ArticleVirology journal2026
Prediction of recent HIV-1 infections using Shannon entropy analysis of HIV-1 group-specific antigen protein sequence.
Article in Virology journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAvidity assays often misclassify chronic HIV-1 infection as recent HIV-1 infection (false recency rate), especially in participants on antiretroviral therapy. The aim of this study was to use Shannon entropy to evaluate HIV-1 group-specific antigen (Gag) sequence diversity for the prediction of recent HIV-1 infections.
methodsThis was a retrospective study that characterised the complete HIV-1 Gag using Sanger sequences obtained from participants with confirmed recent or chronic HIV-1 infection. Shannon entropy was calculated for the entire HIV-1 Gag amino acid (aa) sequence (501aa) and sliding window analysis was computed at intervals of 100aa each. This was followed by searching for aa sites that exhibited a different distribution of mutations between recent and chronic HIV-1 infection stages. Reference sequences were obtained from GenBank and the Los Alamos HIV database to verify the findings obtained from study sequences.
resultsForty-seven participants with a mean age of 28.7 years (18 - 44) were enrolled, and fourteen (30%) of them had recent HIV-1 infection. Shannon entropy analysis showed a significantly higher aa diversity in chronic HIV-1 infection compared to recent HIV-1 infection (p = 0.0003). Analysis of sliding windows led to identification of four aa positions; S54, E55, I256, and S451; with different pattern of distribution between recent and chronic HIV-1 infection stages; however statistical significance was only observed for three of these aa, p values = 0.094, 0.027, 0.027 and 0.045, respectively. The performance of these informative sites for detection of recent HIV-1 infection in study sequences ranged from 71-86%, however, they had a high false recency rate (FRR) ranging from 39%-52%. Similar performance was observed in reference sequences. The combination of some informative aa sites reduced FRR in study sequences to below 24%.
conclusionsOur data show that a Gag-based molecular strategy can be used to detect recent HIV-1 infections where Gag sequences are available. However, the results would have to be interpreted with caution due to an association with a high FRR. Further studies are needed to develop a molecular-based strategy with better performance for detection of recent HIV-1 infections.
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