Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs
Published in: Drugs 23/2003

01-12-2003 | Leading Article

Metabolic Complications Associated with HIV Protease Inhibitor Therapy

Author: Dr David Nolan

Published in: Drugs | Issue 23/2003

Login to get access

Abstract

HIV protease inhibitors were introduced into clinical practice over 7 years ago as an important component of combination antiretroviral drug regimens which in many ways revolutionised the treatment of HIV infection. The significant improvements in prognosis that have resulted from the use of these regimens, combined with the need for lifelong treatment, have increasingly focused attention on the adverse effects of antiretroviral drugs and on the metabolic complications of HIV protease inhibitors in particular. In this review, the cluster of metabolic abnormalities characterised by triglyceride-rich dyslipidaemia and insulin resistance associated with HIV protease inhibitor therapy are considered, along with implications for cardiovascular risk in patients affected by these complications. Toxicity profiles of individual drugs within the HIV protease inhibitor class are examined, as there is an increased recognition of significant intra-class differences both in terms of absolute risk of metabolic complications as well as the particular metabolic phenotype associated with these drugs. Guidelines for clinical assessment and treatment are emphasised, along with pathophysiological mechanisms that may provide a rational basis for the treatment of metabolic complications. Finally, these drug-specific effects are considered within the context of HIV-specific effects on lipid metabolism as well as lifestyle factors that have contributed to a rapidly increasing incidence of similar metabolic syndromes in the general population. These data highlight the importance of individualising patient management in terms of choice of antiretroviral regimen, assessment of metabolic outcomes and use of therapeutic interventions, based on the assessment of baseline (pre-treatment) metabolic status as well as the presence of potentially modifiable cardiovascular risk factors.
Literature
1.
Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853–60PubMedCrossRef
2.
Massip P, Marchou B, Bonnet E, et al. Lipodystrophia with protease inhibitors in HIV patients. Therapie 1997; 52(6): 615PubMed
3.
Viraben R, Aquilina C. Indinavir-associated lipodystrophy. AIDS 1998; 12(6): 37F-9FCrossRef
4.
Hengal RL, Watts NB, Lennox JL. Benign symmetric lipomatosis associated with protease inhibitors [letter]. Lancet 1997; 350: 1596CrossRef
5.
Herry I, Bernard L, de Truchis P, et al. Hypertrophy of the breasts in a patient treated with indinavir. Clin Infect Dis 1997; 25(4): 937–8PubMedCrossRef
6.
Lui A, Karter D, Turett G. Another case of breast hypertrophy in a patient treated with indinavir [letter]. Clin Infect Dis 1998; 26: 1482PubMedCrossRef
7.
Lo JC, Mulligan K, Tai VW, et al. ‘Buffalo hump’ in men with HIV-1 infection. Lancet 1998; 351(9106): 867–70PubMedCrossRef
8.
Wurtz R. Abnormal fat distribution and use of protease inhibitors [letter]. Lancet 1998; 351(9117): 1735–6PubMedCrossRef
9.
Roth VR, Kravcik S, Angel JB. Development of cervical fat pads following therapy with human immunodeficiency virus type 1 protease inhibitors. Clin Infect Dis 1998; 27(1): 65–7PubMedCrossRef
10.
Striker R, Conlin D, Marz M, et al. Localised adipose tissue hypertrophy in patients receiving human immunodeficiency virus protease inhibitors. Clin Infect Dis 1998; 27(1): 218–20PubMedCrossRef
