HTB

Stem cell transplant from HLA-matched CCR5-delta 32 deleted donor suppresses viraemia in recipient for 8 months without HAART

Simon Collins, HIV i-Base

One of the most interesting and intriguing posters at the conference was a case study presented by Gero Hutter from the Medical University of Berlin.

The patient, a 40-year-old man diagnosed in 1995, experienced a relapse of acute myeloid leukemia (AML) that was first diagnosed in 2006. He underwent allogeneic transplant of peripheral stem cells (alloSCT) with an HLA-matched donor, selected to be homozygous for CCR5-delta 32.

A bone marrow registry search identified 232 individuals who had matched HLA, and PCR identified homozygousity for CCR5-d32. HAART was stopped on the day of the transplant. GvHD prophylaxis followed standard regimens and engraftment was achieved on day 13. Complete chimerism detected by competitive PCR was observed on day 60.

Viral load was measured both by RNA-PCR and proviral DNA-PCR. DNA-PCR was negative from day +68.

Previous attempts to use stem cell transplantation as HIV therapy have failed. Here, the investigators claim to have demonstrated the first successful allogeneic stem cell transplantation in an HIV positive patient with a donor selected to be homozygous for the CCR5-delta-32-allele.

This switch of CCR5 genotype was not associated with any increased transplant risk. The patient developed a functional reconstitution of his T-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. The researchers concluded that by re-initiating a ‘gatekeeper’ mechanism against CCR5 virus, similar to initial challenge, leading to a disruption of virus replication.

Comment

If viraemia remains suppressed during long-term follow-up of this patient, this may the most important report relating to immune/genetic therapy in many years.

While viral load usually rebounds quickly when treatment is stopped, it is important to remember that this is still one uncontrolled case study.

It is unclear whether the latent virus is likely to include CXCR4 tropic strains, though this may not be the case in people treated earlier in infection.

Reference:

Hutter G et al. Treatment of HIV-1 infection by allogeneic CCR5-D32/D32 stem cell transplantation: a promising approach. 15th CROI, 2–6 February 2008. Poster abstract 719.
http://www.retroconference.org/2008/Abstracts/31704.htm (abstract) http://www.retroconference.org/2008/PDFs/719.pdf (PDF poster)

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