An abstract released recently reports findings that may have the “potential to reconstitute the immune system” of HIV patients. While the results are preliminary, a small cohort of HIV patients who were administered gene therapy aimed at creating CD4-positive T cells (the target of HIV) subsequently experienced a long-lasting increase in the total number of immune cells circulating within the body. The researchers utilized zinc finger nucleases (ZFNs) – a class of engineered DNA-binding proteins that facilitate targeted editing of the genome by creating double-strand breaks in DNA at pre-specified locations – to try to mimic the results achieved by the one and only patient to ever be cured of HIV. (In 2008, an HIV-positive patient developed an unrelated acute myeloid leukemia. To treat the leukemia, doctors performed a stem cell transplant from a donor purposely chosen for the delta32 mutation on their CCR5 gene to observe its effects on the HIV. After 3.5 years, there is no sign that the HIV has returned.) In this study, researchers extracted immune cells from nine patients, all of whom had well-controlled HIV but less than optimal CD4 cell counts, and modified them using the ZFNs delivered via a viral vector to induce a CCR5 delta32 mutation. The modified or mutated cells were returned to the patients in three separate cohorts. The first group of three received between 5 and 10 billion cells, the second received 20 billion, and the final three received 30 billion. The results? An immediate and long-lasting increase in the number of CD4 cells with no reported safety issues! The most important outcome, however, was the fact that five of the nine patients had CD4 cell counts above 500 cells per microliter – the level that up until this year was used as a benchmark for beginning antiretroviral therapy. Ongoing trials will look at whether this increase in CD4 cells actually produced an immunity to HIV, a factor not included in the prior study. At this point, it’s hard to say for sure whether this outcome has any real significance to HIV patients. However, “the concept that you can improve the immune response in HIV” has great potential according to Douglas Ward, MD, of the Dupont Circle Physician’s Group in Washington.