rofessor Chen Zhiwei, Director of the AIDS Institute and Professor of the Department of Microbiology at the University of Hong Kong (HKU), declared at a press conference on April 26 that through joint efforts with Chinese mainland medical and research institutions, his research team had created a universal antibody drug for HIV-1 prevention and immunotherapy. The findings from the HKU study were recently published in the April issue of the peer-reviewed Journal of Clinical Investigation.
The drug, named BiIA-SG, in tests on mice has been described as a functional cure. It can kill two birds with one stone as it can “first kill the virus and second, if it was already flourishing, prevent it from entering more cells,” Chen said. The tests found the drug was effective against 124 strains of HIV. Chen stressed the scientific discovery had yielded “one of the most potent and effective antibody drugs.”
It has been 37 years since US scientists released a report on the discovery of the first case of AIDS. Globally, HIV/AIDS has resulted in an estimated 40 million deaths while 36.9 million people are still living with the virus.
One reason behind the difficulty in combating the HIV/AIDS pandemic is because the virus is tremendously diverse. Scientists often find that within the body of a single infected person, many different mutated versions of the virus exist. The virus can change quickly, and so it quickly evolves resistance when an infected person takes a single drug.
“HIV mutates fast, so finding a proper drug to contain all these diverse viruses means the targeting position of the specific drug is conservative and effective,” Professor Zhang Linqi, director of the Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, at Tsinghua University, told NewsChina.
In reality, the HIV virus mutates with an annual speed of one percent, while the difference between different subtypes of the virus can be up to 30 percent. New subtypes can stay undetected in the human body for a very long time. Scientists call these long-term cells “memory cells” and their purpose is to live within the host as long as they can. It is believed that HIV and the human body have formed a kind of system to coexist, and despite a certain level of resistance, the body’s system cannot eradicate these genetically divergent HIV-1 subtypes.
Now thanks to the new research, scientists have found a relatively stable feature among the various mutated forms of the virus: the main way HIV-1 gets into body cells.
During the past three decades, scientists have made progress on containing the virus. In 1995, David Ho and his colleagues at the Rockefeller-affiliated Aaron Diamond AIDS Research Center in New York City discovered that treating patients with a combination of three or more antiretroviral drugs could keep the virus in check.
Today, HIV/AIDS is a manageable chronic disease thanks to this cocktail of combination antiretroviral therapy. The mortality and rate of incidence of AIDS have reduced by 70 percent since then.
In 2013, US researchers from Johns Hopkins, the University of Mississippi and the University of Massachusetts claimed to have found a “functional cure” in an HIV-infected infant. The findings were once hailed as having the potential to develop methods to eliminate HIV infection in children. But the effect did not last and the child was later found to have HIV two years after she stopped medication.
So far, there is only one individual worldwide – American Timothy Ray Brown, commonly known as the “Berlin patient” – that doctors regard as having been cured of HIV/AIDS. Brown received a bone marrow transplant from a donor naturally immune to HIV for treatment for leukemia, and was later found to be free of the virus. But this success could not be replicated in follow-up studies and research.
Scientists did learn from their previous failures. “If we could use gene editing methods and donor stem cells to shut off the susceptibility of patients’ body cells to the HIV virus, these cells will be forever immune to HIV infection, and patients would be functionally cured,” Zhang Linqi said.
While the method sounds very promising, considering the infancy of gene editing technology, the development and prospects of this method remain uncertain.
The new success of Professor Chen Zhiwei and his team is an attempt at blocking the entrance of HIV into human cells through adoption of antibody drugs. Theoretically, the method is viable, but to turn it into a practical application, more challenges lie ahead. “We are doing further modifications... to make sure the drug concentration can be maintained for a much longer time,” Chen said at the press conference. He also added that as long as the drug concentration is maintained at an effective level, the team expected it to provide 100-percent protection against infection. The research team has so far only tested the drug on mice but is now looking to experiment on larger animals such as monkeys before conducting clinical trials on humans. Even if the drug progresses to human trials, there are still many questions, such as if the antibody can survive in the human body and for how long.
Among HIV carriers across the world, 0.01 percent can live a long time without the disease progressing into full-blown AIDS. Zhang said these carriers are very important research targets. Now neutralized antibodies have been separated from these carriers as a potential universal antibody drug for virus prevention.
During a recent conference on the AIDS Functional Cure held in Beijing in late April, Chen said that there is a team in Boston that is also conducting similar tests of a neutralizing antibody drug on monkeys. There is a certain crossover with Chen’s research. “If the research results published by this team indicate it has the same mechanism as our team’s results, this neutralizing antibody will definitely be a promising solution to cure the HIV virus,” Chen said, adding that his team is also working on an HIV vaccine, so that in the foreseeable future, there could be an end to this disease.