Lule Daniel Bugembe, Ssemwanga Deogratius, Kaleebu Pontiano, Tully Damien C
Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Medical Research Council/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Unit, Plot 51-59 Nakiwogo Road, P. O. Box 49, Entebbe, Uganda.
Microb Genom. 2025 Mar;11(3). doi: 10.1099/mgen.0.001375.
HIV continues to be a significant global public health concern. In 2022, an estimated 29.8 million people living with HIV received antiretroviral treatment (ART). From this, an estimated 10-15% of individuals living with HIV have drug-resistant strains of the virus. Testing for resistance to antiretroviral drugs is recommended before initiating ART. However, such services are often inaccessible due to costs and the need for complex laboratory infrastructure. The assessment of HIV drug resistance (HIVDR) relies on genotyping sequencing and algorithms to interpret genotypic resistance test results. Genotypic assays involve Sanger sequencing of the reverse transcriptase (), protease () and integrase () genes of circulating RNA in plasma to detect mutations that are known to confer drug resistance. While state-of-the-art sequencing technologies have swept the globe and enhanced our global pandemic response capabilities, they are still sparingly used for HIVDR surveillance. The scale-up of ART, especially in low- and middle-income countries, necessitates the establishment of cheap, expeditious and decentralized methods for HIVDR monitoring. Here, we outline how one low-capital next-generation sequencing platform, namely, nanopore sequencing, could augment efforts in expanding HIVDR surveillance efforts, especially in resource-limited settings. We discuss that because of its versatility, nanopore sequencing can accelerate HIVDR surveillance in conjunction with scaling up ART efforts and outline some of the challenges that need to be considered before its widespread and routine adaptation to detect drug resistance rapidly.
艾滋病毒仍然是一个重大的全球公共卫生问题。2022年，估计有2980万人感染艾滋病毒并接受了抗逆转录病毒治疗（ART）。其中，估计有10%至15%的艾滋病毒感染者携带耐药性病毒株。建议在开始抗逆转录病毒治疗之前进行抗逆转录病毒药物耐药性检测。然而，由于成本和对复杂实验室基础设施的需求，此类检测服务往往难以获得。艾滋病毒耐药性（HIVDR）评估依赖于基因分型测序和算法来解释基因耐药性检测结果。基因检测包括对血浆中循环RNA的逆转录酶（）、蛋白酶（）和整合酶（）基因进行桑格测序，以检测已知会导致耐药性的突变。虽然最先进的测序技术已席卷全球并增强了我们应对全球大流行的能力，但它们仍很少用于艾滋病毒耐药性监测。扩大抗逆转录病毒治疗的规模，尤其是在低收入和中等收入国家，需要建立廉价、快速且分散的艾滋病毒耐药性监测方法。在此，我们概述了一种低资本的下一代测序平台，即纳米孔测序，如何能够加强扩大艾滋病毒耐药性监测工作的力度，特别是在资源有限的环境中。我们讨论了由于其通用性，纳米孔测序可以在扩大抗逆转录病毒治疗工作的同时加速艾滋病毒耐药性监测，并概述了在其广泛常规应用以快速检测耐药性之前需要考虑的一些挑战。
