The following is a summary of “DOUBLING DOLUTEGRAVIR DOSAGE REDUCES HIV PERSISTENCE MARKERS IN ART-TREATED ADULTS”, presented by Celine Fombellida-Lopez, Alexander Pasternak, Aurelija Cicilionytė, Nathalie Maes, Celine Vanwinge, Aurelie Ladang, Etienne Cavalier, Lee Winchester, Courtney V. Fletcher, Fabrice Susin, Dolores Vaira, Marie-Pierre Hayette, Catherine Reenaers, Michel Moutschen, Gilles Darcis
The debate over whether people living with HIV (PLWH) experience ongoing viral replication despite antiretroviral therapy (ART) and low-level residual viremia is still ongoing. In a phase 3 randomized clinical trial, researchers aimed to examine the effects of intensifying the ART regimen by doubling dolutegravir (DTG) dosage on HIV blood and tissue latent reservoirs, residual viremia, immune activation, and inflammation. A total of 20 HIV-infected adults, who had been receiving a triple therapy consisting of DTG 50mg/ABC/3TC and were fully suppressed for at least 2 years, participated in the study.
At different time points over 3 months, peripheral blood mononuclear cells (PBMCs), plasma, and rectal biopsies were collected and analyzed. Single copy assay was done to determine ultrasensitive plasma viral load, while expression of immune activation (HLA-DR, CD38) and exhaustion (PD-1, TIGIT, LAG-3) markers on CD4+ and CD8+ T cells were evaluated. Additionally, the level of various plasma biomarkers, such as sCD14, IL-4, IL-6, IP-10, usCRP, IFN gamma, and TNF alpha was measured to assess inflammation. The concentration of dolutegravir was also measured in plasma and in tissue.
Results showed no significant difference in total HIV DNA in PBMCs and in the tissue between day 0 and day 84 in both groups. However, a significant decrease in US HIV RNA in PBMCs (P=0.020) and ultrasensitive plasma viral load (P=0.016) was observed in the intensified group between day 0 and day 84, whereas no such differences were seen in the control group. This suggests that ongoing viral replication may have occurred prior to intensification, even though there were no measurable impacts on chronic inflammation or immune activation. Further research is needed to confirm these findings in larger clinical trials, as these results could have implications for the clinical management of PLWH.