期刊
JOURNAL OF INFECTIOUS DISEASES
卷 207, 期 11, 页码 1694-1702出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit086
关键词
HIV-1; viral reservoirs; hematopoietic stem cell transplantation; HIV-1 persistence; CCR5; reduced-intensity allogeneic stem cell transplantation
资金
- National Institutes of Health/National Institute of Allergy and Infectious Disease [1K23AI098480-01A1, UM1 AI068636, P30 AI060354]
- Foundation for AIDS Research [108466 52 RGRL, U19 AI096109]
- Bill and Melinda Gates Foundation [OPP1017716]
- Gilead
- Merck
- Bill and Melinda Gates Foundation [OPP1017716] Funding Source: Bill and Melinda Gates Foundation
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 ccr5 delta 32 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.
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