Hematopoietic stem cell transplantation in HIV-1-infected individuals

Durand, Christine M.; Ambinder, Richard F.

doi:10.1097/cco.0b013e32835d814a

Cited by 12 publications

(6 citation statements)

References 51 publications

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“…In most instances, cART was withheld during delivery of chemotherapy and resumed after resolution of GI toxicity. The few reports of allogeneic HCT in HIV+ patients vary with respect to the use of cART during the procedure but in all cases there was no obvious toxicity or complication related to antiretroviral therapy 5, 7, 10, 37 .…”

Section: Discussionmentioning

confidence: 96%

“…cART interruptions may occur during the transplantation process due to concerns about drug interactions between cART and chemotherapy or immune suppressive drugs, toxicities such as bone marrow suppression, or inability to take oral medications due to nausea and mucositis 8–10 However, there are drawbacks to withholding cART during HCT, most notably the potential for reseeding and repletion of the HIV reservoir 11 and the effects of uncontrolled HIV replication on engraftment and immune reconstitution. Here we report our experience transplanting HIV-infected patients and demonstrate the feasibility and safety of providing uninterrupted cART throughout conditioning and after HCT.…”

Section: Introductionmentioning

confidence: 99%

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Safety and Efficacy of Combination Antiretroviral Therapy in Human Immunodeficiency Virus–Infected Adults Undergoing Autologous or Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

Johnston

Harrington

Jain

et al. 2016

Biology of Blood and Marrow Transplantation

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Introduction The ability to continue combination antiretroviral therapy (cART) in HIV-infected patients undergoing hematopoietic cell transplantation (HCT) for treatment of hematologic malignancies is likely a critical factor in preventing establishment of the HIV reservoir in transplanted stem cells. Thus, we studied the feasibility of continued ART therapy in our HIV-infected patients undergoing autologous or allogeneic transplantation. Methods All HIV-infected adults undergoing HCT for hematologic malignancy at Fred Hutchinson Cancer Research Center (FHCRC) between 2006 and 2014 were included; most were enrolled in a prospective clinical study to monitor HIV reservoirs post-transplant (NCT00968630 & NCT00112593). Non-nucleotide reverse transcriptase inhibitor (NNRTI) or integrase-strand inhibitor (INSTI) anchored ART regimens were continued or selected prior to HCT by Infectious Disease physicians. Plasma HIV RNA was measured every other day for the first two weeks post- transplant, then every two weeks. Missed doses of cART and reasons for changing cART regimen during the post-transplant hospitalization were documented through review of inpatient pharmacy records. Results Seven autologous and eight allogeneic transplants were performed. In 9 transplants, the cART regimen was not altered post HCT and no doses were missed. In 2 patients who required alterations in cART regimen due to development of acute renal failure (n=1) and small bowel obstruction PO (n=1) post-HCT, enfuvirtide was used as a bridging component of the regimen. Plasma HIV RNA remained suppressed during the first 28 days in 12 of 15 transplants, and no patients had a plasma HIV RNA>1000 copies/ml during long-term follow up. Conclusions NNRTI and INSTI based cART is safe and effective in HIV-infected persons during the peri-HCT period. Most patients undergoing HCT were able to continue cART without missed doses. Sustained HIV viremia and emergence of resistance were not detected.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Combination Antiretroviral Therapy in Human Immunodeficiency Virus–Infected Adults Undergoing Autologous or Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

Johnston

Harrington

Jain

et al. 2016

Biology of Blood and Marrow Transplantation

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“…The chemotherapy regimen, believed to kill latently infected cells, cannot account for elimination of the reservoir since no differences in HIV DNA and RNA were observed in HIV+ patients with lymphoma before and after chemotherapy. 4 The graft versus host effect in allogeneic HSCT can theoretically eliminate HIV reservoirs similar to GVL, 2 but concomitant GVHD and the viral rebound that results upon ART treatment interruption 1, 5 is a major barrier. In at least some instances this rebound was quite symptomatic and patients became critically ill.…”

Section: Introductionmentioning

confidence: 99%

Functionally Active HIV-Specific T Cells that Target Gag and Nef Can Be Expanded from Virus-Naïve Donors and Target a Range of Viral Epitopes: Implications for a Cure Strategy after Allogeneic Hematopoietic Stem Cell Transplantation

Patel

Lam

Cruz

et al. 2016

Biology of Blood and Marrow Transplantation

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Allogeneic HSCT can potentially cure HIV by eliminating infected recipient cells, particularly in the context of technologies that may confer HIV resistance to these stem cells. But to date, the Berlin patient remains the only case of HIV cure despite multiple attempts to eradicate infection with HSCT. One approach to improve this is to administer virus-specific T cells, a strategy that has proven success in preventing other infections post-transplant. While we have reported that broadly-HIV-specific T cells can be expanded from HIV+ patients, allogeneic transplants only contain virus-naïve T cells. Modifying this approach for the allogeneic setting thus required a robust, reproducible platform that can expand HIV-specific cells from the naïve pool. Hence, we hypothesized that HIV-specific T cells could be primed ex vivo from seronegative individuals to effectively target HIV. Here, we show that ex vivo primed and expanded HIV specific T cells released IFNγ in response to HIV antigens, and that these cells have enhanced ability to suppress replication in vitro. This is the first demonstration of ex vivo priming and expansion of functional, multi-HIV antigen specific T-cells from HIV negative donors, which has implications for use of allogeneic HSCT as a functional HIV cure.

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“…While there is conflicting evidence on the effect of allogeneic HSCT on HIV infection (reviewed in [96,97]), the idea that complete donor chimerism, if achieved following an allogeneic HSCT, would effectively cure an established HIV infection is an interesting one. For this to occur, the donor cells would likely need to be protected from infection during the transition to complete donor chimerism, and in the case of the ccr5 ∆32 transplant that resulted in a cure, that was achieved by using cells resistant to HIV infection.…”

Section: Graft Vs Hiv: Allogeneic Stem Cell Transplantation and Hmentioning

confidence: 99%

Gene Therapy Targeting HIV Entry

Didigu

Doms

2014

Viruses

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Despite the unquestionable success of antiretroviral therapy (ART) in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT) using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

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Hematopoietic stem cell transplantation in HIV-1-infected individuals

Abstract: HIV-1 infection is not a contraindication to blood and marrow transplantation and may offer unique benefits. Particular attention to preventing infectious complications, drug interactions, and drug interruptions in this patient population is required.

Cited by 12 publications

References 51 publications

Safety and Efficacy of Combination Antiretroviral Therapy in Human Immunodeficiency Virus–Infected Adults Undergoing Autologous or Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

Safety and Efficacy of Combination Antiretroviral Therapy in Human Immunodeficiency Virus–Infected Adults Undergoing Autologous or Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

Functionally Active HIV-Specific T Cells that Target Gag and Nef Can Be Expanded from Virus-Naïve Donors and Target a Range of Viral Epitopes: Implications for a Cure Strategy after Allogeneic Hematopoietic Stem Cell Transplantation

Gene Therapy Targeting HIV Entry

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