Background: The increased risk of abacavir in cardiovascular disease (CVD) in HIV-infected patients is still being debated. Maraviroc, a CCR5 blocker, has been shown to decrease immune activation and monocyte infiltration in atherosclerotic plaques in murine experiments. Therefore, we examined the effect of maraviroc intensification on flow-mediated dilatation (FMD) in abacavir-treated HIV-infected patients and its effect on immunological and inflammatory parameters.
Methods: A open-label prospective crossover study with a duration of 16 weeks: 8 weeks of intervention (maraviroc intensification) and 8 weeks of control (unchanged cART regimen). FMD, HIV-specific variables, expression of HIV co-receptors, markers of inflammation and coagulation and cellular markers of immune activation were measured at weeks 0, 8 and 16. The changes (Δ) in these variables were compared between intervention and control periods using non-parametric tests. To evaluate the relation with the change in FMD, linear regression modeling was used.
Results: Twenty-one male patients with suppressed plasma HIV-RNA, on cART, had a known HIV infection for 9.2 years (IQR 6.9-13.5) with abacavir use for 6.5 years (2.8-9.3). A significantly increased FMD of 0.73% (IQR -0.25 to 1.70) was seen after maraviroc intensification compared to a decrease of -0.42% (IQR -1.89 to 0.25; p = 0.049) in the control period. There was a negative relation between ΔFMD with ΔD-dimer (β -22.70, 95% CI -39.27; -6.13, p = 0.011) and ΔCD95+ CD4+ T cells (β -0.16, 95% CI -0.28; -0.04, p = 0.013), adjusted for age and duration of HIV.
Conclusion: Maraviroc intensification modestly improves endothelial function in HIV-infected patients on an abacavir-containing regimen.
Trial Registration: NCT01389063.
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http://dx.doi.org/10.1007/s40121-016-0115-0 | DOI Listing |
AIDS
November 2023
Missouri Institute of Mental Health, University of Missouri - St. Louis, St. Louis, Missouri.
Objectives: Chemokine receptor CCR5 is the principal co-receptor for entry of M-tropic HIV virus into immune cells. It is expressed in the central nervous system and may contribute to neuro-inflammation. The CCR5 antagonist maraviroc (MVC) has been suggested to improve HIV-associated neurocognitive impairment (NCI).
View Article and Find Full Text PDFSci Rep
December 2020
Servicio de Enfermedades Infecciosas, Instituto Ramón Y Cajal de Investigación Sanitaria (IRYCIS) - Hospital Universitario Ramón Y Cajal, Carretera de Colmenar, Km 9.100, 28034, Madrid, Spain.
AIDS Res Hum Retroviruses
October 2020
Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
The efficacy of combined antiretroviral therapy (cART) against HIV-1 is evidenced by reduction of plasma viremia, disease progression, viral transmission, and mortality. However, major challenges still remain in HIV-1 management, especially the emergence of resistant strains and the persistence of viral reservoirs, apparent after cART treatment interruption. Efforts are ongoing to explore the most effective means to intensify cART and successfully control residual viral replication.
View Article and Find Full Text PDFOpen Forum Infect Dis
April 2019
Unit of Infectious Diseases, University of Perugia, Perugia, Italy.
Background: Experimental CCR5 antagonism with maraviroc in atherosclerosis-prone mice and preliminary data in humans suggest an anti-atherosclerotic effect of the drug. We assessed the impact of maraviroc treatment in persons living with HIV on subclinical indicators of atherosclerosis.
Methods: Persons living with HIV on effective antiretroviral therapy (ART) including only protease inhibitors were recruited if they had a Framingham risk score >20% and brachial flow-mediated dilation (bFMD) <4%, as indices of high cardiovascular risk.
Front Immunol
June 2019
Division of Infectious Diseases, Medizinische Klinik und Poliklinik IV, Ludwig Maximilian University of Munich, Munich, Germany.
In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved.
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