Treatment of HIV-1 Infection by Allogeneic Stem Cell Transplantation
Treatment of HIV-1 Infection by Allogeneic CCR5-∆32/∆32 Stem Cell Transplantation: A Promising Approach.
G. Hütter, D. Nowak, M. Mossner, S. Ganepola, K. Allers, T. Schneider, J. Hofmann, I.W. Blau, W.K. Hofmann, E. Thiel
From the Charité – Medical University of Berlin, Germany
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Homozygosity for CCR5-∆32 is associated with a high but not complete HIV-1 resistance. However,there is still possibility of infection by mutated strains (e.g. X4), but although exposure against X4 transplantation (day –1) and changed to CCR5-∆32/∆32 is frequent, the CCR5 tropic strain dominates during ongoing engraftment after day +61. In the past, the attempts to prolong survival during HIV-1 disease by stem cell transplantation failed. Here, we demonstrate the first successful allogeneic stem cell transplantation in an HIV+ patient with a donor selected to be homozygous for the CCR5-∆32-allele.
The patient managed transplantation and engraftment without any remarkable irregularities.
This switch of CCR5 genotype was not associated with an increased risk in terms of the transplant procedure.The patient developed a functional reconstitution of his R-cell immunity. Finally, although HAART was discontinued for over a period of 285 days, HIV-1-load could not be detected, as determined by RNA and proviral DNA PCR assays of peripheral blood, bone marrow, and rectal mucosa.
first allogeneic stem cell transplantation of a 40-year-old blood progenitor cells from donor 61, identified to be
Our data are highly suggestive that the postulated HIV+ “gatekeeper” mechanism for HIV-1 infection preferring the CCR5-tropic strain, has been re-initiated during engraftment leading to a disruption of virus replication.
This finding provides the role of CCR5 during HIV-1 infection and disease progression and encourages further investigations of the development of CCR5 targeted treatment options.