Researchers have found that an investigational treatment combining therapeutic vaccine and an immune stimulator was successful for improving virologic control and delay viral rebound after the discontinuation of anti-retroviral therapy (ART).
The research was conducted on non-human primates infected with SIV, the simian form of HIV.
The study examined the combined effects of therapeutic vaccination with an adenovirus serotype 26 vector vaccine and an MVA vector vaccine (Ad26/MVA) and TLR-7 agonist stimulation in ART-suppressed, SIV-infected monkeys.
This study was led by Beth Israel Deaconess Medical Center (BIDMC) and the US Military HIV Research Programme (MHRP) of the Walter Reed Army Institute of Research (WRAIR).
It also included scientists from Janssen Vaccines & Prevention and Gilead Sciences.
The monkeys were treated with suppressive ART seven days after infection with SIV. After 24 weeks, they received either placebo treatment, Ad26/MVA, TLR7 agonist or a combination intervention of Ad26/MVA and TLR-7/TLR7 agonist.
ART was discontinued at week 72 to assess the ability of the investigational therapies to affect continued virological control.
MHRP director Nelson Michael said: “We found the combination of Ad26/MVA vaccination and TLR7 stimulation proved more effective than either component alone.
“This was especially striking for viral load set-point, which impacts future disease.”
Within the test, the mean viral load set-point was reduced by 100 fold in all animals.
Researchers found a 2.5-fold delay of viral rebound as compared with the other groups.
All monkeys eventually experienced viral rebound after ART interruption except three, who showed effective virologic control to undetectable viral loads following ART discontinuation.
BIDMC’s centre for virology and vaccine research director Dan Barouch said: “Current anti-retroviral drugs, although they’re lifesaving, do not cure HIV. They merely hold it in check. We are trying to develop strategies to achieve ART-free, long-term viral suppression.
“We reasoned that if we can activate the immune cells that might harbour the virus, then the vaccine-induced immune responses might perform better seeking them out and destroying them.”
HIV is known to have a viral reservoir that remains hidden and infects cells throughout the body, which results in a viral rebound in the vast majority of HIV-infected individuals after they discontinue ART.
The Ad26 vaccine was developed in partnership between the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH), BIDMC and Janssen.
Funding for the study was provided by the US Army Medical Research and Materiel Command and the Military HIV Research Programme, Walter Reed Army Institute of Research through its cooperative agreement with the Henry M. Jackson Foundation, NIH, the Ragon Institute of MGH, MIT, and Harvard.
Image: Electron micrograph of HIV-1 emerging from cultured lymphocyte. Photo: Courtesy of C. Goldsmith / Wikipedia