Background: Blood group antigens have been implicated in the susceptibility to various infections, including Human immunodeficiency virus (HIV). Understanding the relationship between these antigens and HIV susceptibility can offer insights for better clinical management and potential therapeutic interventions. This study aimed to investigate the association between blood group antigens and the susceptibility to HIV infection in Port Harcourt, River State, Nigeria. Method: A cross-sectional observational study was conducted involving 250 residual blood samples made up of 150 HIV-positive and 100 HIV-negative individuals from the Rivers State University Teaching Hospital. The presence of various blood group antigens was determined using standard serological methods. Statistical analysis was performed using statistical Package for social science (SPSS) version 29 and graphpad prism version 10.Result: The results show association between blood group A antigen with HIV infection (P-value: 0.019), and Rhc(P<0.001). The RhE antigen exhibits an association with HIV infection (, P<0.001) and Rhe antigen (P<0.001). The RhD positive antigen exhibits an association with HIV infection (P<0.015) while RhD negative antigen association with HIV infection (P<0.015). The P value (P<0.001) was observed in the association between HIV infection and blood group M antigen (P<0.001) , O (P<0.010), s antigen (P<0.001) and Fya (P< 0.001), S antigen (P<0.001), RhC antigen (P: <0.001), and Fya-b- (P< 0.001) . Conversely, a significant association with HIV infection was observed in S antigen (P<0.001), RhC antigen (P: <0.001) and Fya-b- (P< 0.001) antigens which were validated by a logistic regression .. Conclusion: The study concluded that certain blood group antigens, particularly Fya-b- and s antigens may be significantly associated with HIV susceptibility. Whereas, antigens such as RhC seem to confer protection against HIV infection. Additionally, consideration should be given to these antigens in the development of new therapeutic strategies.
