Co‐Occurrence of HIV‐Susceptibility and ‐Protective HLA Alleles Is a Possible Contributor to the Development of Primary HIV‐Associated Thrombocytopenia (PHAT): A Cross‐Sectional Study

Primary HIV-associated thrombocytopenia (PHAT) is an isolated thrombocytopenia in HIV-positive individuals in the absence of secondary causes. The presence of certain Human Leukocyte Antigens (HLA) has been linked to individuals' immune response to HIV and the development of immune-mediated thrombocytopenic disorders. Considering the established associations between HLA and HIV infection and HLA and immune-mediated thrombocytopenias, we hypothesise that specific HLA alleles may also increase the risk of developing PHAT, a condition that links both HIV and immune-mediated thrombocytopenia. Therefore, the study aimed to determine the frequency of high-resolution HLA alleles in patients presenting with possible PHAT. Following a detailed screening process, we evaluated the HLA profiles of 43 participants with probable PHAT using the Axiom Precision Medicine Diversity Array (PMDA) Kit on the GeneTitan Multi-Channel instrument. No single HLA allele was found to be more prominent in our PHAT population. However, 93.02% of participants had both HIV-protective and HIV-susceptible alleles. The potential mechanism causing thrombocytopenia to be the only clinically relevant haematological abnormality in these patients remains to be explored. We concluded that the presence of both an HIV-protective and HIV-susceptibility allele in the same individual may cause antagonistic immune reactions, resulting in thrombocytopenia in HIV-positive individuals. We propose future long-term follow-up studies to determine the progression and outcome in patients with PHAT.