Scientists develop tool to measure success of HIV cure strategies

A new study funded by the National Institutes of Health has found a way to accurately and easily count the cells that comprise the HIV reservoir. This will enable researchers who are trying to eliminate the HIV reservoir and bring about a cure, a way to clearly understand whether their strategies are working.

The research was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH.

The HIV reservoir consists of infected cells that contain DNA molecules that encode HIV proteins. These cells are in a resting state in which they do not produce any part of the virus. Scientists have found that the HIV DNA, or 'provirus' inside the resting cells is usually so defective that it cannot generate new virus particles. However, most available tools that measure HIV reservoir cannot distinguish intact provirus, which can replicate themselves from the vast excess of defective proviruses.

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A team led by Robert F. Siliciano, at the Johns Hopkins University School of Medicine analysed DNA sequences from more than 400 HIV proviruses taken from 28 people with HIV.

Among these proviruses, the scientists mapped two types of flaws: deletions and lethal mutations. The researchers then developed strategically placed genetic probes that could distinguish the deleted or highly mutated HIV proviruses from the intact ones. Finally, the scientists developed a nanotechnology-based method to analyse one provirus at a time with these probes to determine how many proviruses in a sample are intact.

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The researchers demonstrated that their method can readily and accurately measure the number of rare, intact proviruses that make up the HIV reservoir. The hope is that this new method will speed HIV research by allowing scientists to easily quantify the number of proviruses in an individual that must be eliminated to achieve a cure.