Inflammation, immune activation, and cardiovascular disease in HIV

Nou, Eric; Lo, Janet; Grinspoon, Steven

doi:10.1097/qad.0000000000001109

Cited by 161 publications

(135 citation statements)

References 193 publications

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“…The first explanation, no association, could be due to the fact that, despite surrogate outcomes and overt CVD being clearly related,[45–53] and CRP, IL-6 and overt CVD having a clear relation, associations between markers of immune activation and surrogate markers of CVD may be weak.…”

Section: Discussionmentioning

confidence: 99%

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Association between Immune Markers and Surrogate Markers of Cardiovascular Disease in HIV Positive Patients: A Systematic Review

et al. 2017

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BackgroundHIV infection is associated with an increased risk of cardiovascular disease (CVD). Chronic low-grade immune activation is likely one of the driving mechanisms. This systematic review provides an overview of the evidence addressing the relation between immune markers and surrogate markers of CVD (except CIMT) in HIV infection.MethodsA systematic search was performed in PubMed, Embase and Cochrane Library identifying all articles from 1996 to April 2015. It addressed the relation between immune markers and surrogate markers of CVD (except Carotid Intima-media Thickness) in HIV-positive adults. Two authors, using predefined criteria, independently conducted the selection of articles, critical appraisal and extraction of the data. Analysis focused on immune markers that were assessed most frequently. The review was conducted according to the PRISMA guideline and performed as part of an overarching review registered with PROSPERO (CRD42014010516).FindingsTwenty-nine articles were selected, describing 34 immune markers and nine different CVD surrogate outcomes: coronary calcium score (13 times) and flow-mediated dilation (10 times) were used most frequently. Twenty-seven studies had a cross-sectional design. CRP, IL-6 and sVCAM-1 were assessed most frequently. None of the immune markers were clearly associated with any of the surrogate CVD outcomes. No effect estimate could be calculated due to marked heterogeneity in study populations, immune markers, outcomes and statistical approaches.InterpretationThis review could not identify a clear association between any of the immune markers and surrogate CVD outcomes. This may reflect a true lack of association, or may be explained by heterogeneity across studies and lack of follow-up data. Future research should focus on longitudinal studies measuring a select set of immune markers and surrogate CVD outcomes awaiting the primary outcome of clinical cardiovascular events.

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Section: Discussionmentioning

confidence: 99%

“…All these factors have been previously reported to influence both the inflammatory response and the risk of cardiovascular morbidity and mortality. [53–55] Moreover, statin use is not taken into account in most of the included studies, whereas recent evidence suggests that statin use can improve surrogate cardiovascular outcomes. [56,57]…”

Section: Discussionmentioning

confidence: 99%

Association between Immune Markers and Surrogate Markers of Cardiovascular Disease in HIV Positive Patients: A Systematic Review

et al. 2017

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“…Approximately 18 million people are on chronic anti‐retroviral therapy (ART) for HIV 11, which allows HIV‐positive persons to live to healthy middle‐age with normal life‐expectancy. HIV and NCDs are syndemic and associated with an increase in NCDs among HIV‐positive persons; including CVD, HTN, diabetes (DM), hyperlipidaemia, overweight/obesity and cervical cancer 9, 13, 14. Furthermore, these syndemics may emerge also due to socio‐environmental factors that impact biology to increase the prevalence of co‐morbidities.…”

Section: Introductionmentioning

confidence: 99%

High prevalence of HIV and non‐communicable disease (NCD) risk factors in rural KwaZulu‐Natal, South Africa