11.
Ho TT, Chan KC, Wong KH, et al. Abnormal fat distribution and use of protease inhibitors. Lancet 1998; 351(9117): 1736–7PubMedCrossRef
12.
Shaw AJ, McLean KA, Evans BA. Disorders of fat distribution in HIV infection. Int J STD AIDS 1998; 9(10): 595–9PubMedCrossRef
13.
Miller KK, Daly PA, Sentochnik D, et al. Pseudo-Cushing’s syndrome in human immunodeficiency virus infected patients. Clin Infect Dis 1998; 27(1): 68–72PubMedCrossRef
14.
15.
Miller KD, Jones E, Yanovski JA, et al. Visceral abdominal-fat accumulation associated with use of indinavir. Lancet 1998; 351(9106): 871–5PubMedCrossRef
16.
Stricker RB, Goldberg B. Fat accumulation and HIV-1 protease inhibitors [letter]. Lancet 1998; 352(9137): 1392PubMedCrossRef
17.
Carr A, Cooper DA. Images in clinical medicine: lipodystrophy associated with an HIV-protease inhibitor. N Engl J Med 1998; 339(18): 1296PubMedCrossRef
18.
Schambelan M, Benson CA, Carr A, et al. Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: recommendations of an International AIDS Society — USA panel. J Acquir Immune Defic Syndr 2002; 31: 257–75PubMedCrossRef
19.
Mulligan K, Grunfeld C, Tai VW, et al. Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of change in body composition in patients with HIV infection. J Acquir Immune Defic Syndr 2000; 23: 35–43PubMed
20.
Sullivan AK, Nelson MR. Marked hyperlipidemia on ritonavir therapy. AIDS 1997; 11(7): 938–9PubMed
21.
Churchill DR, Pym AS, Babiker AG, et al. Hyperlipidemia following treatment with protease inhibitors in patients with HIV-1 infection. Br J Clin Pharmacol 1998; 46(5): 518–9PubMed
22.
Meyer L, Rabaud C, Ziegler O, et al. Protease inhibitors, diabetes mellitus and blood lipids. Diabetes Metab 1998; 24(6): 547–9PubMed
23.
Dong KL, Bausserman LL, Flynn MM, et al. Changes in body habitus and serum lipid abnormalities in HIV-positive women on highly active antiretroviral therapy (HAART). J Acquir Immune Defic Syndr 1999; 21(2): 107–13PubMed
24.
Behrens G, Dejam A, Schmidt H, et al. Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS 1999; 13(10): F63–70PubMedCrossRef
25.
Schmidt HH-J, Behrens G, Genschel J. Lipid evaluation in HIV-1 positive patients treated with protease inhibitors. Antivir Ther 1999; 4: 163–70PubMed
26.
Echevarria KL, Hardin TC, Smith JA. Hyperlipidemia associated with protease inhibitor therapy. Ann Pharmacother 1999; 33(7–8): 859–63PubMedCrossRef
27.
Periard D, Telenti A, Sudre P, et al. Atherogenic dyslipidemia in HIV infected individuals treated with protease inhibitors. Circulation 1999; 100(7): 700–5PubMedCrossRef
28.
Segerer S, Bogner JR, Walli R, et al. Hyperlipidemia under treatment with proteinase inhibitors. Infection 1999; 27(2): 77–81PubMedCrossRef
29.
Berthold HK, Parhofer KG, Ritter MM, et al. Influence of protease inhibitor therapy on lipoprotein metabolism. J Intern Med 1999; 246(6): 567–75PubMedCrossRef
30.
Tsiodras S, Mantzoros C, Hammer S, et al. Effects of protease inhibitors on hyperglyceamia, hyperlipidaemia, and lipodystrophy: a 5-year cohort study. Arch Intern Med 2000; 160(13): 2050–6PubMedCrossRef
31.
Dube MP, Johnson DL, Currier JS, et al. Protease inhibitor associated hyperglycemia. Lancet 1997; 350(9079): 713–4PubMedCrossRef
32.
Eastone JA, Decker CP. New-onset diabetes mellitus associated with use of a protease inhibitor [letter]. Ann Intern Med 1997; 127: 948PubMed
33.
Visnegarwala F, Krause KL, Musher DM. Severe diabetes associated with protease inhibitor therapy [letter]. Ann Intern Med 1997; 127: 947PubMed
34.
