Maraviroc Intensification Improves Endothelial Function in Abacavir-Treated Patients, an Open-Label Randomized Cross-Over Pilot Study.
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.


CONCLUSIONS
Maraviroc intensification modestly improves endothelial function in HIV-infected patients on an abacavir-containing regimen.


BACKGROUND
NCT01389063.
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht (UMCU), Heidelberglaan 100, F02.126, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. m.krikke@umcutrecht.nl.|Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht (UMCU), Lundlaan 6, KC02.085.2, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands. m.krikke@umcutrecht.nl.
Maaike
M
Krikke
Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht (UMCU), Lundlaan 6, KC02.085.2, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands.
Kiki
K
Tesselaar
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht (UMCU), Heidelberglaan 100, F02.126, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Joop E
JE
Arends
Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht (UMCU), Lundlaan 6, KC02.085.2, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands.
Julia
J
Drylewicz
Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht (UMCU), Lundlaan 6, KC02.085.2, P.O. Box 85090, 3508 AB, Utrecht, The Netherlands.
Sigrid A
SA
Otto
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht (UMCU), Heidelberglaan 100, F02.126, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.|Department of Internal Medicine and Gastroenterology, Spaarne Gasthuis, Boerhaavelaan 22, 2035 RC, Haarlem, The Netherlands.
Steven F L
SF
van Lelyveld
Department of Vascular Medicine, University Medical Center Utrecht (UMCU), Heidelberglaan 100, F02.126, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Frank J L
FJ
Visseren
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht (UMCU), Heidelberglaan 100, F02.126, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Andy I M
AI
Hoepelman
Abacavir; Cardiovascular disease; Immune activation; Inflammation; Maraviroc