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 301–400 of 1,000

Apoptosis of human abdominal preadipocytes before and after differentiation into adipocytes in culture
Papineau, D., Gagnon, A., & Sorisky, A. (2003) · Metabolism · doi:10.1016/s0026-0495(03)00165-3 · Cited by 46
Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications
Tsiodras, S., & Mantzoros, C. S. (2006) · American Journal of Infectious Diseases · doi:10.3844/ajidsp.2006.141.152 · Cited by 46
“145 One of the first theories to be presented to explain the lipodystrophy syndrome was that antiretroviral medications directly decrease adipocyte differentiation by inhibiting the activation of nuclear receptors involved in adipocyte differentiation and insulin induced metabolic changes([124,125]).”
Background
Arterial Stiffness in HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy
Sevastianova, K., Sutinen, J., Westerbacka, J., Ristola, M. A., & Yki‐Järvinen, H. (2005) · Antiviral Therapy · doi:10.1177/135965350501000808 · Cited by 45
Pathogenesis of HIV-associated heart disease
Bárbaro, G. (2003) · AIDS · doi:10.1097/00002030-200304001-00003 · Cited by 46
“, the metabolic and somatic alterations in HAART-treated subjects could be ascribed to the homology of the catalytic region of HIV protease, the molecular target of protease inhibitors, to regions of two human proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein 1 (CRABP1), and low-densit…”
BackgroundInfluential
Dimerization Inhibitors of HIV-1 Protease
Boggetto, N., & Reboud‐Ravaux, M. (2002) · Biological Chemistry · doi:10.1515/bc.2002.150 · Cited by 45
“inhibitor drugs have been shown to produce serious adverse reactions (Carr et al., 1998).”
Background
Modulation of the LDL receptor and LRP levels by HIV protease inhibitors
Tran, H., Robinson, S. E., MIKHAILENKO, I. A., & Strickland, D. K. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m200487-jlr200 · Cited by 45
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:10.1097/00126334-200010001-00002 · Cited by 45
HIV infection, highly active antiretroviral therapy and the cardiovascular system
Barbaro, G. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00828-3 · Cited by 44
Experience in the treatment of HIV-associated lipodystrophy
Nelson, L., & Stewart, K. J. (2007) · Journal of Plastic Reconstructive & Aesthetic Surgery · doi:10.1016/j.bjps.2007.10.031 · Cited by 44
HIV lipodystrophy and its metabolic consequences: implications for clinical practice
Wierzbicki, A. S., Purdon, S. D., Hardman, T. C., Kulasegaram, R., & Peters, B. S. (2008) · Current Medical Research and Opinion · doi:10.1185/030079908x272742 · Cited by 44
Increased bleeding associated with protease inhibitor therapy in HIV‐positive patients with bleeding disorders
Wilde, J. T., Lee, C. A., Collins, P. W., Giangrande, P. L. F., Winter, M. R., & Shiach, C. R. (1999) · British Journal of Haematology · doi:10.1046/j.1365-2141.1999.01748.x · Cited by 44
“…inhibit the low-density lipoprotein-receptor-related protein (LRP), a hepatic receptor which is involved in not only the clearance of post-prandial chylomicrons but also of numerous endogenous proteases including tissue plasminogen activator (tPA) (Carr et al, 1998; Herz, 1993; Deeks et al, 1997).”
Background
Indinavir-Induced Retinoid-Like Effects
a-Silva, J. G. X., Almagro, M., a-Penabad, C. P., & Fonseca, E. (2002) · Drug Safety · doi:10.2165/00002018-200225140-00002 · Cited by 44
Low plasma level of adiponectin is associated with stavudine treatment and lipodystrophy in HIV-infected patients
Lindegaard, B., Keller, P., Brüünsgaard, H., Gerstoft, J., & Pedersen, B. K. (2004) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2004.02367.x · Cited by 43
Protease inhibitors and adipocyte differentiation in cell culture
Gagnon, A., Angel, J. B., & Sorisky, A. (1998) · The Lancet · doi:10.1016/s0140-6736(05)60074-8 · Cited by 44
Alterations in Serum Levels of Lipids and Lipoproteins with Indinavir Therapy for Human Immunodeficiency Virus‐Infected Patients
Roberts, A. D., Muesing, R. A., Parenti, D. M., Hsia, J., Wasserman, A. G., & Simon, G. L. (1999) · Clinical Infectious Diseases · doi:10.1086/520231 · Cited by 44
Mitochondria in the pathogenesis of lipodystrophy induced by anti‐HIV antiretroviral drugs: actors or bystanders?
