Abstract
Objectives: The aim of this study was to evaluate the effect on immune activation of switching from a triple-drug to a dual-drug regimen in HIV-1 infected patients on successful combination antiretroviral treatment (cART). Immunadapt is a prospective study evaluating the impact of cART simplification on immune activation.Methods: We prospectively collected blood samples in HIV-1 infected patients on stable and successful cART switching from triple to dual regimens as a simplifying strategy. We compared immune activation markers: high sensitivity CRP, IL-1, IL-6, IL-8, IP-10, MCP-1, TNF-alpha, soluble CD14 (sCD14), soluble CD163 (sCD163), lipopolysaccharide binding protein, and D-dimer before cART change and at least 6 months after the switch. Patients were stratified according to low or high risk factors of immune activation (low CD4 nadir, previous AIDS-defining condition or very-low-level viremia during follow-up).Results: From April 2019 to May 2020, 20 subjects were included (mean age 57 years, 25 years since HIV infection, CD4 666 cells/mm3, CD8 766 cells/mm3, CD4/CD8 0.94, CD4 nadir 326 cells/mm3, 15% with AIDS, 18 years on cART, 6 cART regimens received, current cART duration: 56 months). Fourteen patients were prescribed Dolutegravir + Rilpivirine and six received Dolutegravir + Lamivudine. After 6.9 months, a significant sCD163 increase (+ 25.5% vs. + 0.5%, p = 0.02) was observed in subjects with high risk factors, despite maintaining a viral load <50 cp/ml.Conclusion: cART simplification in favor of dual therapy is associated with macrophage activation in patients at risk of immune activation despite sustained virological control. Risk factors should thus be considered before generalizing such strategies.
Highlights
Triple-drug antiretroviral regimens are the standard of care for controlling HIV viral replication
Between April 2019 and May 2020, 20 individuals were included in the study (90% men, mean age 57 years, 25 years since known HIV infection, CD4 cell count at inclusion 666 cells/mm3, CD8 count 766 cells/mm3, CD4/CD8 ratio 0.94, CD4 nadir 326 cells/mm3, 18 years on combination antiretroviral therapies (cART), 15% with prior history of AIDS, 6 cART regimens received)
Nine subjects had been receiving a combination of 2 nucleoside reverse transcriptase inhibitors (NRTI) and 1 nucleoside reverse transcriptase inhibitor (NNRTI), nine had been treated with 2 NRTIs and 1 integrase strand transfer inhibitor (INSTI), while the remaining two patients had been receiving either 1 NRTI, 1 NNRTI and 1 protease inhibitor (PI) or 1 NRTI, 1 INSTI and 1 NNRTI
Summary
Triple-drug antiretroviral regimens are the standard of care for controlling HIV viral replication. Thanks to such strategies, life expectancy has dramatically increased in HIV+ patients [1]. Life expectancy has dramatically increased in HIV+ patients [1] These regimens typically include two nucleoside reverse transcriptase inhibitors (NRTI), associated with one of the following drug classes: a non-nucleoside reverse transcriptase inhibitor (NNRTI), an integrase strand transfer inhibitor (INSTI) or a protease inhibitor (PI) [2, 3]. Simplification of cART in favor of certain dual-drug regimens has been shown to maintain virological control, with potential reduction of long-term adverse effects [7, 8]. Several dual drug regimens have been introduced, generally with a NRTI-sparing cART or with a single NRTI associated with another HIV drug class
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