Multiple interventional strategies may be required to decrease HIV-1 reservoir along with antiretroviral therapy (ART). We investigated the effect of treatment intensification with Dolutegravir (DTG) with and without Maraviroc (MVC), the HDAC inhibitor Nicotinamide (NA), and Auranofin (Au), and a dendritic cell vaccine pulsed with autologous HIV (DCv). Au had decreased viral DNA of ART treated SIV infected macaques.
30 ART suppressed individuals for >2 years (CD4 nadir >350) were randomized to six arms of SPARC-7 TRIAL followed for 48 weeks. Patients from two arms received 3 doses of DCv after 48 weeks and were followed for additional 24 weeks. Groups: G1) continuation of ART, G2) intensified ART (ART+DTG+MVC), G3) intensified ART and HDACi (ART+DTG+MVC+NA), G4) intensified ART and Au (ART+DTG+MVC+Au), G5) partially intensified ART (DTG)+DCv, G6) partially intensified ART (DTG)+NA+Auranofin+DCv. Au was used for the first 24 weeks. DC was pulsed with autologous Gag256-367 peptides (nanomers, 3-6 peptides each patient) according to the best immunogenicity based in specific HLA of everyone. Total viral DNA was measured by qPCR in PBMCs and rectal biopsy tissues, and T cell activation by HLADR and CD38 on CD4 and CD8. In vitro immunogenicity of DCv was measured by pulsing patients’ cells with autologous peptides used in DCv or S aureus enterotoxin B and brefaldine (control). IL2, TNF and interferon (IFN) were measured by flow cytometry in CD4 and CD8 collected at 1st 2nd and 3rd DCv dose and 30 days after 3rd dose (dose interval=2 weeks).
There was no virologic failure or intervention-related SAE. Decrease in viral DNA was observed in G6 but not in other groups. (p=0.022; Odds ratio: 9.75, 95%CL: 1.1-72.39), and G1 showed a linear increase of proviral DNA (p<.05). One G6 patient evolved to undetectable proviral DNA during 48-week period and another after receiving the DCv. Rectal biopsy viral DNA was positive at baseline and at study end in each patient. Activation of CD4 and CD8 cells significantly decreased in G6 (p<0.05, 2-way Anova). There was a significant increase in interleukins measurement from 1st DCv dose to last dose at CD4+ T cells, and a significant increase in IL2 and TNF at CD8 from 1st to last dose (Kruskal-Wallis), with no changes in the control experiment.
NA+Au+antiretroviral intensification in combination with DCv reduced the viral reservoir size and cell activation markers among individuals on ART.