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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Background
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Background
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“of Kaposi sarcoma (KS) lesions Range 6-155 Median (range) 22 (28-62) CD4+ lymphocyte count, cells/μL Range 10-807 Median 206 CD4+ 150, No.”
Background
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“[2] Carr A, Samaras K, Chisholm DJ, Cooper DA.”
Background
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Abnormal body-fat distribution in HIV-1-infected children on antiretrovirals
Babl, F. E., Regan, A. M., & Pelton, S. I. (1999) · The Lancet · doi:10.1016/s0140-6736(98)05754-7 · Cited by 54
Recombinant human growth hormone improves truncal adiposity and ‚buffalo humps‚ in HIV-positive patients on HAART
de Torres, R. A., Unger, K. W., Cadman, J. A., & Kassous, J. Y. (1999) · AIDS · doi:10.1097/00002030-199912030-00023 · Cited by 54
British HIV Association (BHIVA) guidelines for the treatment of HIV‐infected adults with antiretroviral therapy
(2003) · HIV Medicine · doi:10.1046/j.1468-1293.4.s1.3.x · Cited by 56
British HIV Association (BHIVA) guidelines for the treatment of HIV‐infected adults with antiretroviral therapy
regimen, S. D. M. H. A. I. I. O. T. R. O. D. I. D. T. A. O. T. D. M. R. I. H. L. O. D. F. W. I. P. T. B. T. L. E., double-blind, W. A., recognize, P.-C. S. M. R. A. I. A. G. B. O. T. L. P. B. I. I. I. T., however, & good., T. C. C. T. P. A. O. T. S. A. R. I. T. ‘. W. A. U. N. A. (2000) · HIV Medicine · doi:10.1046/j.1468-1293.2000.00013.x · Cited by 53
Dyslipidemia and Cardiovascular Risk in Human Immunodeficiency Virus Infection
Kelesidis, T., & Currier, J. S. (2014) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2014.06.003 · Cited by 53
Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy
Miller, T. L. (2003) · AIDS · doi:10.1097/00002030-200304001-00016 · Cited by 53
HIV Infection and the Cardiovascular System
Bárbaro, G., & Klatt, E. C. (2003) · Advances in cardiology · doi:10.1159/isbn.978-3-318-00995-8 · Cited by 53
Lipodystrophy following antiretroviral therapy of primary HIV infection
Miller, J., Carr, A., Smith, D. E., Emery, S., Law, M. G., Grey, P., & Cooper, D. A. (2000) · AIDS · doi:10.1097/00002030-200010200-00025 · Cited by 53
Self-citation
Prospective evaluation of blood concentration of mitochondrial DNA as a marker of toxicity in 157 consecutively recruited untreated or HAART-treated HIV-positive patients
Chiappini, F., Teicher, E., Saffroy, R., Pham, P., Falissard, B., Barrier, A. J., Chevalier, S., Debuire, B., Vittecoq, D., & Lemoine, A. (2004) · Laboratory Investigation · doi:10.1038/labinvest.3700113 · Cited by 53
Amprenavir: A new human immunodeficiency virus type 1 protease inhibitor
Fung, H. B., Kirschenbaum, H. L., & Hameed, R. (2000) · Clinical Therapeutics · doi:10.1016/s0149-2918(00)80044-2 · Cited by 53
Mitochondrial Toxicity of Indinavir, Stavudine and Zidovudine Involves Multiple Cellular Targets in white and brown adipocytes
Viengchareun, S., Caron, M., Auclair, M., Kim, M. J., Frachon, P., Capeau, J., Lombès, M., & Lombès, A. (2007) · Antiviral Therapy · doi:10.1177/135965350701200610 · Cited by 52
Serum Triglycerides, HIV Infection, and Highly Active Antiretroviral Therapy, Aquitaine Cohort, France, 1996 to 1998
Thiébaut, R., Dabis, F., Malvy, D. J.-M., Jacqmin‐Gadda, H., Mercié, P., & Valentin, V. D. (2000) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00042560-200003010-00009 · Cited by 52
Impact of Lipodystrophy on the prevalence and components of metabolic syndrome in HIV-infected patients
Freitas, P., Carvalho, D. M., Souto, S. B., Santos, A. C., Xerinda, S., Marques, R., Martínez, E., Sarmento, A., & Medina, J. L. (2011) · BMC Infectious Diseases · doi:10.1186/1471-2334-11-246 · Cited by 51
Tolerability and Safety of HIV Protease Inhibitors in Adults
Sax, P. E., & Kumar, P. N. (2004) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/01.qai.0000138420.38995.86 · Cited by 51
Metabolic abnormalities and body fat redistribution in HIV-1 infected patients: the lipodystrophy syndrome
Martínez, E., & Gatell, J. M. (1999) · Current Opinion in Infectious Diseases · doi:10.1097/00001432-199902000-00003 · Cited by 51
A randomized study comparing triple versus double antiretroviral therapy or no treatment in HIV-1-infected patients in very early stage disease: the Spanish Earth-1 study
García, F., Romeu, J., Grau, I., Sambeat, M. A., Dalmau, D., Knobel, H., Gómez-Sirvent, J. L., Arrizabalaga, J., Cruceta, A., Clotet, B., et al. (1999) · AIDS · doi:10.1097/00002030-199912030-00009 · Cited by 50
Sexually Transmitted Diseases and Sexual Function
Sadeghi‐Nejad, H., Wasserman, M., Weidner, W., Richardson, D., & Goldmeier, D. (2010) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2009.01622.x · Cited by 51
HIV protease inhibitors and obesity
Anuurad, E., Bremer, A. A., & Berglund, L. (2010) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0b013e32833dde87 · Cited by 50
Lipodystrophy associated with protease inhibitors
Pansé, I., Vasseur, E., Raffin‐Sanson, M., Staroz, F., Rouveix, É., & Saïag, P. (2000) · British Journal of Dermatology · doi:10.1046/j.1365-2133.2000.03363.x · Cited by 50
Use of Fenofibrate in the Management of Protease Inhibitor‐Associated Lipid Abnormalities
Thomas, J. C., Lopes-Virella, M. F., Bene, V. E. D., Cerveny, J. D., Taylor, K. B., Shane‐McWhorter, L., & Bultemeier, N. C. (2000) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.20.7.727.35179 · Cited by 50
“The resulting hyperlipidemia may contribute to central fat deposition, insulin resistance, and, in susceptible individuals, type 2 diabetes.(30) Insulin resistance may be the abnormality leading to glucose intolerance and/or diabetes.”
Background
The HIV-1 protease inhibitor indinavir impairs insulin signalling in HepG2 hepatoma cells
Schütt, M., Meier, M., Meyer, M., Klein, J. C., Aries, S. P., & Klein, H. H. (2000) · Diabetologia · doi:10.1007/s001250051505 · Cited by 50
Gene Expression and Immunohistochemistry in Adipose Tissue of HIV Type 1–Infected Patients with Nucleoside Analogue Reverse‐Transcriptase Inhibitor–Associated Lipoatrophy
Sievers, M., Walker, U. A., Sevastianova, K., Setzer, B., Wågsäter, D., Eriksson, P. O., Yki-Järvinen, H., & Sutinen, J. (2009) · The Journal of Infectious Diseases · doi:10.1086/599986 · Cited by 49
Is estimated cardiovascular risk higher in HIV-infected patients than in the general population?
Socio, G. V. D., Martinelli, L., Morosi, S., Fiorio, M., Roscini, A. R., Stagni, G., & Schillaci, G. (2007) · Scandinavian Journal of Infectious Diseases · doi:10.1080/00365540701230884 · Cited by 50
“Several studies have demonstrated that patients using ART develop atherogenic changes in their lipoprotein profile [8,9].”
Background
Epidemiology of HIV cardiac disease
Cotter, B. R. (2003) · Progress in Cardiovascular Diseases · doi:10.1053/pcad.2003.5 · Cited by 48
The effect of aging, nutrition, and exercise during HIV infection
Miller, T. L., Somarriba, Neri, D. A., & Schaefer (2010) · HIV/AIDS - Research and Palliative Care · doi:10.2147/hiv.s9069 · Cited by 49
Sleep Disordered Breathing, Fatigue, and Sleepiness in HIV-Infected and -Uninfected Men
Patil, S. P., Brown, T. T., Jacobson, L. P., Margolick, J. B., Laffan, A. M., Johnson, L., Godfrey, R., Johnson, J. R., Reynolds, S. M., Schwartz, A. R., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099258 · Cited by 48
Growth Hormone (GH) Responses to GH-Releasing Hormone-Arginine Testing in Human Immunodeficiency Virus Lipodystrophy
Koutkia, P., Hron, B. M., Breu, J. J., & Grinspoon, S. K. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1342 · Cited by 48
Insulin resistance in the HIV-lipodystrophy syndrome
Grinspoon, S. K. (2001) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00472-6 · Cited by 47
Altered Fat Distribution in HIV-Positive Men on Nucleoside Analog Reverse Transcriptase Inhibitor Therapy
Mulligan, K. M., Tai, V., Algren, H. A., Abrams, D. I., Leiser, R. J., Lo, J. C.-M., & Schambelan, M. (2001) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200104150-00006 · Cited by 48
Leisure time physical activity prevents accumulation of central fat in HIV/AIDS subjects on highly active antiretroviral therapy
Florindo, A. A., Latorre, M. D. R. D. D. O., Jaime, P. C., & Segurado, A. A. C. (2007) · International Journal of STD & AIDS · doi:10.1258/095646207782193795 · Cited by 47
Type 2 Diabetes Mellitus
Polonsky, K. S., & Burant, C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00031-9 · Cited by 53
Effect of exercise and strength training on cardiovascular status in HIV-infected patients receiving highly active antiretroviral therapy
Scevola, D., Matteo, A. M. D., Lanzarini, P., Uberti, F., Scevola, S., Bernini, V., Spoladore, G., & Faga, A. (2003) · AIDS · doi:10.1097/00002030-200304001-00015 · Cited by 47
CD36 deficiency induced by antiretroviral therapy
Serghides, L., Nathoo, S., Walmsley, S. L., & Kain, K. C. (2002) · AIDS · doi:10.1097/00002030-200202150-00006 · Cited by 45
HIV, Metabolic Syndrome X, Inflammation, Oxidative Stress, and Coronary Heart Disease Risk : Role of Protease Inhibitor Exposure
Hurwitz, B. E., Klimas, N. G., Llabre, M. M., Maher, K. J., Skyler, J. S., Bilsker, M., McPherson-Baker, S., Lawrence, P. J., LaPerriere, A. R., Greeson, J. M., et al. (2004) · Cardiovascular Toxicology · doi:10.1385/ct:4:3:303 · Cited by 45
“, CRABP-1, LRP) that are involved in lipid metabolism and when bound result in decreased hepatic triglyceride and lipid clearance (59).”
Background
Unmet therapeutic needs in the new era of combination antiretroviral therapy for HIV-1
Taiwo, B., Hicks, C. B., & Eron, J. (2010) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkq096 · Cited by 46
Facial Atrophy in HIV-Related Fat Redistribution Syndrome: Anatomic Evaluation and Surgical Reconstruction
Talmor, M., Hoffman, L. A., & LaTrenta, G. S. (2002) · Annals of Plastic Surgery · doi:10.1097/00000637-200207000-00002 · Cited by 46
Management of Protease Inhibitor-Associated Hyperlipidemia
Penzak, S. R., & Chuck, S. K. (2002) · American Journal of Cardiovascular Drugs · doi:10.2165/00129784-200202020-00003 · Cited by 46
“Two human proteins involved in lipid metabolism, cytoplasmic retinoic-acid binding protein type-1 (CRABP-1) and LDL receptor-related protein (LRP), are similar in amino acid sequence to the catalytic region of HIV-1 protease.[25] This similarity led Carr and coworkers to hypothesize that HIV protease inhibitors bind t…”
Background

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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