Development of novel approaches for HIV drug resistance detection using nanopore sequencing technology

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Antimicrobial resistance (AMR) is one of the greatest global health challenges. AMR can evolve in all groups of pathogens including viruses. Over the past decade, the world has witnessed an unprecedented increase in the use of antiretroviral therapy (ART), The World Health Organisation (WHO) reported over 28 million people receiving treatment globally by the end of 2021, of the over 38 million infected with HIV globally. ART prevents the emergence of AIDS-related illness and has improved the health of millions of people living with HIV/AIDS as well as reduce the rate of new HIV infections. Concurrent with the increased use of treatment has been the emergence of HIV drug resistance. This global rise in resistance to crucial HIV drugs has a significant clinical impact and threatens the significant progress that has been made in suppressing HIV. In Africa, this threat is particularly acute where several countries have reported levels of HIV resistance exceeding 10% to the standard first-line therapy, a level also observed in HIV-infected people who have no previous history of ART use, which may be an indication that transmission of resistant viruses is rife. Also, the WHO estimates that approximately 50% of infants born to HIV positive mothers have HIV drug resistance to one or more of the first-line therapy drugs. The research is supervised by a highly multidisciplinary team with a wealth of experience in epidemiology, virology and computational genomics research. This research will include fieldwork at the MRC/LSHTM Uganda unit where the test specimens will be taken. This work is innovative, implements genome sequencing technologies and big data bioinformatics. This project is expected to yield scientific publications and deliver novel tools to support public health surveillance of drug resistance. The advent of portable sequencing technology means viral genomic sequencing is now positioned to exert a greater public health impact to the upsurge in drug resistance. This project aims to develop a nanopore sequencing-based workflow for identifying HIV drug resistance. This involves optimization, evaluation, and validation of the sequencing method using spiked plasma samples followed by a clinical evaluation from HIV-infected patients with known levels of drug resistance. Lastly, an open-source data processing and analysis workflow will be developed for reporting HIV drug resistance. It is envisaged that this workflow will support public health decisions and aid clinicians and laboratories in interpreting genotypic resistance. Taken together, this project will serve as the underlying basis for exploring how rapid viral sequencing can be best used in the future towards integration into local public health surveillance to decrease the incidence of drug resistance and onward transmission.