Background: Multiple interventional strategies may be fundamental to decrease the size of HIV-1 reservoir along with antiretroviral therapy (ART). To measure the impact of isolated and combined strategies in decreasing total HIV-1 DNA, we investigated the effect of treatment intensification with Dolutegravir (DTG) with and without Maraviroc (MVC), Nicotinamide (NA), and Auranofin. NA is a class III HDAC inhibitor with anti-lymphoproliferative effect, and Auranofin induced decay in viral DNA of ART treated SIVmac251-infected macaques.
Methods: Data from six arms of NCT02961829 with 5 patients each followed every 4 weeks for a total of 48 weeks were analyzed. Selected patients were ART suppressed for >2 years, with CD4 nadir >350. Groups were: 1) continuation of ART, 2) intensified ART (ART+DTG and MVC), 3) intensified ART and HDACi (ART+DTG+MVC+NA), 4) intensified ART and Auranofin (ART+DTG+MVC+Auranofin), 5) partially intensified ART (ART+DTG), 6) partially intensified ART (DTG)+NA+Auranofin. Auranofin was used for the first 24 weeks of the study in G4 and G6. After week 48, Total viral DNA was measured by qPCR in PBMCs and rectal biopsy tissues, this latter performed at baseline.
Results: Treatment intervention was well tolerated, and main adverse events (AE) were anxiety and sleep disorders, attributable to efavirenz/dolutegravir interaction. There were transient non-statistic significant decreases in CD4 counts at weeks 8 and 12 from baseline in auranofin groups, (week 8: -119.3 ±194.7; week 12: -187 ±210.7 cells/mL). A decrease in viral DNA was observed in G6 as compared to all other groups. (p= 0.022; Odds ratio: 9.75, 95%CL: 1.1-72.39). Intensified ART with DTG+MVC presented higher decrease in the total DNA as compared to intensified ART with DTG only (G2 vs G5, p=0014). All individuals presented undetectable viral loads throughout the study, but G1 showed a significant linear trend towards an increase of the viral reservoir (p< 0.05). There was no correlation between proviral DNA from PBMCs and rectal biopsy tissues at baseline.
Conclusions: The interim analysis of this phase II trial suggests that NA+auranofin administration in combination with intensified ART is well tolerated, and an impact on the proviral reservoir size is possible.

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