Single HIV gene therapy may replace lifetime of drug therapy

A phase 2 trial for a radical new, 'one shot' treatment for HIV (human immunodeficiency virus) has shown small but promising results. The research at the University of California, Los Angeles (UCLA), was published in the journal Nature Medicine and was described by the study leader Professor Mitsuyasu as a 'proof of concept' and a reason to continue research in this area.

The technique involved the extraction of white blood stem cells from the patients participating in the study, infecting these cells with a genetically engineered mouse virus called OZ1, which alters the genetic information of the cells in a manner that targets and inactivates HIV genes. These HIV immune cells are then cultured and transfused back into the patients, where they are intended to propagate the immune system with HIV resistant cells as the old infected cells die off.

The study found that after 48 weeks there was no difference between the OZ1 and the placebo groups. However after 100 weeks, even though there was still no statistical difference in viral load, there was a small but significant increase in CD4 cells (the critical immune cells killed by HIV and a standard measure for the severity of a patient's HIV infection.) The study also found that when the patients stopped taking the anti-HIV drugs during one stage of the study, those who had received the dose of gene therapy were able to postpone the reinstatement of their treatment for longer than those who had received the placebo.

Though exciting, Keith Alcorn of the HIV information service NAM, noted that 'the viral load responses in this study were very modest, and for any other sort of product would not justify going forward'. HIV is, however, a highly adaptive virus that is quickly becoming resistant to existing treatments. These retroviral drug treatments, though greatly improving the prognosis for people infected with HIV, are also highly demanding of the patient. Daily dosing, with good time keeping and a stable base of nutrition are required to maintain the effectiveness of the treatment and lapses causes irreparable degradation to health. The possibility of a single shot, once off treatment is, in addition to the need for novel therapies to beat resistance, a major driver behind this research.

It is hope that this new gene therapy may enable a clinical equivalent to the curing of a German patient who needed a bone marrow transplant for leukaemia and received one from an individual with HIV resistance. The 'one shot' treatment might enable not just a much easier means of managing HIV but, potentially, might even become a cure.