Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation.

J Infect Dis 2013 Jun 4;207(11):1694-702. Epub 2013 Mar 4.

Divison of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: The long-term impact of allogeneic hematopoietic stem cell transplantation (HSCT) on human immunodeficiency virus type 1 (HIV-1) reservoirs in patients receiving combination antiretroviral therapy (cART) is largely unknown.

Methods: We studied the effects of a reduced-intensity conditioning allogeneic HSCT from donors with wild-type-CCR5(+) cells on HIV-1 peripheral blood reservoirs in 2 patients heterozygous for the ccr5Δ32 mutation. In-depth analyses of the HIV-1 reservoir size in peripheral blood, coreceptor use, and specific antibody responses were performed on samples obtained before and up to 3.5 years after HSCT receipt.

Results: Although HIV-1 DNA was readily detected in peripheral blood mononuclear cells (PBMCs) before and 2-3 months after HSCT receipt, HIV-1 DNA and RNA were undetectable in PBMCs, CD4(+) T cells, or plasma up to 21 and 42 months after HSCT. The loss of detectable HIV-1 correlated temporally with full donor chimerism, development of graft-versus-host disease, and decreases in HIV-specific antibody levels.

Conclusions: The ability of donor cells to engraft without evidence of ongoing HIV-1 infection suggests that HIV-1 replication may be fully suppressed during cART and does not contribute to maintenance of viral reservoirs in peripheral blood in our patients. HSCTs with wild-type-CCR5(+) donor cells can lead to a sustained reduction in the size of the peripheral reservoir of HIV-1.

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jit086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636784PMC
June 2013
22 Reads

Publication Analysis

Top Keywords

peripheral blood
20
hiv-1
9
donor cells
8
conditioning allogeneic
8
stem cell
8
cell transplantation
8
months hsct
8
hiv-1 dna
8
reduced-intensity conditioning
8
reservoirs patients
8
size peripheral
8
peripheral
6
cells
5
blood
5
hsct
5
temporally full
4
dna rna
4
rna undetectable
4
undetectable pbmcs
4
cd4+ cells
4

References

(Supplied by CrossRef)

Margolis et al.
2011
Article in Topics in HIV medicine : a publication of the International AIDS Society, USA
Siliciano et al.
Topics in HIV medicine : a publication of the International AIDS Society, USA 2010
Article in Blood
Blood 2010
Article in New England Journal of Medicine
Hutter et al.
New England Journal of Medicine 2009
Article in Antiviral therapy
Antiviral therapy 2012
Article in Clinical Infectious Diseases
Clinical Infectious Diseases 2010
Article in Haematologica
Gabarre et al.
Haematologica 2004
Article in Annals of Internal Medicine
Holland et al.
Annals of Internal Medicine 1989
Article in Bone marrow transplantation
Contu et al.
Bone marrow transplantation 1993
Article in AIDS (London, England)
Avettand-Fenoel et al.
AIDS (London, England) 2007
Article in Medical hypotheses
Huzicka et al.
Medical hypotheses 1999

Similar Publications