Within-Subtype HIV-1 Polymorphisms and Their Impacts on Intact Proviral DNA Assay (IPDA) for Viral Reservoir Quantification
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viruses-17-01453-v2.pdf
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1.41 MB
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Author(s)
Arikatla, Mohith Reddy
Mathad, Jyoti S.
Reddy, Kavidha
Reddy, Nicole
Ndung’u, Thumbi
Dupnik, Kathryn M.
Lee, Guinevere Q.
Date Issued
October 31, 2025
Journal
Viruses
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Arikatla, M. R., Mathad, J. S., Reddy, K., Reddy, N., Ndung’u, T., Dupnik, K. M., & Lee, G. Q. (2025). Within-Subtype HIV-1 Polymorphisms and Their Impacts on Intact Proviral DNA Assay (IPDA) for Viral Reservoir Quantification. Viruses, 17(11), 1453.
Version
Final published version
Abstract
The Intact Proviral DNA Assay (IPDA) is widely used to quantify genome-intact HIV proviruses in people living with HIV, but viral sequence diversity has been observed to cause assay failures due to primer/probe mismatches. Adapted for subtype C, IPDA-BC is a modified version of the IPDA validated on South African HIV-1 subtype C. India is also impacted by subtype C, but IPDA performance within-subtype across geographical regions is not well studied. We analyzed Indian (IN) and South African (ZA) subtype C sequences in silico, hypothesizing that IPDA-BC may underperform with IN viruses. Primer/probe binding was predicted using three increasingly stringent nucleotide mismatch criteria, whose sensitivity and specificity were evaluated against experimental IPDA outcomes. Phylogenetic analyses confirmed that IN and ZA subtype C sequences form distinct clusters with significant compartmentalization (p < 0.003). Across criteria, up to 6–10% decreases in primer/probe binding were observed in IN versus ZA, with the env forward primer being the most affected. These criteria showed low sensitivity (18–53%) and variable specificity (67–100%) in predicting experimental outcomes. In conclusion, even within subtype, HIV-1 variation across geographical regions may impact IPDA performance, underscoring the need for improved predictive models to guide assay design for global HIV cure research.
MIT Department
Ragon Institute of MGH, MIT and Harvard
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DOI of Published Version
https://doi.org/10.3390/v17111453
