Article

Hematopoietic Stem Cells and HIV Infection

Department of Pathology and Laboratory Medicine, Division of Transfusion Medicine & Therapeutic Pathology, 705 Stellar Chance Laboratory, Philadelphia, PA 19104.
The Journal of Infectious Diseases (Impact Factor: 6). 04/2013; 207(12). DOI: 10.1093/infdis/jit120
Source: PubMed

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Available from: jid.oxfordjournals.org
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    ABSTRACT: In this issue of Blood, Nixon and colleagues report on the impact of HIV infection on hematopoiesis. Hematopoietic stem cells (HSCs)/progenitor cells were subjected to HIV infection in vitro and in vivo using a humanized mouse model. They conclude that direct infection of intermediate progenitor cells by HIV adversely affects their hematopoietic potential, resulting in the observed cytopenias in HIV patients.1
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    ABSTRACT: Abstract Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS-related lymphomas, and it represents an opportunity to evaluate strategies curing HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir size and stability during combination antiretroviral therapy (cART) after transplantation are unknown. Aiming to obtain information suggesting new functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in autograft and in peripheral blood before and after transplantation in 13 cART-treated HIV-1 relapse/refractoring lymphoma patients. Among them seven discontinued cART after autograft infusion. HIV-DNA was evaluated by a sensitive quantitative real-time polymerase chain reaction (PCR). After debulking chemotherapy/mobilization, the autograft HIV-1 reservoir was higher than and not associated with the peripheral HIV-1 reservoir at baseline [median 215 HIV-DNA copies/10(6) autograft mononuclear cells, range 13-706 vs. 82 HIV-DNA copies/10(6) peripheral blood mononuclear cells (PBMCs), range 13-479, p=0.03]. After high dose chemotherapy and autograft infusion, HIV-DNA levels reached a plateau between month 6 and 12 of follow-up. No association was found between peripheral HIV-DNA levels at baseline and after infusion in both cART interrupting and not interrupting patients. Only in the last subgroup, a stable significant linear association between autograft and peripheral blood HIV-1 reservoir emerged from month 1 (R(2)=0.84, p=0.01) to month 12 follow-up (R(2)=0.99, p=0.0005). In summary, autograft HIV-1 reservoir size could be influenced by the mobilization phase and predicts posttransplant peripheral HIV-1 reservoir size in patients on continuous cART. These findings could promote new research on strategies reducing the HIV-1 reservoir by using the ASCT procedure.
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