Martinez E, Casamitjana R, Conget I, et al. Protease inhibitor-associated hyperinsulinaemia [letter]. AIDS 1998; 12(15): 2077–9PubMedCrossRef
35.
Walli R, Herfort O, Michl GM, et al. Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1 infected patients. AIDS 1998; 12(15): F167–73PubMedCrossRef
36.
Yarasheski KE, Tebas P, Sigmund C, et al. Insulin resistance and HIV protease inhibitor-associated diabetes. J Acquir Immune Defic Syndr 1999; 21(3): 209–16PubMedCrossRef
37.
Carr A, Samsaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidemia and insulin resistance in patients receiving protease inhibitors. AIDS 1998; 12(7): F51–8PubMedCrossRef
38.
Carr A, Samsaras K, Chisholm DJ, et al. Pathogenesis of HIV-1 protease inhibitor associated peripheral lipodystrophy, hyperlipidemia and insulin resistance. Lancet 1998; 351(9119): 1881PubMedCrossRef
39.
Carr A, Samsaras K, Thorisdottir A, et al. Diagnosis, prediction, and natural course of HIV-1 protease inhibitor associated lipodystrophy, hyperlipidemia and diabetes mellitus: a cohort study. Lancet 1999; 353(9170): 2093–9PubMedCrossRef
40.
Ford ES, Giles WH. A comparison of the prevalence of the metabolic syndrome using two proposed definitions. Diabetes Care 2003; 26: 575–81PubMedCrossRef
41.
42.
Dube MP, Zackin R, Tebas P, et al. Prospective study of regional body composition in antiretroviral-naive subjects randomized to receive zidovudine+lamivudine or didanosine+stavudine combined with nelfinavir, efavirenz, or both: A5005s, a susbstudy of ACTG 384 [abstract no. 27]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
43.
Chene G, Angelini E, Cotte L, et al. Role of long-term nucleo-side-analogue therapy in lipodystrophy and metabolic disorders in human immunodeficiency virus-infected patients. Clin Infect Dis 2002; 34: 649–57PubMedCrossRef
44.
Joly V, Flandre P, Meiffredy S, et al. Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial. AIDS 2002; 16: 2447–54PubMedCrossRef
45.
Law M, Emery S, French M, et al. Lipodystrophy and metabolic abnormalities in a cross-sectional study of participants in randomized controlled studies of combination antiretroviral therapy [abstract no. O28]. 2nd International Workshop on Adverse Drug Reactions and Lipodystrophy; 2000 Sep 13–15; Toronto (ON)
46.
Dreschler H, Powderly WG. Switching effective antiretroviral therapy: a review. Clin Infect Dis 2002; 35: 1219–30CrossRef
47.
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287: 356–9PubMedCrossRef
48.
Frayn KN. Insulin resistance, impaired postprandial lipid metabolism and abdominal obesity: a deadly triad. Med Princ Pract 2002; 11 Suppl. 2: 31–40PubMedCrossRef
49.
McGarry JD. Banting Lecture 2001. Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 2002; 51: 7–18PubMedCrossRef
50.
Hadigan C, Meigs JB, Corcoran C, et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001; 32: 130–9PubMedCrossRef
51.
Christeff N, Melchior J-C, de Truchis P, et al. Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations. AIDS 1999; 13: 2251–60PubMedCrossRef
52.
Bonnet E, Ruidavets J-B, Tuech J, et al. Apoprotein C-III and E-containing lipoparticles are markedly increased in HIV-infected patients treated with protease inhibitors: association with the development of lipodystrophy. J Clin Endocrinol Metab 2001; 86: 296–302PubMedCrossRef
53.
Vigouroux C, Gharakanian S, Salhi Y, et al. Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART). Diab Metab (Paris) 1999; 25: 225–32
54.
