HIV This Week

Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, Schneider T, Hofmann J, Kücherer C, Blau O, Blau IW, Hofmann WK, Thiel E. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009;360(7):692-8.

Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. Hütter and colleagues transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a patient with acute myeloid leukemia and HIV-1 infection. The patient remained without viral rebound 20 months after transplantation and discontinuation of antiretroviral therapy. This outcome demonstrates the critical role CCR5 plays in maintaining HIV-1 infection.

Editors’ note: After 20 months, this patient’s CD4+ counts are in the normal range; HIV-1 is not detectable in blood, bone marrow, or rectal mucosa; and the disappearance of the effector T-cells that normally fight HIV suggests that HIV is not around to provoke them. The patient could still be harbouring a CXCR4 type of HIV; many people die from bone marrow transplantation procedures, and people lacking CCR5 may be more susceptible to serious effects from certain infections. Nonetheless, this case will continue to be followed with interest and will no doubt open the door to further innovations in HIV treatment.

Behringer RR, Gonzalez G, Shpall EJ, Gathe J. Cord blood stem cell therapy for acquired immune deficiency syndrome. Stem Cells Dev. 2008. [Epub ahead of print]

Cord blood stem cell transplantation is routinely used to treat hematopoietic diseases. Individuals who are homozygous for the Delta32 polymorphism of the CCR5 locus, encoding a co-receptor for HIV-1, are normal and resistant to HIV infection. Here Behringer and colleagues suggest that public cord blood repositories are likely to contain CCR5 homozygous units that could be used as a therapy for HIV infected individuals.

Editors’ note: Cord blood stem cells, collected non-invasively from the placenta and umbilical cord after separation from a newborn, are less mature and would require less matching between donor and recipient than is the case for a bone marrow transplant. Homozygosity of the CCR5 delta 32 allele (meaning both chromosomes have the same 32 base pair deletion) occurs in 1 to 3% of current cord bank specimens in western populations that have high allele frequencies. The idea of cord stem cells for HIV treatment has yet to be explored but may have some merit.