Researchers in the US have discovered that a latent form of HIV hides in progenitor cells in bone marrow, avoids detection by the immune system and retains the ability to reproduce and spread when the coast is clear (eg when treated people stop taking anti-HIV drugs). The researchers hope their discovery will lead to new and more effective treatments that target these latent reservoirs and that eventually those infected won’t have to take anti-HIV drugs all their lives.

You can read about the research that led to the discovery in the 7 March online issue of Nature Medicine.

Although antivirals that combat HIV (human immunodeficiency virus; the virus that causes AIDS), save lives, they don’t totally eliminate the virus from the body.

Senior author Dr Kathleen L. Collins, associate professor of both internal medicine and microbiology and immunology at the University of Michigan (U-M) Medical School, told the press that:

“Antiviral drugs have been effective at keeping the virus at bay. However once the drug therapy is stopped, the virus comes back.”

She said that their important finding helps to explain why it’s hard to cure the disease:

“Ultimately to cure this disease, we’re going to have to develop specific strategies aimed at targeting these latently infected cells,” she added.

Previous studies have found HIV hiding out in macrophages and some T cells, but Collins and colleagues found evidence that there was still a reservoir somewhere else.

In this study, they examined bone marrow tissue samples of HIV patients who had been treated for at least six months, and found traces of HIV genome. Previously, scientists believed that bone marrow was resistant to HIV.

Collins and colleagues confirmed that the HIV targets long-lived multipotent hematopoietic progenitor cells (HPCs, immature cells that have not yet developed specialized immune functions).

“In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors,” they wrote.

The authors concluded that:

“These findings have major implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection.”

They said further studies would be needed to establish whether the HIV also targets stem cells (cells that have the potential to turn into virtually any cell in the body).

Globally, more than 30 million people, including millions of children, are infected with HIV. Since drugs first became available in the 1990s there have been huge improvements in treatments and a nearly 90 per cent reduction in mortality.

Collins said this has led HIV to become more of a chronic disease than a death sentence. There has been a huge impact on quality of life, however:

“Only 40 percent of people worldwide are receiving anti-viral drugs and unfortunately that means that not everybody is benefiting,” she added.

The hope is that by developing a drug that does not require life-long treatment but only a course of months or a few years, it will be easier to reach and treat more people around the world, especially in countries that are not well resourced.

“HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs.”
Christoph C Carter, Adewunmi Onafuwa-Nuga, Lucy A McNamara, James Riddell IV, Dale Bixby, Michael R Savona & Kathleen L Collins.
Nature Medicine, Published online 07 March 2010

Source: University of Michigan Health System.

Written by: Catharine Paddock, PhD