Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 5, Issue 166, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3004682
Keywords
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Categories
Funding
- Fondo de Investigacion Sanitaria (FIS) [PI10/02984]
- Mutua Madrilena del Automovil
- STREP (UE) Life sciences, genomics and biotechnology for health [LSH2005_2.3.0.10]
- PROFIT [FIT 090100-2005-9]
- MARATO TV3
- RIS (Red Tematica Cooperativa de Grupos de Investigacion en Sida del Fondo de Investigacion Sanitaria)
- ORVACS
- Fundacion Lilly Research Award
- ISCIII (Instituto de Salud Carlos III)
- Health Department of the Catalan Government (Generalitat de Catalunya)
- National Cancer Institute, NIH [HHSN261200800001E]
- [EC10-153]
- [TRA-094]
- [FIS PS09/01297]
- [SAF2008-04395]
- [SAF2010-21224]
- [FIS PI040503]
- [FIS PI070291]
- [SAF 05/05566]
- [FIPSE 36536/05]
- ICREA Funding Source: Custom
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Combination antiretroviral therapy (cART) greatly improves survival and quality of life of HIV-1-infected patients; however, cART must be continued indefinitely to prevent viral rebound and associated disease progression. Inducing HIV-1-specific immune responses with a therapeutic immunization has been proposed to control viral replication after discontinuation of cART as an alternative to cART for life. We report safety, tolerability, and immunogenicity results associated with a control of viral replication for a therapeutic vaccine using autologous monocyte-derived dendritic cells (MD-DCs) pulsed with autologous heat-inactivated whole HIV. Patients on cART with CD4(+) >450 cells/mm(3) were randomized to receive three immunizations with MD-DCs or with nonpulsed MD-DCs. Vaccination was feasible, safe, and well tolerated and shifted the virus/host balance. At weeks 12 and 24 after cART interruption, a decrease of plasma viral load setpoint >= 1 log was observed in 12 of 22 (55%) versus 1 of 11 (9%) and in 7 of 20 (35%) versus 0 of 10 (0%) patients in the DC-HIV-1 and DC-control groups, respectively. This significant decrease in plasma viral load observed in immunized recipients was associated with a consistent increase in HIV-1-specific T cell responses. These data suggest that HIV-1-specific immune responses elicited by therapeutic DC vaccines could significantly change plasma viral load setpoint after cART interruption in chronic HIV-1-infected patients treated in early stages. This proof of concept supports further investigation of new candidates and/or new optimized strategies of vaccination with the final objective of obtaining a functional cure as an alternative to cART for life.
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