HIV Infection Induces Aberrant Myeloid Lineage Differentiation

AbstractIntroduction: Numerous studies on hematopoietic changes caused by HIV infection have focused on immune cell depletion, while research on other hematopoietic lineages development have been sparse and inconclusive. In this study, we used precise markers to detect changes in the distribution of bone marrow hematopoietic stem/progenitor cells in HIV-infected patients and analyzed the dynamic changes of mature cells of each lineages in 782 patients with disease progression. Furthermore, we sought to explore the potential relationship between abnormal development of these lineage cells and survival of HIV patients. Our study provides evidence for a more comprehensive understanding of the effects of HIV on hematopoiesis.

Methods: We included 782 HIV-infected patients who underwent bone marrow aspiration from January 2016 to October 2020 in Zhongnan Hospital, and were followed up until January 2022. Examination including flow cytometry and bone marrow aspiration were performed to detect the development of hematopoietic cells. 509 cases were tested for lymphocyte subsets. According to CD3+CD4+ cell count, 325 patients (63.9%) were in the very low group, 61 patients (12.0%) in the low group, 55 patients (10.8%) in the medium group, and 68 patients (13.4%) in the high group. By January 2022, 84 patients had been lost to follow-up and 425 patients had accurate and complete follow-up data. We analyzed the risk factors for HIV death in 425 patients and established a predictive model.

Results: Flow cytometry analysis showed an increased proportion of granulocytemonocyte progenitors (GMP) but a decreased proportion of common lymphoid progenitors (CLP) in HIV patients. In myelogram, the percentage of granulocytes and granulocytes/erythroid cells (G/E) increased with the decrease of CD3+CD4+ count (both P<0.001). In addition to the increase in cell proportion, we also observed that the morphologic abnormalities in granulocyte increased with the progression of the disease, including toxic granulation, cytoplasmic vacuolization, Intracellular and extracellular plasma (P<0.001), Döhle bodies (P=0.033) and increased lobulation in megakaryocyte (P=0.048). Subsequent LASSO binary logistic regression also confirmed that the increased granulocyte ratio was an important factor in patients' disease.

Conclusion: HIV infection directly or indirectly induces bias on myeloid lineage differentiation. Increased granulocyte ratio is an important risk factor for disease aggravation and death in HIV patients. Our research provide a new perspective for evaluating the status and prognosis of HIV patients by focusing on the changes of myeloid granulocytes.

Disclosures No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.