional cure would leave HIV in the body, but people could stop treatment without their viral loads increasing.
The Visconti Patients (not to be confused with the Visconti Triplets of porn) have achieved a functional cure. These patients began antiretroviral treatment very soon after infection. After achieving an undetectable viral load, they stopped antiretroviral treatment, but their viral loads remained undetectable.
The Berlin Patient has achieved a sterilizing cure, eliminating HIV from his body. While on antiretroviral treatment, he was diagnosed with leukemia and had two bone marrow transplants to control the leukemia. Fortunately, the bone marrow donor carried two copies of a rare genetic mutation that blocked HIV infection. In 2009, the Berlin Patient stopped antiretroviral therapy and has remained free of HIV ever since.
In order to infect a cell, a virus has to bind to it. A virus “seeks out” receptors on the cell to which it binds. Most strains of HIV bind to the CCR5 receptor on immune cells. The Berlin Patient’s mutation blocks cells from expressing the CCR5 receptor. Without a CCR5 receptor, the most common strain of HIV cannot infect the cell.
Researchers tried six times to repeat this sterilizing cure. All patients died within a year from malignancy relapses or transplant complications. One individual also had a strain of HIV that bound to another receptor.
This transplant costs $300,000 and has a 25 percent fatality rate. The mutation only occurs among people of Northern European descent. Even among that population, it occurs rarely.
Theoretically, scientists could modify the gene that controls CCR5 to block its expression. A variant of this technique has succeeded in curing young children of Severe Combined Immunodeficiency Disease. In order to modify that gene, scientists would first harvest stem cells from a subject with HIV infection, and grow those stem cells in the lab. A “molecular scissors” would then cut out the part of the gene for CCR5. Scientists would next grow these modified cells in the lab. When they had enough of these modified cells, they would re-inject these cells back into the original subject.
Stevenson discussed another cure strategy, Kick and Kill. Counter-intuitively, this involves “waking up” the “resting” cells in the reservoir, making them targets to be killed. Studies, however, found this technique to have modest effects.
HIV cure research has a long way to go before it becomes practical. Not all HIV researchers think a cure is possible. At present, managed HIV disease may be the best for which we can hope, but a minority of researchers continues to look for a cure. Managed HIV disease leaves people in a state of chronic low-level inflammation, leading to more health problems. Cure research is still worth following.
AVAC has excellent material about HIV cures from the introductory to the technical level. Please visit, http://www.avac.org/cureiculum