Diversity in HIV Genome Presents Challenges for New Test Measuring HIV Reservoir in Patients

A new test for measuring the reservoir of HIV hidden in the cells of people with HIV failed to detect this reservoir in a significant number of people with a subtype of HIV-1, according to a study from scientists at Weill Cornell Medicine, Simon Fraser University and the British Columbia Centre for Excellence in HIV/AIDS. Modifications to the test, which is frequently used in clinical trials for new HIV-1 treatments and potential cures, could potentially improve its utility.

The HIV reservoir is formed when the virus integrates its genes into the DNA of immune cells it has infected, including cells that are very long-lived and relatively inactive. This pool of latent virus is largely unaffected by standard HIV treatments, but can seed the spread of active HIV within a PWH if he or she ever stops taking these drugs.

The new test, known as the Intact Proviral DNA Assay (IPDA), is meant to detect and quantify this HIV reservoir, and is much easier to use than prior methods. Since its first description in the scientific literature in 2019, it has been commercialized and widely adopted, especially for clinical trials of treatments that aim to clear the HIV reservoir and cure the disease.

Because HIV is highly variable, it will sometimes elude recognition by the molecular probes the IPDA uses to detect small stretches of HIV DNA-causing a failure of the test. However, the first two studies on the new assay reported no such failures in 62 and 81 individuals. A study, published Jan. 8 in Nature Communications, found that the IPDA failed to detect the HIV reservoir-whose presence was confirmed with the current gold standard method-in 13 of 46 participants with a particular subtype, or variation of HIV-1 DNA in their cells, for a failure rate of 28 percent.

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