HIV-1 evolution in patients undergoing immunotherapy with Tat, Rev and Nef expressing dendritic cells followed by treatment interruption

Anna De Goede, H.w. Van Deutekom, B. Vrancken, M Schutten, Sabine Allard, Carel A. Van Baalen, Ab D. Osterhaus, Kris Thielemans, Joeri Aerts, C. Kesmir, P. Lemey, Rob A. Gruters

Onderzoeksoutput: Articlepeer review

7 Citaten (Scopus)

Samenvatting

OBJECTIVES:

This study aimed to evaluate HIV sequence evolution in whole genes and in CD8 T-cell epitope regions following immunotherapy and subsequent analytical treatment interruption (ATI). A second objective of this study was to analyze associations between vaccine-specific immune responses and epitope mutation rates.
DESIGN:

HIV-1-infected patients on combined antiretroviral therapy (cART) were subjected to immunotherapy by the administration of an autologous dendritic cell-based therapeutic vaccine expressing Tat, Rev, and Nef and subsequent ATI.
METHODS:

HIV-1 genes were amplified and sequenced from plasma RNA obtained before initiation of cART as well as during ATI. Control sequences for virus evolution in untreated HIV-1-infected individuals were obtained from the HIV Sequence Database (Los Alamos). CD8 T-cell epitope regions were defined based on literature data and prediction models. HIV-1-specific immune responses were evaluated to analyze their impact on sequence evolution.
RESULTS:

Viral sequence evolution in the tat, rev, and nef genes of vaccinated patients was similar to that of controls. The number of mutations observed inside and outside CD8 T-cell epitopes was comparable for vaccine-targeted and nontargeted proteins. We found no evidence for an impact of vaccine-induced or enhanced immune responses on the number of mutations inside or outside epitopes.
CONCLUSION:

Therapeutic vaccination of HIV-1-infected patients with a dendritic cell-based vaccine targeting Tat, Rev, and Nef did not affect virus evolution at the whole gene level nor at the CD8 T-cell epitope level.
Originele taal-2English
Pagina's (van-tot)2679-2689
Aantal pagina's11
TijdschriftAIDS
Volume27
Nummer van het tijdschrift17
StatusPublished - 13 nov 2013

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