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HIV-Related Research in the Division of Blood Diseases and Resources (DBDR)

HIV-Focused Research Goals

AIDS-related research in the Division of Blood Diseases and Resources (DBDR) encompasses a broad spectrum of topics ranging from basic biology to medical management of blood diseases and the use of blood (hematopoietic stem/progenitor cell-based transplants, T-cells) based-therapies. A major focus of AIDS-related activities in DBDR has been improving the adequacy and safety of the nation's blood supply. DBDR supports pivotal research in transfusion medicine and blood banking, including research to evaluate blood donation screening, manufacturing, and processing technologies. DBDR also has a major responsibility for supporting research in hematopoiesis and hematopoietic cell biology and disease. This includes hematopoietic stem cell transplantation research and the application of stem cell/progenitor cell biology findings to the development of novel cellular therapy approaches to potentially cure chronic diseases such as HIV.

Previously Funded Studies

Research on blood and HIV has focused in great part on transfusion safety and has led to an understanding of staging of the infection, the development and evaluation of new assays for detection of HIV markers among blood donors and transfusion recipients, and a better understanding of the natural history and pathogenicity of HIV infection.

Among the major advances resulting from the conduct of NHLBI-supported studies (including the Retrovirus Epidemiology Donor Study (REDS)external disclaimer and its successor, REDS-II) are: development/refinement of the incidence-window period models that have been employed globally to estimate residual risk of transfusion-transmitted HIV; establishment of HIV replication dynamics (doubling time during the so-called "ramp-up viremia") and a staging classification system (Fiebig Staging) to classify newly diagnosed persons, which is now used worldwide; contribution to the development of nucleic acid amplification technology (NAT) for HIV, hepatitis viruses, and other emerging pathogens and, projection and subsequent documentation of substantial reduction in the infectious window period risk by NAT screening; and establishment of the concept of transmitted/founder (T/F) viruses as well as studies of clusters of HIV infected blood donors and transfusion recipients, which contributed to the understanding of HIV quasispecies, bottleneck of transmission, and rates and viral and immune correlates of quasispecies evolution.

Future Directions

Selected blood-related research examples of interest to the NHLBI AIDS Program include, but are not limited to, studies that:

  • Assess the epidemiology of the prevalence of cytopenias and correlation with other markers of non-infectious HIV complications
  • Investigate the pathogenesis of HIV related cytopenias
    • Primary stem cell defects
    • Reversible/irreversible changes in stem cells or the microenvironment
    • Role of inflammation
  • Understand the incidence/prevalence of venous/arterial thrombosis in HIV-infected patients
  • Explore mechanisms of HIV-related coagulation abnormalities and thrombosis events
  • Investigate stem cells as potential HIV reservoirs
    • Infectivity of defined subsets of stem cells
    • Mechanisms of HIV resistance of hematopoietic stem cells/progenitor cells
    • Role of xenograft experiments in defining functionally important resistant cells
  • Develop novel therapies for HIV-related cytopenias
  • Seek innovative approaches to cure HIV-1
    • Autologous stem cell transplant
      • Better processes for purification
      • Production and expansion
      • Genetic modification
      • Safer and effective autologous transplantation in non-malignant settings
    • Allogeneic stem cell transplant
      • Correlation between extent of allogeneic mismatch, allogeneic reactivity, and clinical Graft versus Host Disease (GvHD) with reduction in proviral DNA
      • Safer and effective allogeneic transplantation in non-malignant settings
    • T-cell therapies

Accordingly, future research on the interaction between HIV and both the vascular endothelium and hematopoietic cell elements could lead to a greater understanding of the impact of HIV on stem cell development, endothelial perturbation leading to activation of coagulation and thrombosis, and the microbiome; as well as lead to the discovery of innovative cell and gene therapies for the eradication and cure of HIV.

Selected HIV-Related Publications Supported by the NHLBI DBDR

  • Kleinman S, King MR, Busch MP, Murphy EL, Glynn SA; National Heart Lung Blood Institute Retrovirus Epidemiology Donor Study; Retrovirus Epidemiology Donor Study-II. The National Heart, Lung, and Blood Institute retrovirus epidemiology donor studies (Retrovirus Epidemiology Donor Study and Retrovirus Epidemiology Donor Study-II): twenty years of research to advance blood product safety and availability. Transfus Med Rev 2012; 26(4):281-304.
  • Glynn SA, Kleinman SH, Schreiber GB, Busch MP, Wright DJ, Smith JW, Nass CC, Williams AE. Trends in incidence and prevalence of major transfusion-transmissible viral infections in US blood donors, 1991 to 1996. Retrovirus Epidemiology Donor Study (REDS). JAMA 2000; 284(2):229-35.
  • Fiebig EW, Satten GA, Wright D, Rawal BD, Garrett PE, Heldebrant C, Smith R, Conrad A, Kleinman SH, Busch MP. Dynamics of HIV Viremia and Antibody Seroconversion in Plasma Donors: Implications for Diagnosis and Staging of Primary HIV Infection. AIDS 2003; 17:1871-1879.
  • Delwart E, Slikas E, Stramer SL, Kamel H, Kessler D, Krysztof D, Tobler LH, Carrick D, Steele W, Todd D, Wright DJ , Kleinman SH, and Busch MP for the NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II) Genetic diversity of recently acquired and prevalent HIV, HBV and HCV infections 1 in US blood donors. JID 2012; 205:875-885.
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