Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation

In the past, there were several attempts to control HIV-1 infection by means of allogeneic stem-cell transplantation without regard to the donor’s CCR5 delta32 status, but these efforts were not successful. In our patient, transplantation led to complete chimerism, and the patient’s peripheral-blood monocytes changed from a heterozygous to a homozygous genotype regarding the CCR5 delta32 allele. Although the patient had non–CCR5-tropic X4 variants and HAART was discontinued for more than 20 months, HIV-1 virus could not be detected in peripheral blood, bone marrow, or rectal mucosa, as assessed with RNA and proviral DNA PCR assays. For as long as the viral load continues to be undetectable, this patient will not require antiretroviral therapy. Our findings underscore the central role of the CCR5 receptor during HIV-1 infection and disease progression and should encourage further investigation of the development of CCR5-targeted treatment options.” (concluding paragraph)

Read more in New England Journal of Medicine, February 12, 2009.

Comment: This 6-page article reports details of a patient in Berlin, who has been in the news recently because he may have been cured of HIV. He had developed leukemia as well as HIV, and needed a bone-marrow transplant for its treatment. His doctor chose a donor who had two copies of the CCR5 mutation (and therefore is largely immune to HIV infection). The transplant was successful for treating the leukemia — and the patient has had undetectable viral load now for 20 months, with no antiretroviral treatment. Previously, when antiretroviral treatment had been discontinued due to other medical problems, viral load had risen to over a million copies.

Of particular interest is that this patient also had CXCR4 virus, which should have been able to infect the transplanted T-cells which had the CCR5 mutation. But no viral load has been detected.

Also see Not an HIV Cure, but Encouraging New Directions, by Jay A Levy, in the same issue. This treatment is too dangerous for widespread use; and also, for most people no suitable donor could be found. But this exceptional case will help direct research toward new treatments that might provide a cure.

Note: Unfortunately the full text of both articles is only available to subscribers to the New England Journal of Medicine.