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

The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.

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

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(98)03391-1

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

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

Sorted by citations

Items 101–200 of 1,000

A 48-Week, Randomized, Open-Label Comparison of Three Abacavir-Based Substitution Approaches in the Management of Dyslipidemia and Peripheral Lipoatrophy
Moyle, G. J., Baldwin, C., Langroudi, B., Mandalia, S., & Gazzard, B. (2003) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200305010-00004 · Cited by 128
Association Between Insulin Resistance and Hepatitis C Virus Chronic Infection in HIV–Hepatitis C Virus–Coinfected Patients Undergoing Antiretroviral Therapy
Duong, M., Petit, J., Piroth, L., Grappin, M., Buisson, M., Chavanet, P., Hillon, P., & Portier, H. (2001) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00042560-200107010-00005 · Cited by 127
HIV-Associated Facial Lipoatrophy
James, J., CARRUTHERS, A. J., & CARRUTHERS, J. D. A. (2002) · Dermatologic Surgery · doi:10.1046/j.1524-4725.2002.02099.x · Cited by 127
A Comparative Insight into Amprenavir Resistance of Mutations V32I, G48V, I50V, I54V, and I84V in HIV-1 Protease Based on Thermodynamic Integration and MM-PBSA Methods
Chen, J., Wang, X., Zhu, T., Zhang, Q., & Zhang, J. Z. H. (2015) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5b00173 · Cited by 125
Recombinant human growth hormone improves the fat redistribution syndrome (lipodystrophy) in patients with HIV
WANKE, C. A., Gerrior, J., Kantaros, J., Coakley, E. P. G., & Albrecht, M. (1999) · AIDS · doi:10.1097/00002030-199910220-00013 · Cited by 125
Hyperlipidemia Associated with HIV Protease Inhibitor Use: Pathophysiology, Prevalence, Risk Factors and Treatment
Penzak, S. K. C. S. R. (2000) · Scandinavian Journal of Infectious Diseases · doi:10.1080/003655400750045196 · Cited by 123
“By this rationale, the degree to which a particular protease inhibitor inhibits CYP3A, may be proportional to its undesirable effects on lipid metabolism (15).”
BackgroundMethodInfluential
Pathogenesis of HIV-associated cardiovascular complications
Bárbaro, G., Fisher, S. D., & Lipshultz, S. E. (2001) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(01)00067-6 · Cited by 122
Fat Distribution in Women With HIV Infection
Infection, F. T. S. O. F. R. A. M. C. I. H. (2006) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/01.qai.0000229996.75116.da · Cited by 121
TNF-α promoter region gene polymorphisms in HIV-positive patients with lipodystrophy
Maher, B., Alfirevic, A., Vilar, F. J., Wilkins, E. G. L., Park, B. K., & Pirmohamed, M. (2002) · AIDS · doi:10.1097/00002030-200210180-00005 · Cited by 121
An interaction between apo C-III variants and protease inhibitors contributes to high triglyceride/low HDL levels in treated HIV patients
Fauvel, J., Bonnet, É., Ruidavets, J., Ferrières, J., Toffoletti, A., Massip, P., Chap, H., & Perret, B. (2001) · AIDS · doi:10.1097/00002030-200112070-00007 · Cited by 120
“[37] proposed that PI impair the activation of the PPARá±RXR heterodimer; this hypothesis is based on the homology between the HIV-1 protease and cytoplasmic retinoic acid binding protein (CRABP), a binding protein that is involved in”
Method
Is chronic HIV infection associated with venous thrombotic disease? A systematic review.
Klein, S. K., Slim, E., de Kruif, M. D., KELLER, T. T., Cate, H. T., Gorp, E. C. M. V., & Brandjes, D. P. M. (2005) · PubMed · Cited by 120
Statins and fibrates for the treatment of hyperlipidaemia in HIV-infected patients receiving HAART
Calza, L., Manfredi, R., & Chiodo, F. (2003) · AIDS · doi:10.1097/00002030-200304110-00010 · Cited by 120
Indinavir uncovers different contributions of GLUT4 and GLUT1 towards glucose uptake in muscle and fat cells and tissues
Rudich, A., Konrad, D., Török, D., Ben-Romano, R., Huang, C., Niu, W., Garg, R. R., Wijesekara, N., Germinario, R. J., Bilan, P. J., et al. (2003) · Diabetologia · doi:10.1007/s00125-003-1080-1 · Cited by 118
“Although nucleoside analogues and the HIV infection itself cause metabolic alterations, recent data support a causative role for HIV protease inhibitors in the development of the metabolic side-effects [39, 40, 41, 42].”
