Assessing risk of a short-term antiretroviral therapy discontinuation as a read-out of viral control in immune-based therapy.

Although analytical treatment interruption is used as a strategy to test immunotherapeutic agents in HIV-infection, it may pose a risk for study participants. The potential risks of short-term interruption of antiretroviral therapy (ART) during treatment with an autologous dendritic cell immune-based therapy (AGS-004-001) were assessed using data from a subgroup of subjects in the strategies for management of antiretroviral therapy (SMART) study with matched eligibility criteria. A retrospective subgroup analysis of the SMART study population using the eligibility criteria and treatment stopping rules of AGS-004-001 study was analyzed. Key inclusion criteria for AGS-004-001 study were applied to the data collected from participants of the SMART study. There were 440 of 2,720 on the drug conservation arm and 436 of 2,752 on the viral suppression arm that matched the AGS-004-001 inclusion criteria and were used in the SMART subgroup analysis. In the first 16 weeks following randomization into the SMART study there were no deaths in either subgroup. There were two AIDS-related events in the drug conservation subgroup and one in the viral suppression subgroup, making the overall risk of AIDS-related events 2 per 100 person years (0.005%) and 1 per 100 person years (0.002%) in the two subgroups, respectively. There were 6/440 subjects (1.4%) in the drug conservation subgroup and 4/436 subjects (0.92%) in the viral suppression subgroup who experienced Grade 2 adverse events. These results demonstrated that analytical treatment interruption within the context of highly selective, closely monitored studies assessing the antiviral activity of immune-based agents should be an acceptable strategy for at least 16 weeks.