Animal research with an experimental two-drug therapy could hold clues for creating long-term HIV remission in people living with the virus, a new report says.
Evaluation planned in humans
The goal: to free patients from the need to take anti-HIV pills each day.
Researchers combined an experimental vaccine with an immune-stimulating drug to create a one-two punch that caused a similar virus to become undetectable in three out of nine test monkeys, said senior author Dr Dan Barouch. He's director of the Centre for Virology and Vaccine Research at Beth Israel Deaconess Medical Centre in Boston.
"Both of these components already are in clinical trials being conducted separately," Barouch said. "We hope to evaluate the combination in humans, and we plan to do further animal studies as well.
The experimental vaccine, called Ad26/MVA, aims to help the immune system target HIV.
The immune-stimulating drug GS-986, meanwhile, "shocks" a person's dormant HIV into activity, so the immune system can better recognise it, explained Rowena Johnston, vice president and director of research for amfAR, The Foundation for Aids Research. She was not involved with the new study.
Vaccines teach the body how to rid itself of harmful viruses through a targeted immune response, but HIV is insidious because it attacks cells of the immune system. The virus kills a majority of infected immune cells but goes dormant in others, creating a hidden reservoir from which new infections can spring forth.
"When it's in that state, the immune system can't see it," Johnston said. "One of the ways that researchers want to cure HIV is to try to wake up that HIV, shock it out of its latency, so now the immune system can see it and come in and destroy those cells."
Johnston predicts HIV researchers "are going to be talking about this with a lot of enthusiasm".
"I think and hope this is going to get a lot of researchers thinking about ways to come up with a similar one-two punch that can deal with HIV the way we'd like it to," she said.
One HIV expert was encouraged by the new finding.
The research is preliminary, but may provide "a path forward to further develop, refine, and improve this concept and potentially move science closer to, one day, achieving a functional cure for HIV in which daily medications are no longer required," said Dr Amesh Adalja. He is senior associate at the University of Pittsburgh's Centre for Health Security.
The two-year study involved 36 monkeys infected with simian immunodeficiency virus (SIV), a virus similar to HIV that infects non-human primates.
Combo worked best
The monkeys initially were treated with antiretroviral drugs for six months. Then they were treated with different combinations of experimental vaccines and immune stimulants.
Researchers gave nine monkeys the combination of Ad26/MVA and GS-986, Barouch said.
Then they stopped the antiretroviral drugs to see whether the different therapies would keep the SIV level in the monkey's blood under control.
The combo worked best at keeping SIV levels down, researchers found. All nine monkeys showed decreased levels, and the virus was undetectable in a third of them.
"They rebounded initially, but after rebounding the virus was controlled," Barouch said. "They have remained undetectable up until the last time they were tested."
The combination therapy will not be available for clinical use for quite some time, Barouch and Johnston said.
'Something to build on'
Johnston pointed out one problem with the study: Researchers started the monkeys on antiretroviral drug therapy far sooner than a human would receive it, given the usual delay in detecting HIV infection.
"In these monkeys, their immune systems were probably pretty largely intact," she said. "That's not true for the vast majority of people living with HIV."
But the results give researchers "something to build on", Johnston added, though research on animals often does not produce the same effect in humans.
The study was supported by the makers of Ad26/MVA (Janssen Vaccines & Prevention) and GS-986 (Gilead Sciences), as well as the Walter Reed Army Institute of Research and the US National Institutes of Health.
The findings were published online in the journal Nature.