Cossarizza, A., Mussini, C., & Viganò, M. (2001) · BioEssays · doi:10.1002/bies.1152 · Cited by 43
HIV-protease inhibitors alter retinoic acid synthesis
Toma, E., Devost, D., Lan, N. C., & Bhat, P. V. (2001) · AIDS · doi:10.1097/00002030-200110190-00010 · Cited by 43
Atorvastatin for protease inhibitor-related hyperlipidaemia
Murillas, J., Martín, T., Ramos, A., & Portero, J. L. (1999) · AIDS · doi:10.1097/00002030-199907300-00030 · Cited by 43
Alopecia Associated with Indinavir Therapy
Bouscarat, F., Prevot, M., & Matheron, S. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908193410818 · Cited by 43
Treatment options for hypertriglyceridemia: From risk reduction to pancreatitis
Berglund, L., Brunzell, J. D., Goldberg, A. C., Goldberg, I. J., & Stalenhoef, A. (2014) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2013.10.002 · Cited by 50
Insulin Resistance and Diabetes Mellitus in HIV-Infected Patients Receiving Antiretroviral Therapy
Calza, L., Manfredi, R., & Chiodo, F. (2004) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2004.2.241 · Cited by 42
Adipose tissue lipin expression levels distinguish HIV patients with and without lipodystrophy
Lindegaard, B., Larsen, L. F., Hansen, A.-B. E., Gerstoft, J., Pedersen, B. K., & Reue, K. (2006) · International Journal of Obesity · doi:10.1038/sj.ijo.0803434 · Cited by 42
Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients
Calza, L., Colangeli, V., Manfredi, R., Bon, I., Re, M. C., & Viale, P. (2016) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkv494 · Cited by 42
HIV protease inhibitors: recent clinical trials and recommendations on use
Fernández-Montero, J. V., Barreiro, P., & Soriano, V. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560902980202 · Cited by 42
“However, soon after their introduction, concerns were raised about the safety profile of PIs, in particular lipodystrophy [3] and associated metabolic complications such as insulin resistance [4] and dyslipidaemias [5].”
Background
Lipodystrophy associated with nevirapine-containing antiretroviral therapies
Aldeen, T., Wells, C., Hay, P., Davidson, F., & Lau, R. (1999) · AIDS · doi:10.1097/00002030-199905070-00021 · Cited by 42
Protease inhibitor–associated angiolipomatosis
Dank, J. P., & Colven, R. M. (2000) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(00)90021-5 · Cited by 42
Lipodystrophy syndrome and cardiovascular risk factors in children and adolescents infected with HIV/AIDS receiving highly active antiretroviral therapy
Werner, M. L. F., Pone, M. V. D. S., Fonseca, V. M., & Chaves, C. R. M. D. M. (2010) · Jornal de Pediatria · doi:10.2223/jped.1961 · Cited by 41
Lipid Evaluation in HIV-1-Positive Patients Treated with Protease Inhibitors
Schmidt, H., Behrens, G. M. N., Genschel, J., Stoll, M., Dejam, A., Haas, R. E., Manns, M. P., & Schmidt, R. E. (1999) · Antiviral Therapy · doi:10.1177/135965359900400305 · Cited by 41
The HIV protease inhibitor ritonavir increases lipoprotein production and has no effect on lipoprotein clearance in mice
Riddle, T. M., Schildmeyer, N. M., Phan, C. T., Fichtenbaum, C. J., & Hui, D. Y. (2002) · Journal of Lipid Research · doi:10.1194/jlr.m200129-jlr200 · Cited by 41
“Unfortunately, despite the effectiveness of these drugs on reducing HIV titer, highly active anti-retroviral therapy is also associated with several undesirable adverse effects including hyperlipidemia, lipodystrophy, and insulin resistance (4, 5).”
Background
HIV Inhibitors: Problems and Reality
Tőzsér, J. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb03909.x · Cited by 41
Paronychia with Pyogenic Granuloma in a Child Treated with Indinavir: The Retinoid-Mediated Side Effect Theory Revisited
Sass, J. O., Jakob-Sölder, B., Heitger, A., Tzimas, G., & Sarcletti, M. (2000) · Dermatology · doi:10.1159/000018313 · Cited by 41
Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders
Csako, G., McGriff, N. J., Rotman-Pikielny, P., Sarlis, N. J., & Pucino, F. (2001) · Annals of Pharmacotherapy · doi:10.1345/aph.1a031 · Cited by 40
Nutrition and the HIV-associated lipodystrophy syndrome
Loonam, C., & Mullen, A. (2012) · Nutrition Research Reviews · doi:10.1017/s0954422411000138 · Cited by 40
Intestinal Pregnane X Receptor Links Xenobiotic Exposure and Hypercholesterolemia
Sui, Y., Helsley, R. N., Park, S., Song, X., Liu, Z., & Zhou, C. (2015) · Molecular Endocrinology · doi:10.1210/me.2014-1355 · Cited by 42
13. HIV-1 infection
Sleasman, J. W., & Goodenow, M. M. (2003) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2003.91 · Cited by 46
From lipodystrophy syndromes to diabetes mellitus
Joffe, B. I., Panz, V. R., & Raal, F. J. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04616-x · Cited by 40
Nutrition and immune function in human immunodeficiency virus infection
Macallan, D. C. (1999) · Proceedings of The Nutrition Society · doi:10.1017/s002966519900097x · Cited by 40
High-density lipoprotein concentrations relate to the clinical course of HIV viral load in patients undergoing antiretroviral therapy
Alonso‐Villaverde, C., Segués, T., Crespo, B. C., Pérez-Bernalte, R., Rabassa, A., Gomila, M. G., Parra, S., Gozález-Esteban, M. A., Jiménez‐Expósito, M. J., & Masana, L. (2003) · AIDS · doi:10.1097/00002030-200305230-00009 · Cited by 39
“A syndrome of peripheral fat wasting, central adiposity, insulin resistance and dyslipaemia has been identified in HIV patients receiving antiretroviral treatment [1].”
