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Metabolic effects of indinavir in healthy HIV-seronegative men

Noor, Mustafa A.a,c; Lo, Joan C.a,d; Mulligan, Kathleena,d; Schwarz, Jean-Marca,d,e; Halvorsen, Robert A.b; Schambelan, Morrisa,d; Grunfeld, Carla,c

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From the Departments of aMedicine and bRadiology, University of California at San Francisco, the cMetabolism and Endocrine Sections, San Francisco Department of Veterans Affairs Medical Center, the dDivision of Endocrinology, San Francisco General Hospital, San Francisco and the eDepartment of Nutritional Sciences, University of California Berkeley, Berkeley, California, USA. *Present address: University Hospital, University of Medicine and Dentistry of New Jersey, USA.

Requests for reprints to Dr M. A. Noor, Department of Veterans Affairs Medical Center, Metabolism Section (111F), 4150 Clement St, San Francisco, California 94121, USA.

Date of receipt: 22 January 2001;

revised: 1 February 2001; accepted: 14 February 2001.

Sponsorship: grants from Merck Research Laboratories (Merck & Co. Inc., Rahway, New Jersey, USA), the AIDS Clinical Research Center of University of California, San Francisco, and the Universitywide AIDS Research Program F99SF-044 (M.N) and by grants from the National Institutes of Health (NIH) DK45833 (M.S) and DK52615 (K.M). The studies were conducted in the General Clinical Research Center (GCRC) at San Francisco General Hospital supported by a grant (RR-00083) from the National Center for Research Resources (NCRR) NIH. J.L. is a Clinical Associate Physician supported by the NCRR. C.G. is supported by the University of California AIDS Clinical Research Center and the Research Service of the Department of Veterans Affairs.

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Abstract

Background: Therapy with HIV protease inhibitors (PI) has been associated with hyperglycemia, hyperlipidemia and changes in body composition. It is unclear whether these adverse effects are drug related, involve an interaction with the host response to HIV or reflect changes in body composition.

Methods: Indinavir 800 mg twice daily was given to 10 HIV-seronegative healthy men to distinguish direct metabolic effects of a PI from those related to HIV infection. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance (OGTT), insulin sensitivity by hyperinsulinemic euglycemic clamp, and body composition were measured prior to and after 4 weeks of indinavir therapy.

Results: Fasting glucose (4.9 ± 0.1 versus 5.2 ± 0.2 mmol/l; P = 0.05) insulin concentrations (61.7 ± 12.2 versus 83.9 ± 12.2 pmol/l; P < 0.05), insulin : glucose ratio (12.6 ± 1.7 versus 15.9 ± 1.9 pmol/mmol; P < 0.05) and insulin resistance index by homeostasis model assessment (1.9 ± 0.3 versus 2.8 ± 0.5; P < 0.05) all increased significantly. During OGTT, 2 h glucose (5.1 ± 0.4 versus 6.5 ± 0.6 mmol/l; P < 0.05) and insulin levels (223.1 ± 48.8 versus 390.3 ± 108.8 pmol/l; P =0.05) also increased significantly. Insulin-mediated glucose disposal decreased significantly (10.4 ± 1.4 versus 8.6 ± 1.2 mg/kg ⋅ min per μU/ml insulin; 95% confidence interval 0.6–3.0; P < 0.01). There was no significant change in lipoprotein, triglycerides or free fatty acid levels. There was a small loss of total body fat (15.8 ± 1.4 versus 15.2 ± 1.4 kg; P = 0.01) by X-ray absorptiometry without significant changes in weight, waist : hip ratio, and visceral or subcutaneous adipose tissue by computed tomography.

Conclusions: In the absence of HIV infection, treatment with indinavir for 4 weeks causes insulin resistance independent of increases in visceral adipose tissue or lipid and lipoprotein levels.

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Introduction

Therapy with HIV protease inhibitors (PI) has had a significant beneficial impact on HIV plasma viremia, immune function, opportunistic infections and mortality from AIDS [1,2]. However, treatment with a PI has been associated with abnormalities in carbohydrate and lipid metabolism, including insulin resistance, hyperglycemia [3–5] and hyperlipidemia [6–11]. Therapy with a PI is also reported to be accompanied by changes in body composition, which include visceral fat accumulation [12], symmetrical lipomatosis [13], dorsocervical fat deposition (buffalo hump) [14], and peripheral fat loss [15]. However, some of these changes in body composition and metabolism have also been reported in HIV-infected subjects not receiving PI therapy [16–18]. It is unclear whether adverse metabolic effects associated with PI are drug related, involve an interaction with the host response to HIV infection, or reflect changes in body composition.

In a recent prospective cohort study [10], treatment of HIV-infected subjects with a regimen that included a PI was found to induce hyperlipidemia and insulin resistance in the absence of changes in body composition. Studies on HIV-seronegative volunteers have shown that ritonavir caused significant hyperlipidemiaafter only 2 weeks of treatment, but effects on glucose metabolism were not reported [19]. These results are compatible with direct drug effects of a PI inducing hyperlipidemia and insulin resistance.

Controversy still remains as to whether the observed metabolic effects are unique to individual drugs or common to all PI, as adverse metabolic effects may be more pronounced with some PI than others [11]. Additionally, effects may be more severe in patients with ethnic [20] and genetic risk factors [21] for dyslipidemia and the metabolic syndrome. Finally, HIV infection itself induces changes in lipid metabolism [22], and therapy with PI may exacerbate these effects.

To resolve these issues, we gave indinavir to HIV-negative healthy volunteers to determine the effects of this PI drug in the absence of HIV infection and immune dysregulation. We studied glucose and lipid metabolism before and after 4 weeks of treatment to optimize detection of direct metabolic effects and minimize changes in body composition.

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Methods

The study protocol was approved by the Committee on Human Research of the University of California, San Francisco (UCSF) and informed consent was obtained from each subject. Healthy volunteer subjects were recruited from staff at UCSF and from the community. Subjects had no history of medical illnesses (including nephrolithiasis), showed no abnormalities on screening physical examination and had stable weight over the preceding 6 months. Family history alone was not used as a criterion for exclusion. All subjects had a negative HIV-1 antibody test prior to and at the end of the study.

