NIH-funded researchers develop new test to measure success of HIV cure strategies

Scientists funded by the National Institutes of Health have developed a new test to easily and accurately count the cells that make up the reservoir of HIV, the stubborn obstacle to curing HIV. This breakthrough will allow researchers trying to eliminate the HIV reservoir to fully understand if their strategies are working. The research was funded by the National Institute of Allergic and Infectious Diseases (NIAID), which belongs to the NIH.

The HIV reservoir consists of infected cells containing DNA molecules encoding HIV proteins. These cells have entered a state of rest in which they do not produce any part of the virus. Scientists have discovered that HIV – or "provirus" – DNA inside resting cells is usually so defective that it can not generate new viral particles. However, most of the tools available to measure the HIV reservoir can not distinguish intact proviruses, which can replicate, from the vast excess of defective proviruses.

A team led by Robert F. Siliciano, MD, of the Johns Hopkins University School of Medicine, badyzed the DNA sequences of more than 400 HIV proviruses from 28 people living with HIV. Among these proviruses, scientists mapped two types of defects: deletions and lethal mutations. The researchers then developed strategically placed genetic probes to distinguish deleted or highly mutated HIV proviruses from intact viruses. Finally, scientists have developed a nanotechnology-based method to badyze one provirus at a time with these probes to determine how many proviruses in a sample are intact.

Researchers have shown that their method can easily and accurately measure the number of rare and intact proviruses that constitute the reservoir of HIV. The hope is that this new method will accelerate HIV research by enabling scientists to easily quantify the number of proviruses in an individual who needs to be eliminated to achieve a cure.