Background
Estado nutricional, clínico e padrão alimentar de pessoas vivendo com HIV/Aids em assistência ambulatorial no município de São Paulo
Silva, E. F. R., Lewi, D. S., Vedovato, G. M., Garcia, V. R. S., Tenore, S. B., & Bassichetto, K. C. (2010) · Revista Brasileira de Epidemiologia · doi:10.1590/s1415-790x2010000400012 · Cited by 39
Safety and Tolerability: Current Challenges to Antiretroviral Therapy for the Long-Term Management of HIV Infection.
Troya, J., & Bascuñana, J. (2016) · PubMed · Cited by 39
Surgical Algorithm for Management of HIV Lipodystrophy
Davison, S. P., Timpone, J. G., & Hannan, C. M. (2007) · Plastic & Reconstructive Surgery · doi:10.1097/01.prs.0000267341.14550.a7 · Cited by 39
Drug-Induced Cardiovascular Disorders
Murphy, C. A., & Dargie, H. J. (2007) · Drug Safety · doi:10.2165/00002018-200730090-00005 · Cited by 39
HIV Sequence Sigmatires and Similarities
Korber, B. (2002) · Springer eBooks · doi:10.1007/0-306-46900-6_4 · Cited by 39
Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome and Cardiovascular Risk
Bárbaro, G., & Barbarini, G. (2006) · Chemotherapy · doi:10.1159/000093034 · Cited by 39
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:10.1097/00126334-200003010-00009 · Cited by 39
In Vitro Activity of Human Immunodeficiency Virus Protease Inhibitors againstPneumocystis carinii
Atzori, C., Angeli, E., Mainini, A., AGOSTONI, F., Micheli, V., & Cargnel, A. (2000) · The Journal of Infectious Diseases · doi:10.1086/315437 · Cited by 39
“, lipodystrophy) or insulin signaling [31].”
HIV/AIDS e Treinamento Concorrente: a Revisão Sistemática
Lazzarotto, A. R., Deresz, L. F., & Sprinz, E. (2010) · Revista Brasileira de Medicina do Esporte · doi:10.1590/s1517-86922010000200015 · Cited by 42
“Os fármacos utilizados nos esquemas terapêuticos e, dentre eles, principalmente os inibidores de protease introduzidos nesses esquemas em 1996, são responsáveis pela maior expectativa de vida dos indivíduos infectados pelo HIV; entretanto, têm sido associados à síndrome lipodistrófica do HIV, caracterizada pelos segui…”
Background
The role of efavirenz compared with protease inhibitors in the body fat changes associated with highly active antiretroviral therapy
Pérez-Molina, J. A., Domingo, P., Martínez, E., & Moreno, S. (2008) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkn191 · Cited by 38
“fat at baseline was slightly lower in the ACTG 5005s patients, whereas in the other three studies, it was almost normal.(1,91) In ACTG 5005s, for the group as a whole, limb fat increased during the first 32 weeks and subsequently declined.”
BackgroundResult
Frequency of and outcome of acute coronary syndromes in patients with human immunodeficiency virus infection
Ambrose, J. A., Gould, R. B., Kurian, D. C., DeVoe, M. C., Pearlstein, N. B., Coppola, J. T., & Siegal, F. P. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(03)00631-3 · Cited by 38
Respiratory chain dysfunction associated with multiple mitochondrial DNA deletions in antiretroviral therapy-related lipodystrophy
Miró, Ò., Gómez, M., Pedrol, E., Cardellach, F., Nunes, V., & Casademont, J. (2000) · AIDS · doi:10.1097/00002030-200008180-00024 · Cited by 38
“Protease inhibitors have been invoked as the main cause of the syndrome through disturbing adipocyte metabolism and causing apoptosis by means of altered retinoid signalling [1,9].”
