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 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). 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 cellbased vaccine targeting Tat, Rev, and Nef did not affect virus evolution at the whole gene level nor at the CD8+ T-cell epitope level.

Biological evolution, Cytotoxic T lymphocyte escape, Genetic diversity, HIV-1, Immunotherapy, Molecular sequence data, Phylogeny
dx.doi.org/10.1097/01.aids.0000433813.67662.92, hdl.handle.net/1765/65229
Department of Pharmacy

de Goede, A.L, Deutekom, M, Vrancken, B, Schutten, M, Allard, S.D, van Baalen, C.A, … Gruters, R.A. (2013). HIV-1 evolution in patients undergoing immunotherapy with Tat, Rev, and Nef expressing dendritic cells followed by treatment interruption. AIDS, 27(17), 2679–2689. doi:10.1097/01.aids.0000433813.67662.92