Hyperlipidemias: Fichtenbaum CJ

Dubé MP, Stein JH, Aberg JA, Fichtenbaum CJ, Gerber JG, Tashima KT, Henry WK, Currier JS, Sprecher D, Glesby MJ, Anonymous00228, Anonymous00229. · Indiana University, Indianapolis, USA. · Clin Infect Dis. · Pubmed #12942391 No free full text.

This publication has no abstract.

Fichtenbaum CJ. · Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0405, USA. · HIV Clin Trials. · Pubmed #15682355 links to  free full text

Abstract: Dyslipidemia and coronary heart disease (CHD) are of increasing concern in persons with human immunodeficiency virus (HIV) infection who are living longer because of the benefits of highly active antiretroviral therapy (HAART). All classes of drugs used in HAART have been associated with atherogenic changes in lipid profiles. The management of HIV-infected persons with dyslipidemia and/or CHD currently emphasizes the importance of monitoring and optimizing lipid levels through lifestyle changes, switching antiretrovirals (ARVs), and lipid-lowering treatments utilizing guidelines developed for persons without HIV infection. In HIV-infected persons, the use of lipid-lowering drugs may result in pharmacokinetic interactions with ARVs, complicating the management of patients. Recent advances in our understanding of the differential effects of specific ARVs on lipids is beginning to alter the clinical approach to management. In the absence of randomized clinical trials, clinicians should aggressively treat atherogenic dyslipidemia by primarily utilizing or switching to ARVs with the lowest potential to induce CHD or, when this is not possible or is ineffective, secondarily by the addition of lipid-lowering therapy. The current optimal management of HIV infection requires careful selection of ARVs with consideration given to the potential development of CHD and an understanding of how to manage dyslipidemia.

Gerber JG, Kitch DW, Fichtenbaum CJ, Zackin RA, Charles S, Hogg E, Acosta EP, Connick E, Wohl D, Kojic EM, Benson CA, Aberg JA. · Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA. · J Acquir Immune Defic Syndr. · Pubmed #17971707 No free full text.

Abstract: INTRODUCTION: Fish oil has been shown to reduce serum triglyceride (TG) concentrations. In HIV-infected patients on antiretroviral therapy, high TG concentrations likely contribute to increased risk of cardiovascular disease. AIDS Clinical Trials Group A5186 examined the safety and efficacy of fish oil plus fenofibrate in subjects not achieving serum TG levels < or =200 mg/dL with either agent alone. METHODS: One hundred subjects on highly active antiretroviral therapy with serum TG concentrations > or =400 mg/dL and low-density lipoprotein cholesterol < or =160 mg/dL were randomized to 3 g of fish oil twice daily or 160 mg of fenofibrate daily for 8 weeks. Subjects with a fasting TG level >200 mg/dL at week 8 received a combination of fish oil and fenofibrate in the same doses from week 10 to week 18. RESULTS: Median baseline TG was 662 mg/dL in the fish oil group and 694 mg/dL in the fenofibrate group (P = not significant). Fish oil reduced TG levels by a median of 283 mg/dL (46%), fenofibrate reduced them by 367 mg/dL (58%), and combination therapy reduced them by 65.5%. Combination therapy achieved TG levels of < or =200 mg/dL in 22.7% subjects. Fish oil had no measurable effect on immunologic parameters or the pharmacokinetics of lopinavir. CONCLUSIONS: Fish oil was safe when administered alone or combined with fenofibrate and significantly reduced TG levels in HIV-infected subjects with hypertriglyceridemia.

Aberg JA, Zackin RA, Brobst SW, Evans SR, Alston BL, Henry WK, Glesby MJ, Torriani FJ, Yang Y, Owens SI, Fichtenbaum CJ, Anonymous00493. · AIDS Clinical Trials Unit, Bellevue Hospital Center, New York University, New York, New York 10016, USA. · AIDS Res Hum Retroviruses. · Pubmed #16218799 No free full text.

Abstract: There is a paucity of information on the safety and efficacy of lipid-lowering therapy for dyslipidemia associated with human immunodeficiency virus (HIV) and antiretroviral therapy. Our objective was to determine whether fenofibrate and pravastatin were equivalent for the treatment of combined dyslipidemia in HIV as measured by a composite of the National Cholesterol Education Project (NCEP) goals based on absolute values for low-density lipoprotein (LDL), triglycerides (TG), and high-density lipoprotein (HDL) and to compare the safety of these agents through 48 weeks. This was a randomized, open-label trial with subjects assigned to fenofibrate 200 mg (n = 88) or pravastatin 40 mg (n = 86) daily. Subjects who failed to reach the NCEP composite goal on monotherapy by week 12 received both drugs. The composite goal at week 12 was achieved in 1% of fenofibrate and 5% of pravastatin subjects. At week 16, 69/88 subjects on fenofibrate added pravastatin (FP) and 67/86 subjects on pravastatin added fenofibrate (PF). At week 48, 7% FP subjects and 3% PF subjects achieved the composite goal. Median changes in LDL/HDL/TG/non-HDL were -8/+5/-144/+50 and -14/+2/-66/+34 mg/dl in subjects receiving FP and PF, respectively. There were few adverse events and no rhabdomyolysis reported. Combination therapy with fenofibrate and pravastatin for HIV-related dyslipidemia provides substantial improvements in lipid parameters and appears safe, but is unlikely to achieve all NCEP targets for lipid levels.

