Two people whose CD4 T-cells were modified to make them resistant to HIV entry experienced substantial CD4 cell gains and were able to maintain viral suppression after interruption of antiretroviral therapy (ART), according to a late-breaker presentation yesterday at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Denver.
People with a naturally occurring genetic mutation known as CCR5-delta-32 – present in about 10% of Europeans – do not produce this co-receptor. Individuals with two copies of the mutation (one inherited from each parent) may be elite controllers who maintain undetectable viral load without treatment, whilst those with one copy may have lower than normal virus levels.
Researchers have attempted to replicate this natural phenomenon as a potential strategy for curing HIV. The Berlin patient, who received stem cell transplants to treat leukemia from a bone marrow donor with a double CCR5-delta-32 mutation, appears to be free of HIV several years after stopping ART.
The zinc finger technique aims to produce the same effect by using 'molecular scissors' to disrupt the normal CCR5-producing gene in chromosomes of T-cells (or ultimately the hematopoietic stem cells that give rise to all immune cells). A portion of CD4 cells are collected through apheresis, treated with the zinc finger protein in a lab and the modified and multiplied cells – known as SB-728-T – are then returned to the patient.
