HIV-1 reservoir dynamics after vaccination and antiretroviral therapy interruption are associated with dendritic cell vaccine-induced T cell responses

Cristina Andrés, Montserrat Plana, Alberto C. Guardo, Carmen Alvarez-Fernández, Nuria Climent, Teresa Gallart, Agathe León, Bonaventura Clotet, Brigitte Autran, Nicolas Chomont, Josep M. Gatell, Sonsoles Sánchez-Palomino, Felipe García, Jiménez Díaz, José Miguel Benito, Norma Rallón, Berta Torres, Lorna Leal, Constanza Lucero, Alexy InciarteLlucia Alós Hernández, Miguel Caballero Borrego, Joan Romeu Fontanillas, Margarita Bofill Soliguer, Christian Brander, Nuria Izquierdo, Judith Dalmau, Javier Martinez-Picado, Louis Chonco, Nickola Wever, Marjorie Pion, María Jesús Serramía, Miguel Relloso, Paula Ortega, Javier de la Mata, Rafael Gómez, María ángeles Muñoz-Fernández, José Peña Martínez, Rafael González Fernández, Mario Frias Casas, Barbara Manzanares Martín, Laura Castro, Nuria González Fernandez, José Alcamí, Teresa Perez Olmeda, Javier Garcia Perez, Luis Miguel Bedoya del Olmo

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27 Citations (Scopus)

Abstract

© 2015, American Society for Microbiology. HIV-1-specific immune responses induced by a dendritic cell (DC)-based therapeutic vaccine might have some effect on the viral reservoir. Patients on combination antiretroviral therapy (cART) were randomized to receive DCs pulsed with autologous HIV-1 (n=24) (DC-HIV-1) or nonpulsed DCs (n=12) (DC-control). We measured the levels of total and integrated HIV-1 DNA in CD4 T cells isolated from these patients at 6 time points: before any cART; before the first cART interruption, which was at 56 weeks before the first immunization to isolate virus for pulsing DCs; before and after vaccinations (VAC1 and VAC2); and at weeks 12 and 48 after the second cART interruption. The vaccinations did not influence HIV-1 DNA levels in vaccinated subjects. After the cART interruption at week 12 postvaccination, while total HIV-1 DNA increased significantly in both arms, integrated HIV-1 DNA did not change in vaccinees (mean of 1.8 log10 to 1.9 copies/106 CD4 T cells, P=0.22) and did increase in controls (mean of 1.8 log10 to 2.1 copies/106 CD4 T cells, P=0.02) (P=0.03 for the difference between groups). However, this lack of increase of integrated HIV-1 DNA observed in the DC-HIV-1 group was transient, and at week 48 after cART interruption, no differences were observed between the groups. The HIV-1-specific T cell responses at the VAC2 time point were inversely correlated with the total and integrated HIV-1DNAlevels after cART interruption in vaccinees (r [Pearson's correlation coefficient]=0.69, P= 0.002, and r=0.82, P<0.0001, respectively). No correlations were found in controls. HIV-1-specific T cell immune responses elicited byDCtherapeutic vaccines drive changes in HIV-1DNAafter vaccination and cART interruption. (This study has been registered at ClinicalTrials.gov under registration no. NCT00402142.).
Original languageEnglish
Pages (from-to)9189-9199
JournalJournal of Virology
Volume89
Issue number18
DOIs
Publication statusPublished - 1 Jan 2015

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    Andrés, C., Plana, M., Guardo, A. C., Alvarez-Fernández, C., Climent, N., Gallart, T., León, A., Clotet, B., Autran, B., Chomont, N., Gatell, J. M., Sánchez-Palomino, S., García, F., Díaz, J., Benito, J. M., Rallón, N., Torres, B., Leal, L., Lucero, C., ... Bedoya del Olmo, L. M. (2015). HIV-1 reservoir dynamics after vaccination and antiretroviral therapy interruption are associated with dendritic cell vaccine-induced T cell responses. Journal of Virology, 89(18), 9189-9199. https://doi.org/10.1128/JVI.01062-15