Autologous Dendritic Cell Vaccine in HIV1 Infection

Phase I/II Evaluation of Therapeutic Immunization With Autologous Dendritic Cells Pulsed With Autologous, Inactivated HIV-1 Infected, Apoptotic Cells

This study aims to look at the safety and tolerability of immunization with dendritic cell vaccine prepared using the patient's own cells and virus. It also aims to explore the virologic efficacy of the vaccine as determined by a decrease in the viral load 12 weeks after analytic treatment interruption.

This is a phase I/II, open label, single-arm, single-site clinical trial designed to evaluate the safety and antiviral activity of the ApB DC vaccine, a therapeutic vaccine derived from autologous dendritic cells loaded with autologous HIV-1 infected apoptotic cells. The study will be conducted in three phases. The first is the pre-vaccination phase that includes study entry, isolation of autologous virus, and initiation of antiretroviral therapy. Once the patient's viral load has been suppressed to undetectable levels (<50 copies/mL) and sufficient virus has been isolated, the second phase will begin. This includes leukapheresis in order to harvest monocytes and lymphocytes necessary for vaccine preparation. Three vaccine doses will be administered subcutaneously every other week. Six weeks after the last vaccination, the third phase, analytic treatment interruption (ATI) phase, will begin. A fourth, booster dose of vaccine will be given two weeks after the start of treatment interruption. The treatment interruption will be continued for twelve weeks after which the primary HIV provider will decide whether or not antiretroviral therapy should be restarted. CD4 and viral load will be closely monitored throughout the study especially during treatment interruption. Follow-up will be continued for 24 weeks after the 12-week treatment interruption.

Inclusion Criteria:

• Confirmed HIV-1 infection.
• CD4 greater than or equal to 350 cells/mL within 8 weeks prior to study entry.
• Plasma HIV-1 RNA level of 5000-100,000 copies/mL within 8 weeks prior to study entry.
• Antiretroviral therapy naive.
• Willingness to interrupt ART for at least 12 weeks.
• Written informed consent.

Exclusion Criteria:

• Treatment within 30 days prior to study entry with systemic steroids or other immunosuppressives, or any underlying disease which may require use of such medications during the study period.
• Receipt of any vaccinations other than routine ones within 6 months of study entry
• Pregnancy or breastfeeding
• Previous or current CDC Category C event
• Receipt of any investigational product within 12 weeks prior to study entry.