Researchers find drug-resistant HIV patients with unimpaired immune cells

Nov 30, 2010

Mayo Clinic researchers have shown why, in a minority of HIV patients, immune function improves despite a lack of response to standard anti-retroviral treatment. In these cases, researchers say, the virus has lost its ability to kill immune cells. The findings appear in the online journal PLoS Pathogens.

The goal of current treatments for HIV is to block the virus from reproducing, thereby allowing the to repair itself. These findings show for the first time that not all HIV viruses are equally bad for the immune system. Patients who harbor these viruses do not develop certain complications of the disease because of mutations that render some HIV drugs ineffective -- but also impair the ability of the virus to cause disease.

"These findings suggest -- in contrast to how these patients have been treated in the past -- that changing treatments might not be needed in order to help the immune system," says Andrew Badley, M.D., Mayo infectious disease researcher and senior author of the study.

HIV causes disease by progressively killing CD4 T cells, whose function is to orchestrate the immune system. Loss of these cells renders patients susceptible to unusual infections and cancers. Over time, HIV mutates and can become resistant to the drugs used for treatment. Mayo researchers have discovered that viruses with certain mutations that render a component of the drug cocktail used to treat ineffective also have an impaired ability to kill CD4 T cells. Even though mutated viruses replicate as well as normal HIV, they fail to cause the infected cells to die. Not all mutant viruses share this effect; only selected mutations cause the impairment in cell killing, without effecting .

HIV has evolved many ways to cause the death of CD4 T cells, most of which involve HIV accelerating the normal . One kind of cell death that is unique to HIV involves the HIV enzyme protease, whose normal job is to cut up viral proteins so they can be used. This same process also cuts a normal cell protein which creates a novel protein called Casp8p41. This protein is only created during HIV infection. Casp8p41 in turn is responsible for the death of many of the infected cells. Researchers found that cells infected with HIV that also contain the mutations, produced less Casp8p41, and therefore fewer of the infected cells died.

The current treatment for HIV involves measuring virus levels in the blood and using drugs to stop that virus from reproducing. When drugs stop working, virus levels in the blood rise and physicians typically respond by changing medications. However, effective drugs may not always be available.

"Results from the current study suggest that if a patient is failing their current treatment, and other effective drugs are not available, then it may be best to take advantage of the virus' lessened ability to kill CD4 T cells, by staying on the same medication" says Dr. Badley. "We have begun to study whether the best approach might be instead to monitor Casp8p41 levels as opposed to measuring virus levels, and use that to determine whether or not to change treatment."

Researchers have already developed a way to measure Casp8p41 in the blood of patients, and this new knowledge may ultimately lead to a new diagnostic tool for HIV treatment, based upon predicting whether a patient's virus will deplete .

Explore further: Virus-killing molecules may need all their skills, including inflammation, to fight HIV infection

add to favorites email to friend print save as pdf

Related Stories

Scientists find another key to HIV success

Mar 22, 2006

Weill Cornell Medical College scientists say they've determined a protein produced by HIV infected cells prevents immune B cells from producing antibodies.

Exhausted B cells hamper immune response to HIV

Jul 14, 2008

Recent studies have shown that HIV causes a vigorous and prolonged immune response that eventually leads to the exhaustion of key immune system cells--CD4+ and CD8+ T-cells--that target HIV. These tired cells become less ...

HIV measurement is questioned

Sep 27, 2006

Preliminary U.S. research indicates the HIV RNA level in untreated HIV-infected patients has little value in predicting the rate of CD4 cell count decrease.

Exhausted B cells fail to fight HIV

Jul 14, 2008

HIV tires out the cells that produce virus-fighting proteins known as antibodies, according to a human study that will be published online July 14 in the Journal of Experimental Medicine.

HIV persists in the gut despite long-term HIV therapy

Feb 13, 2008

Even with effective anti-HIV therapies, doctors still have not been able to eradicate the virus from infected individuals who are receiving such treatments, largely because of the persistence of HIV in hideouts known as viral ...

Immune exhaustion in HIV infection

May 06, 2008

As HIV disease progresses in a person infected with the HIV virus, a group of cells in the immune system, the CD8+ T lymphocytes, become “exhausted,” losing many of their abilities to kill other cells infected by the ...

Recommended for you

Clinical trial of herpes vaccine now enrolling patients

Jul 28, 2014

Creating a successful vaccine against two members of the family, the sexually transmitted herpes simplex virus 1 (HSV-1) and 2 (HSV-2), has proven to be challenging. A clinical trial being conducted by a ...

How we got ahead in HIV control

Jul 25, 2014

When AIDS first emerged in the early 1980s, HIV infection was a death sentence. But a global effort has ensured this is no longer the case for a growing number of people.

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

baudrunner
not rated yet Nov 30, 2010
It was discovered, at least written about, in 1997 that a minority of HIV patients had an immunity to host cell invasion by the virus because of the lack of CCR5 receptor sites which are required, along with CD4 receptors, for the invasion of the host cell to take place. That left it up to the immune system to eradicate the virus, which it can do effectively. In the other class of patients, antigens cannot reach the virus, which is free to replicate inside the host cell. A few years ago, Pfizer developed a CCR5 receptor blocker to facilitate treatment of HIV patients with full-blown AIDS. I don't know what happened to that study.