Eradication of HIV by Transplantation of CCR5-Deficient Hematopoietic Stem Cells

Abstract

Today, 30 years after the onset of the HIV pandemic, although treatment strategies have considerably improved, there is still no cure for the disease. Recently, we described a successful hematopoietic stem cell transplantation in an HIV-1–infected patient, transferring donor-derived cells with a natural resistance against HIV infection. These hematopoietic stem cells engrafted, proliferated, and differentiated into mature myeloid and lymphoid cells. To date, the patient has not required any antiretroviral treatment, more than 4 years after allogeneic transplantation. In the analysis of peripheral blood cells and different tissue samples, including gut, liver, and brain, no viral load or proviral DNA could be detected. Our report raises the hope for further targeted treatment strategies against HIV and represents a successful personalized treatment with allogeneic stem cells carrying a beneficial gene. However, this case has ignited a controversy regarding the question of whether this patient has achieved complete eradication of HIV or not. Here we give an update on open questions, unsolved aspects, and clinical consequences concerning this unique case.

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

“…The role of each one of these parameters must be dissected, as they all may have contributed to the Berlin patient's cure (5). The Berlin patient was removed from cART concurrent with his first transplant in February of 2007, when transplant-dependent immunodeficiency was most pronounced and the patient had not yet engrafted the donor cells which would facilitate the control of HIV (6). Thus, virus eradication/stable remission may have been achieved immediately following chemo-and radiotherapy conditioning regimens and allogeneic transplantation with CCR5 Δ32 donor cells.…”

Lentivirus-mediated Gene Transfer in Hematopoietic Stem Cells Is Impaired in SHIV-infected, ART-treated Nonhuman Primates

“…5,6 To date, only a limited number of studies have specifically examined the putative therapeutic benefit of conducting autologous HSCT in the context of reducing viral reservoirs in HIV-1-infected patients [7][8][9] Notably, although autologous HSCT has been the standard approach for treating HIV-1-infected patient with NHL and HL, the elimination of viral reservoirs has yet to be reported. 10 The potential to eliminate viral reservoirs following autologous transplantation of genetically modified hematopoietic stem cells (HSCs) has garnered a renewed optimism for the development of a curative strategy for HIV/AIDS. 11,12 Allogeneic HSCT from a CCR5Δ32 donor to a HIV-1-infected patient with acute myelogenous leukemia (AML) was shown to induce a functional cure.…”

Novel Approaches Based on Autologous Stem Cell Engineering and Gene- Modification; Evidence for the Cure of HIV/AIDS

“…Cc-chemokine receptor-5 (CCR5) -known as a main co-receptor in HIV-1 infection-because homozygote 32bp deletion (Δ32) in both allele of CCR5 provide natural resistance to HIV-1 infection [10][11][12]. This resistance was applied in Berlin patient that transplanted by allogeneic hematopoietic stem cell (HSC)from a donor with CCR5 Δ32/Δ32genotype to HIV-1 infected patient and introduced effective cure in the absent of ART [13][14][15][16][17]. Afterwards, same strategy was exhibited satisfactory results for HIV-1 treatment in Boston patients [18].…”