Background
Body Habitus Changes and Metabolic Alterations in Protease Inhibitor–Naive HIV-1–Infected Patients Treated With Two Nucleoside Reverse Transcriptase Inhibitors
Galli, M., Ridolfo, A. L., Adorni, F., Gervasoni, C., Ravasio, L., Corsico, L., Gianelli, E., Piazza, M., Vaccarezza, M., Monforte, A. D., et al. (2002) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200201010-00003 · Cited by 118
Molecular Mechanisms of HIV Protease Inhibitor-Induced Endothelial Dysfunction
Wang, X., Chai, H., Yao, Q. C., & Chen, C. (2007) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e3180322542 · Cited by 118
Activation of PXR induces hypercholesterolemia in wild-type and accelerates atherosclerosis in apoE deficient mice
Zhou, C., King, N., Chen, K. Y., & Breslow, J. L. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m800608-jlr200 · Cited by 116
Cerebral CD8+ lymphocytosis in HIV-1 infected patients with immune restoration induced by HAART
Miller, R. F., Isaacson, P. G., Hall-Craggs, M. A., Lucas, S. B., Gray, F., Scaravilli, F., & An, S. (2004) · Acta Neuropathologica · doi:10.1007/s00401-004-0852-0 · Cited by 116
“[9]; promoting additional phagocytosis of myelin by monocytes–macrophages [15]; or by relocation into peripheral blood of CD4+ and CD8+ T-lymphocytes [12], including CD8+ memory cells, previously sequestered in lymphoid tissue [23].”
Background
Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort
Cherry, C. L., Skolasky, R. L., Lal, L., Creighton, J. A., Hauer, P., Raman, S. P., Moore, R. D., Carter, K. A., Thomas, D. L., Ebenezer, G. J., et al. (2006) · Neurology · doi:10.1212/01.wnl.0000203336.12114.09 · Cited by 116
Improved Insulin Sensitivity and Body Fat Distribution in HIV-Infected Patients Treated With Rosiglitazone: A Pilot Study
Gelato, M. C., Mynarcik, D. C., Quick, J. L., Steigbigel, R. T., Fuhrer, J., BRATHWAITE, C. E. M., Brebbia, J. S., Wax, M. R., & McNurlan, M. A. (2002) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200210010-00006 · Cited by 116
Treatment of Primary Human Immunodeficiency Virus Type 1 Infection with Potent Antiretroviral Therapy Reduces Frequency of Rapid Progression to AIDS
Berrey, M. M., Schacker, T. W., Collier, A. C., Shea, T., Brodie, S. J., Mayers, D. L., Coombs, R. W., Krieger, J. N., Chun, T., Fauci, A. S., et al. (2001) · The Journal of Infectious Diseases · doi:10.1086/320189 · Cited by 111
Fasting Hyperinsulinemia in Human Immunodeficiency Virus-Infected Men: Relationship to Body Composition, Gonadal Function, and Protease Inhibitor Use1
Hadigan, C. M., Corcoran, C. P., Stanley, T. L., Piecuch, S., Klibanski, A., & Grinspoon, S. K. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.1.6264 · Cited by 115
Peripheral and Central Fat Changes in Subjects Randomized to Abacavir-Lamivudine or Tenofovir-Emtricitabine With Atazanavir-Ritonavir or Efavirenz: ACTG Study A5224s
McComsey, G. A., Kitch, D. W., Sax, P. E., Tebas, P., Tierney, C., Jahed, N. C., Myers, L., Melbourne, K., Ha, B., & Daar, E. S. (2011) · Clinical Infectious Diseases · doi:10.1093/cid/cir324 · Cited by 113
Hepatotoxicity of antiretroviral therapy.
