New compound activates hiding HIV, may make drug treatment more effective: Study

IIT-M researchers working on effective drugs against HIV/AIDS

Washington:

Researchers have found a novel compound that can trigger latent HIV residing in mice to come out of hiding, a major breakthrough in treating the infection since current drug treatment fails to completely cure the disease when some of the viruses become dormant.

To combat HIV, which has infected nearly 38 million people around the world, patients currently take antiretroviral therapy (ART) — drugs that suppress the virus to undetectable levels in blood, the study, published in the journal Nature, said.

However, it added that the virus still persists throughout the body in these patients in latently infected CD4+ T cells of the immune system.

According to the researchers, including those from the University of North Carolina (UNC) in the US, the immune system cannot recognise these dormant cells, and no current therapies can eliminate them.

When ART is stopped, they said, the virus levels spike in the blood.

Hence, the scientists explained that people with HIV must take ART continuously, and the latent reservoir of the virus is the greatest obstacle to a cure against the deadly disease.

In the current study, the researchers used a compound called AZD5582 to activate latently infected CD4+ T cells in blood and many different tissues with no, or very little toxicity.

“Previously, no one had successfully tested a latency reversal molecule in humans, or in an animal model with human cells, demonstrating systemic HIV induction in peripheral blood, in resting CD4+ T cells from multiple tissues, and then replicated this success in a completely different species,” said study co-author J. Victor Garcia from UNC.

The scientists tested AZD5582 on ART-suppressed mouse models which were genetically engineered to produce human CD4+ T cells in tissues throughout the body.

They documented increases in viral genetic material expressed in the mice blood and nearly all tissues, including lymph nodes, thymus, bone marrow, liver, lung, and brain.

According to the study, the viral genetic material, ribonucleic acid, increased by more than 20 fold after treating with the compound.

When the researchers tested AZD5582 in ART-suppressed macaques infected with the HIV-like virus SIV, they found similar results, but with multiple, weekly doses.

In this experiment, they observed a spike in RNA expression in lymph nodes and blood of the primates.

According to the scientists, this is the first time a latency reversal agent accomplished this feat with little toxicity in both animal models used to study HIV.

Based on these findings, the researchers believe HIV can be pushed out of hiding, opening a range of possibilities for the development of new therapies that may lead to a cure for the disease.