Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis

Lorenz, Matthias; Stephan, Christoph; Harmjanz, A.; Staszewski, Schlomo; Buehler, Alexandra; Bickel, Markus; Kegler, Stefan von; Ruhkamp, D.; Steinmetz, Helmuth; Sitzer, Matthias

doi:10.1016/j.atherosclerosis.2006.12.022

Cited by 168 publications

(137 citation statements)

References 27 publications

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“…This is in agreement with the results of Lorenz et al . who obtained a higher ‘vascular’ age of four to five years for HIV-infected patients (treated) compared to controls 13. Our results indicate that HIV-1 without the effect of treatment might contribute to accelerated vascular aging and possible early atherosclerosis.…”

Section: Discussionmentioning

confidence: 49%

“…Accelerated atherosclerosis has also been detected in HIV-infected patients,1,13 and a wide range of coagulation disorders may be associated with HIV infection itself 5…”

Section: Introductionmentioning

confidence: 99%

“…Although data of Lorenz et al . support the hypothesis that HIV infection promotes early atherosclerosis independently of the ‘classical’ vascular risk factors,13 the role of HIV infection as a risk factor for premature atherosclerosis is still controversial 9,19. There is also uncertainty about the relative contribution of the viral infection, the virus itself, the associated inflammatory response, antiretroviral therapy, and the interaction between them and the cardiovascular risk factors seen in the HIV-infected population 20,21…”

Section: Introductionmentioning

confidence: 99%

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Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

Fourie¹,

Rooyen²,

Pieters³

et al. 2011

CardioVascular Journal of Africa

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The chronic infection status suffered by HIV-infected individuals promotes chronic arterial inflammation and injury, which leads to dysfunction of the endothelium, atherosclerosis and thrombosis. Although HIV-1 subtype C is prevalent in South Africa and accounts for almost a third of the infections worldwide, this subtype differs genetically from HIV-1 subtype B on which the majority of studies have been done. The objective of this study was to assess whether newly identified, never-treated, HIV-1-infected South African participants showed signs of endothelial dysfunction, accelerated atherosclerosis and increased blood coagulation.We compared 300 newly diagnosed (never antiretroviral-treated) HIV-infected participants to 300 age-, gender-, body mass index- and locality-matched uninfected controls. Levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, interleukin-6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), fibrinogen and plasminogen activator inhibitor-1 (PAI-1), and carotid radialis pulse wave velocity (cr-PWV) were determined. The HIV-infected participants showed lower HDL-C and higher IL-6, CRP, ICAM-1 and VCAM-1 levels compared to the uninfected controls. No differences in fibrinogen and PAI-1 levels were detected. A continuous positive trend of increasing age with cr-PWV was detected in the HIV-infected group.Our findings suggest inflammatory injury of the endothelium, pointing to endothelial dysfunction of never-treated HIV-1-infected South Africans of African ancestry. Although no indication of a prothrombotic state could be detected, there was an indication of accelerated vascular aging and probable early atherosclerosis in the older HIV-infected participants.

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Section: Discussionmentioning

confidence: 49%

“…Accelerated atherosclerosis has also been detected in HIV-infected patients,1,13 and a wide range of coagulation disorders may be associated with HIV infection itself 5…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

Fourie¹,

Rooyen²,

Pieters³

et al. 2011

CardioVascular Journal of Africa

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“…As long-term HIV infection as well as ARVs are independent risk factors for atherosclerosis (Lorenz et al 2007), and as ARVs may lead to endothelial dysfunction (Jiang et al 2006), our HIV+ARV subjects might also have reduced vascular reactivity, which in turn could lead to abnormal BOLD responses on fMRI. While our HIV+ARV subjects did have slightly longer duration of HIV infection, it was not significantly different from the untreated HIV group.…”

Section: Discussionmentioning

confidence: 98%

“…Hence, HIV+ARV subjects may have had higher viral burden in the brain parenchyma, despite undetectable plasma viral load, and hence greater inflammatory responses in the brain and greater BOLD signals. Previous study has shown that higher levels of glial markers, myoinositol, and to a lesser degree, total creatine and choline compounds, predicted higher BOLD signals in the brain .Whether the ARVs cause direct neurotoxicity or increase inflammatory response in the brain remains unclear, but most of the NRTIs in our HIV patients' regimen were of the less neurotoxic type; only one patient was on ddI and one on d4T.As long-term HIV infection as well as ARVs are independent risk factors for atherosclerosis (Lorenz et al 2007), and as ARVs may lead to endothelial dysfunction (Jiang et al 2006), our HIV+ARV subjects might also have reduced vascular reactivity, which in turn could lead to abnormal BOLD responses on fMRI. While our HIV+ARV subjects did have slightly longer duration of HIV infection, it was not significantly different from the untreated HIV group.…”

mentioning

confidence: 86%

Antiretroviral Treatment is Associated with Increased Attentional Load-Dependent Brain Activation in HIV Patients

Chang

Yakupov

Nakama

et al. 2007

J Neuroimmune Pharmacol

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Objective-The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection.Methods-Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n=18), HIV subjects treated with antiretroviral medications (HIV+ ARV, n=12), or not treated with antiretroviral medications (HIV+NARV, n=12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging.Results-HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to . HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected=0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs.Interpretation-These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention. Prior functional magnetic resonance imaging (fMRI) studies demonstrated increased usage of reserve brain regions during working memory and attention tasks in HIV patients with mild dementia as well as in those who were neuroasymptomatic (Ernst et al. 2002). With effective antiretroviral treatments (ARVs), HIV-infected individuals are living longer, and the full clinical manifestation of HIV-dementia is less common (Dore et al. 2003;Ghafouri et al. 2006). However, the prevalence of a milder form of cognitive impairment appears to be rising among HIV-infected individuals, possibly due to the longer duration of illness and the additional effect of aging in these patients. Although treatment with ARVs typically leads to improved cognitive performance in HIV patients with dementia or cognitive deficits (Larussa et al. 2006;Sacktor et al. 2006;Sacktor et al. 2000), some studies suggest that some ARV treatments may not benefit the cognitive performance of those with lower nadir CD4 counts (Cysique et al. 2006). In addition, patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy (Dalakas 2001); however, the effects of these drugs on brain function are not well understood. As NRT...

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Cardiovascular Toxicities of Life‐Saving Drugs: Antiviral Therapy

Kohler

Lewis

2010

Cardiotoxicity of Non‐Cardiovascular Drugs

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Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis

Cited by 168 publications

References 27 publications

Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

Antiretroviral Treatment is Associated with Increased Attentional Load-Dependent Brain Activation in HIV Patients

Cardiovascular Toxicities of Life‐Saving Drugs: Antiviral Therapy

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