Exclusion criteria included body mass index (BMI) > 27 kg/m2, fasting serum total cholesterol > 6.2 mmol/l, triglycerides > 3.84 mmol/l, fasting glucose > 7 mmol/l, serum aspartate or alanine aminotransferases > 50 U/l and creatinine > 1.4 mg/dl. Twelve subjects enrolled in the study. One subject failed to return after baseline studies; a second withdrew during the baseline study. The data from these two subjects were not used.

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Study design

This was an open-label study of indinavir. Subjects were admitted to the General Clinical Research Center (GCRC) at San Francisco General Hospital (SFGH) for 5 days and placed on a constant calorie diet with fixed proportions of carbohydrate, fat and protein designed to maintain body weight and minimize dietary influences on metabolism [23]. After baseline studies, subjects were discharged, given indinavir (Crixivan, Merck & Co, Rahway, New Jersey, USA) 800 mg every 8 h (0700, 1500, and 2100 h) and seen weekly for safety and adherence monitoring (see below). They were instructed to resume their usual diet and physical activity. After 4 weeks on treatment, subjects were re-admitted to the GCRC for a second 5-day period for repeat studies.

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Measurements

Fasting lipids and free fatty acids were measured by enzymatic colorimetric methods (Sigma Diagnostics, St Louis, Missouri, and Wako Chemicals, Richmond, Virginia, USA, respectively). Lipoprotein subfractions and lipoprotein (a) were measured by microultracentrifugation (Atherotech, Birmingham, Alabama, USA). Whole blood and plasma glucose and lactate were measured using a glucose analyzer (YSI 2300 STAT-Plus Glucose & Lactate Analyzer, YSI Inc., Yellow Springs, Ohio, USA). Serum insulin levels were determined by Coat-A-Count radioimmunoassay (Diagnostic Products Corp, Los Angeles, California, USA) with interassay coefficient of variation of 7.3%, lower detection limit of 1.3 μU/ml and 40% cross-reactivity with pro-insulin. Indinavir levels were measured by liquid chromatography mass spectrometry (lower detection limit of 5 ng/ml) at the Drug Research Unit, SFGH.

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Fat clearance

At 8:00 a.m., after a 10 h overnight fast, clearance of triglyceride-rich particles was determined by intravenous fat tolerance test, as described previously [24]. Intralipid (Liposyn II 20%, Abbott Laboratories, Chicago Illinois, USA) was infused at 0.1 g/kg body weight over 2 min and blood samples were collected at 0, 5, 10, 15, 20, 30, 40 and 50 min for nephelometry.

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Oral glucose tolerance test

At 8:00 a.m., after a 10 h overnight fast, subjects received 75 g glucose orally. Blood samples were collected at 0, 30, 60, 90, 120 and 180 min for the measurement of plasma glucose (NaF-containing tubes) and serum insulin. The areas under the curve (AUC) for glucose and insulin were calculated by the trapezoid method. Fasting plasma glucose (FPG) and serum insulin (FSI) levels were measured on 2 days and averaged data were used to calculate insulin resistance index (RI) by the homeostasis model assessment (HOMA) [25] (RI = FSI × FPG/22.5) and insulin : glucose (I:G) ratios.

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Studies of body composition

BMI was calculated as weight in kilograms divided by height in meters squared (kg/m2). Total and regional body composition were measured by dual-energy X-ray absorptiometry (DEXA; Lunar model DPX, Madison, Wisconsin, USA, software version 3.65) [26]. Analysis of scans was performed as previously described [18] with coefficient of variation for repeated regional analysis of trunk, arm, and leg fat at 1.0, 2.7, and 1.4%, respectively. Central abdominal region (at L2–L4) was analyzed as described by Carey et al. [27]

Computed tomography was performed on a helical HiSpeed CTI Scanner (General Electric Medical Systems, Milwaukee, Wisconsin, USA). A single 7 mm slice obtained at the level of the L4–L5 intervertebral disc space was used for quantification of visceral and subcutaneous fat. All images were analyzed in a matrix of 512 × 512 pixels by one investigator, with a coefficient of variation < 1% on repeat analysis.

Waist (at the level of the umbilicus) and hip circumferences were measured in triplicate and waist : hip ratio calculated. Bioelectric impedance analysis was performed using a tetra polar BIA101 Quantum (RJL Systems Inc, Clinton Township, Michigan, USA). Body cell mass and total body water were calculated using software version 3.1b.

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Hyperinsulinemic euglycemic clamp

The hyperinsuliemic euglycemic clamp was performed as described by DeFronzo et al. [28]. Polyethylene cannulae were placed into an antecubital vein for infusion and into a vein in the dorsum of the contralateral hand, which was kept in a heated box at 50–55°C for ‘arterialized’ blood sampling. Subjects fasted overnight prior to the procedure. Beginning at 9:00 a.m., insulin (Humulin R, Eli Lilly, Indianapolis, Indiana, USA) was administered as a primed continuous intravenous infusion, followed by a constant infusion at the rate of 40 mU/m2 ⋅ min for 180 min. Whole blood glucose concentration was measured every 5 min after the start of the insulin infusion. A variable infusion of 20% dextrose was used to maintain plasma glucose concentration at 4.4 mmol/l (80 mg/dl) with a coefficient of variation < 5% based on the negative feedback principle. Blood samples were collected for post-hoc determination of plasma glucose and serum insulin concentrations.

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Adherence

Subjects were instructed to take indinavir 800 mg three times daily with two glasses of water. Adherence was monitored at each weekly visit by four methods: (i) self-report and direct questioning; (ii) manual pill counts; (iii) electronic pill counts using a Medication Event Management System (MEMS, Aprex Corp. Union City, California, USA) for quantification of adherence rate and dosing intervals; and (iv) measurement of plasma indinavir trough levels.

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Statistical analyses

Data were analyzed using Sigma Stat v. 2.03 (SPSS, Inc. San Rafael, California, USA). Paired t-tests were used for normally distributed data. Non-parametric data were analyzed using Mann–Whitney or Wilcoxon Rank Sum test. Data are presented as mean ± SEM. P values are two-tailed.

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Results

Ten subjects completed the study. Subjects ranged in age from 30 to 65 years (mean 42.1 ± 3.9); four were non-white (two Hispanic, two African-American). Average weekly indinavir trough levels were 0.726 ± 0.205 μmol/l (range, 0.161–1.239) (446 ± 126 ng/ml) (range, 99–761 ng/ml). Average therapeutic coverage as measured by MEMS was 95 ± 2% (range, 86–100). The most common reported adverse effects were dry skin and dry mouth (in seven) followed by nausea and muscle aches (in three). Three subjects developed asymptomatic elevations in total bilirubin (peak levels 23, 17, and 16 mg/l) and one had aspartate aminotransferase elevation to twice the upper limit of normal value. No subject withdrew from the study because of adverse events related to indinavir.

