Therapeutic Vaccination With Dendritic Cells Loaded With Autologous HIV Type 1–Infected Apoptotic Cells

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Abstract

Background. We report the results of a phase I/II, open-label, single-arm clinical trial to evaluate the safety and anti–human immunodeficiency virus type 1 (HIV-1) efficacy of an autologous dendritic cell (DC)–based HIV-1 vaccine loaded with autologous HIV-1–infected apoptotic cells.

Methods. Antiretroviral therapy (ART)–naive individuals were enrolled, and viremia was suppressed by ART prior to delivery of 4 doses of DC-based vaccine. Participants underwent treatment interruption 6 weeks after the third vaccine dose. The plasma HIV-1 RNA level 12 weeks after treatment interruption was compared to the pre-ART (ie, baseline) level.

Results. The vaccine was safe and well tolerated but did not prevent viral rebound during treatment interruption. Vaccination resulted in a modest but significant decrease in plasma viremia from the baseline level (from 4.53 log10 copies/mL to 4.27 log10 copies/mL; P = .05). Four of 10 participants had a >0.70 log10 increase in the HIV-1 RNA load in plasma following vaccination, despite continuous ART. Single-molecule sequencing of HIV-1 RNA in plasma before and after vaccination revealed increases in G>A hypermutants in gag and pol after vaccination, which suggests cytolysis of infected cells.

Conclusions. A therapeutic HIV-1 vaccine based on DCs loaded with apoptotic bodies was safe and induced T-cell activation and cytolysis, including HIV-1–infected cells, in a subset of study participants.

Clinical Trials Registration. NCT00510497.

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