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

© 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.).