Saint-Marc T, Partisani M, Poizot-Martin I, et al. Fat distribution evaluated by computed tomography and metabolic abnormalities in patients undergoing antiretroviral therapy: preliminary results of the LIPOCO study. AIDS 2000; 14(1): 37–49PubMedCrossRef
55.
Van der Valk M, Bisschop PH, Romijn JA, et al. Lipodystrophy in HIV-1-positive patients is associated with insulin resistance in multiple metabolic pathways. AIDS 2001; 15: 2093–100PubMedCrossRef
56.
Sekhar RV, Jahoor F, White AC, et al. Metabolic basis of HIV-lipodystrophy syndrome. Am J Physiol Endocrinol Metab 2002; 283: E332–7PubMed
57.
Nolan D, John M, Mallal S. Antiretoviral therapy and the lipodystrophy syndrome, part 2: concepts in aetiopathogenesis. Antivir Ther 2001 Sep; 6(3): 145–60PubMed
58.
Merwood MA, Sosman JM, Bellehumeur JL, et al. Increased levels of post-prandial triglyceride-rich lipoproteins in patients taking HIV protease inhibitors [abstract no. 51]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
59.
Stein JH, Klein MA, Bellehumeur JL, et al. Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation 2001; 104(3): 257–62PubMedCrossRef
60.
Krauss RM. Atherogenicity of triglyceride-rich lipoproteins. Am J Cardiol 1998; 81: 13B-7BCrossRef
61.
Sniderman AD, Scantlebury T, Cianflone K. Hypertriglyceridemic hyperapoB: the unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus. Ann Intern Med 2001; 135: 447–59PubMed
62.
Hadigan C, Borgonha S, Rabe J, et al. Increased rates of lipolysis among human immunodeficiency virus-infected men receiving highly active antiretroviral therapy. Metabolism 2002; 51: 1143–7PubMedCrossRef
63.
Hadigan C, Rabe J, Meininger G, et al. Inhibition of lipolysis improves insulin sensitivity in protease inhibitor-treated HIV-infected men with fat redistribution. Am J Clin Nutr 2003; 77: 490–4PubMed
64.
Noor MA, Seneviratne T, Aweeka FT, et al. Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study. AIDS 2001; 16(5): F1–8CrossRef
65.
Gan SK, Samaras K, Thompson CH, et al. Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy. Diabetes 2002; 51: 3163–9PubMedCrossRef
66.
Behrens GMN, Boerner A-R, Weber K, et al. Impaired glucose phosphorylation and transport in skeletal muscle cause insulin resistance in HIV-1-infected patients with lipodystrophy. J Clin Invest 2002; 110: 1319–27PubMed
67.
Kosmiski LA, Kuritzkes DR, Lichtenstein KA, et al. Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome. AIDS 2001; 15: 1993–2000PubMedCrossRef
68.
Dube MP, Edmonson-Melancon H, Qian D, et al. Prospective evaluation of the effect of initiating indinavir-based therapy on insulin sensitivity and B-cell function in HIV-infected patients. J Acquir Immune Defic Syndr 2001; 27: 130–4PubMed
69.
Sutinen J, Hakkinen A-M, Westerbacka J, et al. Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy. AIDS 2002; 16: 2183–93PubMedCrossRef
70.
Meininger G, Hadigan C, Laposata M, et al. Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution. Metabolism 2002; 51: 260–6PubMedCrossRef
71.
Worm D, Kirk O, Andersen O, et al. Clinical lipoatrophy in HIV-1 patients on HAART is not associated with increased abdominal girth, hyperlipidaemia or glucose intolerance. HIV Med 2002; 3: 239–46PubMedCrossRef
72.
Purnell JQ, Zambon A, Knopp RH, et al. Effect of ritonavir on lipids and post-heparin lipase in normal subjects. AIDS 2000; 14: 51–7PubMedCrossRef
73.
Lee GA, Senviratne T, Noor MA, et al. Metabolic effects of lopinavir/ritonavir (Kaletra) in healthy HIV-seronegative men [abstract no. 748]. 10th Conference on Retroviruses and Opportunistic Infections; 2003 Feb 10–14; Boston (MA)
74.
