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Treatment of HIV-1 Infection by Allogeneic CCR5-D32/D32 Stem Cell Transplantation: A Promising Approach
Gero Hutter*, D Nowak, M Mossner, S Ganepola, K Allers, T Schneider, J Hofmann, I Blau, W K Hofmann, and E Thiel
Med Univ of Berlin, Germany

Background: In the past, first approaches to decelerate the HIV-1 disease by allogeneic stem cell transplantation (allo SCT) failed. Here, we report a 40-year-old man with HIV-1 infection since 1995 having a relapse of acute myeloid leukemia (AML) first diagnosed in 2006. He underwent allogeneic stem cell transplant (alloSCT) with a donor selected to be homozygous for CCR5-δ32.

Methods: The request at the Bone Marrow Donor Registry revealed 232 HLA-identical donors for this patient. Donors were screened for the deletion using a genomic polymerase chain reaction (PCR) assay. The patient received peripheral stem cells from donor #61, identified to be homozygous for CCR5-δ32. HAART was stopped from day of transplantation. To determine co-receptor usage of the patients` HIV-1 phenotype, the V3 region of the HIV-1 env gene was amplified. The susceptibility of peripheral blood mononuclear cells (PBMC) towards infection was determined by limiting dilution experiments using defined HIV-1 strains. Quantification of HIV-1 infection was measured by measurement of HIV-1 RNA and proviral cDNA using the env and long terminal repeat (LTR) region in peripheral blood, bone marrow, and rectal mucosa.

Results: With ongoing engraftment, CCR5-polymerase chain reaction (PCR) patterns of PBMC transformed into a homozygous δ32/δ32 genotype. From rectal biopsies, taken on day +145, macrophages showed an expression of CCR5, whereas a remarkable CCR5-expressing population could not be found on the mucosal CD4+ T cells. Analysis of HIV-1 co-receptor phenotype indicates a CCR5 usage of our patients` HIV-1 strain. After engraftment, PBMC were not susceptible for CCR5-tropic strains. During the whole follow-up period, measurement of serum HIV-1-RNA remained negative and the semi-quantitative proviral DNA assay was under the limit of detection since day +61.

Conclusions: We could demonstrate the first successful performance of an allogeneic stem cell transplantation in an HIV+ patient with a donor selected to be homozygous for the CCR5-δ32-allele. The switch of the patients CCR5 genotype was not associated with an increased risk regarding the transplant procedure. Although HAART is discontinued since more than 200 days, HIV-1-load could not be detected in peripheral blood, bone marrow, and rectal mucosa. Our data are highly suggestive that the postulated “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 a possible therapeutic option for HIV-infected patients.


http://www.retroconference.org/2008/Abstracts/31704.htm

Metodo interessante,ma molto rischioso (si può uccidere il paziente solo col trapianto) e costoso.
Vedremo cosa ne verrà fuori.