Advanced International Journal for Research

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Genomic Determinants of Antifungal Resistance Among Non-albicans Candida Isolates From HIV-Positive Patients in Southwestern Uganda: A Study Protocol

Author(s) Nusifah Mbatudde
Country Uganda
Abstract Background

Non-albicans Candida (NAC) species have emerged as important opportunistic pathogens among people living with HIV (PLHIV), increasingly contributing to treatment failure and recurrent fungal infections worldwide. Although Candida albicans has historically been regarded as the predominant cause of candidiasis, recent evidence indicates a shift towards NAC species such as Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei. These species frequently exhibit intrinsic or acquired resistance to commonly used antifungal agents, particularly azoles, posing significant therapeutic challenges. In Uganda, routine fungal diagnostics rely predominantly on phenotypic methods, which cannot accurately distinguish cryptic NAC species or identify resistance mechanisms. Consequently, the genomic determinants underlying antifungal resistance among NAC isolates remain poorly understood. This study aims to investigate the genomic mechanisms associated with antifungal resistance among NAC isolates recovered from HIV-positive patients in Southwestern Uganda.

Methods

This protocol describes a laboratory-based cross-sectional genomic study involving archived and prospectively collected NAC isolates obtained from HIV-positive patients attending Mbarara, Kabale, and Fort Portal Regional Referral Hospitals. Clinical isolates will undergo phenotypic identification and antifungal susceptibility testing using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Approximately 390 clinical isolates and 100–150 environmental samples will be included. Isolates demonstrating phenotypic resistance to one or more antifungal agents, together with representative susceptible isolates, will undergo whole genome sequencing using Illumina platforms. Bioinformatics analyses will be performed using established pipelines to identify mutations in resistance-associated genes, including ERG11, FKS1, FKS2, CDR1, CDR2, MDR1, and PDR1. Genotype–phenotype associations between identified mutations and antifungal susceptibility profiles will subsequently be evaluated using appropriate statistical methods.

Discussion

This study will generate the first comprehensive genomic dataset describing antifungal resistance mechanisms among NAC isolates from HIV-positive patients in Uganda. By integrating phenotypic susceptibility testing with whole genome sequencing, the study will improve understanding of resistance pathways circulating within high-risk HIV populations. The findings are expected to strengthen fungal disease surveillance, inform antifungal stewardship programmes, guide evidence-based treatment decisions, and support the development of context-specific diagnostic and therapeutic guidelines for candidiasis management in resource-limited settings.

Trial Registration

Ethical approval will be sought from the Mbarara University of Science and Technology Research Ethics Committee and the Uganda National Council for Science and Technology. At the time of manuscript submission, participant recruitment had not commenced.
Keywords Non-albicans Candida, HIV, antifungal resistance, whole genome sequencing, genomic epidemiology, Uganda, antifungal stewardship.
Field Medical / Pharmacy
Published In Volume 7, Issue 3, May-June 2026
Published On 2026-06-26
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E-ISSN 3048-7641
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