Indinavir increases glucose production in healthy HIV-negative men

Schwarz, Jean-Marc; Lee, Grace A.; Park, Seongsoo; Noor, Mustafa A.; Lee, Jeongae; Wen, Ming; Lo, Joan C.; Mulligan, Kathleen; Schambelan, Morris; Grünfeld, Carl

doi:10.1097/00002030-200409030-00017

Cited by 31 publications

(26 citation statements)

References 11 publications

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“…Previously, multiple studies have described the relationship between IR and the use of HAART, particularly PIs and some NRTIs. It has been shown that some PIs such as lopinavir or indinavir increase insulinemia in healthy volunteers (22,30,31), although it is debated whether this could be compensated in prolonged treatments (32). PIs could inhibit proteases responsible for conversion of proinsulin into insulin, as well as protease regulating insulin catabolism, generating a state of hyperinsulinemia and hyperglycemia (33).…”

Section: Discussionmentioning

confidence: 99%

Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs

Araújo

Bañón

Machuca

et al. 2014

European Journal of Endocrinology

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Objective: HIV-infected patients had a higher prevalence of insulin resistance (IR) and risk of diabetes mellitus (DM) than that observed in healthy controls, but there are no data about the current prevalence considering the changes in HIV presentation and the use of newer antiretroviral drugs. Design: Longitudinal study which involved 265 HIV patients without DM, receiving first (nZ71) and advanced lines of antiretroviral therapy (nZ194). Methods: Prevalence of IR according to clinical and anthropometric variables, including dual X-ray absorptiometry (DXA) scan evaluation. IR was defined as homeostasis model assessment of IR R3.8. Incident DM was assessed during the follow-up. Results: First-line patients had a short time of HIV infection, less hepatitis C virus coinfection, and received mainly an efavirenz-based regimen. Overall, the prevalence of IR was 21% (55 patients, 6% in first-line, 27% in pretreated). In a logistic regression analysis, significant associations were found between the waist/hip circumference ratio (RR 10; 95% CI 1.66-16; P!0.01, per unit), and central fat in percentage (RR 1.08; 95% CI 1.01-1.17; PZ0.04, per unit) as evaluated by DXA, and IR. During 770.8 patient-years, DM was diagnosed in 8% (22 patients), mostly in pretreated patients (10 vs 4%; PZ0.1). Thus, the overall rate of incident DM was 2.85 per 100 person-years, mostly in previous IR (10.39 vs 0.82/100 person-years; PZ0.01). Conclusions: A lower prevalence of IR is observed in the current HIV-infected patients with fewer risk factors and receiving newer antiretroviral drugs. IR continues to identify patients at high risk for developing DM in the short term.

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Section: Discussionmentioning

confidence: 99%

Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs

Araújo

Bañón

Machuca

et al. 2014

European Journal of Endocrinology

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“…Treatment with indinavir (protease inhibitor) for four weeks, of individuals not infected with HIV promoted an increase in the levels of glucose and a 20% reduction in insulin sensitivity 46 . Schwarz et al 47 also showed a 17% decrease in insulin sensitivity, associated with an increase in the production of glucose and glycogenolysis, indicating that indinavir induces peripheral insulin resistance and increases the production of endogenous glucose. It is noteworthy that this condition may be associated with HIV infection, probably by direct action of the virus on pancreatic β-cell function or in the mechanism of action of insulin 48 .…”

Section: Changes In Glycolytic Metabolicmentioning

confidence: 96%

Alterações metabólicas, terapia antirretroviral e doença cardiovascular em idosos portadores de HIV

Krämer

Lazzarotto

Sprinz

et al. 2009

Arq. Bras. Cardiol.

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SummaryOne of the most recent phenomena related to the acquired immunodeficiency syndrome (AIDS) is the emergence of a new vulnerable population: the elderly. One of the factors that account for this increase is the development of combination antiretroviral therapy (ART), which has provided better quality of life and life expectancy for HIV-positive patients. However, ART is associated with adverse effects such as dyslipidemia, diabetes mellitus and insulin resistance, which are risk factors for cardiovascular disease. Due to the impact of ART on lipid and glucose metabolism, many studies were published involving HIV infection and cardiovascular disease, as well as their risk factors and the use of ART, but few of them reported on the cardiotoxicity of this therapy in the elderly. The objective of this study is to review the main metabolic changes caused by the use of antiretroviral therapy and its impact on an increased risk of cardiovascular disease in elderly people with HIV.