Fasting glucose, insulin, I : G ratio and insulin resistance index by HOMA all increased significantly with indinavir (Table 1). Fasting lactate levels did not change. Seven subjects had an increase in HOMA index while three had no change (Fig. 1). During OGTT, glucose and insulin levels at 2 h also increased (Table 1). Of note, based on glucose levels at 2 h on OGTT, one subject developed diabetes (2 h glucose 11.3 mmol/l), one became glucose intolerant (2 h glucose 7.9 mmol/l), and one nearly developed impaired glucose tolerance (2 h glucose 7.7 mmol/l) (Fig. 2). A trend towards an increase in AUC for glucose was observed (Fig. 3a). Insulin levels at 2 h were significantly increased (Table 1 and Fig. 3b).

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Fig. 2
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Fig. 3
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Table 1
Table 1
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During hyperinsulinemic euglycemic clamp, a steady-state insulin level of ≃500 pmol/l was achieved after 30 min (Fig. 4a). Steady-state glucose levels of ≃4.5 mmol/l were reached at 60 min and were maintained for 180 min (Fig. 4a). After 4 weeks of indinavir treatment, insulin-mediated glucose disposal rate per unit of insulin from 60 to 180 min declined in nine out ten subjects by an average of 1.4 mg/kg ⋅ min per μU/ml (95% confidence interval, 0.6–3.0; P < 0.01) (Fig. 4b).

Fig. 4
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Total, direct cholesterol levels in low density lipoproteins (LDL), high density lipoproteins (HDL) and intermediate density lipoproteins did not change (Table 2). The mean difference in plasma triglyceride levels was not significant (P = 0.22), nor was there a significant change in plasma free fatty acids, lipoprotein (a) or subclasses of LDL and HDL. The density pattern of LDL particles increased in two subjects [type A (light) to type B (dense) and type AB (intermediate) to type B] and decreased in another (type AB to type A). The clearance time of triglycerides as measured by an intravenous fat tolerance test increased slightly (Table 2). After 4 weeks of indinavir treatment, there was no significant change in weight, waist : hip ratio, percentage body fat, body cell mass, total body water by bioelectric impedance analysis, or in visceral fat or subcutaneous fat by computed tomography. There was a small loss of total fat and trunk fat, but no change in L2–L4 fat. Total and regional lean body mass remained unchanged (Table 3).

Table 2
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Table 3
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Discussion

The metabolic effects of indinavir in HIV-seronegative subjects was studied to distinguish direct drug effects from those caused by the host response to HIV that occurs in the context of immune reconstitution. Following 4 weeks of treatment, there was a small decrease in total fat by DEXA but no increase in abdominal visceral fat and subcutaneous fat or the ratio of visceral to total adipose tissue by computed tomographic scanning. Consequently the effects on intermediary metabolism cannot be attributed to an increase in visceral fat, although they could be part of a more complex syndrome that subsequently would lead to changes in body composition.

Indinavir caused insulin resistance in these HIV-negative subjects. Insulin resistance could be demonstrated using fasting samples (HOMA index and insulin : glucose ratio), OGTT, and, more significantly, hyperinsulinemic euglycemic clamp. Based on 2 h glucose during OGTT, diabetes mellitus developed in one subject, impaired glucose tolerance in another and near impaired glucose tolerance in a third. These changes occurred despite only a small increase in fasting glucose and insulin levels. The increase of 5% in fasting glucose after 4 weeks of treatment was less than the average increase of 11% after 3 months on a PI drug seen in HIV-positive subjects in a prospective study [10], and the 15% reported in a cross-sectional study with average duration on PI of 18 months [5]. One previous study reported a delay in the peak of insulin levels in PI-treated compared with PI-naive HIV-infected patients [5]. However, there was a typical early peak of insulin levels in our HIV-negative patients treated with indinavir.

Genetic factors may play a role in susceptibility to the effects of indinavir. Three subjects had first-degree relatives with diabetes. These included the subject who developed diabetes and the subject who developed near impaired glucose tolerance by OGTT criteria. The third subject with a family history of diabetes had the greatest decline in glucose disposal rate (M value) during hyperinsulinemic euglycemic clamp on indinavir.

Peripheral insulin resistance has been reported as a complication of therapy with PI in HIV-infected patients, but the mechanism is not completely understood [5,10,15,19]. In this study there was a 20% decrease in sensitivity of the peripheral tissues to insulin action (i.e. insulin-mediated glucose disposal) during a hyperinsulinemic euglycemic clamp. Insulin-mediated glucose disposal occurs primarily in muscle and adipose tissues [29]. Insulin signaling induces translocation of the glucose transporter vesicles (predominantly GLUT4) to the plasma membrane [30]. In vitro study of the effect of PI on glucose uptake in cultured adipocytes has shown that indinavir at near-peak therapeutic concentration of 10 μmol/l (7120 ng/ml) caused inhibition of the insulin-stimulated glucose uptake [31]. This 26% decrease is similar to our finding of 20% decline in insulin-mediated glucose disposal, although findings in cultured cells cannot be directly extrapolated to results in vivo. Moreover, our data do not exclude another independent effect of indinavir on the liver that causes insulin resistance.

Our study demonstrates that treatment with indinavir for 4 weeks has little direct effect on lipid and lipoprotein levels in HIV-seronegative subjects. Total cholesterol values were within 8% of baseline and lipoprotein (a) remained unchanged. Triglycerides were 26% higher; however, this increase was not statistically significant as the increase in the mean level after indinavir treatment was driven primarily by a single subject. Lipoprotein subfraction analysis revealed no significant alteration in HDL subclasses. It is, therefore, unlikely that a defect in lipid metabolism is the cause of indinavir-induced insulin resistance. However, the finding of a small change in plasma triglyceride levels and an increased rate of clearance of triglycerides suggest that some changes occur that may increase in magnitude with longer exposure to PI or as a consequence of subsequent changes in body composition.

