AI Article Synopsis
- The Intact Proviral DNA Assay (IPDA) is a droplet digital PCR-based method designed to accurately measure the amount of intact HIV-1 in the body, which is crucial for understanding HIV-1 persistence.
- In a study of a diverse group of people with HIV-1 subtype B in North America, the IPDA experienced a 28% failure rate due to variations in the virus, known as polymorphisms.
- This variability can cause the IPDA to inaccurately estimate the size of the HIV-1 reservoir, highlighting the need to consider HIV-1 diversity before widely using the IPDA in clinical trials for HIV-1 treatment and remission.
Article Abstract
The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a scalable method for intact HIV-1 reservoir quantification. This droplet digital PCR-based assay simultaneously targets two HIV-1 regions to distinguish genomically intact proviruses against a large background of defective ones, and its application has yielded insights into HIV-1 persistence. Reports of assay failures however, attributed to HIV-1 polymorphism, have recently emerged. Here, we describe a diverse North American cohort of people with HIV-1 subtype B, where the IPDA yielded a failure rate of 28% due to viral polymorphism. We further demonstrate that within-host HIV-1 diversity can lead the IPDA to underestimate intact reservoir size, and provide examples of how this phenomenon could lead to erroneous interpretation of clinical trial data. While the IPDA represents a major methodological advance, HIV-1 diversity should be addressed before its widespread adoption as a principal readout in HIV-1 remission trials.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794580 | PMC |
| http://dx.doi.org/10.1038/s41467-020-20442-3 | DOI Listing |
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