An Approach to the Cure of HIV using Cord Blood Hematopoietic Cell Transplantation

Abstract

The patient, Timothy Brown, had acute myeloid leukemia and HIV infection and is now referred to as "The Berlin Patient". It was well known at that time that HIV-1 enters host cells by binding to a CD4 receptor and then interacting with either CCR5 or the CXC chemokine receptor (CXCR4). Homozygosity for a 32-bp deletion (delta32/delta32; CCR5-/-) in the CCR5 allele results in an inactive CCR5 gene product and consequently confers high resistance against HIV-1 infection. Following transplantation using stem cells from an adult donor who had the CCR5-/-mutation, HIV could not be detected in Timothy Brown's peripheral blood, spinal fluid, lymph nodes, bone marrow, brain or GI mucosa as assessed with RNA and proviral DNA PCR assays. Further, there has been no recurrence of HIV in more than 10 years. Thus, the "Berlin Patient" has had a functional cure if not a sterilizing cure of HIV.