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“…Compared with administration of low-dose RTV alone, co-administration of darunavir resulted in slightly lower RTV C max (563 vs. 669 ng Á h/mL) and AUC 24 h (4729 vs. 5442 ng/h/mL) values, whereas coadministration of atazanavir and RTV led to higher RTV C max (1120 vs. 691 ng/mL) and AUC 24 h (9277 vs. 5717 ng/h/ mL) values. Relative to treatment with low-dose RTV alone, the least squares mean ratios (90% CIs) for RTV C min , C max and AUC 24 …”

Section: Effect Of Darunavir and Atazanavir On Rtv Pharmacokineticsmentioning

confidence: 99%

Effects of ritonavir‐boosted darunavir vs. ritonavir‐boosted atazanavir on lipid and glucose parameters in HIV‐negative, healthy volunteers

Tomaka¹,

Lefebvre

Sekar³

et al. 2009

HIV Medicine

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Background Darunavir (TMC114) is a new HIV protease inhibitor (PI). DesignThis Phase I, randomized, open-label trial compared the effects of darunavir plus low-dose ritonavir (RTV) (darunavir/RTV) with those of atazanavir/RTV on lipid and glucose parameters. MethodsForty-nine HIV-negative, healthy male volunteers received RTV 100 mg once a day (qd) for 7 days, followed by either darunavir/RTV 800/100 mg qd (n 5 25) or atazanavir/RTV 300/100 mg qd (n 5 24) for 21 days. Mean changes in fasting lipid and glucose parameters at day 28 were calculated using post-RTV alone (day 7) and baseline (day À 1) values as references. Short-term safety, tolerability and RTV pharmacokinetic parameters were evaluated. ResultsAfter 7 days of RTV treatment, the mean triglyceride concentration increased by approximately 30 mg/dL in both groups, changes in other lipid and glucose parameters were relatively small. Mean concentrations of lipids and glucose over the treatment period were mostly similar between the treatment groups. Mean changes from day 7 to day 28 for the darunavir/RTV and atazanavir/RTV groups, respectively, were À 3.6 and À 0.5 mg/dL for high-density lipoprotein cholesterol; 5.0 and 5.3 mg/dL for low-density lipoprotein cholesterol; 4.9 and 1.2 mg/dL for total cholesterol; 6.4 and 14.0 mg/dL for triglycerides; À 1.7 and À 2.4 mg/dL for glucose; and À 1.4 and 0.3 mg/dL for insulin. No grade 3 or 4 lipid or glucose laboratory abnormalities were reported. Treatmentemergent hyperbilirubinaemia was reported for all volunteers (including five grade 4 cases) during atazanavir/RTV treatment. ConclusionsCo-administration of darunavir or atazanavir with low-dose RTV resulted in minor and similar changes in lipid and glucose parameters in HIV-negative healthy volunteers. IntroductionThe introduction of HIV protease inhibitors (PIs) as part of highly active antiretroviral therapy (HAART) has drastically reduced the morbidity and mortality associated with HIV infection [1]. A new PI, darunavir (TMC114), has recently been shown to have considerable antiretroviral (ARV) activity in treatment-experienced patients. Darunavir boosted with low-dose ritonavir (RTV) (darunavir/RTV) led to significantly higher 24-and 48-week virological and immunological responses compared with currently available PIs in the POWER 1 and 2 (TMC114-C213 and TMC114-C202) studies in treatment-experienced HIVinfected patients, and was well tolerated [2][3][4].Given the need for lifelong antiretroviral therapy (ART), consideration of long-term toxicities is becoming increasingly important when choosing among different treatment regimens. It is therefore important to characterize the longterm tolerability profile of any new treatment, including DOI: 10.1111/j.1468-1293.00690.x HIV Medicine (2009 r 2009 British HIV Association 318 long-term metabolic abnormalities such as fat redistribution, dyslipidaemia, glucose intolerance and insulin resistance [5][6][7]. The association between ART and changes in lipid metabolism is well documented, particularly with PIs [...

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Indinavir increases glucose production in healthy HIV-negative men

Cited by 31 publications

References 11 publications

Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs

Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs

Alterações metabólicas, terapia antirretroviral e doença cardiovascular em idosos portadores de HIV

Effects of ritonavir‐boosted darunavir vs. ritonavir‐boosted atazanavir on lipid and glucose parameters in HIV‐negative, healthy volunteers

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