Hyperlipidaemia in HIV-Infected Patients on Lopinavir/Ritonavir Monotherapy in Resource-Limited Settings

Matoga, Mitch; Hosseinipour, Mina C.; Aga, Evgenia; Ribaudo, Heather J.; Kumarasamy, Nagalingeswaran; Bartlett, John A.; Hughes, Michael D.

doi:10.3851/imp3101

Cited by 20 publications

(16 citation statements)

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“…In addition, PI appears to bind to the LDL receptor-related protein (LRP), and thus inhibit the function of the LRP-lipoprotein lipase complex (the cleavage of fatty acids from plasma triglycerides) [ 35 ]. PI-induced abnormal lipid metabolism may occur due to the alterations of genes in the adipocytes and hepatocytes through sterol regulatory element-binding proteins (SREBPs), cytoplasmic retinoic-acid binding proteins (CRABP-1), peroxisome proliferator activated receptors (PPARs), and apoCIII [ 35 , 38 , 39 ]. Our detailed information firstly showed that among these eight PI-containing regimens, lopinavir/ritonavir was associated with the highest risk of hyperlipidemia, followed by ritonavir ( Supplementary Tables 1 and 2 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of antiretroviral therapy use and adherence on the risk of hyperlipidemia among HIV-infected patients, in the highly active antiretroviral therapy era

et al. 2017

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HIV-infected patients exposed to antiretroviral therapy (ART) have an increased risk for hyperlipidemia and cardiovascular disease. We performed a longitudinal, comprehensive, and population-based study to investigate the cumulative effect of different types of ART regimens on hyperlipidemia risk in the Taiwanese HIV/ART cohort. A total of 13,370 HIV-infected patients (2,674 hyperlipidemia and 10,696 non-hyperlipidemia patients) were recruited after matching for age, gender, and the first diagnosis date of HIV infection by using the National Health Insurance Research Database in Taiwan. Hyperlipidemia risk associated with cumulative ART use, ART adherence, and their combination was assessed. The matched hyperlipidemia group had a larger number of patients using ART and a higher incidence of comorbidities, specifically, respiratory disease and diabetes. Patients with high ART dosage and dose-dependent manner adherence, respectively, demonstrated an increased risk of hyperlipidemia. For single ART regimens, patients receiving nucleoside reverse-transcriptase inhibitors (NRTI/NRTI)- containing regimen had the highest hyperlipidemia risk, followed by protease inhibitor (PI)- containing and non-NRTI- containing regimens. For combination ART regimens, patients receiving a NRTI/NRTI + PI regimen had the highest hyperlipidemia risk. An increased cumulative drug dose was observed in patients who received the PI, NRTI/NRTI, NRTI, and NNRTI regimens in the hyperlipidemia group, when compared to the non-hyperlipidemia group. In conclusion, ART cumulative use, adherence, and regimen may affect hyperlipidemia risk among HIV-infected patients in a dose-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Effect of antiretroviral therapy use and adherence on the risk of hyperlipidemia among HIV-infected patients, in the highly active antiretroviral therapy era

et al. 2017

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“…Our results also showed that treatment of mice with Aba/Lam and Lop/Rit enhanced the lipid accumulation in the liver, and decreased AMPK phosphorylation and/or the expression of ACC acetyl-CoA. ART drugs may bind to the LDL receptor-related protein (LRP), thereby inhibiting the function of the LRP-Lpl complex (the cleavage of fatty acids from plasma triglycerides) ( Carr et al, 1998 ; Matoga et al, 2017 ). ART drugs may also induce abnormal lipid metabolism by causing alterations in particular genes, including genes encoding sterol regulatory element-binding proteins, cytoplasmic retinoic-acid binding proteins, peroxisome proliferator activated receptors, and apoCIII ( Prot et al, 2006 ; Matoga et al, 2017 ).…”

Section: Discussionmentioning

confidence: 78%

“…HIV-1-infected patients receiving Aba/Lam-containing regimens were also found to have increased blood cholesterol levels ( Moyle et al, 2015 ). Lop/Rit has been also associated with hyperlipidemia in both human clinical studies and murine models ( Gupta et al, 2012 ; Wangpatharawanit and Sungkanuparph, 2016 ; Matoga et al, 2017 ). Our results also showed that treatment of mice with Aba/Lam and Lop/Rit enhanced the lipid accumulation in the liver, and decreased AMPK phosphorylation and/or the expression of ACC acetyl-CoA.…”

Section: Discussionmentioning

confidence: 99%

“…ART drugs may bind to the LDL receptor-related protein (LRP), thereby inhibiting the function of the LRP-Lpl complex (the cleavage of fatty acids from plasma triglycerides) ( Carr et al, 1998 ; Matoga et al, 2017 ). ART drugs may also induce abnormal lipid metabolism by causing alterations in particular genes, including genes encoding sterol regulatory element-binding proteins, cytoplasmic retinoic-acid binding proteins, peroxisome proliferator activated receptors, and apoCIII ( Prot et al, 2006 ; Matoga et al, 2017 ). Furthermore, tissue lipids and hyperlipidemia may be affected by the signaling mechanism that is involved in phosphorylation and expression of AMPK protein and its downstream target, ACC protein, which is known to play a role in fatty acid oxidation and lipid synthesis ( Zang et al, 2004 , 2006 ; Hou et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Oral Antiretroviral Drugs in Mice With Metabolic and Neurologic Complications

Tsai

Lai

et al. 2018

Front. Pharmacol.

