Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation
New England Journal of Medicine: 360:692-698, DOI: 10.1056/NEJMoa0802905
February 12, 2009
Gero Hütter, M.D., Daniel Nowak, M.D., Maximilian Mossner, B.S., Susanne Ganepola, M.D., Arne Müßig, M.D., Kristina Allers, Ph.D., Thomas Schneider, M.D., Ph.D., Jörg Hofmann, Ph.D., Claudia Kücherer, M.D., Olga Blau, M.D., Igor W. Blau, M.D., Wolf K. Hofmann, M.D., and Eckhard Thiel, M.D.
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. We 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. Read more>>
Challenges in Detecting HIV Persistence during Potentially Curative Interventions:
A Study of the Berlin Patient
PLOS Pathogens: DOI: 10.1371/journal.ppat.100334
May 09, 2013
There is intense interest in developing a cure for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the study of an HIV+ adult who has exhibited evidence of cure after a stem cell transplant. Samples from blood, spinal fluid, lymph node, and gut were analyzed in multiple laboratories using different approaches. No HIV was detected in blood cells, spinal fluid, lymph node, or small intestine, and no infectious virus was recovered from blood. However, HIV was detected in plasma (2 laboratories) and HIV DNA was detected in the rectum (1 laboratory) at levels considerably lower than those expected in antiretroviral treated patients. The occasional, low-level HIV signals might be due to persistent HIV or might reflect false positives. The sensitivity of the current generation of assays to detect HIV RNA, HIV DNA, and infectious virus are close to the limits of detection. Improvements in these tests will be needed for future curative studies. The lack of rebounding virus after five years without therapy, the failure to isolate infectious virus, and the waning HIV-specific immune responses all indicate that the Berlin Patient has been effectively cured.
We thank Steven Lada (UCSD) and Steffney Rought (UCSD) for technical assistance. We also acknowledge Rebecca Hoh, Lorrie Epling, Ma Somsouk, Hiroyu Hatano, Jeffrey Martin, Rick Hecht, Vivek Jain, Richard Price and Peter Hunt for assistance in managing the clinical procedures. Finally, we would like to acknowledge the study participant, who made many sacrifices for this study, and who is very committed to advancing HIV cure research. Read More >>