CTN 229: Effect of AGS-004 immunotherapeutic agent in HIV-positive people on HAART

About The Study

This study assessed the safety and efficacy of AGS-004, an autologous (personalized) HIV immunotherapeutic, in HIV-infected adults who are on highly active antiretroviral therapy (HAART). AGS-004 is created from a person’s own dendritic cells—white blood cells that stimulate the body’s immune system—and a sample of their HIV virus. This is the first experimental treatment designed from a person’s HIV genetic material and their body’s cells.

Study Approach

Ten participants were recruited for this study at the Montreal Chest Institute at McGill University Health Centre (MUHC). Participants were aged eighteen years and older with a maximum viral load of 200 copies/ml and a maximum CD4 count of 200 cells/ml at the time of the pre-HAART sample. Selected participants must also have been on their first HAART regime for at least twelve weeks before starting the study.

Participants were required to undergo a procedure called leukopheresis—a blood filtering machine—that collects and separates dendritic cells from the blood. The dendritic cells taken from the procedure, in combination with stored blood taken before participants begin their first anti-HIV medications, were used for the injections into the skin.

This was a one-year, open-label, (where both the investigator and participant know who is receiving the experimental drug) pilot study that enrolled 10 participants from the Montreal Chest Institute in Montreal. Participants were injected with .6 mL of AGS-004 four times each month.

Results

This trial demonstrated the ability of AGS-004 to stimulate a patient-specific and effective immune response to the virus. It was also noted that the treatment targeted CD8+ rather than the CD4+ cells. CD8+ cells have been linked to slower disease progression and a better prognosis for HIV-infected persons. Patients treated with ART within six months of infection had higher anti-viral immune responses than those in whom ART was started at six months post infection or later.

No serious adverse effects were reported after 12 months of follow-up, and the therapy was well tolerated. In addition, no spikes in viral load, significant changes in CD4 or CD8 cell counts, or signs of autoimmunity (the immune system’s reaction against elements of the body itself) were observed during or after injections.

Conclusions

This Phase I trial demonstrated the feasibility, safety and ability of AGS-004 to provoke an immune response in ART controlled participants. This data supports the implementation of a Phase II multi-centre study in North America (CTN 239).