Evaluation of the HIV-1 polymerase gene sequence diversity for prediction of recent HIV-1 infections using Shannon entropy analysis

Abstract

SUPPLEMENTARY MATERIALS : TABLE S1: List of articles from which HIV-1 subtype C reference sequences were obtained; Supplementary TABLE S2: Nucleotide differences within amino acid mutations found to have a different distribution between recent and chronic infection sequences; FIGURE S1: Amino acid sequence alignment to show the difference in sequences between recent and chronic HIV-1 infection; FIGURE S2: Comparison of differences in amino acids E628 and R629 in study sequences and non-subtype C reference sequences, for recent and chronic sequences.DATA AVAILABILITY STATEMENT : All data generated or analysed during this study are included in this manuscript and its supplementary information files.HIV-1 incidence is an important parameter for assessing the impact of HIV-1 interventions. The aim of this study was to evaluate HIV-1 polymerase (pol) gene sequence diversity for the prediction of recent HIV-1 infections. Complete pol Sanger sequences obtained from 45 participants confirmed to have recent or chronic HIV-1 infection were used. Shannon entropy was calculated for amino acid (aa) sequences for the entire pol and for sliding windows consisting of 50 aa each. Entropy scores for the complete HIV-1 pol were significantly higher in chronic compared to recent HIV-1 infections (p < 0.0001) and the same pattern was observed for some sliding windows (p-values ranging from 0.011 to <0.001), leading to the identification of some aa mutations that could discriminate between recent and chronic infection. Different aa mutation groups were assessed for predicting recent infection and their performance ranged from 64.3% to 100% but had a high false recency rate (FRR), which was decreased to 19.4% when another amino acid mutation (M456) was included in the analysis. The pol-based molecular method identified in this study would not be ideal for use on its own due to high FRR; however, this method could be considered for complementing existing serological assays to further reduce FRR.The National Research Foundation (NRF), Poliomyelitis Research Foundation, Discovery Foundation, National Health Laboratory Service Research Trust (NHLS-RT), South African Medical Research Council Self-Initiated Research (MRC-SIR), University of Pretoria Faculty of Health Sciences Research Committee, the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa and the Division of Intramural Research.https://www.mdpi.com/journal/virusesam2023Medical Virolog

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