Since HIV became the worldwide scourge it is today, a very few people have somehow become infected, yet avoided disease progression and in some cases, cleared the infection. Such an observation has also been made in at least one HIV-infected person who received a bone marrow transplant and has subsequently remained virus-free for four years. As Rick and I discuss on PodMed this week, one common denominator among some of these folks is an aberrant receptor needed by HIV to gain entry to T cells, the class of lymphocytes preferentially infected by the virus. As reported in the New England Journal of Medicine, this receptor, CCR5, has been genetically modified in the laboratory in T cells, the cells subsequently infused back into the person from whom they originated, and have been able to survive in spite of existing HIV infection. WOW!
This study enrolled 12 patients who were HIV positive and taking antiretroviral therapy. Each of them received an infusion of autologous CD4 enriched T cells that had been modified with the use of a technology known as 'zinc finger nucleases,' or ZFNs. These amazing reagents can be used to generate specific double-strand cuts in DNA. For this purpose they were used to bind to a site within the human chemokine receptor 5 gene (CCR5) and modify it so that HIV was unable to dock to the receptor. Previous research had shown that lymphocytes modified in this way were still capable of responding to stimulation and otherwise functioned normally. Only one subject experienced an adverse reaction which researchers speculate was a transfusion reaction.
Over time these modified lymphocytes remained alive, HIV DNA decreased in most patients, and in one patient HIV RNA became undetectable. Pretty cool, no? The authors note that future steps need to include modification of both alleles for this receptor, after discovering that the patient whose HIV was rendered silent already possessed one copy of the CCR5 gene that was modified. They further speculate that autologous stem cells could be modified at both alleles and reinfused into patients, or any number of other strategies. What seems clear is that this study brings to fruition a long term goal of genetic modification that could expand well beyond HIV management. Kudos!
Other topics this week include two provocative studies in JAMA on strategies to improve the life of children: the impact of casino opening on obesity in Native American children and the mental health impact in children of moving to more affluent neighborhoods from poverty stricken areas. Our final study was another look at hepatitis C incidence in the United States in Annals of Internal Medicine. Until next week, y'all live well.