The HIV-1/HAART associated metabolic syndrome – Novel adipokines, molecular associations and therapeutic implications

Tsiodras, Sotirios; Perelas, Apostolos; Wanke, Christine; Mantzoros, Christos S.

doi:10.1016/j.jinf.2010.06.002

Cited by 47 publications

(53 citation statements)

References 192 publications

(136 reference statements)

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“…5,[19][20][21][22] In the HIV-1-infected population, lipodystrophy is an umbrella term that encompasses all changes in fat distribution, including lipohypertrophy, which can include accumulation of fat in the neck, chest, back, breasts, and/or abdomen, and lipoatrophy, which may include fat loss from the limbs, buttocks, and/or face. [23][24][25] HIV-1-associated changes in body shape have the potential to impact a subject's quality of life and well-being, and several studies have linked quality of life to survival of HIV-1-infected subjects. [26][27][28] Interestingly, subjects' perceptions of the changes to their body during ARV therapy are not always in accordance with the objective changes measured in a clinical setting.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Aberg

Tebas

Overton

et al. 2012

AIDS Research and Human Retroviruses

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We assessed metabolic changes for darunavir/ritonavir (DRV/r) once daily (qd) versus atazanavir/ritonavir (ATV/r) qd with fixed-dose tenofovir/emtricitabine. This was a phase 4, multicenter, open-label, randomized exploratory study. Treatment-naive, HIV-1-infected adults received DRV/r 800/100 mg qd or ATV/r 300/ 100 mg qd, both with emtricitabine/tenofovir 200/300 mg qd. Primary end point: change in triglyceride levels from baseline to week 12. Secondary end points: week 12 and week 48 changes in lipid parameters, insulin sensitivity, inflammatory/coagulation/bacterial translocation biomarkers, viral load, CD4 + cell count, and week 48 changes in adipose tissue distribution and subjects' perceptions of body changes. In the DRV/r arm, 32/34 and 29/34 subjects completed weeks 12 and 48, respectively; in the ATV/r arm, 30/31 and 25/31 subjects completed weeks 12 and 48, respectively. Small changes in lipid parameters from baseline to weeks 12 and 48 were observed in both arms. Differences were noted between arms in mean changes in total cholesterol (DRV/r, 20.3 mg/dl; ATV/r, 4.6 mg/dl) and apolipoprotein A1 (DRV/r, 10.7 mg/dl; ATV/r, -0.7 mg/dl) at week 12. At week 48, no clinically relevant differences between arms were noted for changes in any lipid parameter, fasting glucose, or insulin sensitivity. Biomarkers generally decreased and efficacy parameters improved in both arms over 48 weeks. Changes in adipose tissue were small and comparable between arms. Subjects' perceptions of body changes generally improved in both study arms. This first pilot comparison in HIV-1-infected subjects suggests that DRV/r has a metabolic profile similar to ATV/r over 48 weeks of treatment. Further randomized studies are warranted.

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Section: Introductionmentioning

confidence: 99%

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Aberg

Tebas

Overton

et al. 2012

AIDS Research and Human Retroviruses

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“…PIs have been shown to suppress adipocyte differentiation [9,[22][23][24]. The catalytic site of HIV-protease, to which PIs bind shares approximately 63% of 12-amino acid sequence homology with a region incorporating a lipid binding domain in the low-density lipoprotein receptor-related protein (LRP) and 58% with a C-terminal region of the cytoplasmic retinoic acid binding protein type 1 (CRABP-1) [15,17], respectively.…”

Section: Pis and Lipid Metabolismmentioning

confidence: 99%

“…Furthermore, PIs have been reported to impair insulin secretion in the pancreatic β cells [24,29] and also contribute to insulin resistance by inhibiting LDL-receptor activity leading to elevated plasma TG [10]. PI-induced insulin resistance is also potentiated by reduced conversion of pro-insulin to insulin, decreased secretion of adiponectin (which leads to increased hepatic gluconeogenesis and reduced glucose uptake by adipose tissue and skeletal muscles) and also down-regulates the expression of SREBP-1, a transcriptional regulator involved in lipid homeostasis [22,24,28].…”

Section: Pi-induced Glucose Intolerance and Insulin Resistancementioning

confidence: 99%

“…PI-induced insulin resistance is also potentiated by reduced conversion of pro-insulin to insulin, decreased secretion of adiponectin (which leads to increased hepatic gluconeogenesis and reduced glucose uptake by adipose tissue and skeletal muscles) and also down-regulates the expression of SREBP-1, a transcriptional regulator involved in lipid homeostasis [22,24,28].…”

Section: Pi-induced Glucose Intolerance and Insulin Resistancementioning

confidence: 99%

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Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome and Lipodystrophy: Pathophysiology and Current Therapeutic Interventions

et al. 2017

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The use of highly active antiretroviral therapy (HAART) has extremely enhanced the clinical outcome of HIV disease with a decrease in mortality and morbidity. However, the inclusion of protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (tNRTIs) has strongly been linked to the development of metabolic abnormalities and lipodystrophy. Lipodystrophy is defined by the loss of peripheral subcutaneous fat and central adiposity, mainly in the abdomen, breast and dorsocervical region. These disorders are reported to be cosmetically distressing and socially stigmatizing to many patients leading to decreased adherence to antiretroviral therapy. Metabolic syndrome precedes lipodystrophy leading to increased risk of diabetes and cardiovascular diseases. With a shifted trajectory of HIV/AIDS morbidity from immunodeficiency and opportunistic infections to metabolic complications, clinical management of these patients has therefore become more complex. Currently there are no evidence-based standard guidelines for the management of HIV-associated lipodystrophy. Several pharmacological interventions such as using anti-diabetic, anti-dyslipidemic drugs or hormone replacement therapy have been tried to effectively improve metabolic syndrome and lipodystrophy but have been hampered by low efficacy, drug interactions, or unwanted side-effects. Non-pharmacological interventions including surgical manipulations, dietary and lifestyle modifications have also been tried with limited success. This review focuses on the proposed mechanisms involved in the development of metabolic syndrome and lipodystrophy, and highlights suggested potential therapeutic interventions to prevent lipodystrophy associated with HAART.

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“…3, 18 It should be stressed that, in contrast to other studies, we recruited only those patients who were treated with 2 NRTIs (with the exclusion of stavudine and didanosine) combined with PIs. PIs, which interact with the adipocyte proteosomal system, affect proteins involved in lipid metabolism/trafficking and cause insulin resistance.…”

Section: 15-17mentioning

confidence: 99%

Metabolic complications and selected cytokines in HIV‑infected individuals

Bociąga‐Jasik¹,

Polus²,

Góralska³

et al. 2013

Polish Archives of Internal Medicine

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The HIV-1/HAART associated metabolic syndrome – Novel adipokines, molecular associations and therapeutic implications

Cited by 47 publications

References 192 publications

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome and Lipodystrophy: Pathophysiology and Current Therapeutic Interventions

Metabolic complications and selected cytokines in HIV‑infected individuals

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