Hematopoietic stem cell transplantation for HIV cure

Kuritzkes, Daniel R.

doi:10.1172/jci80563

Cited by 40 publications

(33 citation statements)

References 61 publications

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“…Transplantation of HIV-protected cells in the autologous setting is safer than allogeneic transplantation and more readily available for patients (8)(9)(10). We have developed a model of cART-suppressed simian-human immunodeficiency viremia in the pigtail macaque (Macaca nemestrina).…”

Section: Introductionmentioning

confidence: 99%

Loss of immune homeostasis dictates SHIV rebound after stem-cell transplantation

Peterson¹,

Benne²,

Polacino³

et al. 2017

JCI Insight

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Section: Introductionmentioning

confidence: 99%

Loss of immune homeostasis dictates SHIV rebound after stem-cell transplantation

Peterson¹,

Benne²,

Polacino³

et al. 2017

JCI Insight

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“…The near-full-length HIV-1 envelope sequence from the viral rebound in both patients was related to HIV-1 DNA sequences before HSCT. The treatment interruption gave rise to some appreciable lessons (Kuritzkes, 2016): (i) HSCT may have decreased HIV-1 reservoir, but there was some degree of virus persistency in infected cell or tissue, (ii) a small number of infected cells seemed to be sufficient to trigger HIV-1 replication upon ART interruption, (iii) limited sensitivity of assay to detect tissue reservoirs that persist in compartments of the cells, (iv) the longer the interval between HSCT and ART interruption, the longer the period the HIV remission would have taken place, and (v) newer approaches to assess the extent of HIV-1 reservoir depletion after therapeutic interventions should be considered.…”

Section: Boston Patientsmentioning

confidence: 99%

“…On day 391, he received HSCT again from the same donor, with a single dose of whole-body irradiation, which ultimately led to complete eradication of his AML. Two years after the transplantation, HIV-1 RNA and proviral DNA were no longer found in his blood, bone marrow or rectal mucosa using PCR assays (Kuritzkes, 2016;Martinez-Vesga, 2018). This phenomenon concluded that the donor-derived cells (CCR5 32 mutation) had successfully replaced Brown's HIV-1 infected cells.…”

Section: Berlin Patientmentioning

confidence: 99%

Lessons Learned From Failures and Success Stories of HIV Breakthroughs: Are We Getting Closer to an HIV Cure?

Kalidasan

Das

2020

Front. Microbiol.

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There is a continuous search for an HIV cure as the success of ART in blocking HIV replication and the role of CD4 + T cells in HIV pathogenesis and immunity do not entirely eradicate HIV. The Berlin patient, who is virus-free, serves as the best model for a 'sterilizing cure' and many experts are trying to mimic this approach in other patients. Although failures were reported among Boston and Essen patients, the setbacks have provided valuable lessons to strengthen cure strategies. Following the Berlin patient, two more patients known as London and Düsseldorf patients might be the second and third person to be cured of HIV. In all the cases, the patients underwent chemotherapy regimen due to malignancy and hematopoietic stem cell transplantation (HSCT) which required matching donors for CCR5 32 mutation-an approach that may not always be feasible. The emergence of newer technologies, such as long-acting slow-effective release ART (LASER ART) and CRISPR/Cas9 could potentially overcome the barriers due to HIV latency and persistency and eliminate the need for CCR5 32 mutation donor. Appreciating the failure and success stories learned from these HIV breakthroughs would provide some insight for future HIV eradication and cure strategies.

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“…As is reviewed by Daniel Kuritzkes in this issue (40), elimination of the latent reservoir in this patient likely involved the conditioning regimen given prior to transplant as well as the graft-versus-host reactions that occurred following transplant. Together, these factors resulted in complete or near-complete replacement of the host immune system (including latently infected cells) with HIV-resistant donor cells.…”

Section: The Latent Reservoir As a Barrier To Curementioning

confidence: 99%