Back in March 2010, the laboratory of Kathleen Collins at the University of Michigan published a paper in Nature Medicine suggesting that CD34+ hematopoietic progenitor cells can be infected with HIV and represent a reservoir of virus in some individuals on ART (4 out of 9 participants in their study). The paper generated a great deal of press coverage at the time, with headlines such as “HIV Hides Out in Bone Marrow Cells” and multiple outlets featuring interviews with Collins describing the findings.
Today in the Journal of Infectious Diseases, the laboratory of Bob Siliciano at Johns Hopkins—which has been investigating HIV persistence and latency since the mid-90s—offers compelling evidence that HIV infection of CD34+ hematopoietic progenitor cells is an extremely rare event (if it occurs at all). The study authors, led by Christine Durand from the Siliciano lab, show that HIV can be detected in some CD34+ cell preparations from individuals on ART due to contamination of the samples by HIV-infected CD4+ T cells. In contrast, no evidence of HIV infection could be found in highly purified CD34+ cells from any of their 11 study participants. The researchers write: “We can conclude that in the majority of HIV-1 subtype-B–infected patients on ART, the frequency of HIV-infected CD34+ is <0.002%. These conclusions extend a large body of clinical and translational data reported over the past 2 decades, indicating that CD34+ cells do not constitute a significant reservoir for HIV-1 in vivo.” Durand and colleagues suggest that the previous results reported in Nature Medicine are most likely explained by low-level contamination of CD34+ cell preparations with HIV-infected CD4+ T cells.
J Infect Dis. (2012)
First published online: January 24, 2012
Christine M. Durand1, Gabriel Ghiaur1, Janet D. Siliciano1, S. Alireza Rabi1, Evelyn E. Eisele1,3, Maria Salgado1, Liang Shan1, Jun F. Lai1, Hao Zhang4, Joseph Margolick4, Richard J. Jones2, Joel E. Gallant1, Richard F. Ambinder2 and Robert F. Siliciano1,5
1Department of Medicine
2Department of Oncology, The Sidney Kimmel Cancer Center
3Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine
4Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Public Health
5Howard Hughes Medical Institute, Baltimore, Maryland
Identifying cellular reservoirs of human immunodeficiency virus type 1 (HIV-1) in patients on antiretroviral therapy (ART) is critical to finding a cure for HIV-1. In addition to resting CD4+ T cells, CD34+ hematopoietic progenitor cells have been proposed as another reservoir. We obtained bone marrow aspirates from 11 patients on ART who had undetectable plasma HIV-1 RNA. HIV-1 DNA was detected in CD4+ T cells from peripheral blood in all patients and from bone marrow cellular fractions containing T cells in most patients. We did not find HIV-1 DNA in highly purified CD34+ populations using either a sensitive real-time polymerase chain reaction assay or a coculture assay for replication-competent HIV-1.