Characterization and role analyses of classical human leucocyte antigen in HIV molecular epidemiology, drug resistance and Molecular adaptation in Ghana
Genetic data have increasingly provided important scientific insights that have influenced patient management. With regards to HIV infection and AIDS, knowledge gained from studies into host factors involved in HIV replication have served to provide potential therapeutic targets to suppress replication of the virus. Furthermore, immunogenetic studies have shown that polymorphisms occur in HIV sequences that become selected in a reproducible manner, all as a result of pressure exerted by specific HLA allele. Such HLA-associated polymorphisms lead to viral escape and persistence; but HIV immune escape is known to incur viral fitness cost.
According to studies, the HLA class I and class II alleles have been differentially associated with HIV-1 disease outcomes in different populations. Identification of HLA alleles present in different ethnic populations is thus crucial for the ongoing efforts towards designing CTL-based anti-HIV vaccine. To date, findings on HLA-driven escape pathways in HIV sequences and the consequent functional costs are largely limited to HIV subtype B; and, to some extent, subtype C, but none yet in other major HIV-1 subtypes such as the CRF02_AG, which is the dominant type in Ghana and the West African sub-region. This study represents the first comprehensive characterization of HLA in West Africans and HLA-driven adaptation pathways in HIV subtype CRF02_AG predominant population.
The aim of this study is to describe, for the first time, major HLA class I and class II genes associated with control of HIV-1 replication and reveal unique HLA driven HIV-1 CRF02_AG-specific immune escape patterns in Ghanaian HIV sequences and specifically to :
- Characterize plasma HIV RNA sequences along with HLA class I and class II allele and haplotype frequency distributions in Ghanaian HIV-1-infected and healthy individuals at the Fevers Unit of Korle-Bu Teaching Hospital in Accra
- Determine frequency of SARS-CoV-2 in the HIV patients at time of sampling
- Identify HLA alleles and haplotypes that influence outcome of HIV-1 infections in Ghana
- Describe unique immunogenic regions and pathways of HLA-mediated adaptation in HIV-1 CRF02_AG sequences
- Investigate transmitted drug resistance in the studied Ghanaian population using an in-house drug resistance testing approach
Ethics approval has been obtained, samples have been collected and are being analysed.