Kontorinis, N., & Dieterich, D. T. (2003) · PubMed · Cited by 112
Role of Long-Term Nucleoside-Analogue Therapy in Lipodystrophy and Metabolic Disorders in Human Immunodeficiency Virus--Infected Patients
Chêne, G., Angelini, E., Cotte, L., Lang, J.-M., Morlat, P., Rancinan, C., May, T., Journot, V., Raffi, F., Jarrousse, B., et al. (2002) · Clinical Infectious Diseases · doi:10.1086/338811 · Cited by 112
Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus
Grinspoon, S. K. (2005) · The American Journal of Medicine Supplements · doi:10.1016/j.amjmed.2005.01.047 · Cited by 111
Prospective, Intensive Study of Metabolic Changes Associated with 48 Weeks of Amprenavir‐Based Antiretroviral Therapy
Dubé, M. P., Qian, D., Edmondson‐Melançon, H., Sattler, F. R., Goodwin, D., Martinez, C., Williams, V. C., Johnson, D., & Buchanan, T. A. (2002) · Clinical Infectious Diseases · doi:10.1086/341489 · Cited by 110
“It has been suggested that insulin resistance is a consequence of the lipid abnormalities induced by PI therapy [31].”
Background
Aortic Stiffness in Untreated Adult Patients With Human Immunodeficiency Virus Infection
Schillaci, G., Socio, G. V. D., Pucci, G., Mannarino, M. R., Helou, J., Pirro, M., & Mannarino, E. (2008) · Hypertension · doi:10.1161/hypertensionaha.108.114660 · Cited by 108
Stavudine Versus Zidovudine and the Development of Lipodystrophy
Bogner, J. R., Vielhauer, V., Beckmann, R., Michl, G. M., Wille, L., Salzberger, B., & Goebel, F.-D. (2001) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00042560-200107010-00004 · Cited by 108
Lipodystrophy Syndrome in HIV Infection
Behrens, G. M. N., Stoll, M., & Schmidt, R. E. (2000) · Drug Safety · doi:10.2165/00002018-200023010-00004 · Cited by 107
Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy
Pakker, N. G., Kroon, E. D. M. B., Roos, M. T. L., Otto, S. A., Hall, D. B., Wit, F. W. N. M., Hamann, D., van der Ende, M. E., Claessen, F. A. P., Kauffmann, R. H., et al. (1999) · AIDS · doi:10.1097/00002030-199902040-00008 · Cited by 107
Adverse cutaneous reactions associated with the newest antiretroviral drugs in patients with human immunodeficiency virus infection
Borrás‐Blasco, J., Navarro‐Ruiz, A., Borrás, C., & Castera, E. (2008) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkn292 · Cited by 106
“Homologies between the amino acid sequences of retinoic acid-binding protein 1 and the catalytic site of HIV type-1 (HIV-1) proteases have been noted.(9) Moreover, drug-induced nail pigmentation typically involves several nails and is usually reversible.”
Background
Hepatotoxicity of Antiretrovirals
ez, M. N., & Soriano, V. (2005) · Drug Safety · doi:10.2165/00002018-200528010-00004 · Cited by 106
Myocardial Infarction in HIV-Infected Men Receiving Protease Inhibitors
Flynn, T. E., & Bricker, L. A. (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-131-7-199910050-00032 · Cited by 106
Long-Term Efficacy and Safety of Atazanavir With Stavudine and Lamivudine in Patients Previously Treated With Nelfinavir or Atazanavir
Wood, R., Phanuphak, P., Cahn, P. E., Pokrovskiy, V., Rozenbaum, W., Pantaleo, G., Sension, M., Murphy, R. L., Mancini, M., Kelleher, T., et al. (2004) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200406010-00005 · Cited by 102
British HIV Association (BHIVA) guidelines for the treatment of HIV‐infected adults with antiretroviral therapy (2005)
Gazzard, B. (2005) · HIV Medicine · doi:10.1111/j.1468-1293.2005.0311b.x · Cited by 102
HIV Replication Enhances Production of Free Fatty Acids, Low Density Lipoproteins and Many Key Proteins Involved in Lipid Metabolism: A Proteomics Study
Rasheed, S., Yan, J. S., Lau, A., & Chan, A. S. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003003 · Cited by 101
HIV protease inhibitors activate the unfolded protein response and disrupt lipid metabolism in primary hepatocytes
Zhou, H., Gurley, E. C., Brimson, S. J., Ding, H., Fang, Y., Xu, Z., Pandak, W. M., & Hylemon, P. B. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00182.2006 · Cited by 101
Highly Active Antiretroviral Therapy–Associated Metabolic Syndrome: Pathogenesis and Cardiovascular Risk*
Bárbaro, G. (2006) · American Journal of Therapeutics · doi:10.1097/01.mjt.0000162013.66614.16 · Cited by 100
“PI binding to LRP would impair hepatic chylomicron uptake and endothelial triglyceride clearance, resulting in hyperlipidemia and insulin resistance.(1,4) Ultrastructural analysis of adipocytes in PI-induced lipodystrophy reveals changes including disruption of cell membranes, fragmented cytoplasmic rims, irregular ce…”
BackgroundInfluential
Indinavir
Plosker, G. L., & Noble, S. (1999) · Drugs · doi:10.2165/00003495-199958060-00011 · Cited by 101
Ischemic Cardiovascular Disease in Persons with Human Immunodeficiency Virus Infection
David, M. H., Hornung, R., & Fichtenbaum, C. J. (2002) · Clinical Infectious Diseases · doi:10.1086/324745 · Cited by 99
Mitochondrial involvement in antiretroviral therapy-related lipodystrophy
Zaera, M. G., Miró, Ò., Pedrol, E., Soler, A., Picón, M., Cardellach, F., Casademont, J., & Nunes, V. (2001) · AIDS · doi:10.1097/00002030-200109070-00006 · Cited by 99
“pointed out the fact that there is a 63% homology between HIV-1 protease and the low-density lipoprotein-receptor-related protein, and 58% between this protease and the cytoplasmic retinoic-acid binding protein type 1 [8].”
Background
Agent and cell-type specificity in the induction of insulin resistance by HIV protease inhibitors
Ben-Romano, R., Rudich, A., Török, D., Vanounou, S., Riesenberg, K., Schlaeffer, F., Klip, A., & Bashan, N. (2003) · AIDS · doi:10.1097/00002030-200301030-00005 · Cited by 98
Metabolic Complications Associated with HIV Protease Inhibitor Therapy
Nolan, D. A. (2003) · Drugs · doi:10.2165/00003495-200363230-00001 · Cited by 98
Cutaneous manifestations of antiretroviral therapy
Ward, H. A., Russo, G., & Shrum, J. P. (2002) · Journal of the American Academy of Dermatology · doi:10.1067/mjd.2002.119105 · Cited by 97
Effect of highly active antiretroviral therapy on fat, lean, and bone mass in HIV-seropositive men and women
McDermott, A. Y., Shevitz, A., Knox, T. A., Roubenoff, R., Kehayias, J. J., & Gorbach, S. L. (2001) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/74.5.679 · Cited by 97
Colour-Doppler ultrasonography of carotid vessels in patients treated with antiretroviral therapy
Maggi, P., Lillo, A., Perilli, F., Maserati, R., & Chirianni, A. (2004) · AIDS · doi:10.1097/00002030-200404300-00010 · Cited by 96
Diabetes Mellitus, Preexisting Coronary Heart Disease, and the Risk of Subsequent Coronary Heart Disease Events in Patients Infected With Human Immunodeficiency Virus
Worm, S. W., Wit, S. D., Weber, R. K., Sabin, C. A., Reiss, P., El‐Sadr, W., Monforte, A. D., Kirk, O., Fontas, É., Dabis, F., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.790857 · Cited by 99
Antiretroviral therapy-associated hyperlipidaemia in HIV disease
Mooser, V., & Carr, A. (2001) · Current Opinion in Lipidology · doi:10.1097/00041433-200106000-00011 · Cited by 96
Self-citation
Antiretroviral Treatment Patterns and Incident HIV-Associated Morphologic and Lipid Abnormalities in a Population-Based Cohort
Heath, K., Hogg, R. S., Singer, J., Chan, K., O’Shaughnessy, M. V., & Montaner, J. S. G. (2002) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00042560-200208010-00010 · Cited by 96
Changes in health-promoting behavior following diagnosis with HIV: Prevalence and correlates in a national probability sample.
Collins, R. L., Kanouse, D. E., Gifford, A. L., Senterfitt, J. W., Schuster, M. A., McCaffrey, D. F., Shapiro, M. F., & Wenger, N. S. (2001) · Health Psychology · doi:10.1037/0278-6133.20.5.351 · Cited by 95
Antiretroviral Therapy and the Lipodystrophy Syndrome
John, M., Nolan, D. A., & Mallal, S. A. (2001) · Antiviral Therapy · doi:10.1177/135965350100600102 · Cited by 95
Deficiency of PXR decreases atherosclerosis in apoE-deficient mice
Sui, Y., Xu, J., Rios-Pilier, J., & Zhou, C. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m017376 · Cited by 97
Impact of Treatment With Protease Inhibitors on Aortic Stiffness in Adult Patients With Human Immunodeficiency Virus Infection
Schillaci, G., Socio, G. V. D., Pirro, M., Savarese, G., Mannarino, M. R., Baldelli, F., Stagni, G., & Mannarino, E. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000183744.38509.de · Cited by 94
Lipid profile of HIV-infected patients in relation to antiretroviral therapy: a review
Souza, S. J., Luzia, L. A., dos Santos, S. D. S., & Rondó, P. H. D. C. (2013) · Revista da Associação Médica Brasileira · doi:10.1016/j.ramb.2012.11.003 · Cited by 93
Role of Pregnane X Receptor in Obesity and Glucose Homeostasis in Male Mice
Spruiell, K., Richardson, R. M., Cullen, J. M., Awumey, E. M., Gonzalez, F. J., & Gyamfi, M. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.494575 · Cited by 99
“Second, relevant PXR ligands can alter plasma lipid levels in patients, where activated PXR alters expression of genes involved in lipid homeostasis (11, 12).”
Background
Non-nucleoside reverse transcriptase inhibitor efavirenz activates PXR to induce hypercholesterolemia and hepatic steatosis
Gwag, T., Meng, Z., Sui, Y., Helsley, R. N., Park, S., Wang, S., Greenberg, R. N., & Zhou, C. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2018.12.038 · Cited by 92
The HIV Protease Inhibitor Indinavir Decreases Insulin- and Contraction-Stimulated Glucose Transport in Skeletal Muscle
Nolte, L. A., Yarasheski, K. E., Kawanaka, K., Fisher, J. S., Le, N., & Holloszy, J. O. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1397 · Cited by 92
“One proposed mechanism is that HIV protease inhibitors induce development of central/visceral obesity, which in turn causes insulin resistance (2).”
Background
Lipodystrophy Syndrome in Patients with HIV Infection
Martínez, E., García-Viejo, M. A., Blanch, J., & Gatell, J. M. (2001) · Drug Safety · doi:10.2165/00002018-200124030-00001 · Cited by 91
The Effect of Protease Inhibitor Therapy on Growth and Body Composition in Human Immunodeficiency Virus Type 1-Infected Children
Miller, T. L., Mawn, B. E., Orav, E. J., Wilk, D., Weinberg, G. A., Nicchitta, J., Furuta, L., Cutroni, R., McIntosh, K., Burchett, S. K., et al. (2001) · PEDIATRICS · doi:10.1542/peds.107.5.e77 · Cited by 91
Metabolic and Cardiovascular Complications of Highly Active Antiretroviral Therapy for HIV Infection
Bárbaro, G. (2005) · Current HIV Research · doi:10.2174/157016206775197664 · Cited by 89
Dyslipidemia related to antiretroviral therapy.
Estrada, E., & Portilla, J. (2011) · PubMed · Cited by 89
Monogenic forms of insulin resistance: apertures that expose the common metabolic syndrome
Hegele, R. A. (2003) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(03)00142-5 · Cited by 86
Treatment of metabolic syndrome
Wagh, A., & Stone, N. J. (2004) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.2.2.213 · Cited by 87
Human immunodeficiency virus and host cell lipids. Interesting pathways in research for a new HIV therapy
Raulin, J. (2002) · Progress in Lipid Research · doi:10.1016/s0163-7827(01)00019-4 · Cited by 86
Intramyocellular lipid accumulation and reduced whole body lipid oxidation in HIV lipodystrophy
Luzi, L., Perseghin, G., Tambussi, G., Meneghini, E., Scifo, P., Pagliato, E., Maschio, A. D., Testolin, G., & Lazzarin, A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00391.2001 · Cited by 85
“(6), suggested a major role of protease inhibitors (PIs) in the induction of hypertriglyceridemia (and insulin resistance), since they can interact with retinoic acid receptors at the liver site (6).”
Background
Cellular mechanisms of insulin resistance, lipodystrophy and atherosclerosis induced by HIV protease inhibitors
Rudich, A., Ben-Romano, R., Etzion, S., & Bashan, N. (2005) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.2004.01383.x · Cited by 83
Nelfinavir Mesylate: A Protease Inhibitor
Pai, V. B., & Nahata, M. C. (1999) · Annals of Pharmacotherapy · doi:10.1345/aph.18089 · Cited by 83
Influence of protease inhibitor therapy on lipoprotein metabolism
Berthold, H. K., Parhofer, K. G., Ritter, M. M., Addo, M. M., Wasmuth, J., Schliefer, K., Spengler, U., & Rockstroh, J. K. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00615.x · Cited by 81
Hypofibrinolytic State in HIV-1–Infected Patients Treated With Protease Inhibitor–Containing Highly Active Antiretroviral Therapy
Koppel, K., Bratt, G., Schulman, S., Bylund, H., & Sandström, E. (2002) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00042560-200204150-00003 · Cited by 83
Antiretroviral treatment in 1998
Montaner, J. S. G., Hogg, R. S., Raboud, J., Harrigan, R., & O’Shaughnessy, M. V. (1998) · The Lancet · doi:10.1016/s0140-6736(98)07532-1 · Cited by 83
The prevalence of lipodystrophy in an ambulant HIV‐infected population: it all depends on the definition
Carter, V. M., Hoy, J., Bailey, M., Colman, P. G., Nyulasi, I. B., & Mijch, A. M. (2001) · HIV Medicine · doi:10.1046/j.1468-1293.2001.00073.x · Cited by 82
Morphogenesis of the developing mammary gland: Stage-dependent impact of adipocytes
Landskroner-Eiger, S., Park, J.-Y., Israel, D. D., Pollard, J. W., & Scherer, P. E. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.06.019 · Cited by 80
“…highlights the distinct characteristics of each fat pad, similar to the situation seen in a number of lipodystrophies (such as a HIV-associated lipodystrophy) in which fat pads are differentially affected, and therefore display a distinct behavior in different anatomical sites (Carr et al., 1998).”
Background
The Evaluation of Subcutaneous Proleukin® (interleukin-2) in a Randomized International Trial
Emery, S., Abrams, D. I., Cooper, D. A., Darbyshire, J. H., Lane, H. C., Lundgren, J. D., & Neaton, J. D. (2002) · Controlled Clinical Trials · doi:10.1016/s0197-2456(01)00179-9 · Cited by 81
Self-citation
Mitochondrial Functionality and Mitochondrial DNA Content in Lymphocytes of Vertically Infected Human Immunodeficiency Virus–Positive Children with Highly Active Antiretroviral Therapy–Related Lipodystrophy
Cossarizza, A., Pinti, M., Moretti, L., Bricalli, D., Bianchi, R., Troiano, L., Garcia‐Fernandez, M. I., Balli, F., Brambilla, P., Mussini, C., et al. (2002) · The Journal of Infectious Diseases · doi:10.1086/338564 · Cited by 80
“On the one hand, PI could bind and inhibit human proteins that share a high homology with HIV protease, such as the lowdensity lipoprotein receptor–related protein and the cytoplasmic retinoic acid–binding protein type 1 [4, 5].”
Background
HIV-1 Protease Inhibitor Induced Oxidative Stress Suppresses Glucose Stimulated Insulin Release: Protection with Thymoquinone
Chandra, S., Mondal, D., & Agrawal, K. C. (2009) · Experimental Biology and Medicine · doi:10.3181/0811-rm-317 · Cited by 80
“Long-term treatment with HIV-1 PI containing HAART regimen has been associated with clear manifestations of the metabolic syndrome in HIV-1 positive patients, including cardiovascular dysfunction, lipodystrophy and insulin resistance (1, 4, 5, 34).”
Background
HIV protease inhibitors block human preadipocyte differentiation, but not via the PPARgamma/RXR heterodimer
Wentworth, J. M., Burris, T. P., & Chatterjee, K. (2000) · Journal of Endocrinology · doi:10.1677/joe.0.164r007 · Cited by 80
Dissecting the interaction between COVID‐19 and diabetes mellitus
Chee, Y. J., Tan, S. K., & Yeoh, E. C. K. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13326 · Cited by 82
Perspective on HIV Infection and Aging: Emerging Research on the Horizon
Mayer, K. H., & Casau, N. C. (2005) · Clinical Infectious Diseases · doi:10.1086/432797 · Cited by 78
Opiate Drug Use: A Potential Contributor to the Endocrine and Metabolic Complications in Human Immunodeficiency Virus Disease
Cooper, O. B., Brown, T. T., & Dobs, A. S. (2003) · Clinical Infectious Diseases · doi:10.1086/375879 · Cited by 77
Apoprotein C-III and E-Containing Lipoparticles Are Markedly Increased in HIV-Infected Patients Treated with Protease Inhibitors: Association with the Development of Lipodystrophy
Bonnet, É., Ruidavets, J., Tuech, J., Ferrières, J., Collet, X., Fauvel, J., Massip, P., & Perret, B. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.1.296 · Cited by 77
Clinical and Immunologic Response without Decrease in Virus Load in Patients with AIDS after 24 Months of Highly Active Antiretroviral Therapy
Mezzaroma, I., Carlesimo, M., Pinter, E., Muratori, D. S., Sora, F. D., Chiarotti, F., Cunsolo, M. G., Sacco, G., & Aiuti, F. (1999) · Clinical Infectious Diseases · doi:10.1086/313520 · Cited by 77
“Moreover, in long-term PI administration, occurrence of initially unknown adverse events, such as the recently described lipodystrophy syndrome [12, 13], must be taken into consideration.”
Background
HIV‐Associated Lipodystrophy Syndrome
Qaqish, R. B., Fisher, E., Rublein, J., & Wohl, D. A. (2000) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.20.1.13.34667 · Cited by 75
“It is coexpressed on capillary endothelium with lipoprotein lipase (LPL).(32) The LPL-LRP complex cleaves fatty acids from circulating triglycerides, permitting free fatty acid entry into adipocytes for storage of fat.”
BackgroundInfluential
Repositioning HIV protease inhibitors as cancer therapeutics
Bernstein, W. B., & Dennis, P. A. (2008) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0b013e328313915d · Cited by 74
Adrenal Function in the Human Immunodeficiency Virus–Infected Patient
Mayo, J., Collazos, J., Martínez, E., & Ibarra, S. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.10.1095 · Cited by 74
Diabetes, metabolic syndrome and dyslipidemia in people living with HIV in Africa: re-emerging challenges not to be forgotten
Husain, N. E., Noor, S. K., Elmadhoun, W. M., Almobarak, A. O., Awadalla, H., Woodward, C., Mital, D., & Ahmed, M. (2017) · HIV/AIDS - Research and Palliative Care · doi:10.2147/hiv.s137974 · Cited by 74
Effects of antiretroviral drug combinations on the differentiation of adipocytes
Roche, R., Poizot‐Martin, I., Yazidi, C. M.-E., Compe, E., Gastaut, J., Torrésani, J., & Planells, R. (2002) · AIDS · doi:10.1097/00002030-200201040-00003 · Cited by 74
“This syndrome is frequently associated with dyslipaemia [5,7,8], insulin resistance [7,9] and less often with diabetes mellitus [7,10].”