In the prospective cohort study of HIV-infected subjects cited above [10], those who initiated therapy with a PI had an average increase of 22% in total cholesterol, 20% in LDL cholesterol and 47% in triglycerides, consistent with other prospective studies of similar duration [9] in HIV-infected subjects. Also in contrast to our data, Purnell et al. found that HIV-seronegative subjects treated with ritonavir for only 2 weeks had an average increase of 24% in total cholesterol, 40% in lipoprotein (a), and 245% in triglycerides [32]. Though apparently contradictory, these data are supported by other observations indicating that ritonavir has a more potent effect on plasma lipids than other PI [8,11,21]. For example, ritonavir increased triglycerides, while nelfinavir and indinavir did not; ritonavir and nelfinavir caused statistically greater increases in LDL than did indinavir (150%, 144% and 126%, respectively) [11]. These data, therefore, support an early and more potent effect of ritonavir on lipids than with indinavir or nelfinavir. The differing effects of individual PI on lipids support the concept of drug-specific rather than class-specific effects.

Our study has a number of potential limitations. We have studied only one PI and therefore our data may not be applicable to all drugs in this class. We studied men only; metabolic effects might be different in pre- and postmenopausal women. While it was advantageous to study metabolism after 4 weeks of treatment with indinavir, we cannot determine if longer duration of treatment would lead to significant changes in body composition. Furthermore, we cannot determine whether changes in body composition, if they occurred, would compound the metabolic effects we have reported in this study. Data presented in this paper cannot be used to determine whether indinavir causes insulin resistance in the liver. Finally, combination drug regimens (e.g. indinavir in combination with ritonavir or stavudine) may have additional unique metabolic effects.

In summary, our study suggests that the earliest direct effect of treatment with indinavir on metabolism is peripheral insulin resistance, which can be detected within 4 weeks in the absence of any increases in visceral fat tissue. In that period, indinavir has little effect on lipid and lipoprotein levels in healthy HIV-negative subjects. The mechanism by which indinavir induces insulin resistance is unknown. Future studies are needed to assess whether these effects are common to other PI and how they might be influenced by genetic predisposition and interact with the changes in body composition.

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Acknowledgments

The authors thank Miyin Pang, Barbara Chang, Joy Hirai, Natalie Patterson, Carlynn Yee-Hicaiji and the GCRC nursing staff for technical assistance and Dr Francesca Aweeka for measuring indinavir levels.

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Jama-Journal of the American Medical Association
Antiretroviral treatment for adult HIV infection in 2002 - Updated recommendations of the international AIDS Society-USA panel
Yeni, PG; Hammer, SM; Carpenter, CCJ; Cooper, DA; Fischl, MA; Gatell, JM; Gazzard, BG; Hirsch, MS; Jacobsen, DM; Katzenstein, DA; Montaner, JSG; Richman, DD; Saag, MS; Schechter, M; Schooley, RT; Thompson, MA; Vella, S; Volberding, PA
Jama-Journal of the American Medical Association, 288(2): 222-235.

AIDS
Valuation and management of metabolic and coagulative disorders in HIV-infected patients receiving highly active antiretroviral therapy
Fantoni, M; Del Borgo, C; Autore, C
AIDS, 17(): S162-S169.

Herz
Metabolic syndrome and hyperlipidemia in HIV-positive patients
Behrens, GMN
Herz, 30(6): 458-466.
10.1007/s00059-005-2722-5
CrossRef
Expert Opinion on Drug Metabolism & Toxicology
Toxic metabolic syndrome associated with HAART
Haugaard, SB
Expert Opinion on Drug Metabolism & Toxicology, 2(3): 429-445.
10.1517/17425255.2.3.429
CrossRef
Journal of Endocrinological Investigation
Is resistin a link between highly active antiretroviral therapy and fat redistribution in HIV-infected children?
Spagnuolo, MI; Bruzzese, E; Vallone, GF; Fasano, N; De Marco, G; Officioso, A; Valerio, G; Volpicelli, M; Iorio, R; Franzese, A; Guarino, A
Journal of Endocrinological Investigation, 31(7): 592-596.

Journal of Viral Hepatitis
Predictors of insulin resistance among Hispanic adults infected with or at risk of infection with the human immunodeficiency virus and hepatitis C virus
Castaneda-Sceppa, C; Bermudez, OI; Wanke, C; Forrester, JE
Journal of Viral Hepatitis, 15(): 878-887.
10.1111/j.1365-2893.2008.01021.x
CrossRef
AIDS
Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers
Lee, GA; Rao, M; Mulligan, K; Lo, JC; Aweeka, F; Schwarz, JM; Schambelan, M; Grunfeld, C
AIDS, 21(): 2183-2190.

Hiv Clinical Trials
Update on HIV lipodystrophy
Kravcik, S
Hiv Clinical Trials, 5(3): 152-167.

Plos Medicine
Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy
Foulkes, AS; Wohl, DA; Frank, I; Puleo, E; Restine, S; Wolfe, ML; Dube, MP; Tebas, P; Reilly, MP
Plos Medicine, 3(3): 337-347.
ARTN e52
CrossRef
American Journal of Physiology-Endocrinology and Metabolism
Insulin sensitivity is preserved despite disrupted endothelial function
Shankar, SS; Considine, RV; Gorski, JC; Steinberg, HO
American Journal of Physiology-Endocrinology and Metabolism, 291(4): E691-E696.
10.1152/ajpendo.00006.2006
CrossRef
Biochimie
HIV antiretroviral treatment alters adipokine expression and insulin sensitivity of adipose tissue in vitro and in vivo
Lagathu, C; Kim, MJ; Maachi, M; Vigouroux, C; Cervera, P; Capeau, J; Caron, M; Bastard, JP
Biochimie, 87(1): 65-71.
10.1016/j.biochi.2004.12.007
CrossRef
Hiv Medicine
Enhanced glucagon-like peptide-1 (GLP-1) response to oral glucose in glucose-intolerant HIV-infected patients on antiretroviral therapy
Andersen, O; Haugaard, SB; Holst, JJ; Deacon, CF; Iversen, J; Andersen, UB; Nielsen, JO; Madsbad, S
Hiv Medicine, 6(2): 91-98.

Antiviral Therapy
A 6-month interruption improves adipose tissue of antiretroviral therapy function in HIV-infected patients: the ANRS EP29 Lipostop Study
Kim, MJ; Leclercq, P; Lanoy, E; Cervera, P; Antuna-Puente, B; Maachi, M; Dorofeev, E; Slama, L; Valantin, MA; Costagliola, D; Lombes, A; Bastard, JP; Capeau, J
Antiviral Therapy, 12(8): 1273-1283.

