Nkone Paballo, Loubser Shayne, Quinn Thomas C, Redd Andrew D, Laeyendecker Oliver, Tiemessen Caroline T, Mayaphi Simnikiwe H
Department of Medical Virology, University of Pretoria, Tshwane 0031, South Africa.
National Institute for Communicable Diseases and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa.
Viruses. 2022 Jul 21;14(7):1587. doi: 10.3390/v14071587.
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.
HIV-1发病率是评估HIV-1干预措施效果的一个重要参数。本研究的目的是评估HIV-1聚合酶(pol)基因序列多样性,以预测近期的HIV-1感染情况。研究使用了从45名确诊为近期或慢性HIV-1感染的参与者中获得的完整pol Sanger序列。计算了整个pol的氨基酸(aa)序列以及由50个氨基酸组成的滑动窗口的香农熵。与近期HIV-1感染相比,慢性HIV-1感染中完整HIV-1 pol的熵得分显著更高(p < 0.0001),并且在一些滑动窗口中也观察到了相同的模式(p值范围为0.011至<0.001),从而确定了一些可以区分近期和慢性感染的氨基酸突变。对不同的氨基酸突变组进行了预测近期感染的评估,其性能范围为64.3%至100%,但假近期率(FRR)较高;当分析中纳入另一个氨基酸突变(M456)时,该假近期率降至19.4%。由于高FRR,本研究中确定的基于pol的分子方法单独使用并不理想;然而,该方法可考虑用于补充现有的血清学检测,以进一步降低FRR。