Quest for HIV Cure: Strategy for Long Term Viral Suppression

Viral loads were reduced in SIV-infected rhesus monkeys given an experimental vaccine in combination with an immune stimulant.

An experimental vaccine used in combination with an innate immune stimulant could be the answer to achieving viral remission in HIV-positive individuals.

There have been dramatic developments in the treatment of HIV over the years, with lifesaving antiretroviral (ART) drugs that allow patients to manage their disease. Although these drugs have improved the quality of live in HIV patients, they do not cure the virus.

In a study published in Nature, researchers sought to find a way to take hold of HIV without the use of ART.

“The objective of our study was to identify a functional cure for HIV — not to eradicate the virus, but to control it without the need for ART,” said lead study author Dan Barouch, MD, PhD. “Current antiretroviral 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.”

Attacking HIV is tricky because of the reservoir of dormant infected cells that allows the virus to hide during ART. This is one of the main reasons that HIV cannot be cured at this time.

In the study, researchers used different strategies to try and draw the virus out of hiding, with the primary goal of eradicating it from the body.

“We reasoned that if we can activate the immune cells that might harbor the virus, then the vaccine-induced immune responses might perform better seeking them out and destroying,” Barouch said. “Indeed, we saw the best results when we combined the vaccine together with the innate immune stimulant.”

The study was conducted over the course of 2 years, and involved 36 rhesus monkeys infected with simian immunodeficiency virus (SIV). During this time, researchers monitored the viral loads of the infected monkeys.

First the monkeys were administered suppressive ART drugs for 6 months. After 6 months, they were given either the experimental vaccines adenovirus serotype 26 vector vaccine and an MVA vector vaccine (Ad26/MVA) alone, TLR-7 immune stimulant alone, or the Ad26/MVA and stimulant combination. No active treatment was given to the control group.

“We found the combination of Ad26/MVA vaccination and TLR7 stimulation proved more effective than either component alone,” said Col. Nelson Michael, director of MHRP, who helped designed the preclinical study. “This was especially striking in viral load set-point, which impacts the future course of the disease.”

The results of the study showed that the Ad26/MVA vaccine induced a robust immune response in both magnitude and breadth.

In order to evaluate the vaccine and the immune stimulant’s efficacy, researchers stopped ART in all monkeys while continuing to monitor their viral loads. Animals that were administered only the vaccine had some reduction of viral load, but those that were give the vaccine and immune stimulant combination showed a reduction in plasma viral RNA levels as well as a 2.5-fold delay of viral rebound compared to the controls.

All 9 of the monkeys showed a decrease in viral loads, and in one-third of the animals the virus was undetectable.

“If all the animals’ viral loads had been undetectable, that would have been a home run,” Barouch said. “But the fact that all animals showed a reduction in viral load and 3 out of 9 were undetectable, that’s a solid base hit. It’s definitely something that we can work from.”