Despres J-P, Couillard C, Gagnon J, et al. Race, visceral adipose tissue, plasma lipids, and lipoprotein lipase activity in men and women: the health, risk factors, exercise training, and genetics (HERITAGE) family study. Arterioscler Thromb Vasc Biol 2000; 20: 1932–8PubMedCrossRef
75.
Mynarcik DC, McNurlan MA, Steigbigel RT, et al. Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy. J Acquir Immune Defic Syndr 2000; 25: 312–21PubMedCrossRef
76.
Reiss P. New insights in the clinical management of HIV-1 associated metabolic complications: putting guidelines into perspective [abstract no. 163]. 10th Conference on Retroviruses and Opportunistic Infections; 2003 Feb 10–14; Boston (MA)
77.
Martinez E, Arnaiz JA, Podzamczer D, et al. Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection. N Engl J Med 2003; 349: 1036–46PubMedCrossRef
78.
Fajas L, Schoonjans K, German L, et al. Regulation of peroxisome proliferator-activated receptor γ expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1: implications for adipocyte differentiation and metabolism. Mol Cell Biol 1999; 19: 5495–503PubMed
79.
Flier JS, Hollenberg AN. ADD-1 provides new insight into the mechanisms of insulin action. Proc Natl Acad Sci U S A 1999; 96: 14191–2PubMedCrossRef
80.
Osborne TF. Sterol regulatory element-binding proteins (SREBPs): key regulators of nutritional homeostasis and insulin action. J Biol Chem 2000; 275: 32379–82PubMedCrossRef
81.
Caron M, Auclair M, Vigoureux C, et al. The HIV-protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. Diabetes 2001; 50: 1378–88PubMedCrossRef
82.
Bastard JP, Caron M, Vidal H, et al. Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance. Lancet 2002; 359: 1026–31PubMedCrossRef
83.
Miserez AR, Muller PY, Spaniol V. Indinavir inhibits sterolregulatory element-binding protein-1c-dependent lipoprotein lipase and fatty acid synthase gene activations. AIDS 2002; 16: 1587–94PubMedCrossRef
84.
Rudich A, Vanounou S, Reisenberg K, et al. The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes. Diabetes 2001; 50: 1425–31PubMedCrossRef
85.
Stevens GJ, Lankford AC, Chen M, et al. Inhibition of adipocyte differentiation in HIV-1 protease inhibitors: potential mechanisms based on changes in gene expression [abstract]. Antivir Ther 2000; 5 Suppl. 5: 26
86.
Hegele RA. Molecular basis of partial lipodystrophy and prospects for therapy. Trends Mol Med 2001; 7: 121–6PubMedCrossRef
87.
Caron M, Auclair M, Kornprobst M, et al. Differential in vitro effects of indinavir, nelfinavir and amprenavir on cell differentiation, insulin sensitivity and apoptosis in an adapted adipose cell model: preventive impact of rosiglitazone [abstract no. 24]. 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2001 Oct 23–26; Athens
88.
Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem 2000; 275: 20251–4PubMedCrossRef
89.
Murata H, Hruz PW, Mueckler M. Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS 2002; 16: 859–63PubMedCrossRef
90.
Hruz PW, Murata H, Qiu H, et al. Indinavir induces acute and reversible peripheral insulin resistance in rats. Diabetes 2002; 51: 937–42PubMedCrossRef
91.
Ben-Romano R, Rudich A, Torok D, et al. Agent and cell-type specificity in the induction of insulin resistance by HIV protease inhibitors. AIDS 2003; 17: 23–32PubMedCrossRef
92.
Andre P, Groettrup M, Klenerman P, et al. An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses. Proc Natl Acad Sci U S A 1998; 95: 13120–4PubMedCrossRef
93.
Nguyen AT, Gagnon A, Angel JB, et al. Ritonavir increases the level of active ADD-1/SREBP-1 protein during adipogenesis. AIDS 2000; 14: 2467–73PubMedCrossRef
