Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
State Key Laboratory of Pathogens and Biosafety, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
BMC Infect Dis. 2023 Sep 25;23(1):627. doi: 10.1186/s12879-023-08492-6.
Human immunodeficiency virus type one (HIV-1) is the leading cause of acquired immunodeficiency syndrome (AIDS). AIDS remains a global public health concern but can be effectively suppressed by life-long administration of combination antiretroviral therapy. Early detection and diagnosis are two key strategies for the prevention and control of HIV/AIDS. Rapid and accurate point-of-care testing (POCT) provides critical tools for managing HIV-1 epidemic in high-risk areas and populations.
In this study, a POCT for HIV-1 RNA was developed by CRISPR-Cas13a lateral flow strip combined with reverse transcriptase recombinase-aided amplification (RT-RAA) technology, the results can be directly observed by naked eyes.
Moreover, with the degenerate base-binding CRISPR-Cas13a system was introduced into the RT-RAA primer designing, the technology developed in this study can be used to test majority of HIV-1 RNA with limit of detection (LOD) 1 copy/μL, while no obvious cross-reaction with other pathogens. We evaluated this method for detecting HIV-1 RNA of clinical samples, the results showed that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 91.81% (85.03- 96.19%), 100% (92.60-100%), 100% (96.41-100%), 39.14% (25.59-54.60%) and 92.22% (86.89-95.88%), respectively. The lowest viral load detectable by this method was 112copies/mL.
Above all, this method provides a point-of-care detection of HIV-1 RNA, which is stable, simple and with good sensitivity and specificity. This method has potential to be developed for promoting early diagnosis and treatment effect monitoring of HIV patients in clinical.
人类免疫缺陷病毒 1 型(HIV-1)是获得性免疫缺陷综合征(AIDS)的主要原因。艾滋病仍然是全球公共卫生关注的问题,但通过终生联合抗逆转录病毒治疗可以有效地抑制它。早期发现和诊断是预防和控制 HIV/AIDS 的两个关键策略。快速、准确的即时检测(POCT)为管理高危地区和人群中的 HIV-1 流行提供了重要工具。
在这项研究中,我们开发了一种基于 CRISPR-Cas13a 侧向流动条带与逆转录酶重组酶辅助扩增(RT-RAA)技术的 HIV-1 RNA POCT,结果可以通过肉眼直接观察。
此外,通过引入退化碱基结合的 CRISPR-Cas13a 系统到 RT-RAA 引物设计中,我们开发的这项技术可以用于检测大多数 HIV-1 RNA,检测限(LOD)为 1 拷贝/μL,同时与其他病原体无明显交叉反应。我们评估了该方法对临床样本中 HIV-1 RNA 的检测,结果表明,该方法的灵敏度、特异性、阳性预测值(PPV)、阴性预测值(NPV)和准确性分别为 91.81%(85.03-96.19%)、100%(92.60-100%)、100%(96.41-100%)、39.14%(25.59-54.60%)和 92.22%(86.89-95.88%)。该方法可检测到的最低病毒载量为 112 拷贝/mL。
综上所述,该方法提供了一种 HIV-1 RNA 的即时检测方法,具有稳定、简单、灵敏度和特异性好的特点。该方法有可能用于促进临床 HIV 患者的早期诊断和治疗效果监测。