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J Infect Dis. 2012 Jul 1;206(1):28-34. doi: 10.1093/infdis/jis301. Epub 2012 Apr 25.

Hematopoietic precursor cells isolated from patients on long-term suppressive HIV therapy did not contain HIV-1 DNA.

Author information

  • 1Department of Diagnostics and Vaccinology, Swedish Institute for Communicable Disease Control, Karolinska Institutet, Solna, Sweden.

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.

PMID:
22536001
[PubMed - indexed for MEDLINE]
PMCID:
PMC3415927
Free PMC Article

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