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AIDS:
doi: 10.1097/01.aids.0000433813.67662.92
Basic Science

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

de Goede, Anna L.a,b; van Deutekom, Hanneke W.M.c; Vrancken, Bramd; Schutten, Martina; Allard, Sabine D.f; van Baalen, Carel A.a; Osterhaus, Albert D.M.E.a; Thielemans, Krise; Aerts, Joeri L.e; Keşmir, Canc; Lemey, Philipped; Gruters, Rob A.a

Supplemental Author Material
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Abstract

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.

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins

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