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Antiretroviral (ART) drugs has previously been associated with lipodystrophic syndrome, metabolic consequences, and neuropsychiatric complications. ART drugs include three main classes of protease inhibitors (PIs), nucleoside analog reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Our previous work demonstrated that a high risk of hyperlipidemia was observed in HIV-1-infected patients who received ART drugs in Taiwan. Patients receiving ART drugs containing either Abacavir/Lamivudine (Aba/Lam; NRTI/NRTI), Lamivudine/Zidovudine (Lam/Zido; NRTI/NRTI), or Lopinavir/Ritonavir (Lop/Rit; PI) have the highest risk of hyperlipidemia. The aim of this study was to investigate the effects of Aba/Lam (NRTI/NRTI), Lam/Zido (NRTI/NRTI), and Lop/Rit (PI) on metabolic and neurologic functions in mice. Groups of C57BL/6 mice were administered Aba/Lam, Lam/Zido, or Lop/Rit, orally, once daily for a period of 4 weeks. The mice were then extensively tested for metabolic and neurologic parameters. In addition, the effect of Aba/Lam, Lam/Zido, and Lop/Rit on lipid metabolism was assessed in HepG2 hepatocytes and during the 3T3-L1 preadipocyte differentiation. Administration with Aba/Lam caused cognitive and motor impairments in mice, as well as their metabolic imbalances, including alterations in leptin serum levels. Administration with Lop/Rit also caused cognitive and motor impairments in mice, as well as their metabolic imbalances, including alterations in serum levels of total cholesterol, and HDL-c. Treatment of mice with Aba/Lam and Lop/Rit enhanced the lipid accumulation in the liver, and the decrease in AMP-activated protein kinase (AMPK) phosphorylation and/or its downstream target acetyl-CoA carboxylase (ACC) protein expression. In HepG2 hepatocytes, Aba/Lam, Lam/Zido, and Lop/Rit also enhanced the lipid accumulation and decreased phosphorylated AMPK and ACC proteins. In 3T3-L1 pre-adipocyte differentiation, Aba/Lam and Lop/Rit reduced adipogenesis by decreasing expression of transcription factor CEBPb, implicating the lipodystrophic syndrome. Our results demonstrate that daily oral administration of Aba/Lam and Lop/Rit may produce cognitive, motor, and metabolic impairments in mice, regardless of HIV-1 infection.

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“…One study showed that at 12 weeks of treatment of lopinavir/ritonavir in patients with human immunodefieciency virus, small but significant increase from baseline in the fasting total cholesterol and triglyceride was observed. 2 Our patients developed lipemic serum within 2 weeks of treatment. In Morrison's cases, it is possible that the lopinavir/ ritonavir had contributed to or even caused the hypertriglyceridemia.…”

mentioning

confidence: 65%

Lipemic serum in patients with Coronavirus Disease 2019 (COVID‐19) undergoing treatment

Rubel¹,

Chong

Abdullah

et al. 2020

Journal of Medical Virology

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We read with interest the article by Morrison et al. on acute hypertriglyceridemia secondary to tocilizumab in patients with severe coronavirus disease . 1 One patient also had pancreatitis, a dreaded complication of hypertriglyceridemia.Both patients were already on lopinavir/ritonavir before tocilizumab (added day 9 and 13) was added. Propofol was briefly used.We recently had two out of 47 patients with moderate/severe COVID-19 who were treated with lopinavir/ritonavir and developed significant hypertriglyceridemia resulting in lipemic serum. The first patient (51-year-old man) with undiagnosed stage II chronic kidney disease (estimated glomerular filtration rate 61.12 mL/min) and no history of lipid disorder or diabetes mellitus was started on lopinavir/ritonavir (400 and 100 mg twice daily for 14 days) on the 10th day of admission. Blood serum became lipemic on the 10th day of treatment (Figure 1). Serum triglyceride levels ranged between 921.2 and 1071.7 mg/dL (normal range <150 mg/dL). His serum amylase was normal. He was started on bezafibrate and the lipemic serum settled. The second patient (45-year-old man) with hypertension, dyslipidemia and uncontrolled diabetes mellitus was started lopinavir/ritonavir monotherapy on the 4th day of admission. His blood was reported to be lipemic on the 11th day of treatment despite being on atorvastatin. Fortunately he completed treatment without any complications. Follow-up showed no recurrence of lipemic serum in both patients. The second patient had risk factors for hypertriglyceridemia.Lopinavir/ritonavir is known to be associated with lipid abnormality, 2,3 more so than tocilizumab. One study showed that at 12 weeks of treatment of lopinavir/ritonavir in patients with human immunodefieciency virus, small but significant increase from baseline in the fasting total cholesterol and triglyceride was observed. 2 Our patients developed lipemic serum within 2 weeks of treatment. In Morrison's cases, it is possible that the lopinavir/ ritonavir had contributed to or even caused the hypertriglyceridemia. Therefore it is important for clinicians to be aware and monitor for complications given that the COVID-19 pandemic will continue and these two medications continue to be used until better treatment options become available.

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Hyperlipidaemia in HIV-Infected Patients on Lopinavir/Ritonavir Monotherapy in Resource-Limited Settings

Cited by 20 publications

References 31 publications

Effect of antiretroviral therapy use and adherence on the risk of hyperlipidemia among HIV-infected patients, in the highly active antiretroviral therapy era

Effect of antiretroviral therapy use and adherence on the risk of hyperlipidemia among HIV-infected patients, in the highly active antiretroviral therapy era

Evaluation of Oral Antiretroviral Drugs in Mice With Metabolic and Neurologic Complications

Lipemic serum in patients with Coronavirus Disease 2019 (COVID‐19) undergoing treatment

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