Institution: Makerere University

Project Affiliation: BRecA

Abstract

Introduction/Background: I am Alfred Ssekagiri, a bioinformatics PhD fellow supported by the Nurturing Bioinformatics and Genomics Research Capacity in Africa (BRecA) training program at Makerere University. Broadly, am assessing the impact of minority HIV-1 drug resistant variants in HIV-1 patients on Dolutegravir-based regimens. There is conflicting evidence on the clinical significance of minority HIV-1 drug resistant variants across populations and this requires evaluation.

Objectives/Motivation: Specifically, we set out to; (i) establish the threshold at which minority drug resistant variants are associated with virological failure (ii) estimate the time taken to virological failure since treatment initiation, (iii) develop a local resource for storage and analysis of Next Generation Sequencing (NGS) based HIV-1 drug resistance data. Given the sophisticated nature of NGS data and the scarcity of bioinformatics skills in resource limited settings, it is important to build capacity to appropriately manage, analyze, and interpret these data to ensure prompt insights. This is critical to HIV drug resistance monitoring and pathogen genomic surveillance in general.

Methodology/Skillsets: This is a case-control study in which archived plasma samples will be sequenced using Illumina MiSeq. Quasitools will be used for data processing and identifying HIV-1 variants. Drug resistance mutations will be obtained in reference to the Stanford HIV drug resistance algorithm. Through various H3Africa powered engagements, I have accumulated skills which are applicable to this study in areas of database development, workflow development, scientific writing, and publishing.Results/achievements: We developed an automated workflow for analysis of NGS-based HIV drug resistance data, published in a peer reviewed journal. In addition, we developed a local webserver for storage of NGS data. I have co-authored ten peer reviewed publications with colleagues from Makerere University, Uganda Virus Research Institute and H3Africa consortium.

Acknowledgements/Mentors/Influencers: Broadly, I acknowledge the H3Africa consortium for the opportunities including fellowships and trainings. Specifically, I appreciate the BRecA community, H3ABioNet consortium, Uganda Virus Research Institute, Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Georgia Institute of Technology.

Next Steps: Acquiring full ethical approvals, sample acquisition, library preparation, sequencing, manuscripts’ writing, thesis writing.

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