Cardiovascular Toxicology
Severe impairment of endothelial function with the HIV-1 protease inhibitor indinavir is not mediated by insulin resistance in healthy subjects
Dube, MP; Gorski, JC; Shen, CY
Cardiovascular Toxicology, 8(1): 15-22.
10.1007/s12012-007-9010-y
CrossRef
Bmc Complementary and Alternative Medicine
Pharmacokinetic and metabolic effects of American ginseng (Panax quinquefolius) in healthy volunteers receiving the HIV protease inhibitor indinavir
Andrade, ASA; Hendrix, C; Parsons, TL; Caballero, B; Yuan, CS; Flexner, CW; Dobs, AS; Brown, TT
Bmc Complementary and Alternative Medicine, 8(): -.
ARTN 50
CrossRef
Hiv Medicine
The prevalence of metabolic syndrome in Danish patients with HIV infection: the effect of antiretroviral therapy
Hansen, BR; Petersen, J; Haugaard, SB; Madsbad, S; Obel, N; Suzuki, Y; Andersen, O
Hiv Medicine, 10(6): 378-387.
10.1111/j.1468-1293.2009.00697.x
CrossRef
Expert Opinion on Drug Metabolism & Toxicology
Indinavir/ritonavir remains an important component of HAART for the treatment of HIV/AIDS, particularly in resource-limited settings
Cressey, TR; Plipat, N; Fregonese, F; Chokephaibulkit, K
Expert Opinion on Drug Metabolism & Toxicology, 3(3): 347-361.
10.1517/17425255.3.3.347
CrossRef
Journal of Clinical Endocrinology & Metabolism
The effects of recombinant human growth hormone on body composition and glucose metabolism in HIV-infected patients with fat accumulation
Lo, JC; Mulligan, K; Noor, MA; Schwarz, JM; Halvorsen, RA; Grunfeld, C; Schambelan, M
Journal of Clinical Endocrinology & Metabolism, 86(8): 3480-3487.

AIDS
Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome
Kosmiski, LA; Kuritzkes, DR; Lichtenstein, KA; Glueck, DH; Gourley, PJ; Stamm, ER; Scherzinger, AL; Eckel, RH
AIDS, 15(): 1993-2000.

Jaids-Journal of Acquired Immune Deficiency Syndromes
Managing antiretroviral-associated liver disease
Dieterich, D
Jaids-Journal of Acquired Immune Deficiency Syndromes, 34(): S34-S39.

AIDS Patient Care and Stds
Optimizing care for African-American HIV-positive patients
Smith, KY; Brutus, A; Cathcart, R; Gathe, J; Johnson, W; Jordan, W; Kwakwa, HA; Nkwanyou, J; Page, C; Scott, R; Vaughn, AC; Virgil, LA; Williamson, D
AIDS Patient Care and Stds, 17(): 527-538.

AIDS
The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults
Noor, MA; Parker, RA; O'Mara, E; Grasela, DM; Currie, A; Hodder, SL; Fiedorek, FT; Haas, DW
AIDS, 18(): 2137-2144.

Clinical Infectious Diseases
Modifiable dietary habits and their relation to metabolic abnormalities in men and women with human immunodeficiency virus infection and fat redistribution
Hadigan, C; Jeste, S; Anderson, EJ; Tsay, R; Cyr, H; Grinspoon, S
Clinical Infectious Diseases, 33(5): 710-717.

Journal of Clinical Endocrinology & Metabolism
Regulation of adiponectin in human immunodeficiency virus-infected patients: Relationship to body composition and metabolic indices
Tong, Q; Sankale, JL; Hadigan, CM; Tan, G; Rosenberg, ES; Kanki, PJ; Grinspoon, SK; Hotamisligil, GS
Journal of Clinical Endocrinology & Metabolism, 88(4): 1559-1564.
10.1210/jc.2002-021600
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Endocrinology
Adiponectin ameliorates dyslipidemia induced by the human immunodeficiency virus protease inhibitor ritonavir in mice
Xu, AM; Yin, SN; Wong, LC; Chan, KW; Lam, KSL
Endocrinology, 145(2): 487-494.
10.1210/en.2003-1140
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Jaids-Journal of Acquired Immune Deficiency Syndromes
Do new protease inhibitors offer improved management options? Issues of PI tolerability and safety
Sax, PE
Jaids-Journal of Acquired Immune Deficiency Syndromes, 35(): S22-S34.

Naunyn-Schmiedebergs Archives of Pharmacology
Direct interference of HIV protease inhibitors with pancreatic beta-cell function
Dufer, M; Neye, Y; Krippeit-Drews, P; Drews, G
Naunyn-Schmiedebergs Archives of Pharmacology, 369(6): 583-590.
10.1007/s00210-004-0933-6
CrossRef
Antiviral Therapy
Management of dyslipidaemia in HIV-infected patients receiving antiretroviral therapy
Martinez, E; Tuset, M; Milinkovic, A; Miro, JM; Gatell, JM
Antiviral Therapy, 9(5): 649-663.

Clinical Infectious Diseases
Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: Recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group
Dube, MP; Stein, JH; Aberg, JA; Fichtenbaum, CJ; Gerber, JG; Tashima, KT; Henry, WK; Currier, JS; Sprecher, D; Glesby, MJ
Clinical Infectious Diseases, 37(5): 613-627.

Indian Journal of Medical Research
Obstacles to successful antiretroviral treatment of HIV-1 infection: problems & perspectives
Potter, SJ; Chew, CB; Steain, M; Dwyer, DE; Saksena, NK
Indian Journal of Medical Research, 119(6): 217-237.

AIDS
Indinavir increases glucose production in healthy HIV-negative men
Schwarz, JM; Lee, GA; Park, S; Noor, MA; Lee, J; Wen, M; Lo, JC; Mulligan, K; Schambelan, M; Grunfeld, C
AIDS, 18(): 1852-1854.

Arquivos Brasileiros De Cardiologia
Metabolic Abnormalities, Antiretroviral Therapy and Cardiovascular Disease in Elderly Patients with HIV
Kramer, AS; Lazzarotto, AR; Sprinz, E; Manfroi, WC
Arquivos Brasileiros De Cardiologia, 93(5): 519-526.