94.
Riddle TM, Kuhel DG, Woollett LA, et al. HIV protease inhibitor therapy increases hepatic lipoprotein production via stabilisation of activated Sterol Regulatory Element-Binding Protein-1 (SREBP-1) in the nucleus [abstract no. 659]. Program and Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; 2001 Feb 4–8; Chicago (IL)
95.
Liang JS, Distler O, Cooper DA, et al. HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia. Nat Med 2001 Dec; 7(12): 1327–31PubMedCrossRef
96.
Noor MA, Lo JC, Mulligan K, et al. Metabolic effects of indinavir in healthy HIV-seronegative men. AIDS 2001; 15: F11–8PubMedCrossRef
97.
Murphy R, Thiry A, Mancini M, et al. Twelve weeks of atazanavir treatment reverses nelfinavir-associated hyperlipidaemia: results from BMS AI424-044 [abstract no. 15]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
98.
Wang S, Mulvrey R, Laing N, et al. Differentiation of atazanavir from other HIV-protease inhibitors in preclinical models of glucose uptake, lipogenesis and proteasome function [abstract no. 10]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
99.
Dube MP, Qian D, Edmondson-Melancon H, et al. Prospective, intensive study of metabolic changes associated with 48 weeks of amprenavir-based antiretroviral therapy. Clin Infect Dis 2002; 35: 475–81PubMedCrossRef
100.
Thompson M, Tashima K, Schooley R, et al. Different impact on metabolic parameters of amprenavir/ritonavir regimens with tenofovir versus efavirenz [abstract no. 45]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
101.
Costa A, Pulido F, Rubio R, et al. Lipid changes in HIV-infected patients who started rescue therapy with an amrenavir/ ritonavir-based highly active antiretroviral therapy. AIDS 2002; 16: 1983–4PubMedCrossRef
102.
Davignon J, Genest Jr J. Genetics of lipoprotein disorders. Endocrinol Metab Clin North Am 1998; 27(3): 521–50PubMedCrossRef
103.
King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025. Diabetes Care 1998; 21: 1414–31PubMedCrossRef
104.
105.
106.
Grunfeld C, Pang M, Doerrler W, et al. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab 1992; 74: 1045–52PubMedCrossRef
107.
Henry K, Melroe H, Huebsch J, et al. Severe premature coronary artery disease with protease inhibitors [letter]. Lancet 1998; 351: 1328PubMedCrossRef
108.
Behrens G, Schmidt H, Meyer D, et al. Vascular complications associated with use of HIV protease inhibitors [letter]. Lancet 1998; 351: 1958PubMedCrossRef
109.
Gallet B, Pulik M, Genet P, et al. Vascular complications associated with use of HIV protease inhibitors. Lancet. 1998; 351: 1958–9PubMedCrossRef
110.
Vittecoq D, Escaut L, Monsuez JJ. Vascular complications associated with use of HIV protease inhibitors [letter]. Lancet 1998; 351: 1959PubMedCrossRef
111.
Laurence J. Vascular complications associated with use of HIV protease inhibitors [letter]. Lancet 1998; 351: 1960PubMedCrossRef
112.
SoRelle R. Vascular and lipid syndromes in selected HIV-infected patients. Circulation 1998; 98: 829–30PubMedCrossRef
113.
Eriksson U, Opravil M, Amann FW, et al. Is treatment with ritonavir a risk factor for myocardial infarction in HIV-infected patients? AIDS 1998; 12: 2079–80PubMedCrossRef
114.
Sullivan AK, Nelson MR, Moyle GJ. Coronary artery disease occurring with protease inhibitor therapy. Int J STD AIDS 1998; 9: 711–2PubMedCrossRef
115.
Jutte A, Schwenk A, Franzen C, et al. Increasing morbidity from myocardial infarction during HIV protease inhibitor treatment? AIDS 1999; 13: 1796–7PubMedCrossRef
116.
