Nowhere to Hide For HIV Virus as Scientists Make Breakthrough

Scientists have confirmed Human Immuno-deficiency Virus (HIV) can survive in another less-explored type of white blood cell. Until now, treatment and cure research has focused on blocking the virus from T-cells, a type of white blood cell that is key to the immune system.

However, new research by the University of North Carolina (UNC), United States (U.S.), reveals the virus can also persist exclusively in macrophages, large white blood cells found in the liver, lung, bone marrow and brain.

The breakthrough discovery could explain why – despite monumental advances in suppressing the virus – no treatment has successfully cured anyone of the disease.

“These results are paradigm changing because they demonstrate that cells other than T cells can serve as a reservoir for HIV,” said Dr Jenna Honeycutt, lead-author and postdoctoral research associate in the UNC Division of Infectious Diseases. “The fact that HIV-infected macrophages can persist means that any possible therapeutic intervention to eradicate HIV might have to target two very different types of cells.”

HIV treatments have advanced to the extent that a daily regimen of pills can make the virus undetectable and non transmittable. Roughly 30 percent of America’s 1.2 million people with HIV have reached an undetectable viral load.

A person with HIV becomes ‘undetectable’ when treatment targeting T-cells suppresses the virus to a level so low in their blood that it cannot be detected by measurements. If a person is undetectable and stays on treatment, they cannot pass HIV on to a partner. No study has ever shown HIV transmission from someone with an undetectable viral load.

To date, an undetectable load is almost always achieved with daily doses of antiretroviral drugs.

But a number of clinical trials – including PRO-140 by CytoDyn, which Charlie Sheen is involved in – hope to be developing treatments that could be administered on a weekly or fortnightly basis.

This endeavor could be transformed by the latest UNC research, which builds on years of speculation in the HIV research community. Last spring, UNC School of Medicine demonstrated that tissue macrophages supported HIV’s survival in the body, independent of human T cells.

But how macrophages would respond to antiretroviral therapy (ART) was unknown. They also were not sure whether macrophages could be a de facto reservoir for HIV after treatment, or whether they simply supported the virus.

Macrophages are myeloid lineage cells that have been implicated in HIV pathogenesis and in the trafficking of virus into the brain.

Using a humanized myeloid-only mouse (MoM) model devoid of T cells, Garcia and his team showed that ART strongly suppresses HIV replication in tissue macrophages.

Yet when HIV treatment was interrupted, viral rebound was observed in one third of the animals. This is consistent with the establishment of persistent infection in tissue macrophages.

 

“This is the first report demonstrating that tissue macrophages can be infected and that they respond to antiretroviral therapy,” Honeycutt said.

“In addition, we show that productively infected macrophages can persist despite ART; and most importantly, that they can reinitiate and sustain infection upon therapy interruption even in the absence of T cells – the major target of HIV infection.”

Now that Garcia and his team know HIV persists in macrophages, the next step will be to determine why and how HIV persists in tissue macrophages.

They will also investigate where in the body persistently infected macrophages reside during HIV treatment, and how macrophages respond to therapeutic interventions.