AIDS
Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the multicenter AIDS cohort study
Brown, TT; Li, XH; Cole, SR; Kingsley, LA; Palella, FJ; Riddler, SA; Chmiel, JS; Visscher, BR; Margolick, JB; Dobs, AS
AIDS, 19(): 1375-1383.

AIDS Reviews
Switching strategies to improve lipid profile and morphologic changes
Barragan, P; Fisac, C; Podzamczer, D
AIDS Reviews, 8(4): 191-203.

AIDS
Highly active antiretroviral therapy and coronary heart disease: the need for perspective
Egger, M; Junghans, C; Friis-Moller, N; Lundgren, JD
AIDS, 15(): S193-S201.

Pediatrics
Impact of protease inhibitor substitution with efavirenz in HIV-infected children: Results of the first pediatric switch study
McComsey, G; Bhumbra, N; Rathore, M; Alvarez, A
Pediatrics, 111(3): -.
ARTN e275
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Metabolism-Clinical and Experimental
Lipodystrophy in human immunodeficiency virus patients impairs insulin action and induces defects in beta-cell function
Andersen, O; Haugaard, SB; Andersen, LB; Friis-Moller, N; Storgaard, H; Volund, A; Nielsen, JO; Iversen, J; Madsbad, S
Metabolism-Clinical and Experimental, 52(): 1343-1353.
10.1016/S0026-0495(03)00201-4
CrossRef
Annals of Internal Medicine
Metabolic effects of rosiglitazone in HIV lipodystrophy - A randomized, controlled trial
Hadigan, C; Yawetz, S; Thomas, A; Havers, F; Sax, PE; Grinspoon, S
Annals of Internal Medicine, 140(): 786-794.

Expert Opinion on Pharmacotherapy
Treatment of dyslipidaemia in HIV-infected persons
Manuel, O; Thiebaut, R; Darioli, R; Tarr, PE
Expert Opinion on Pharmacotherapy, 6(): 1619-1645.
10.1517/14656566.6.10.1619
CrossRef
American Heart Journal
Indinavir impairs endothelial function in healthy HIV-negative men
Shankar, SS; Dube, MP; Gorski, JC; Klaunig, JE; Steinberg, HO
American Heart Journal, 150(5): -.
ARTN 933.e2
CrossRef
Antiviral Therapy
Key reports from the 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 2007
Nestorowicz, A; Cameron, S
Antiviral Therapy, 12(6): 987-998.

Jaids-Journal of Acquired Immune Deficiency Syndromes
Insulin resistance and diabetes mellitus associated with antiretroviral use in HIV-infected patients: Pathogenesis, prevention, and treatment options
Tebas, P
Jaids-Journal of Acquired Immune Deficiency Syndromes, 49(): S86-S92.

Journal of the National Medical Association
Managing the metabolic and morphologic complications of HIV
Rawlings, MK; Santos, G
Journal of the National Medical Association, 96(2): 17-20.

Journal of Acquired Immune Deficiency Syndromes
Changes in metabolic parameters and body shape after replacement of protease inhibitor with efavirenz in virologically controlled HIV-1-positive persons: Single-arm observational cohort
Moyle, G; Baldwin, C; Mandalia, S; Comitis, S; Burn, P; Gazzard, B
Journal of Acquired Immune Deficiency Syndromes, 28(4): 399-401.

Jaids-Journal of Acquired Immune Deficiency Syndromes
Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: Recommendations of an International AIDS Society-USA panel
Schambelan, M; Benson, CA; Carr, A; Currier, JS; Dube, MP; Gerber, JG; Grinspoon, SK; Grunfeld, C; Kotler, DP; Mulligan, K; Powderly, WG; Saag, MS
Jaids-Journal of Acquired Immune Deficiency Syndromes, 31(3): 257-275.

Progress in Cardiovascular Diseases
HIV infection and lipodystrophy
Kotler, DP
Progress in Cardiovascular Diseases, 45(4): 269-284.
10.1053/pcad.2003.2
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Diabetes
Mechanisms for the deterioration in glucose tolerance associated with HIV protease inhibitor regimens
Woerle, IJ; Mariuz, PR; Meyer, H; Reichman, RC; Popa, EM; Dostou, JM; Welle, SL; Gerich, JE
Diabetes, 52(4): 918-925.

Comparative Biochemistry and Physiology C-Toxicology & Pharmacology
Site-specific differences in the action of NRTI drugs on adipose tissue incubated in vitro with lymphoid cells, and their interaction with dietary lipids
Mattacks, CA; Sadler, D; Pond, CM
Comparative Biochemistry and Physiology C-Toxicology & Pharmacology, 135(1): 11-29.
10.1016/S1532-0456(03)00024-3
CrossRef
AIDS Patient Care and Stds
Overcoming obstacles to the success of protease inhibitors in highly active antiretroviral therapy regimens
Moyle, G
AIDS Patient Care and Stds, 16(): 585-597.

Diabetologia
Indinavir uncovers different contributions of GLUT4 and GLUT1 towards glucose uptake in muscle and fat cells and tissues
Rudich, A; Konrad, D; Torok, D; Ben-Romano, R; Huang, C; Niu, W; Garg, RR; Wijesekara, N; Germinario, RJ; Bilan, PJ; Klip, A
Diabetologia, 46(5): 649-658.
10.1007/s00125-003-1080-1
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AIDS
C-reactive protein levels over time and cardiovascular risk in HIV-infected individuals suppressed on an indinavir-based regimen: AIDS Clinical Trials Group 5056s
Henry, K; Kitch, D; Dube, M; Zackin, R; Parker, RA; Sprecher, D; Hammer, S; Currier, J
AIDS, 18(): 2434-2437.

Lancet
Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance
Bastard, JP; Caron, M; Vidal, H; Jan, V; Auclair, M; Vigouroux, C; Luboinski, J; Laville, M; Malachi, M; Girard, PM; Rozenbaum, W; Levan, P; Capeau, J
Lancet, 359(): 1026-1031.

