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Lina Josefsson, Susanne Eriksson, Elizabeth Sinclair, Terence Ho, Maudi Killian, Lorrie Epling, Wei Shao, Bradley Lewis, Peter Bacchetti, Lisa Loeb, Jeff Custer, Lauren Poole, Frederick M. Hecht, Sarah Palmer, Hematopoietic Precursor Cells Isolated From Patients on Long-term Suppressive HIV Therapy Did Not Contain HIV-1 DNA, The Journal of Infectious Diseases, Volume 206, Issue 1, 1 July 2012, Pages 28–34, https://doi.org/10.1093/infdis/jis301
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Abstract
Background. We address the key emerging question of whether Lin−/CD34+ hematopoietic precursor cells (HPCs) represent an important latent reservoir of human immunodeficiency virus type 1 (HIV-1) during long-term suppressive therapy.
Methods. To estimate the frequency of HIV-1 infection in bone marrow, we sorted Lin−/CD34+ HPCs and 3 other cell types (Lin−/CD34−, Lin−/CD4+, and Lin+/CD4+) from 8 patients who had undetectable viral loads for 3–12 years. Using a single-proviral sequencing method, we extracted, amplified, and sequenced multiple single HIV-1 DNA molecules from these cells and memory CD4+ T cells from contemporaneous peripheral blood samples.
Results. We analyzed 100 000–870 000 bone marrow Lin−/CD34+ HPCs from the 8 patients and found no HIV-1 DNA. We did isolate HIV-1 DNA from their bone marrow Lin+/CD4+ cells that was genetically similar to HIV-1 DNA from lymphoid cells located in the peripheral blood, indicating an exchange of infected cells between these compartments.
Conclusions. The absence of infected HPCs provides strong evidence that the HIV-1 infection frequency of Lin−/CD34+ HPCs from bone marrow, if it occurred, was <.003% (highest upper 95% confidence interval) in all 8 patients. These results strongly suggest that Lin−/CD34+ HPCs in bone marrow are not a source of persistent HIV-1 in patients on long-term suppressive therapy.
