Safety and Impact of Low-dose Methotrexate on Endothelial Function and Inflammation in Individuals With Treated Human Immunodeficiency Virus: AIDS Clinical Trials Group Study A5314

Hsue, Priscilla Y.; Ribaudo, Heather J.; Deeks, Steven G.; Bell, Tanvir K.; Ridker, Paul M.; Fichtenbaum, Carl J.; Daar, Eric S.; Havlir, Diane V.; Yeh, Eunice; Tawakol, Ahmed; Lederman, Michael M.; Currier, Judith S.; Stein, James H.

doi:10.1093/cid/ciy781

Cited by 42 publications

(32 citation statements)

References 53 publications

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“…Methotrexate was also associated with elevations in liver enzymes, reductions in leukocyte counts and haematocrit, and a higher incidence of non–basal‐cell skin cancers than placebo. Similar results were reported by Hsue et al in a phase 2 trial of PLHIV at increased risk of atherosclerotic events treated with low‐dose methotrexate (5–15 mg/week) or placebo for 24 weeks [124]. In that trial low‐dose methotrexate had no effect on the primary endpoint of brachial artery flow‐mediated dilation, nor did it have any positive effect on a panel of inflammatory biomarkers (hs‐CRP, IL‐6, IP‐10, sCD163, sCD14, D‐dimer, fibrinogen, VCAM).…”

Section: Interventions To Target Immune Dysfunction and Inflammationsupporting

confidence: 85%

Managing HIV‐associated inflammation and ageing in the era of modern ART

et al. 2020

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Objectives This paper aims to address the concerns around ongoing immune activation, inflammation, and resistance in those ageing with HIV that represent current challenges for clinicians. Methods Presentations at a symposium addressing issues of ageing with HIV infection were reviewed and synthesised. Results The changing natural history and demographics of human immunodeficiency virus (HIV)‐infected individuals means new challenges in contemporary management. In the early years of the epidemic,management was focussed on acute, potentially life‐threatening AIDS‐related complications. From initial monotherapy with first‐generation antiretroviral therapy (ART), the development of combination highly active ART (HAART) allowed HIV control but ART toxicities, treatment adherence and drug resistance emerged as major issues. Today, the availability of potent and tolerable ART has made viral suppression achievable in most people living with HIV (PLHIV), and clinicians are confronted with managing a chronic condition among an ageing population. The combination of diseases of ageing and the co‐morbidities associated with HIV‐infection, even when well controlled, results in a complex set of challenges for many older PLHIV. There is a growing appreciation that many non‐AIDS‐related co‐morbidities are caused, at least in part, by persistent, low‐grade immune activation, inflammation, and hypercoagulability, despite suppressive ART. Conclusions In order to further improve HIV management, it is important to understand the enduring effects of chronically suppressed HIV infection, the potential contribution of these factors to the ageing process, the possibility of drug resistance, and the impact of different treatment strategies, including early ART initiation.

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Section: Interventions To Target Immune Dysfunction and Inflammationsupporting

confidence: 85%

Managing HIV‐associated inflammation and ageing in the era of modern ART

et al. 2020

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“…1). Our finding, as well as findings by others, has stimulated interest in evaluating various anti-inflammatory agents such as statins and methotrexate for primary prevention of CVD among PLWH (Mosepele et al 2018;Hsue et al 2018).…”

Section: F-18 Fdg Pet For Arterial Inflammation In People Living Withsupporting

confidence: 77%

Radionuclide imaging of inflammation in atherosclerotic vascular disease among people living with HIV infection: current practice and future perspective

Lawal

Ankrah

Stoltz

et al. 2019

European J Hybrid Imaging

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People living with human immunodeficiency virus (HIV) infection have twice the risk of atherosclerotic vascular disease compared with non-infected individuals. Inflammation plays a critical role in the development and progression of atherosclerotic vascular disease. Therapies targeting inflammation irrespective of serum lipid levels have been shown to be effective in preventing the occurrence of CVD. Radionuclide imaging is a viable method for evaluating arterial inflammation. This evaluation is useful in quantifying CVD risk and for assessing the effectiveness of anti-inflammatory treatment. The most tested radionuclide method for quantifying arterial inflammation among people living with HIV infection has been with F-18 FDG PET/CT. The level of arterial uptake of F-18 FDG correlates with vascular inflammation and with the risk of development and progression of atherosclerotic disease. Several limitations exist to the use of F-18 FDG for PET quantification of arterial inflammation. Many targets expressed on macrophage, a significant player in arterial inflammation, have the potential for use in evaluating arterial inflammation among people living with HIV infection. The review describes the clinical utility of F-18 FDG PET/CT in assessing arterial inflammation as a risk for atherosclerotic disease among people living with HIV infection. It also outlines potential newer probes that may quantify arterial inflammation in the HIV-infected population by targeting different proteins expressed on macrophages.

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“…Compared with placebo, methotrexate did not lower levels of IL-1b, IL-6, or CRP, and had no effect on CV events. Similarly, in a multicentre study, our group reported no effect of low-dose methotrexate on inflammatory markers or endothelial function 80 but methotrexate did favourably affect coronary artery echogenicity, a surrogate marker of plaque composition. 81 These preliminary studies with inflammatory biomarkers as surrogate end points will hopefully lead to larger trials of anti-inflammatory treatments with CV events as end points among individuals living with HIV.…”

Section: Treating Lipids In Hiv Patientsmentioning

confidence: 59%

Lipid Abnormalities in Persons Living With HIV Infection

Waters

Hsue

2019

Canadian Journal of Cardiology

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Lipid abnormalities are prevalent among persons living with HIV infection and contribute to increasing the risk of cardiovascular events. Antiretroviral therapy (ART) is associated with lipid abnormalities, most commonly hypertriglyceridemia, but also increases in low-density lipoprotein cholesterol and total cholesterol. Different classes of ART, and different drugs within classes, have differing effects on lipid levels, but in general newer drugs have more favourable effects compared with older ones. Low-level inflammation and chronic immune activation act on lipids through a variety of mechanisms to make them more atherogenic. As a consequence, risk is higher than would be expected for any given cholesterol level. Clinical outcome trials of cholesterollowering therapies have not yet been completed in people living with HIV, so that treatment decisions depend on extrapolation from studies in uninfected populations. Traditional risk assessment tools underestimate cardiovascular risk in individuals with HIV. Statins are the mainstay of lipid-lowering drug treatment; however, drugedrug interactions with ART must be considered.

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Safety and Impact of Low-dose Methotrexate on Endothelial Function and Inflammation in Individuals With Treated Human Immunodeficiency Virus: AIDS Clinical Trials Group Study A5314

Cited by 42 publications

References 53 publications

Managing HIV‐associated inflammation and ageing in the era of modern ART

Managing HIV‐associated inflammation and ageing in the era of modern ART

Radionuclide imaging of inflammation in atherosclerotic vascular disease among people living with HIV infection: current practice and future perspective

Lipid Abnormalities in Persons Living With HIV Infection

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