Pharmacoepidemiology and Drug Safety
Indinavir did not further increase mean triglyceride levels in HIV-infected patients treated with nucleoside reverse transcriptase inhibitors: An analysis of three randomized clinical trials
Rojas, C; Coplan, PM; Rhodes, T; Robertson, MN; DiNubile, MJ; Guess, HA
Pharmacoepidemiology and Drug Safety, 12(5): 361-369.
10.1002/pds.808
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Journal of Clinical Endocrinology & Metabolism
Evaluation of insulin sensitivity in healthy volunteers treated with olanzapine, risperidone, or placebo: A prospective, randomized study using the two-step hyperinsulinemic, euglycemic clamp
Sowell, M; Mukhopadhyay, N; Cavazzoni, P; Carlson, C; Mudaliar, S; Chinnapongse, S; Ray, A; Davis, T; Breier, A; Henry, RR; Dananberg, J
Journal of Clinical Endocrinology & Metabolism, 88(): 5875-5880.
10.1210/jc.2002-021884
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Diabetes
Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy
Gan, SK; Samaras, K; Thompson, CH; Kraegen, EW; Carr, A; Cooper, DA; Chisholm, DJ
Diabetes, 51(): 3163-3169.

Medizinische Klinik
The HIV protease inhibitor-induced insulin resistance syndrome
Schutt, M; Meier, M; Klein, HH
Medizinische Klinik, 98(5): 271-276.

Expert Opinion on Pharmacotherapy
Review of atazanavir: a novel HIV protease inhibitor
Fuster, D; Clotet, B
Expert Opinion on Pharmacotherapy, 6(9): 1565-1572.
10.1517/14656566.6.9.1565
CrossRef
American Journal of Physiology-Endocrinology and Metabolism
Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy
Hadigan, C; Kamin, D; Liebau, J; Mazza, S; Barrow, S; Torriani, M; Rubin, R; Weise, S; Fischman, A; Grinspoon, S
American Journal of Physiology-Endocrinology and Metabolism, 290(2): E289-E298.
10.1152/ajpendo.00273.2005
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American Journal of Clinical Nutrition
Body-composition measurements as predictors of glucose and insulin abnormalities in HIV-positive men
Meininger, G; Hadigan, C; Rietschel, P; Grinspoon, S
American Journal of Clinical Nutrition, 76(2): 460-465.

Jaids-Journal of Acquired Immune Deficiency Syndromes
Metabolic abnormalities in HIV disease and injection drug use
Dobs, A; Brown, T
Jaids-Journal of Acquired Immune Deficiency Syndromes, 31(): S70-S77.
10.1097/01.QAI.0000028067.79472.C2
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American Journal of Clinical Nutrition
Independent associations of insulin resistance with high whole-body intermuscular and low leg subcutaneous adipose tissue distribution in obese HIV-infected women
Albu, JB; Kenya, S; He, Q; Wainwright, M; Berk, ES; Heshka, S; Kotler, DP; Engelson, ES
American Journal of Clinical Nutrition, 86(1): 100-106.

AIDS
Antiretroviral therapy exposure and incidence of diabetes mellitus in the Women's Interagency HIV Study
Tien, PC; Schneider, MF; Cole, SR; Levine, AM; Cohen, M; DeHovitz, J; Young, M; Justman, JE
AIDS, 21(): 1739-1745.

Croatian Medical Journal
Effect of rosiglitazone and metformin on insulin resistance in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy containing protease inhibitor: Randomized prospective controlled clinical trial
Silic, A; Janez, A; Tomazic, J; Karner, P; Vidmar, L; Sharma, P; Maticic, M
Croatian Medical Journal, 48(6): 791-799.
10.3325/cmj.2007.6.791
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Expert Opinion on Drug Safety
Metabolic complications associated with antiretroviral therapy in HIV-infected and HIV-exposed uninfected paediatric patients
Vigano, A; Cerini, C; Pattarino, G; Fasan, S; Zuccotti, GV
Expert Opinion on Drug Safety, 9(3): 431-445.
10.1517/14740330903579991
CrossRef
American Journal of Physiology-Endocrinology and Metabolism
Metabolic basis of HIV-lipodystrophy syndrome
Sekhar, RV; Jahoor, F; White, AC; Pownall, HJ; Visnegarwala, F; Rodriguez-Barradas, MC; Sharma, M; Reeds, PJ; Balasubramanyam, A
American Journal of Physiology-Endocrinology and Metabolism, 283(2): E332-E337.
10.1152/ajpendo.00058.2002
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Clinical Infectious Diseases
Prospective, intensive study of metabolic changes associated with 48 weeks of amprenavir-based antiretroviral therapy
Dube, MP; Qian, DJ; Edmondson-Melancon, H; Sattler, FR; Goodwin, D; Martinez, C; Williams, V; Johnson, D; Buchanan, TA
Clinical Infectious Diseases, 35(4): 475-481.

Journal of Virology
Antiretroviral Therapy in the Clinic
Tsibris, AMN; Hirsch, MS
Journal of Virology, 84(): 5458-5464.
10.1128/JVI.02524-09
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Internist
Adverse events of antiretroviral therapy: aspects of pathogenesis
Seybold, U; Draenert, R; Goebel, FD
Internist, 44(6): 701-+.
10.1007/s00108-003-0927-3
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AIDS Research and Human Retroviruses
Incidence of myocardial infarction in randomized clinical trials of protease inhibitor-based antiretroviral therapy: An analysis of four different protease inhibitors
Coplan, PM; Nikas, A; Japour, A; Cormier, K; Maradit-Kremers, H; Lewis, R; Xu, Y; DiNubile, MJ
AIDS Research and Human Retroviruses, 19(6): 449-455.

Nature Reviews Drug Discovery
Toxicity of antiretroviral therapy and implications for drug development
Carr, A
Nature Reviews Drug Discovery, 2(8): 624-634.
10.1038/nrd1151
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Infectious Disease Clinics of North America
Antiretroviral therapy in HIV-infected children: The metabolic cost of improved survival
Leonard, EG; McComsey, GA
Infectious Disease Clinics of North America, 19(3): 713-+.
10.1016/j.idc.2005.05.006
CrossRef
Metabolism-Clinical and Experimental
Impaired proinsulin secretion before and during oral glucose stimulation in HIV-infected patients who display fat redistribution
Haugaard, SB; Andersen, O; Halsall, I; Iversen, J; Hales, CN; Madsbad, S
Metabolism-Clinical and Experimental, 56(7): 939-946.
10.1016/j.metabol.2007.02.007
CrossRef
Toxicologic Pathology
The Role of Protease Inhibitors in the Pathogenesis of HIV-Associated Lipodystrophy: Cellular Mechanisms and Clinical Implications
Flint, OP; Noor, MA; Hruz, PW; Hylemon, PB; Yarasheski, K; Kotler, DP; Parker, RA; Bellamine, A
Toxicologic Pathology, 37(1): 65-77.
10.1177/0192623308327119
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Clinical Infectious Diseases
Difficulties in understanding the metabolic complications of acquired immune deficiency syndrome
Grunfeld, C; Tien, P
Clinical Infectious Diseases, 37(): S43-S46.

