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

Objectives

This study aimed to evaluate HIV sequence evolution in whole genes and
in CD8þ 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 cellbased
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). CD8þ 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
CD8þ T-cell epitopes was comparable for vaccine-targeted and non targeted 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 cellbased
vaccine targeting Tat, Rev, and Nef did not affect virus evolution at the whole
gene level nor at the CD8þ T-cell epitope level.

2011 AIDS
Anna L. de Goede, Hanneke W.M. van Deutekom,Bram Vrancken, Martin Schutten, Sabine D. Allard,Carel A. van Baalen, Albert D.M.E. Osterhaus, Kris Thielemans,
Joeri L. Aerts, Can Kesmir, Philippe Lemey and Rob A. Gruters