Longitudinal Analysis of the Associations between Antiretroviral Therapy, Viraemia and Immunosuppression with Lipid Levels: The D:A:D Study

Kamara, David A; Smith, Colette; Ryom, Lene; Reiss, Peter; Rickenbach, Martin; Phillips, Andrew; Mocroft, Amanda; Wit, Stéphane De; Law, Matthew; Monforte, Antonella d’Arminio; Dabis, François; Pradier, Christian; Lundgren, Jens D; Sabin, Caroline

doi:10.3851/imp3051

Cited by 22 publications

(10 citation statements)

References 46 publications

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“…11,12 Among HIVinfected persons, associations have also been observed between markers of HIV disease progression and antiretroviral treatment responses and serum lipid concentrations. Lower CD4 T lymphocyte cell count and/or higher HIV RNA viral load (VL) have been associated with increased concentrations of triglycerides and decreased concentrations of total cholesterol, LDL-C, and HDL-C. [13][14][15][16][17][18] One epidemiologic study explored whether associations between CD4 cell count and HIV VL and markers of metabolic function, including lipid concentrations, might differ by age group, categorized in that study as <30, 30-50, and >50 years. 13 A statistically significant synergistic interaction between CD4 count and age was detected when modeling serum albumin and hemoglobin concentrations, whereby stronger positive associations between CD4 count and albumin or hemoglobin concentrations were observed among patients older than 50 years.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppression and HIV Viremia Associated with More Atherogenic Lipid Profile in Older People with HIV

Levy

Greenberg

Magnus

et al. 2019

AIDS Research and Human Retroviruses

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To explore reasons for the disproportionate metabolic and cardiovascular disease burdens among older HIVinfected persons, we investigated whether associations of CD4 count and HIV viral load (VL) with non-highdensity lipoprotein cholesterol (non-HDL-C) and high-density lipoprotein cholesterol [HDL-C] differed by age. Longitudinal clinical and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients in the DC Cohort study. Using data for patients aged ‡21 years with ‡1 cholesterol result and contemporaneous CD4/VL results, we created multivariable linear regression models with generalized estimating equations. Among 3,912 patients, the median age was 50 years, 78% were male, 76% were non-Hispanic black, 93% were using antiretroviral therapy, 8% had a CD4 count <200 cells/lL, and 18% had an HIV VL ‡200 copies/mL. Overall, CD4 count <200 (vs. >500) cells/lL and VL ‡200 copies/mL were associated with lower non-HDL-C concentrations (p < .01), but associations were more positive with increasing age (CD4-age/VL-age interactions, p < .01). CD4 count <200 cells/lL was associated with lower non-HDL-C among patients aged <50 years [b =-7.8 mg/dL (95% confidence interval, CI:-13.2 to-2.4)] but higher non-HDL-C among patients aged 60-69 years [b = +8.1 mg/dL (95% CI: 0.02-16.2)]. VL ‡200 copies/mL was associated with lower non-HDL-C among patients aged <50 years [b =-3.3 mg/dL (95% CI:-6.7 to 0.1)] but higher non-HDL-C among patients aged ‡70 years [b = +16.0 mg/dL (95% CI:-1.4 to 33.3)], although precision was reduced in age-stratified analyses. Although no age differences were detected for HDL-C, VL ‡200 copies/mL was more strongly associated with lower HDL-C concentrations when CD4 count was <200 cells/lL [b =-7.0 mg/dL (95% CI:-9.7 to-4.3)] versus 200-500 cells/lL [b =-4.2 (95% CI:-5.9 to-2.6)] or >500 cells/lL [b =-2.2 (95% CI:-3.7 to-0.8)] (CD4-VL interaction, p < .01). We detected a novel age-modified relationship between immunosuppression and viremia and atherogenic cholesterol patterns. These findings may contribute to our understanding of the high risk of dyslipidemia observed among persons aging with HIV.