Gerber JG, Rosenkranz SL, Fichtenbaum CJ, Vega JM, Yang A, Alston BL, Brobst SW, Segal Y, Aberg JA, Anonymous00307. · University of Colorado Health Sciences Center, Denver, CO 80262, USA. · J Acquir Immune Defic Syndr. · Pubmed #15980690 No free full text.

Abstract: Efavirenz (EFV) is associated with hyperlipidemia when used in combination with other antiretroviral drugs. EFV is a mixed inducer/inhibitor of cytochrome P450 (CYP) 3A4 isozyme and may interact with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that are primarily metabolized via CYP3A4. To assess the drug-drug interaction of EFV used in combination with simvastatin (SIM), atorvastatin (ATR), or pravastatin (PRA), an open-label trial was conducted in 52 healthy adult HIV-seronegative subjects across AIDS Clinical Trials Group sites in the United States. Subjects received 40 mg of SIM, 10 mg of ATR, or 40 mg of PRA daily on days 0 through 3 and days 15 through 18. EFV was administered daily at a dose of 600 mg on days 4 through 18. SIM, ATR, and PRA concentrations were determined before and after EFV, and EFV concentrations were determined before and after statins. EFV reduced SIM acid exposure (area under the curve at 0 to 24 hours [AUC0-24 h]) by 58% (Wilcoxon signed rank test, P=0.003) and active HMG-CoA reductase inhibitory activity by 60% (P<0.001). EFV reduced ATR exposure by 43% (P<0.001) and the total active ATR exposure by 34% (P=0.005). EFV administration resulted in a 40% decrease in PRA exposure (P=0.005). SIM, ATR, and PRA had no effect on non-steady-state EFV concentrations. In conclusion, EFV, when administered with SIM, ATR, or PRA, can result in significant induction of statin metabolism. The reduced inhibition of HMG-CoA reductase activity during coadministration of EFV may result in diminished antilipid efficacy at usual doses of SIM, ATR, and PRA.

Evans SR, Fichtenbaum CJ, Aberg JA, Anonymous00212. · Harvard School of Public Health, Boston, MA, USA. · HIV Clin Trials. · Pubmed #17434848 links to  free full text

Abstract: BACKGROUND: Hypertriglyceridemia is common in HIV-infected individuals on antiretroviral therapy. Triglyceride (TG) levels >400 mg/dL interfere with the accurate determination of low-density lipoproteins (LDL-C) by the Friedewald equation, making it difficult to assess coronary heart disease risk. OBJECTIVE: The objective of this study is to compare the agreement of the direct LDL-C assay and the Friedewald equation with a reference ultracentrifugation method in the estimation of LDL-C concentrations. METHOD: Samples from ACTG 5087 were assayed by ultracentrifugation and a direct enzymatic assay and calculated using the Friedewald equation. RESULTS: In subjects with TG <400 mg/dL (n = 271), 90% of the direct LDL-C values and Friedewald calculations were within 30 mg/dL and 32 mg/dL of the ultracentrifugation values, respectively. With TG > or = 400 mg/dL (n = 186), 90% of the direct assay and Friedewald observations were within 68 mg/dL and 120 mg/dL of the ultracentrifugation results, respectively. Only 27% of the LDL-C values were within 15 mg/dL of the ultracentrifugation LDL-C results for direct assay and 16.3% for the Friedewald equation. CONCLUSION: The direct LDL-C assay and the calculated LDL-C values did not display adequate agreement with the reference ultracentrifugation method. In subjects with TG >400 mg/dL, the direct assay overestimates the actual LDL-C whereas the Friedewald calculation underestimates the actual LDL. Clinical usage of these methods may lead to misclassification of the severity of dyslipidemia, resulting in improper management.

Riddle TM, Fichtenbaum CJ, Hui DY. · Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA. · J Acquir Immune Defic Syndr. · Pubmed #12902799 No free full text.

Abstract: A major complication associated with the use of protease inhibitors (PIs) in treatment of HIV-infected patients is lipid abnormalities including dyslipidemia, lipodystrophy, and liver steatosis. Previous studies revealed that these abnormalities are associated with PI-induced accumulation of activated sterol regulatory element binding proteins (SREBPs) in the nucleus of liver and adipose tissues, resulting in constitutive activation of lipid metabolism genes. This study used the mouse model to determine the potential of polyunsaturated fatty acid (PUFA) diet or leptin replacement therapy to alleviate these PI-induced metabolic abnormalities. Results showed that feeding C57BL/6 mice with a PUFA-rich diet failed to normalize plasma cholesterol and triglyceride levels in ritonavir-treated mice. The PUFA-rich diet also had no effect on ritonavir-induced interscapular fat accumulation and liver steatosis. In contrast, daily administration of leptin significantly reversed the elevated plasma cholesterol level induced by ritonavir. Leptin replacement therapy also significantly reduced the ritonavir-induced interscapular fat mass and improved liver steatosis. Taken together, these data suggest that PI-induced lipid abnormalities, especially dyslipidemia, lipodystrophy, and liver steatosis, may be reduced with leptin replacement therapy.

Fichtenbaum CJ. · No affiliation provided · AIDS Clin Care. · Pubmed #12945527 No free full text.

This publication has no abstract.

Fichtenbaum CJ. · University of Cincinnati College of Medicine, USA. · AIDS Clin Care. · Pubmed #11769116 No free full text.

This publication has no abstract.