by Stem cell transplants were used to cure two monkeys of Simian Immunodeficiency Virus (SIV), the relative of HIV that infects 45 species of primates. Although some human cures had already been achieved, the technique had too many side effects for widespread application. In the monkey cases, however, the responsible researchers think they understand why the approach worked and what needs to be done to consistently apply it to humans.
It’s been 14 years since Timothy Ray Brown, known as the Berlin patient, was cured of HIV, so it’s easy to wonder why it’s taking so long. However, the Berlin patient also had acute myelogenous leukemia, forcing him to undergo a dangerous stem cell transplant. The stem cells he received were from a donor with a mutation in the CCR5 gene, which meant he lacked the receptor that HIV uses to infect white blood cells. The recipient proceeded to produce white blood cells impregnable to HIV. Without the ability to infect new cells, the virus died and he was eventually cured.
There have been four similar cases reported since then, representing the only known cures for HIV. If this were still the 1980s, when HIV was an almost certain death sentence, such treatments might be widely adopted, despite the high cost. However, with the development of highly effective treatments, most people would rather take medication for the rest of their lives than undergo painful, dangerous and unreliable treatment, unless in exceptional circumstances, such as suffering from cancer. The work published in the journal Immunity could be a big step towards changing that.
Four of the five humans cured using stem cell treatment suffered from Graft Versus Host Disease (GVHD), in which the donor’s white blood cells attack the host’s cells. The single exception offers hope, but controlling GVHD and understanding the causes is essential for cures to spread.
Professor Jonah Sacha of Oregon Health & Science University led a team that transplanted SIV-negative donor stem cells into four Mauritian cynomolgus monkeys with the disease, while four others were kept as controls. Initially, SIV samples dropped by a factor of about 1,000 in all four monkeys treated. Two treated monkeys were cured by the process and remained healthy four years later, while the SIV in the other two eventually recovered. Unsurprisingly, none of the controls experienced remission.
A 50% success rate is still not something anyone would want to bring to humans as long as alternatives are available, but comparing the monkeys where SIV disappeared and where it came back revealed a lot about what works. Virologists have debated what was causing the success in cured humans, and the authors think they now have many answers.
The authors noted that HIV in the blood of the animals’ limbs dropped below detectable levels first, followed by the lymph nodes in the arms and legs, and finally in the abdomen. They think that the fact that the whole body was not cleared at once might explain why some patients appear to be HIV-free, only to have the infection come back, particularly if the abdominal lymph nodes are not tested.
The team realized that two processes were occurring at the same time. The transplanted stem cells identified the HIV-infected cells as foreign to the body and attacked them in a way that resembles a technique widely used to cure leukemia.
In the cured monkeys, the CCR5 receptor deficiency helped prevent SIV rebound, but in the other two monkeys it didn’t work perfectly. The team behind this paper also demonstrated that a CCR5-blocking antibody can mimic the effects of transplanting a CCR5-deficient host, and hope to use it in the future.
“We hope our findings will help make this cure work for anyone – and ideally through a single injection rather than a stem cell transplant,” Sacha said in a statement.
The study was published in the journal Immunity.
