doi:10.1038/nindia.2016.132 Published online 14 October 2016
A successful experiment in rhesus monkeys has opened the doors for a potential new treatment for Human Immunodeficiency Virus (HIV) that causes AIDS1.
The new therapy consists of antiretroviral treatment (ART) followed by infusion with an antibody that targets a receptor known as alpha4-beta7 (α4β7) on surfaces of CD4 cells – the immune cells that are the main target of HIV.
More than 35 million people worldwide are living with HIV. Currently they are required to take antiretroviral drugs for life to ensure the virus does not replicate. Long-term (ART) is not only costly but has adverse health outcomes like gut damage.
"This is where the new therapy can be a boon to patients if translated to humans," Siddappa Byrareddy, associate professor at University of Nebraska Medical Center and co-first author of the paper told Nature India.
"If what we found in the monkeys is true in humans, patients would not need to take anti-retroviral drugs continuously," he said.
In an experiment conducted by a 29-member multinational team at the Primate Research Center of Emory University in Atlanta, Byrareddy and colleagues used the ART + α4β7 combination therapy to treat rhesus macaques infected with simian immunodeficiency virus (SIV), a close relative of HIV.
They found that animals that received the combined therapy, controlled the viral loads and restored the CD4+ T cells. These effects were sustained for more than nine months after all treatment was stopped. In contrast, in control animals that received only ART, the viral loads rapidly rebounded and CD4+ T cells dipped after ART removal.
According to the study, the combination therapy allows macaques to effectively control viremia and reconstitute their immune systems without a need for further therapy.
“It is incredible that the virus remission was controlled in the animal model for such an extended period," Byrareddy said. "If we learn the mechanisms behind such control it will aid in developing an HIV cure, which is our ultimate goal."
The researchers admit that several questions need to be answered before their findings in macaques can be translated to the clinic. For instance, "the precise mechanism(s) by which ART + α4β7 antibody therapy promoted virologic control remains to be defined."
The study has, however, identified a series of correlates that individually or in combination may have contributed to that control. Also some biomarkers have been identified that could help predict whether someone's immune system is ready for stopping antiretrovirals.
"The new therapy certainly seems promising and is what the entire medical world engaged in HIV management is looking for," Ishwar Gilada, president of AIDS Society of India told Nature India.
Byrareddy said that a pilot clinical trial on HIV infected patients for testing the safety of such therapy with vedolizumab (the humanized analog of α4β7 antibody) has already begun at the U. S. National Institute of Allergy and Infectious Diseases.