et al. 2017

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IntroductionSouth Africa faces epidemics of HIV and non‐communicable diseases (NCDs). The aim of this study was to characterize the prevalence of non‐communicable disease risk factors and depression, stratified by HIV status, in a community with a high burden of HIV.MethodsWe conducted a home‐based HIV counselling and testing study in KwaZulu‐Natal, South Africa between November 2011 and June 2012. Contiguous households were approached and all adults ≥18 years old were offered an HIV test. During follow‐up visits in January 2015, screening for HIV, depression, obesity, blood glucose, cholesterol and blood pressure were conducted using point‐of‐care tests.ResultsOf the 570 participants located and screened; 69% were female and 33% were HIV‐positive. NCD risk factor prevalence was high in this sample; 71% were overweight (body mass index (BMI) 25 to 29.9 kg/m2) or obese (BMI≥30 kg/m2), 4% had hyperglycaemia (plasma glucose >11.0 mmol/l/200 mg/dl), 33% had hypertension (HTN, >140/90 mmHg), 20% had hyperlipidaemia (low density cholesterol >5.2 mmol/l/193.6 mg/dl) and 12% had major depressive symptoms (nine item Patient Health Questionnaire ≥10). Of the 570 participants, 87% had one or more of HIV, hyperglycaemia, HTN, hyperlipidaemia and/or depression. Over half (56%) had two or more. Older age and female gender were significantly associated with the prevalence of both HIV infection and NCD risk factors. Around 80% of both HIV‐positive and negative persons had one of the measured risk factors (i.e. obesity, hyperglycaemia, hyperlipidaemia, HTN), or depression.ConclusionsIn a community‐based sample of adults in KwaZulu‐Natal, South Africa, the prevalence of both HIV infection and NCD risk factors were high. This study is among the first to quantify the substantial burden of NCD risk factors and depression in this non‐clinic based population.

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“…However, even with ART HIV-1 infected adults remain at higher risk of cardiovascular disease, dyslipidemia, insulin resistance, liver, kidney and bone dysfunction, neurocognitive disorders, accelerated biological aging, and cancer [1, 2]. Although the precise pathophysiology of many of these disorders is poorly understood, a syndrome of chronic immune activation and inflammation is a common feature [3, 4]. …”

Section: Introductionmentioning

confidence: 99%

Intracellular HIV-1 RNA and CD4+ T-cell activation in patients starting antiretrovirals

El-Diwany

Breitwieser

Soliman

et al. 2017

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Objective To assess if the reduction in HIV-1 RNA in CD4+ T cells is correlated with the persistence of immune activation following early antiretroviral therapy (ART) Design Clinical trial (NCT01285050). Methods Next-generation sequencing was used to study total RNA from activated CD4+ T cells (CD38 and HLA-DR expressing) collected from 19 treatment-naïve HIV-1/HCV infected patients before and early after ART initiation (≥12 weeks after plasma HIV RNA < 50 c/ml). To validate comparisons, pre- and post-ART measures were adjusted for input RNA and overall read number. Results As expected, ART use was associated with a median (IQR) 4.3 (2.2–8.3) reduction in the proportion of activated CD4+ T cells (P=0.0008). Whereas in those activated CD4+ T cells no consistent differences in overall gene expression were detected, interferon stimulated gene expression declined (P<2×10−16). Pre-ART, sorted activated CD4+ T cells contained a median (IQR) of 959 (252–1614) HIV-1 reads/107 reads compared to 72 (55–152) HIV-1 reads/107 reads after ≥12 weeks of suppressive ART (P=8×10−5). The decrease in HIV-1 reads in activated CD4+ T cells was associated with the change in plasma HIV-1 RNA levels (r=0.77, P=2×10−4) and the change in the proportion of activated CD4+ T cells (r=0.70, P=0.0016). Conclusions Months of ART led to a marked decrease in cell-associated HIV-1 RNA and ISG expression in activated CD4+ T cells that were strongly associated with the reduction in the proportion of activated CD4+ T cells.

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Inflammation, immune activation, and cardiovascular disease in HIV

Cited by 161 publications

References 193 publications

Association between Immune Markers and Surrogate Markers of Cardiovascular Disease in HIV Positive Patients: A Systematic Review

Association between Immune Markers and Surrogate Markers of Cardiovascular Disease in HIV Positive Patients: A Systematic Review

High prevalence of HIV and non‐communicable disease (NCD) risk factors in rural KwaZulu‐Natal, South Africa

Intracellular HIV-1 RNA and CD4+ T-cell activation in patients starting antiretrovirals

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