A phase II study testing the activity and safety of AGS-004 as an immunotherapeutic in successfully ART-treated subjects infected with HIV-1 in combination with ART followed by ART interruption
CTN 239 aimed to assess the efficacy and safety of a personalized immunotherapy during a 12-week ART structured treatment interruption. This was a two-year, open label (where both the investigator and participant knew who is receiving the experimental drug) examination of the ability of AGS-004 to improve immune control of viral replication.
Following screening and leukopheresis, participants received one injection of 0.6 ml AGS-004 every four weeks four times while continuing on ART. At week 12, participants with a viral load of less than 1000 copies/ml continued with AGS-004 and an ART interruption. At week 26, participants discussed with the study doctor, according to their viral load rebound, whether to continue with AGS-004 or restart ART alone.
The study agent, 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.
Forty-seven participants who were on their first antiretroviral drug regimen and had a CD4 cell count greater than or equal to 450 cells/mm3 for at least three months before study onset were recruited for the study.
Final analysis of this phase II study of an autologous dendritic cell immunotherapy (AGS-004) showed positive outcomes in primary endpoint of viral load control.
Researchers concluded that the experimental treatment resulted in an unexpectedly long delay in viral rebound, time to peak viral load during structured treatment interruption and a reduced viral load when compared to pre-ART levels.
Routy JP, Boulassel MR, Nicolette CA, Jacobson JM. Assessing risk of a short-term antiretroviral therapy discontinuation as a read-out of viral control in immune-based therapy. J Med Virol. 2012;84(6):885-9.
Dr. Jean-Pierre Routy