Bringing HIV Out of Hiding

March 15, 2013

By Medical Discovery News

Still tall, strong, and vibrant, Magic Johnson radiates the good health he exuded while playing professional basketball more than two decades ago. Yet for all that time he has been living with HIV, an infection controlled with a mix of potent drugs.

Though these antiretroviral drugs are highly effective, finding a cure for the lifelong disease remains elusive mainly due to a hidden pool of HIV-infected cells unreachable by current therapies. Recently a group of scientists successfully activated these cells, raising the hope of finding a cure for AIDS.

When HIV, the virus that causes AIDS, infects a cell, a copy of its genetic information is inserted in the cell’s genome and becomes a permanent part of that cell’s genetic information. After that, all future generations of the cell also contain the virus. 

In particular, HIV infects CD4+T white blood cells that become activated during infections.  After a patient is treated, the HIV-infected cells that survive revert back to a resting state, allowing the virus to become latent, lying dormant and unreachable by the immune system and current HIV drugs. This latent reservoir of infected cells is a major barrier to curing the disease, because anytime they’re activated the once-dormant viruses trigger a new round of infection.

The current standard therapy for HIV is called HAART, Highly Active Antiretroviral Therapy, which consists of three anti-HIV drugs given in combination.  Though highly effective in controlling HIV replication and in prolonged suppression of HIV levels in the blood, HAART isn’t capable of killing the virus in dormant infected CD4+T cells.

In the new study led by David Margolis at the University of North Carolina at Chapel Hill, a drug called Zolinza (Vorinostat) activated the virus in dormant infected T-cells, which may allow the immune system to locate and target the cells for eradication. Recent studies by Margolis and others have also shown that the drug attacks enzymes that keep HIV hiding in certain CD4+T cells.  Zolinza is a histone deacetylase (HDAC) inhibitor that is normally prescribed for mood disorders, certain lymphomas, and epileptic seizures.

Margolis’ team administered the drug to six HIV-infected men on HAART therapy. Within eight hours of taking Zolinza, all patients showed a five-fold increase in the amount of viral RNA, a marker of HIV replication in the CD4+T-cells. This means the latent HIV was activated, which will hopefully make it vulnerable to current treatment, but will more likely pave the way to a means of marking the infected cells for eradication by drugs or the body’s immune system.

The study also showed that while Zolinza promoted HIV replication, the viral loads in the blood did not go up since all the study patients were on the HAART regimen. Scientists will no doubt need to develop several treatment approaches to target latent HIV, but at least this latest discovery offers new hope for a cure.

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