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Section: Introductionmentioning

confidence: 99%

Immunosuppression and HIV Viremia Associated with More Atherogenic Lipid Profile in Older People with HIV

Levy

Greenberg

Magnus

et al. 2019

AIDS Research and Human Retroviruses

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“…Lamivudine and telbivudine have been associated with myopathy and peripheral neuropathy, with the incidence of these effects being similar across all age groups and both genders [10]. The proposed mechanism underlying this reaction is the depletion of mitochondrial DNA [11]. An interesting report of two cases of lamivudine induced dystonia has been reported, which responded to prompt administration of anticholinergic agents and did not recur after lamivudine discontinuation [12].…”

Section: Neuropsychiatric Effects Of Antiviral Therapy For Chronic Hementioning

confidence: 99%

Neuropsychiatric Effects of Antiviral Drugs

Zareifopoulos¹,

Lagadinou²,

Karela³

et al. 2020

Cureus

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The adverse events of antiviral drugs are dose-dependent and often reversible. The nervous system is often affected and to date, many studies have been published regarding the central nervous system toxicity of antiviral agents. They may cause significant neuropsychiatric complications, which range from mild symptoms such as irritability and difficulty sleeping to severe complications such as depression, psychosis, and painful peripheral neuropathy, side effects which may necessitate discontinuation of treatment. The pathogenetic mechanisms may involve molecular targets common to other centrally active drugs, including human monoamine oxidase-A (MAO-A), serotonin receptors, gamma-aminobutyric acid (GABA) GABA-A receptors, 5-HT2A and 5-HT2C receptors and others. Notable examples include oseltamivir which may act as MAO inhibitor and efavirenz, which has an affinity for serotonin 5-HT2 and GABA-A receptors, the serotonin transporter, the MAO enzyme, and the vesicular monoamine transporter, with subjective effects which may be similar to those of the psychedelic hallucinogen lysergic acid diethylamide (LSD). Other antiviral drugs with prominent nervous system effects include nucleoside reverse transcriptase inhibitors, which are associated with the development of peripheral neuropathy after prolonged use (an effect strongly associated with older drugs which have since fallen into disfavor such as stavudine) and interferons, which may cause depression. Clinicians should be familiar with such adverse effects in order to recognise them promptly once they occur and manage them appropriately.

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“…Older protease inhibitors have also been associated with an increased cardiovascular risk because of their effects on lipid metabolism (Group DADS et al, 2007). On the other hand, until recently it was thought that newer protease inhibitors (e.g., atazanavir and darunavir) did not confer these risks (Overton et al, 2012;Kamara et al, 2016;Noor et al, 2006;Yan and Hruz, 2005;Aberg et al, 2012;Monforte et al, 2013). However, recent data from the D:A:D cohort showed that darunavir was independently associated with a 59% higher risk of CVD per 5 years of exposure, while atazanavir was protective (Ryom et al, 2017).…”

Section: Use Of Safer Artmentioning

confidence: 99%

Understanding mechanisms to promote successful aging in persons living with HIV

Escota

O’Halloran

Powderly

et al. 2018

International Journal of Infectious Diseases

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The mortality rate associated with HIV infection plummeted after the introduction of effective antiretroviral therapy pioneered two decades ago. As a result, HIV-infected people now have life expectancies comparable to that of HIV-uninfected individuals. Despite this, increased rates of osteoporosis, chronic liver disease, and in particular cardiovascular disease have been reported among people living with HIV infection. With the aging HIV-infected population, the burden of these comorbid illnesses may continue to accrue over time. In this paper, we present an overview of the aging HIV-infected population, its epidemiology and the many challenges faced. How to define and measure successful aging will also be reviewed. Finally, opportunities that may help mitigate the challenges identified and ensure successful aging among people living with HIV infection will be examined.

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Longitudinal Analysis of the Associations between Antiretroviral Therapy, Viraemia and Immunosuppression with Lipid Levels: The D:A:D Study

Cited by 22 publications

References 46 publications

Immunosuppression and HIV Viremia Associated with More Atherogenic Lipid Profile in Older People with HIV

Immunosuppression and HIV Viremia Associated with More Atherogenic Lipid Profile in Older People with HIV

Neuropsychiatric Effects of Antiviral Drugs

Understanding mechanisms to promote successful aging in persons living with HIV

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