Journal of Lipid Research
Increased VLDL-apoB and IDL-apoB production rates in nonlipodystrophic HIV-infected patients on a protease inhibitor-containing regimen: a stable isotope kinetic study
Petit, JM; Duong, M; Florentin, E; Duvillard, L; Chavanet, P; Brun, JM; Portier, H; Gambert, P; Verges, B
Journal of Lipid Research, 44(9): 1692-1697.
10.1194/jlr.M300041-JLR200
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Drugs
Metabolic complications associated with HIV protease inhibitor therapy
Nolan, D
Drugs, 63(): 2555-2574.

Jaids-Journal of Acquired Immune Deficiency Syndromes
State of the science conference initiative to decrease cardiovascular risk and increase quality of care for patients living with HIV/AIDS - Executive summary
Grinspoon, SK; Grunfeld, C; Kotler, DP; Currier, JS; Lundgren, JD; Dube, MP; Lipshultz, SE; Hsue, PY; Squires, K; Schambelan, M; Wilson, PWF; Yarasheski, KE; Hadigan, CM; Stein, JH; Eckel, RH
Jaids-Journal of Acquired Immune Deficiency Syndromes, 48(4): 369-380.

Metabolic Syndrome and Related Disorders
Relationship of Postprandial Nonesterified Fatty Acids, Adipokines, and Insulin Across Gender in Human Immunodeficiency Virus-Positive Patients Undergoing Highly Active Antiretroviral Therapy
Lu, GJ; Thomas-Geevarghese, A; Anuurad, E; Raghavan, S; Minolfo, R; Ormsby, B; Karmally, W; El-Sadr, WM; Albu, J; Berglund, L
Metabolic Syndrome and Related Disorders, 7(3): 199-204.
10.1089/met.2008.0066
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Progress in Lipid Research
Effects of HIV protease inhibitor therapy on lipid metabolism
Hui, DY
Progress in Lipid Research, 42(2): 81-92.
PII S0163-7827(02)00046-2
CrossRef
Journal of Cellular Biochemistry
In vitro and in vivo prevention of HIV protease inhibitor-induced insulin resistance by a novel small molecule insulin receptor activator
Cheng, MS; Chen, SY; Schow, SR; Manchem, VP; Spevak, WR; Cristobal, CP; Shi, SY; Macsata, RW; Lum, RT; Goldfine, ID; Keck, JG
Journal of Cellular Biochemistry, 92(6): 1234-1245.
10.1002/jcb.20150
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Antiviral Therapy
Insulin resistance, glucose intolerance and diabetes mellitus in HIV-infected patients
Florescu, D; Kotler, DP
Antiviral Therapy, 12(2): 149-162.

Current Medical Research and Opinion
HIV lipodystrophy and its metabolic consequences: implications for clinical practice
Wierzbicki, AS; Purdon, SD; Hardman, TC; Kulasegaram, R; Peters, BS
Current Medical Research and Opinion, 24(3): 609-624.
10.1185/030079908X272742
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Clinical Infectious Diseases
No impairment of endothelial function or insulin sensitivity with 4 weeks of the HIV protease inhibitors atazanavir or lopinavir-ritonavir in healthy subjects without HIV infection: A placebo-controlled trial
Dube, MP; Shen, CY; Greenwald, M; Mather, KJ
Clinical Infectious Diseases, 47(4): 567-574.
10.1086/590154
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Journal of Endocrinological Investigation
Growth and puberty in children with HIV infection
Majaliwa, ES; Mohn, A; Chiarelli, F
Journal of Endocrinological Investigation, 32(1): 85-90.

Diabetes Obesity & Metabolism
Antiretroviral therapy and the human immunodeficiency virus - improved survival but at what cost?
Bradbury, RA; Samaras, K
Diabetes Obesity & Metabolism, 10(6): 441-450.
10.1111/j.1463-1326.2007.00760.x
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Current Atherosclerosis Reports
HIV Therapy, Metabolic Syndrome, and Cardiovascular Risk
Pao, V; Lee, GA; Grunfeld, C
Current Atherosclerosis Reports, 10(1): 61-70.

Clinical Infectious Diseases
Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy
Saves, M; Raffi, F; Capeau, J; Rozenbaum, W; Ragnaud, JM; Perronne, C; Basdevant, A; Leport, C; Chene, G
Clinical Infectious Diseases, 34(): 1396-1405.

Journal of Lipid Research
The HIV protease inhibitor ritonavir increases lipoprotein production and has no effect on lipoprotein clearance in mice
Riddle, TM; Schildmeyer, NM; Phan, C; Fichtenbaum, CJ; Hui, DY
Journal of Lipid Research, 43(9): 1458-1463.

Current Hiv Research
Pharmacological cyclin-dependent kinase inhibitors as HIV-1 antiviral therapeutics
de la Fuente, C; Maddukuri, A; Kehn, K; Baylor, SY; Deng, LW; Pumfery, A; Kashanchi, F
Current Hiv Research, 1(2): 131-152.

Endocrinology and Metabolism Clinics of North America
Lipodystrophies: rare disorders causing metabolic syndrome
Garg, A; Misra, A
Endocrinology and Metabolism Clinics of North America, 33(2): 305-+.
10.1016/j.ecl.2004.03.003
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AIDS
Hepatitis C virus infection is associated with insulin resistance among older adults with or at risk of HIV infection
Howard, AA; Lo, Y; Floris-Moore, M; Klein, RS; Fleischer, N; Schoenbaum, EE
AIDS, 21(5): 633-641.
10.1097/QAD.0b013e3280464db7
PDF (137) | CrossRef
AIDS
Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: A randomized, placebo-controlled study
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Keywords:

HIV protease inhibitors; indinavir; insulin resistance; body composition; cholesterol; triglycerides; diabetes; lipodystrophy; HIV; AIDS

© 2001 Lippincott Williams & Wilkins, Inc.

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