Flynn TE, Bricker LA. Myocardial infarction in HIV-infected men receiving protease inhibitors. Ann Intern Med 1999; 131: 548PubMed
117.
Mary-Krause M, Cotte L, Partisani M, et al. Impact of treatment with protease inhibitors on myocardial infarction occurrence in HIV-infected men [abstract no. 657]. Program and Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; 2001 Feb 4–8; Chicago (IL)
118.
Holmberg S, Moorman A, Tong T, et al. Protease inhibitor use and adverse cardiovascular outcomes in ambulatory HIV patients [abstract no. 698]. 9th Conference on Retroviruses and Opportunistic Infections; 2002 Feb 24–28; Seattle (WA)
119.
Currier J, Taylor A, Boyd F, et al. Coronary heart disease in HIV-infected individuals: associations with antiretroviral therapy [abstract no. 54]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
120.
Bozzette SA, Carpenter A, Bommakanty U, et al. Cardio- and cerebrovascular outcomes with changing process of anti-HIV therapy in 36,776 US veterans [abstract no. LB9]. 9th Conference on Retroviruses and Opportunistic Infections; 2002 Feb 24–28; Seattle (WA)
121.
Klein D, Hurley LB, Quesenberry CP, et al. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acquir Immune Defic Syndr 2002; 30: 471–7PubMedCrossRef
122.
Grunfeld C, Kotier DP, Hamadeh R, et al. Hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med 1989; 86: 27–31PubMedCrossRef
123.
Shor-Posner G, Basit A, Lu Y, et al. Hypercholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection. Am J Med 1993; 94: 515–9PubMedCrossRef
124.
125.
126.
Frostegard J, Ulfgren AK, Nyberg P, et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of proinflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis 1999; 145: 33–43PubMedCrossRef
127.
Stemme S, Faber B, Holm J, et al. T lymphocytes from human atherosclerotic plaques recognize oxidised LDL. Proc Natl Acad Sci U S A 1995; 92: 3893–7PubMedCrossRef
128.
Stemme S, Holm J, Hansson G. T lymphocytes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA-1. Arterioscler Thromb 1992; 12: 206–11PubMedCrossRef
129.
Austin MA, King M-C, Vranizan KM, et al. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease. Circulation 1990; 82: 495–506PubMedCrossRef
130.
Hodis HN, Mack WJ, Krauss RM, et al. Pathophysiology of triglyceride-rich lipoproteins in atherothrombosis: clinical aspects. Clin Cardiol 1999; 22 (6 Suppl.): II15–20PubMedCrossRef
131.
Phillips NR, Waters D, Havel RJ. Plasma lipoproteins and progression of coronary artery disease evaluated by angiography and clinical events. Circulation 1993; 88: 2762–70PubMedCrossRef
132.
Weber T-J, Bengel F, Bogner J-R, et al. Cardiovascular dysregulation in HIV-infected individuals treated with HAART [abstract no. O26]. Program and abstracts of the 2nd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2000 Sep 13–15; Toronto (ON)
133.
Talwani R, Falusi OM, Mendes de Leon CF, et al. Electron beam computed tomography for assessment of coronary artery disease in HIV-infected men receiving antiretroviral therapy. J Acquir Immune Defic Syndr 2002; 30: 191–5PubMed
134.
Heart Protection Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised, placebo-controlled trial. Lancet 2002; 360: 7–22CrossRef
135.
Stein JH, Merwood MA, Bellehumeur JL, et al. Effects of pravastatin on lipids and lipoprotein sub-fractions in patients receiving HIV protease inhibitors [abstract no. 50]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
136.
Doser N, Kubli S, Telenti A, et al. Efficacy and safety of fluvastatin in hyperlipidemic protease inhibitor-treated HIV-infected patients. AIDS 2002; 16: 1982–3PubMedCrossRef
137.
Visnegarwala F, Sajja P, Rodriguez-Barraddas MC, et al. Inconsistent effects of lipid-lowering drugs in the management of HIV-associated dyslipidemias [abstract no. 30]. 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2001 Oct 23–26; Athens
138.
Aberg JA, Zackin R, Evans S, et al. A prospective multicenter randomized trial comparing the efficacy and safety of fenofibrate versus pravastatin in HIV-infected subjects with lipid abnormalities [abstract no. 26]. ACTG 5087. 40th Annual Meeting of the Infectious Diseases of America; 2002 Oct 24–27; Chicago (IL)
139.
Iloeje UH, Yu-Isenberg KS, Ventura EP, et al. Treatment of HIV-associated dyslipidemia: a time trend analysis 1998–2001 [abstract no. 42]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
140.
Iloeje UH, Kawabata H, Wu Y. Age and gender differences in treatment of antiretroviral treatment-associated dyslipidemia among HIV/AIDS patients [abstract no. 43]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
141.
Van Der Valk M, Kastelein JJ, Murphy RL, et al. Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile. AIDS 2001; 15: 2407–14PubMedCrossRef
142.
Simon GL, Liappis AP, Granger SL, et al. Antiretroviral therapy-induced changes in lipoprotein subclass phenotype: comparison of protease inhibitor and non-nucleoside reverse transcriptase inhibitor regimens [abstract no. 14]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
143.
144.
Barrios A, Blanco F, Garcia-Benayas T, et al. Effect of dietary intervention on highly active antiretroviral therapy-associated dyslipidemia. AIDS 2002; 16: 2079–81PubMedCrossRef
145.
Raghavan S, Iqbal S, Levine K, et al. Effectiveness of supervised exercise programme on fat accumulation and metabolic levels in HIV-infected African Americans and Latinos [abstract no. 60]. 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; 2002 Sep 22–25; San Diego (CA)
146.
American Diabetes Association. Standards of medical care of patients with diabetes mellitus. Diabetes Care 2000; 23 Suppl. 1: S32–42
147.
Arioglu E, Duncan-Morin J, Sebring N, et al. Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Ann Intern Med 2000; 133: 263–74PubMed
148.
Gelato M, Mynarcik DC, Quick JL, et al. Improved insulin sensitivity and body fat distribution in HIV-infected patients treated with rosiglitazone. J Acquir Immune Defic Syndr 2002; 31: 163–70PubMedCrossRef
149.
Walli R, Michl GM, Muhlbayer D, et al. Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated diabetes mellitus. Res Exp Med (Berl) 2000; 199: 253–62CrossRef
150.
Saint-Marc T, Touraine J-L. Effects of metformin on insulin resistance and central adiposity in patients receiving effective protease inhibitor therapy. AIDS 1999; 13: 1000–2PubMedCrossRef
151.
Hadigan C, Corcoran C, Basgoz N, et al. Metformin in the treatment of HIV lipodystrophy syndrome. JAMA 2000; 284: 472–7PubMedCrossRef
Metadata
Title
Metabolic Complications Associated with HIV Protease Inhibitor Therapy
Author
Dr David Nolan
Publication date
01-12-2003
Publisher
Springer International Publishing
Published in
Drugs / Issue 23/2003
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.2165/00003495-200363230-00001

Other articles of this Issue 23/2003

Drugs 23/2003 Go to the issue

Leading Article

Phosphodiesterase-4 Inhibitors in the Treatment of Inflammatory Lung Disease

Adis Drug Evaluation

Vardenafil

Adis Drug Profile

Azelnidipine

Adis Drug Profile

Azelnidipine

Adis Drug Profile

Azelnidipine

Adis Drug Profile

Azelnidipine