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A series of animal and human studies published this week are providing a sad footnote to a controversial 2016 experiment in monkeys that pointed to a possible cure for HIV but was later flagged for a glaring omission in its design. The animal studies failed to replicate the promising results of the original paper, while a clinical trial in humans using a similar strategy largely failed as well.
In 2016, researchers published a study in the well-respected journal Science. They experimented with rhesus macaque monkeys, infecting them with the simian immunodeficiency virus (SIV), a close relative of the HIV virus that causes AIDS in people. Then they gave the monkeys a short combination dose of the standard HIV treatment—antiretroviral therapy (ART)—and an antibody that targeted a protein, called a4b7, found in immune cells.
Current treatments for HIV can drive levels of the virus so low as to make a person completely not contagious and relatively healthy. But HIV seeds itself into reservoirs of the immune system, where some amount of it is able to survive these drugs. If someone stops taking their daily dose of ART or the treatment otherwise starts to fail, the virus can then emerge from its dormancy and wreak havoc again. Earlier research had suggested HIV uses a4b7 to help pull off its disappearing trick inside cells, so it was hoped that using both treatments at once could eradicate the virus completely, or at least provide a sustained remission that would let people no longer need daily ART. And in the 2016 study, that’s what it seemed to do for the monkeys. Nine months after their treatment, their immune systems looked perfectly normal and no traces of SIV could be found. It was understandably seen as the first step to an HIV cure.
In science, though, no single study is the final word. Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) and elsewhere quickly began to carry out their own larger studies that would replicate the original study’s design. Another U.S. government study was planned to test out the human version of the a4b7 antibody—an existing anti-inflammatory drug called vedolizumab—in a small clinical trial with people.
“We conducted these studies because we felt that the results reported in the 2016 Byrareddy study had the potential to transform the HIV cure field if the findings were reproducible and generalizable,” Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center at Harvard Medical and senior author of one of the studies, told Gizmodo via email. As all this was going on, however, it came to light that one of the study’s co-authors, Francois Villinger, now a pathologist at the University of Louisiana at Lafayette, had provided the research team a different type of SIV virus than was stated in the paper. To spare the technical details here, this version of the virus wasn’t programmed to produce a protein made by SIV in the wild, at least not for the first weeks of infection. According to the authors, only Villinger was aware of the omission. And he told the journal’s editors that he used the modified virus because it more closely mimicked how HIV behaves in humans (wild SIV tends to kill monkeys very quickly, while HIV infection is usually slower to kill).
“While there was no malfeasance, there was clearly a major negligence in our studies reported in the Science paper,” Ansari Aftab, senior author of the 2016 study, told Gizmodo via email....
The earlier study not replicated was published in Science on Oct.14, 2016: https://doi.org/10.1126/science.aag1276
Recent study failing to replicate above work published September 6, 2019 in Science:
