Cited by 1,065HIV-related health complications and treatmentsLipid metabolism and disordersPeroxisome Proliferator-Activated Receptors

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Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance.

Carr, Andrew, Samaras, Katherine, Chisholm, Donald J, Cooper, David A·1998·The Lancet

DOI 10.1016/s0140-6736(98)03391-1

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Abstract

HIV-1 protease-inhibitor treatments are associated with a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidaemia, and insulin resistance. The catalytic region of HIV-1 protease, to which protease inhibitors bind, has approximately 60% homology to regions within two proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1 (CRABP-1) and low density lipoprotein-receptor-related protein (LRP). We hypothesise that protease inhibitors inhibit CRABP-1-modified, and cytochrome P450 3A-mediated synthesis of cis-9-retinoic acid, a key activator of the retinoid X receptor; and peroxisome proliferator activated receptor type gamma (PPAR-gamma) heterodimer, an adipocyte receptor that regulates peripheral adipocyte differentiation and apoptosis. Protease-inhibitor binding to LRP would impair hepatic chylomicron uptake and triglyceride clearance by the endothelial LRP-lipoprotein lipase complex. The resulting hyperlipidaemia contributes to central fat deposition (and in the breasts in the presence of oestrogen), insulin resistance, and, in susceptible individuals, type 2 diabetes. Understanding the syndrome's pathogenesis should lead to treatment strategies and to the design of protease inhibitors that do not cause this syndrome.

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The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus
Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963) · The Lancet · doi:10.1016/s0140-6736(63)91500-9 · Cited by 5,093
Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor
Tontonoz, P., Hu, E., & Spiegelman, B. M. (1994) · Cell · doi:10.1016/0092-8674(94)90006-x · Cited by 3,564
A decade of molecular biology of retinoic acid receptors
Chambon, P. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.9.8801176 · Cited by 2,889
15-Deoxy-Δ12,14-Prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ
FORMAN, B. M., Tontonoz, P., Chen, J., Brun, R. P., Spiegelman, B. M., & Evans, R. M. (1995) · Cell · doi:10.1016/0092-8674(95)90193-0 · Cited by 2,857
A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors
Carr, A., Samaras, K., Burton, S., Law, M. G., Freund, J., Chisholm, D. J., & Cooper, D. A. (1998) · AIDS · doi:10.1097/00002030-199807000-00003 · Cited by 2,364
Self-citation
Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1
Navia, M. A., Fitzgerald, P. M. D., McKeever, B. M., Leu, C., Heimbach, J. C., Herber, W. K., Sigal, I. S., Darke, P. L., & Springer, J. P. (1989) · Nature · doi:10.1038/337615a0 · Cited by 892
Visceral abdominal-fat accumulation associated with use of indinavir
Miller, K. D., Jones, E. C., Yanovski, J. A., Shankar, R., Feuerstein, I. M., & Falloon, J. (1998) · The Lancet · doi:10.1016/s0140-6736(97)11518-5 · Cited by 697
The LDL–receptor–related protein, LRP, is an apolipoprotein E-binding protein
Beisiegel†, U., Weber, W. T., Ihrke, G., Herz, J., & Stanley, K. K. (1989) · Nature · doi:10.1038/341162a0 · Cited by 680
HIV-1 protease inhibitors. A review for clinicians
Deeks, S. G. (1997) · JAMA · doi:10.1001/jama.277.2.145 · Cited by 675
Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists
Mukherjee, R., Davies, P. J., Crombie, D. L., Bischoff, E. D., Cesario, R. M., Jow, L., Hamann, L. G., Boehm, M. F., Mondon, C. E., Nadzan, A. M., et al. (1997) · Nature · doi:10.1038/386407a0 · Cited by 601

Show all 24 references

Research works printed but not linked: 1

Despres, 1995, The insulin-resistance-dysipidemic syndrome: contributioin of visceral obesity and therapeutic implications, Int J Obesity, 19, S76

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Ledru, É., Christeff, N., Patey, O., de Truchis, P., Melchior, J., & Gougeon, M. (2000) · Blood · doi:10.1182/blood.v95.10.3191 · Cited by 176
Clinical and metabolic presentation of the lipodystrophic syndrome in HIV-infected children
Jaquet, D., Lévine, M., Ortega-Rodriguez, E., Faye, A., Polak, M., VILMER, E., & Lévy‐Marchal, C. (2000) · AIDS · doi:10.1097/00002030-200009290-00008 · Cited by 174
Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection
van der Valk, M., Gisolf, E. H., Reiss, P., Wit, F. W. N. M., Japour, A. J., Weverling, G. J., & Danner, S. A. (2001) · AIDS · doi:10.1097/00002030-200105040-00005 · Cited by 175
Lipodystrophy, Metabolic Disorders, and Human Immunodeficiency Virus Infection: Aquitaine Cohort, France, 1999
Thiébaut, R., Daucourt, V., Mercié, P., Ekouévi, D. K., Malvy, D. J.-M., Morlat, P., Dupon, M., Neau, D., Farbos, S., Marimoutou, C., et al. (2000) · Clinical Infectious Diseases · doi:10.1086/317477 · Cited by 174
Early Structural and Functional Changes of the Vasculature in HIV-Infected Children
Charakida, M., Donald, A. E., Green, H., Storry, C., Clapson, M., CASLAKE, M. J., Dunn, D. T., Halcox, J., Gibb, D. M., Klein, N. J., et al. (2005) · Circulation · doi:10.1161/circulationaha.104.517144 · Cited by 171
Interactions Between Antiretroviral Drugs and Drugs Used for the Therapy of the Metabolic Complications Encountered During HIV Infection
Fichtenbaum, C. J., & Gerber, J. G. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241140-00004 · Cited by 167
Intracellular Pharmacokinetics of Antiretroviral Drugs in HIV-Infected Patients, and their Correlation with Drug Action
Bazzoli, C., Jullien, V., Tiec, C. L., Rey, E., Mentré, F., & Taburet, A. (2009) · Clinical Pharmacokinetics · doi:10.2165/11318110-000000000-00000 · Cited by 174
“For example, PIs could alter adipose tissue and lipid metabolism by inhibiting the heterodimeric nuclear receptor complex composed of peroxisome proliferator-activated receptor g and the retinoid X receptor, the cellular retinoic acid-binding protein, and the synthesis of cis-9-retinoic acid.([157]) PIs could also inh…”
Drug/Drug Interaction Between Lopinavir/Ritonavir and Rosuvastatin in Healthy Volunteers
Kiser, J. J., Gerber, J. G., Predhomme, J. A., Wolfe, P., Flynn, D. M., & Hoody, D. W. (2008) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e318160a542 · Cited by 159
HIV protease inhibitors block adipogenesis and increase lipolysis in vitro
Lenhard, J. M., Furfine, E. S., Jain, R. G., Ittoop, O. R. R., Orband‐Miller, L. A., Blanchard, S. G., Paulik, M. A., & Weiel, J. E. (2000) · Antiviral Research · doi:10.1016/s0166-3542(00)00102-9 · Cited by 160
“For example, PIs may interact with common proteins (proteases or cytochrome P450) in other tissues and this may neck and abdomen (Carr et al., 1998a; Lo et al., 1998; Miller et al., 1998; Walli et al., 1998).”
BackgroundResultInfluential
Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy
Langford, D., Letendre, S. L., Marcotte, T. D., Ellis, R. J., McCutchan, J. A., Grant, I., Mallory, M. E., Hansen, L. A., Archibald, S. L., Jernigan, T. L., et al. (2002) · AIDS · doi:10.1097/00002030-200205030-00008 · Cited by 160
“lipoprotein-receptor-related protein) and CRABP-1 (cytoplasmic retinoic acid binding protein type 1) [51].”
Background
Longitudinal Analysis of Bone Density in Human Immunodeficiency Virus-Infected Women
Dolan, S. E., Kanter, J. R., & Grinspoon, S. K. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0127 · Cited by 156
Endocrine and Metabolic Evaluation of Human Immunodeficiency Virus-Infected Patients with Evidence of Protease Inhibitor-Associated Lipodystrophy
Yanovski, J. A., Miller, K. D., Kino, T., Friedman, T. C., Chrousos, G. P., Tsigos, C., & Falloon, J. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.6.5740 · Cited by 153
Drug–Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors
Chauvin, B., Drouot, S., Barrail‐Tran, A., & Taburet, A. (2013) · Clinical Pharmacokinetics · doi:10.1007/s40262-013-0075-4 · Cited by 156
Metabolic complications associated with antiretroviral therapy
Jain, R. G., Furfine, E. S., Pedneault, L., White, A. J., & Lenhard, J. M. (2001) · Antiviral Research · doi:10.1016/s0166-3542(01)00148-6 · Cited by 150
Effects of Testosterone Supplementation on Whole Body and Regional Fat Mass and Distribution in Human Immunodeficiency Virus-Infected Men with Abdominal Obesity
Bhasin, S., Parker, R. A., Sattler, F. R., Haubrich, R., Alston, B., Umbleja, T., & Shikuma, C. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2060 · Cited by 149
Use of HIV protease inhibitors to block Kaposi's sarcoma and tumour growth
Sgadari, C., Monini, P., Barillari, G., & Ensoli, B. (2003) · The Lancet Oncology · doi:10.1016/s1470-2045(03)01192-6 · Cited by 147
Altered Myocellular and Abdominal Fat Partitioning Predict Disturbance in Insulin Action in HIV Protease Inhibitor-Related Lipodystrophy
Gan, S. K., Samaras, K., Thompson, C. H., Kraegen, E. W., Carr, A. D., Cooper, D. A., & Chisholm, D. J. (2002) · Diabetes · doi:10.2337/diabetes.51.11.3163 · Cited by 148
Self-citation
Fibrates, dyslipoproteinaemia and cardiovascular disease
Watts, G. F., & Dimmitt, S. B. (1999) · Current Opinion in Lipidology · doi:10.1097/00041433-199912000-00011 · Cited by 146
Prevalence and Pathogenesis of Diabetes Mellitus in HIV-1 Infection Treated With Combined Antiretroviral Therapy
Samaras, K. (2009) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e31819c291b · Cited by 146
Self-citation
Nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity as an etiology for lipodystrophy
Kakuda, T. N., Brundage, R. C., Anderson, P. L., & Fletcher, C. V. (1999) · AIDS · doi:10.1097/00002030-199911120-00019 · Cited by 144
Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations
Christeff, N., Melchior, J., de Truchis, P., Perronne, C., Nunez, E. A., & Gougeon, M. (1999) · AIDS · doi:10.1097/00002030-199911120-00007 · Cited by 142
Effects of metformin on insulin resistance and central adiposity in patients receiving effective protease inhibitor therapy
Saint-Marc, T., & Touraine, J. L. (1999) · AIDS · doi:10.1097/00002030-199905280-00023 · Cited by 142
HIV Protease Inhibitors Stimulate Hepatic Triglyceride Synthesis
Lenhard, J. M., Croom, D. K., Weiel, J. E., & Winegar, D. A. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.12.2625 · Cited by 138
Bile acid-activated receptors in the treatment of dyslipidemia and related disorders
Fiorucci, S., Cipriani, S., Baldelli, F., & Mencarelli, A. (2009) · Progress in Lipid Research · doi:10.1016/j.plipres.2009.11.001 · Cited by 142
HIV-associated dyslipidaemia: pathogenesis and treatment
Oh, J., & Hegele, R. A. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70287-6 · Cited by 137
A Randomized Clinical Trial Comparing Nelfinavir Or Nevirapine Associated to Zidovudine/Lamivudine in HIV-Infected Naive Patients (The Combine Study)
Podzamczer, D., Ferrer, E., Consiglio, E., Gatell, J. M., Pérez, P., Pérez, J. L., Luna, E., González, A., Pedrol, E., Lozano, L., et al. (2002) · Antiviral Therapy · doi:10.1177/135965350200700202 · Cited by 137
“Protease inhibitor (PI)-containing regimens are uncomfortable, and are associated with a considerable incidence of adverse effects – the most worrisome being the probable association between PIs and the occurrence of lipodystrophy and other metabolic disorders – making adherence difficult and negatively influencing pa…”
Background
Use of observational databases to evaluate the effectiveness of antiretroviral therapy for HIV infection: comparison of cohort studies with randomized trials
Phillips, A. N., Grabar, S., Tassie, J.-M., Costagliola, D. G., Lundgren, J. D., & Egger, M. (1999) · AIDS · doi:10.1097/00002030-199910220-00010 · Cited by 136
HIV Protease Inhibitor Ritonavir Induces Cytotoxicity of Human Endothelial Cells
Zhong, D.-S., Lu, X.-H., Conklin, B. S., Lin, P. H., Lumsden, A. B., Yao, Q. C., & Chen, C. (2002) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000034707.40046.02 · Cited by 135
The metabolic abnormalities associated with non-alcoholic fatty liver disease
Haque, M., & Sanyal, A. J. (2002) · Best Practice & Research Clinical Gastroenterology · doi:10.1053/bega.2002.0325 · Cited by 136
Effects of HIV protease inhibitor therapy on lipid metabolism
Hui, D. Y. (2003) · Progress in Lipid Research · doi:10.1016/s0163-7827(02)00046-2 · Cited by 135
Elevated blood pressure in subjects with lipodystrophy
Sattler, F. R., Qian, D., Louie, S. G., Johnson, D., Briggs, W., DeQuattro, V. L., & Dubé, M. P. (2001) · AIDS · doi:10.1097/00002030-200110190-00013 · Cited by 132
“used to treat HIV [22], but other reports suggest that individuals may develop these abnormalities despite never having received PI [7,8,9,10,23±26].”
Coronary Artery Disease and Human Immunodeficiency Virus Infection
Mayer, K. H., Passalaris, J. D., Sepkowitz, K. A., & Glesby, M. J. (2000) · Clinical Infectious Diseases · doi:10.1086/313995 · Cited by 132
Adipocytes Targets and Actors in the Pathogenesis of HIV-Associated Lipodystrophy and Metabolic Alterations
Gougeon, M., Pénicaud, L., Fromenty, B., Leclercq, P., Viard, J., & Capeau, J. (2004) · Antiviral Therapy · doi:10.1177/135965350400900206 · Cited by 129
Human Immunodeficiency Virus/Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome: Clinical Presentation, Pathophysiology, and Therapeutic Strategies
Leow, M. K., Addy, C., & Mantzoros, C. S. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021704 · Cited by 129
Peroxisome proliferator-activated receptors in cutaneous biology
Kuenzli, S., & Saurat, J. ‐. (2003) · British Journal of Dermatology · doi:10.1046/j.1365-2133.2003.05532.x · Cited by 128

Authors: Carr, A., Samaras, K., Chisholm, D. J., & Cooper, D. A.
Affiliations: UNSW Sydney (AU)
Garvan Institute of Medical Research (AU)
Corresponding author: Carr, Andrew
ORCID: Samaras, Katherine
Chisholm, Donald J
Venue: The Lancet
Publisher: Elsevier BV
Published: 1998-06
Volume: 351
Issue: 9119
Pages: 1881-1883
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(98)03391-1
OpenAlex: W2171030070
Cited by: 1,065
References: 24
Citations by year: 2026: 2 · 2025: 3 · 2024: 12 · 2023: 2 · 2022: 12 · 2021: 7 · 2020: 10 · 2019: 16 · 2018: 15 · 2017: 18 · 2016: 15 · 2015: 18 · 2014: 17 · 2013: 30 · 2012: 23
FWCI: 143.69
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Funders: National Health and Medical Research Council
National Medical Research Council
Topics: Health Sciences › Medicine › Infectious Diseases › HIV-related health complications and treatments
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: HIV-1 protease inhibitors, hyperlipidemia, insulin resistance, abdominal obesity, breast hypertrophy, LRP, retinoic acid synthesis, retinoid X receptor, PPARγ, adipogenesis, adipocyte apoptosis, lipoprotein lipase, type 2 diabetes
MeSH terms: Cytochrome P-450 Enzyme System, Diabetes Mellitus, Type 2, Female, Humans, Hyperlipidemias, Insulin Resistance, Lipodystrophy, Obesity, Receptors, Immunologic, HIV Protease Inhibitors, Sequence Homology, Amino Acid, Receptors, Retinoic Acid, Low Density Lipoprotein Receptor-Related Protein-1

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Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance.

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