The so-called "Berlin patient" has been potentially cured of HIV infection and has been off of treatment since 2006 with no detectable virus. This was achieved through two bone marrow transplants that replaced his immune system with a donor's that did not have the CCR5 cell surface receptor, which is needed for some variants of HIV to enter a cell. Bone marrow transplants carry their own significant risks including potential death and was only attempted because it was necessary to treat a blood cancer he had. Attempts to replicate this have not been successful and given the risks, expense and rarity of CCR5 negative donors, bone marrow transplant is not seen as a mainstream option. It has inspired research into other methods to try to block CCR5 expression through gene therapy. A procedure zinc-finger nuclease-based gene knockout has been used in a Phase I trial of 12 humans and led to an increase in CD4 count and decrease in their viral load while off antiretroviral treatment. Attempt to reproduce this failed in 2016. Analysis of the failure showed that gene therapy only successfully treats 11–28% of cells, leaving the majority of CD4+ cells capable of being infected. The analysis found that only patients where less than 40% of cells were infected had reduced viral load. The Gene therapy was not effective if the native CD4+ cells remained. This is the main limitation which must be overcome for this treatment to become effective.HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene
