ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Lentivirus-mediated Gene Transfer in Hematopoietic Stem Cells Is Impaired in SHIV-infected, ART-treated Nonhuman Primates.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Antigen-boosted CD4CAR T cells fail to expand or control viremia in multiple nonhuman primate models of HIV.Blood · 2026Article
- CAR/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection.PLoS pathogens · 2022Article
- The clonal repopulation of HSPC gene modified with anti-HIV-1 RNAi is not affected by preexisting HIV-1 infection.Science advances · 2020Article
- Assessment and streamlined preparation of low-cytotoxicity lentiviral vectors for mobilized human hematopoietic stem cell transduction.Experimental hematology · 2020Article
- Rapid Transduction and Expansion of Transduced T Cells with Maintenance of Central Memory Populations.Molecular therapy. Methods & clinical development · 2020Article
- Autologous, Gene-Modified Hematopoietic Stem and Progenitor Cells Repopulate the Central Nervous System with Distinct Clonal Variants.Stem cell reports · 2019Article
- Genetic Strategies for HIV Treatment and Prevention.Molecular therapy. Nucleic acids · 2018Review
- A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates.Science translational medicine · 2017Article
- Article
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- Stem cell-based therapies for HIV/AIDS.Advanced drug delivery reviews · 2016Review
- Article
- Multilineage polyclonal engraftment of Cal-1 gene-modified cells and in vivo selection after SHIV infection in a nonhuman primate model of AIDS.Molecular therapy. Methods & clinical development · 2016Article
- Lack of viral control and development of combination antiretroviral therapy escape mutations in macaques after bone marrow transplantation.AIDS (London, England) · 2015Article
- Progress toward curing HIV infection with hematopoietic cell transplantation.Stem cells and cloning : advances and applications · 2015Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies have demonstrated that genetically modified hematopoietic stem cells (HSCs) can reduce HIV viremia. We have developed an HIV/AIDS-patient model in Simian/human immunodeficiency virus (SHIV)-infected pigtailed macaques that are stably suppressed on antiretroviral therapy (ART: raltegravir, emtricitabine and tenofovir). Following SHIV infection and ART, animals undergo autologous HSC transplantation (HSCT) with lentivirally transduced cluster of differentiation (CD)34(+) cells expressing the mC46 anti-HIV fusion protein. We show that SHIV(+), ART-treated animals had very low gene marking levels after HSCT. Pretransduction CD34(+) cells contained detectable levels of all three ART drugs, likely contributing to the low gene transfer efficiency. Following HSCT recovery and the cessation of ART, plasma viremia rebounded, indicating that myeloablative total body irradiation cannot completely eliminate viral reservoirs after autologous HSCT. The kinetics of recovery following autologous HSCT in SHIV(+), ART-treated macaques paralleled those observed following transplantation of control animals. However, T-cell subset analyses demonstrated a high percentage of C-C chemokine receptor 5 (CCR5)-expressing CD4(+) T-cells after HSCT. These data suggest that an extended ART interruption time may be required for more efficient lentiviral transduction. To avoid complications associated with ART interruption in the context of high percentages of CD4(+)CCR5(+)T-cells after HSCT, the use of vector systems not impaired by the presence of residual ART may also be beneficial.
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