Characterising the HIV Reservoir in Long-Term Nonprogressors and Elite Controllers in Nigeria: Implications for Functional Cure Strategies

HIV long-term nonprogressors (LTNPs) and elite controllers (ECs) suppress HIV replication naturally without antiretroviral therapy, representing a biological model for understanding HIV reservoir dynamics and immune-mediated control relevant to functional cure research. Nigerian LTNPs and ECs have not been systematically characterised, and their reservoir and immunological profiles are entirely unknown. This study establishes the first Nigerian cohort of LTNPs and ECs and comprehensively characterises the HIV reservoir and immune control mechanisms in these individuals. HIV-positive individuals not on ART with CD4 counts above 500 cells per microlitre for more than ten years will be recruited through national ART programme databases across Lagos, Abuja, and Kano. HIV-1 total DNA, integrated proviral DNA, and replication-competent reservoir (quantitative viral outgrowth assay) will be quantified. High-resolution characterisation of T cell receptor repertoires, exhaustion markers, and clonotypic specificity by CITE-seq will be performed. Viral genomic sequences from reservoir cells will be analysed for replication fitness defects by site-directed mutagenesis and cell-based assays. Cross-correlation of reservoir size, T cell immunophenotype, and HIV-specific neutralising antibody breadth will generate an integrated immune control signature. This study advances the theoretical understanding of HIV reservoir dynamics in sub-Saharan African genetic and viral diversity contexts and provides a foundation for designing functional cure strategies applicable to West African HIV epidemics. Keywords: HIV reservoir, elite controllers, long-term nonprogressors, functional cure, Nigeria