Zidovudine/lamivudine contributes to insulin resistance within 3 months of starting combination antiretroviral therapy

Blümer, Regje M. E.; Vonderen, Marit G. A. van; Sutinen, Jussi; Hassink, Elly A. M.; Ackermans, Mariëtte T.; Agtmael, Michiel A. van; Yki‐Järvinen, Hannele; Danner, Sven A.; Reiss, Peter; Sauerwein, Hans P.

doi:10.1097/qad.0b013e3282f33557

Cited by 79 publications

(66 citation statements)

References 50 publications

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“…NRTIs inhibit DNA polymerase gamma, an enzyme essential for mitochondrial DNA replication, resulting in mitochondrial DNA depletion, adipocyte death and lipoatrophy [143]. It has been also demonstrated that treatment with a NRTI-containing regimen of lamivudine or zidovudine in the absence of significant changes in body fat distribution, led to a 25% decrease in insulin-mediated peripheral glucose disposal and a 22% increase in fasting lipolysis [144]. However, a very recent study showed that substitution of stavudine with zidovudine could result in decreased severity or resolution of lipodystrophy among HIV-infected children and adolescents [145].…”

Section: Pathogenesis Of Hiv Lipodystrophymentioning

confidence: 99%

Metabolic Disorders in HIV-infected Children Metabolic Disorders in HIVinfected Children

Liguoro¹

2014

J Metabolic Synd

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The introduction of highly active antiretroviral therapy (HAART) for the treatment of acquired immunodeficiency syndrome (AIDS) has resulted in greater survival of patients infected with the human immunodeficiency virus (HIV). However, the use of these drugs has been associated with lipodystrophic syndrome (LS), which is characterized by metabolic alterations (dyslipidemia, insulin resistance, diabetes, and lactic acidosis) and abnormal corporal fat distribution. Clinically, LS may manifest as three different forms: lipohypertrophy (accumulation of fat in the central part of the body), lipoatrophy (loss of fat in the extremities, face and buttocks) and mixed (lipohypertrophy + lipoatrophy). Although its physiopathology has not been elucidated, some mechanisms have been described, including leptin and adiponectin deficiency, mitochondrial dysfunction and use of antiretroviral drugs. The type, dose and duration of the antiretroviral treatment, as well as age and puberty are the main risk factors. LS are also associated with increased incidence of cardiovascular illnesses, atherosclerosis and diabetes mellitus. Follow up must be periodic, consisting of measurement of body fat distribution, evaluation of the lipid profile and insulin resistance.

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Section: Pathogenesis Of Hiv Lipodystrophymentioning

confidence: 99%

Metabolic Disorders in HIV-infected Children Metabolic Disorders in HIVinfected Children

Liguoro¹

2014

J Metabolic Synd

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“…Nucleo side reverse-transcriptase inhibitors have also been shown to induce insulin resistance in clamp studies [47]. After 4 weeks of stavudine treatment in healthy, HIV-negative controls, clamp insulin sensitivity was reduced, and associated with falls in striated muscle mitochondrial DNA and reduced mitochondrial function (by 31 P magnetic resonance spectroscopy) [52].…”

Section: Glucose Disorders In Treated Hiv Infection and Potential Suscementioning

confidence: 99%

“…In a separate study of HIV-negative subjects, ritonavir reduced insulin sensitivity by 15%; no effect was found with amprenavir [46]. In treatment-naive HIV-infected subjects, insulin sensitivity by clamp reduced 3 months after initiation of ritonavir-boosted International Diabetes Federation [37] n Waist >94 cm men/>80 cm women n Plus two of: -Glucose >5.6 mmol/l -High-density lipoprotein <1.20 mmol/l -Triglycerides >1.7 mmol/l -Systolic blood pressure >130 mmHg -Diastolic blood pressure >85 mmHg National Cholesterol Education Program-ATP III [38] n Any three of: -Waist >102 cm men/>88 cm women -Glucose >6. Review | Samaras lopinavir plus zidovudine/lamivudine [47]. By contrast, ritonavir-boosted lopinavir plus nevirapine had no observable effect on insulin sensitivity [47].…”

Section: Glucose Disorders In Treated Hiv Infection and Potential Suscementioning

confidence: 99%

How Sweet It Is? Susceptibility to Diabetes Mellitus in HIV-1 Treatment

Samaras

2009

HIV Ther.

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Treatment of HIV-1 infection with combined antiretroviral therapy substantially improves survival and quality of life, but is associated with metabolic disturbances such as insulin resistance, dyslipidemia and body fat partitioning disorders. These metabolic complications in the setting of suppression of viral replication are associated with increased observed risk for Type 2 diabetes mellitus. Disorders of glucose metabolism present additional challenges in the management of HIV infection, including the long-term complications of hyperglycemia, such as nephropathy, neuropathy and retinopathy, and magnified cardiovascular risk. This article considers how HIV infection and its treatment increases susceptibility to disorders of glucose metabolism. Diagnostic criteria, historical and clinical antecedents that assist the clinician in detection of diabetes susceptibility and treatment objectives are discussed.

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“…There are differences in the pathways through which various PIs induce IR and in their propensity to do so. Certain PIs, such as indinavir (IDV), lopinavir, and ritonavir, have been shown to www.intechopen.com reversibly induce IR, probably by inhibition of glucose translocation through GLUT4 (67) . In contrast, atazanavir had no effect on IR.The NRTIs, zidovudine and stavudine, also have direct and indirect effects on glucose metabolism (68,69) .…”

Section: Insulin Resistance (Ir) As One Of the Possible Mechanisms Inmentioning

confidence: 99%

HIV-Infection: The Role of Insulin Resistance and Alternative Treatments

Aghdassi¹

2011

HIV Infection in the Era of Highly Active Antiretroviral Treatment and Some of Its Associated Complications

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Zidovudine/lamivudine contributes to insulin resistance within 3 months of starting combination antiretroviral therapy

Cited by 79 publications

References 50 publications

Metabolic Disorders in HIV-infected Children Metabolic Disorders in HIVinfected Children

Metabolic Disorders in HIV-infected Children Metabolic Disorders in HIVinfected Children

How Sweet It Is? Susceptibility to Diabetes Mellitus in HIV-1 Treatment

HIV-Infection: The Role of Insulin Resistance and Alternative Treatments

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