BackgroundResult
Use of Fibrates in the Management of Hyperlipidemia in HIV-Infected Patients Receiving HAART
Calza, L., Manfredi, R., & Chiodo, F. (2002) · Infection · doi:10.1007/s15010-001-2052-3 · Cited by 72
The Thrifty Genotype in Type 2 Diabetes: An Unfinished Symphony Moving to Its Finale?
Joffe, B., & Zimmet, P. (1998) · Endocrine · doi:10.1385/endo:9:2:139 · Cited by 73
Metabolic Disorders Among HIV-Infected Patients Treated With Protease Inhibitors: A Review
Graham, N. M. H. (2000) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00042560-200010001-00002 · Cited by 73
Subcutaneous fat in normal and diseased states
Avram, M. M., Avram, A. S., & James, W. D. (2005) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2005.05.014 · Cited by 77
Unexplained thrombosis in HIV-infected patients receiving protease inhibitors: report of seven cases
George, S. L., Swindells, S., Knudson, R., & Stapleton, J. T. (1999) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00296-x · Cited by 72
Paracrine interactions of mammalian adipose tissue
Pond, C. M. (2002) · Journal of Experimental Zoology Part A Comparative Experimental Biology · doi:10.1002/jez.a.10215 · Cited by 71
Management of the metabolic effects of HIV and HIV drugs
Brown, T. T., & Glesby, M. J. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.151 · Cited by 73
Enterovirus RNA in serum is a risk factor for beta-cell autoimmunity and clinical type 1 diabetes: A prospective study
Lönnrot, M., Salminen, K., Knip, M., Savola, K., Kulmala, P., Leinikki, P., Hyypiä, T., Åkerblom, H. K., Hyöty, H., & Childhood Diabetes in Finland (DiMe) Study Group: The members of the Childhood Diabetes in Finland (DiMe) Study Group are listed in the Appendix. (2000) · Journal of Medical Virology · doi:10.1002/(sici)1096-9071(200006)61:2 · Cited by 165
Body-composition measurements as predictors of glucose and insulin abnormalities in HIV-positive men
Meininger, G. E., Hadigan, C. M., Rietschel, P., & Grinspoon, S. K. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.2.460 · Cited by 71
HIV-1 Protease Inhibitors
Eron, J. J. (2000) · Clinical Infectious Diseases · doi:10.1086/313853 · Cited by 70
“in lipid metabolism has been hypothesized as a mechanism for this dysregulation [108].”
Background
Immunological and virological responses in HIV-1-infected adults at early stage of established infection treated with highly active antiretroviral therapy
Bart, P., Rizzardi, G. P., Tambussi, G., Chave, J., Chapuis, A. G., Graziosi, C., Corpataux, J.-M., Halkic, N., Meuwly, J., Muñoz, M., et al. (2000) · AIDS · doi:10.1097/00002030-200009080-00002 · Cited by 70
Expert Panel Review on Nonalcoholic Fatty Liver Disease in Persons With Human Immunodeficiency Virus
Lake, J. E., Overton, T., Naggie, S., Sulkowski, M., Loomba, R. S., Kleiner, D. E., Price, J. C., Chew, K. W., Chung, R. T., & Corey, K. E. (2020) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.10.018 · Cited by 70
HIV protease inhibitors and onset of cardiovascular diseases: A central role for oxidative stress and dysregulation of the ubiquitin–proteasome system
Reyskens, K. M. S. E., & Essop, M. F. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.11.019 · Cited by 70
HIV-associated vascular diseases: Structural and functional changes, clinical implications
Monsuez, J.-J., Charniot, J., Escaut, L., Teicher, E., Wyplosz, B., Couzigou, C., Vignat, N., & Vittecoq, D. (2009) · International Journal of Cardiology · doi:10.1016/j.ijcard.2008.11.113 · Cited by 70
“Protease inhibitor dyslipidemia has been attributed to inhibition of lipid metabolism and adipocyte regulatory proteins that have partial homology to the catalytic site of HIV-1 protease, to which protease inhibitors bind [128,129].”
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks