Potential of Stem Cells to Cure HIV

Source: www.timesofindia.com

Looked upon as a potential cure for HIV, the CCR5 gene and its deletion allele (CCR5-∆32) have been much studied since their discovered involvement in HIV infection. Approximately 5% to 14% of Europeans have the CCR5-∆32 allele, but it is absent in African, East Asian, and Native American populations. The mutation is thought to have arisen over 5000 years ago, casting aside theories that it was caused by positive selection during the bubonic plague (Sabeti et al., 2005). While heterozygous CCR5-∆32 individuals (having only one copy of CCR5-∆32) lessen HIV infection, individuals homozygous for CCR5-∆32 confer very high HIV resistance, though they make up approximately only 1% of the European population (Hütter et al., 2009; Liu et al., 1996; Lederman et al., 2006). Homozygous individuals have no apparent health problems. Based off of the known resistance the CCR5-∆32 mutation creates, anti-HIV drugs have been created that bind the CCR5 receptor, preventing HIV binding (Lederman et al., 2006).
A few weeks ago it was reported that a 40-year-old Caucasian patient with leukemia and HIV underwent hematopoietic stem cell transplants using peripheral blood from a donor homozygous for CCR5-∆32 and, over 20 months later, not only has the leukemia gone into complete remission, but the patient has no HIV detectable in his body either (Hütter et al., 2009). Before the transplant, the patient was on highly active antiretroviral therapy (HAART), the combined use of several antiretroviral drugs that has been found most effective in decreasing mortality rates caused by AIDS (Palella et al., 1998). The patient ceased taking HAART immediately prior to undergoing chemotherapy, due to the toxicity of the powerful drugs, but after the following stem cell transplant he has not since resumed the therapy and there have been no detectable signs of HIV in his system. The CCR5-∆32 homozygous hematopoietic stem cells appear to have replaced his irradiated immune system with CCR5-∆32 homozygous, HIV-resistant cells. Previously, hematopoietic stem cell transplants have been attempted to cure patients with both HIV and leukemia with some success (Sorà et al., 2001; Huzicka, 1997), but none used CCR5-∆32 homozygous donors.
References

Hütter, G., Nowak, D., Mossner, M., Ganepola, S., Müßig, A., Allers, K., Schneider, T., Hofmann, J., Kücherer, C., Blau, O., Blau, I. W., Hofmann, W. K., and Thiel, E. Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation. N. Engl. J. Med. 2009. 360:692-8.

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