Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon alpha-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical Trial

Introduction: Functional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches. Materials and Methods: We conducted a double-blind randomized placebo-controlled clinical trial to evaluate the safety, immunogenicity, and effect on viral dynamics of a therapeutic vaccine produced with monocyte-derived dendritic cells (MD-DC) loaded with a high dose of heat-inactivated autologous (HIA) HIV-1 in combination with pegylated interferon alpha 2a (IFN alpha-2a) in people with chronic HIV-1. Results: Twenty-nine male individuals on successful ART and with CD4+ >= 450 cells/mm(3) were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine similar to 10(7) MD-DC pulsed with HIA-HIV-1 (10(10) HIV RNA copies) (n = 8); (2) vaccine plus three doses of 180 mcg IFN alpha-2a at weeks 4-6 (n = 6); (3) placebo = saline (n = 7); and (4) placebo plus three doses of 180 mcg IFN alpha-2a (n = 8). Thereafter, treatment was interrupted (ATI). Vaccines, IFN alpha-2a, and the administration procedures were safe and well tolerated. All patients' viral load rebounded during the 12-week ATI period. According to groups, changes in viral set-point between pre-ART and during ATI were not significant. When comparing all groups, there was a tendency in changes in viral set-point between the vaccine group vs. vaccine + IFN alpha-2a group (>0.5log(10) p = 0.05). HIV-1-specific T-cell responses (IFN-gamma Elispot) were higher at baseline in placebo than in the vaccine group (2,259 +/- 535 vs. 900 +/- 200 SFC/10(6) PBMC, p = 0.028). A significant difference in the change of specific T-cell responses was only observed at week 4 between vaccine and placebo groups (694 +/- 327 vs. 1,718 +/- 282 SFC/10(6) PBMC, p = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INF alpha-2a administration. Discussion: Results from this study show that intranodally administered DC therapeutic vaccine in combination with IFN alpha-2a was safe and well-tolerated but had a minimal impact on viral dynamics in HIV-1 chronic infected participants.