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Abstract :
[en] BACKGROUND
Antiretroviral therapy (ART) suppresses HIV replication and prevents the development of AIDS. However, ART is not curative. Persistence of viral reservoirs forms the major obstacle to an HIV cure. HIV reservoirs persist mainly through cellular longevity and proliferation, but replenishment by residual virus replication despite ART has been proposed as a potential mechanism of HIV persistence. In recent years, there has been a clear trend towards ART regimens that include fewer drugs (e.g., dual instead of triple therapy). In this study, we evaluated the possible increase in viral replication and reservoir replenishment in blood and tissue upon ART simplification and the impact of simplification on chronic immune activation and inflammation.
MATERIALS AND METHODS
Thirty-six people living with HIV, who received a triple therapy consisting of Dolutegravir (DTG), Abacavir (ABC) and Lamivudine (3TC) and had been fully suppressed for at least 2 years, were enrolled in a phase 3 randomised clinical trial. Half of them were switched to a dual therapy (DTG/3TC). Peripheral blood mononuclear cells (PBMCs), plasma and rectal biopsies were longitudinally collected over 1 year. We quantified total HIV DNA and cell-associated unspliced (US) HIV RNA in PBMCs and rectal tissue. Ultrasensitive single-copy HIV RNA assay was performed to determine residual plasma viremia. Expression of immune activation (HLA-DR, CD38) and exhaustion (PD-1, TIGIT) markers and the levels of inflammatory plasma biomarkers including sCD14, IL-6, IL-1β, IL-17α, IFN-γ, and TNF-α were quantified.
RESULTS
There were no significant differences in the longitudinal dynamics of total HIV DNA and unspliced HIV RNA in PBMCs between the two groups. In the simplified group, we observed a transient increase in residual viremia at month 9 of the study that returned to baseline by month 12. Similarly, we observed a transient decrease in the CD4/CD8 ratio that returned to baseline by the end of the study. A significant reduction in the percentages of CD4+TIGIT+ T cells and in levels of 5 plasma inflammation markers was also observed. In the control group, we observed a significant decrease in the total HIV DNA in tissue and a significant decrease in CD4+TIGIT+ T cells.
CONCLUSIONS
Switching to DTG/3TC maintained plasma viral load suppression, didn’t measurably impact HIV persistence markers in blood or tissue, and reduced systemic inflammation. These findings support the use of DTG/3TC in people living with HIV.
