Anti-HIV drugs have transformed infection with the AIDS virus from a death sentence to a chronic, manageable condition with a normal life expectancy. But although it is now possible to attack HIV at every stage of its life cycle, effectively controlling viral replication and allowing the immune system to rebuild itself, a cure still eludes scientists and treatment is far from perfect. Resistance is still a problem, some of the medications have major side effects, and a number of patients poorly respond to therapy.

While it is sometimes difficult to get excited when we see so many reports of “breakthroughs” in HIV research, promising results from a series of small trials investigating an innovative therapy in the U.S. have led to renewed hope that a cure could be in sight. The novel therapy involves modifying the DNA of white blood cells to make them largely resistant to HIV and injecting these into patients.

After demonstrating last year in a very small trial that the treatment could be tolerated, researchers extended the study to include a larger number of participants. Once again, the results were encouraging, with several patients achieving long-term control of the virus. Now, the FDA has just granted approval for a further extension of the trial, and another trial using a similar but more aggressivel technique is also due to commence shortly.

Rather than using drugs to block viral replication, this new therapy involves removing a patient’s white blood cells, called T cells, and then using a genome editing technique to modify the gene that produces one of the cell surface molecules HIV uses to get inside these target cells. The idea is to mimic a natural mutation found in a small percentage of the population that confers resistance to HIV. These individuals have an alteration in the gene that produces receptors called CCR5, which HIV has to latch onto to gain cell entry. Individuals with this mutation produce a slightly altered and nonfunctioning version of CCR5, but this doesn’t seem to adversely affect their health.

The reasons scientists believe that this therapy could be effective is because a few years ago, the famous "Berlin patient" Timothy Ray Brown was cured of HIV after receiving a stem cell transplant from a donor with this particular mutation. Brown remains the first and only person to be considered cured of the virus.

For the first trial, 12 patients were infused with a single dose of the modified T cells. The main goal of this study was to assess the safety and side-effect profile of the cells. They found that the cells displayed long-term persistence in the body and were generally safe, but since such a small number of individuals were used, they could not generalize this conclusion. The trial was therefore extended, and now more than 70 individuals have been treated. So far, it has been well-tolerated, and the cells were found to persist for up to four years. Furthermore, a lasting increase in T cell counts was also observed, even after a planned interruption of the patients’ anti-HIV drug regimen. Now, after receiving FDA approval, two new trials are set to commence in the U.S., one of which involves a slightly different method to disable CCR5, and the other that will use the same strategy as before but on patients who have failed to respond to conventional therapy.

[Via Medscape, NEJM and Imperial Valley News]