Background
The feature of Metabolic Syndrome in HIV naive patients is not the same of those treated: Results from a prospective study
Bonfanti, P., Socio, G. V. D., Ricci, E. D., Antinori, A., Martinelli, C. V., Vichi, F., Penco, G., Madeddu, G., Orofino, G., Valsecchi, L., et al. (2012) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2012.01.005 · Cited by 37
“In our sample, PIs seemed related to a significant WC increase, as is well documented [24].”
Background
Exercise Stress Testing for Detection of Silent Myocardial Ischemia in Human Immunodeficiency Virus—Infected Patients Receiving Antiretroviral Therapy
Duong, M., Cottin, Y., Piroth, L., Fargeot, A., Lhuiller, I., Bobillier, M., Grappin, M., Buisson, M., Zeller, M., Chavanet, P., et al. (2002) · Clinical Infectious Diseases · doi:10.1086/338398 · Cited by 37
HIV-1 protease inhibitor–associated partial lipodystrophy: Clinicopathologic review of 14 cases☆, ☆☆
Pujol, R. M., Domingo, P., XAVIERMATIASGUIU, Francia, E., SANBEAT, M., Alomar, A., & VAZQUEZ, G. (2000) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(00)90125-7 · Cited by 37
Protease inhibitor–induced lipodystrophy
Williamson, K., Reboli, A. C., & Manders, S. M. (1999) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(99)70452-4 · Cited by 37
MEDICAL MANAGEMENT OF HIV DISEASE IN CHILDREN
Laufer, M., & Scott, G. B. (2000) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(05)70198-x · Cited by 37
Emerging concepts in gastrointestinal aspects of HIV-1 pathogenesis and management
Janoff, E. N., & Smith, P. D. (2001) · Gastroenterology · doi:10.1053/gast.2001.22427 · Cited by 36
“141, 171, 174 Mitochondrial dysfunction has been invoked as one potential unifying mechanism underlying these syndromes in patients taking PI-containing combination therapy.”
Background
Epigenetic impact of endocrine disrupting chemicals on lipid homeostasis and atherosclerosis: a pregnane X receptor-centric view
Helsley, R. N., & Zhou, C. (2017) · Current Zoology · doi:10.1093/eep/dvx017 · Cited by 38
White matter loss and oligodendrocyte dysfunction in HIV: A consequence of the infection, the antiretroviral therapy or both?
Jensen, B. K., Roth, L. M., Grinspan, J. B., & Jordan‐Sciutto, K. L. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146397 · Cited by 40
“Ultimately, dysfunction through this mechanism leads to pathologies culminating in atherosclerosis, hypercholesterolemia, lipodystrophy, and insulin resistance (Carr et al., 1998; Cohen, 2005; Parker et al., 2005; Zhou et al., 2005).”
Background
Coronavirus (COVID-19), Coagulation, and Exercise: Interactions That May Influence Health Outcomes
Zadow, E. K., Wundersitz, D. W. T., Hughes, D. L., Adams, M. J., Kingsley, M., Blacklock, H. A., Wu, S. S. X., Benson, A. C., Dutheil, F., & Gordon, B. A. (2020) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0040-1715094 · Cited by 36
Alterações metabólicas, terapia antirretroviral e doença cardiovascular em idosos portadores de HIV
Kramer, A. S., Lazzarotto, A. R., Sprinz, E., & Manfrói, W. C. (2009) · Arquivos Brasileiros de Cardiologia · doi:10.1590/s0066-782x2009001100019 · Cited by 36
High Plasma Level of Interleukin-18 in HIV-Infected Subjects With Lipodystrophy
Lindegaard, B., Hansen, A. E., Gerstoft, J., & Pedersen, B. K. (2004) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200405010-00006 · Cited by 36
Atherosclerotic Cardiovascular Disease Risk in the HAART-Treated HIV-1 Population
Nehal, M. F. E.-S., & Reilly, M. P. (2005) · HIV Clinical Trials · doi:10.1310/ht0w-nx2n-u2bm-7luu · Cited by 35
Initial experience with bariatric surgery in asymptomatic human immunodeficiency virus-infected patients
Flancbaum, L., Drake, V., Colarusso, T., & Belsley, S. (2005) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2005.02.004 · Cited by 36
Reverse Transcriptase Inhibitors Alter Uncoupling Protein-1 and Mitochondrial Biogenesis in Brown Adipocytes
de la Concepción, M. L. R., Yubero, P., Domingo, J. C., Iglesias, R., Domingo, P., Villarroya, F., & Giralt, M. (2005) · Antiviral Therapy · doi:10.1177/135965350501000407 · Cited by 36
“PIs were believed to interf e re with retinoid metabolism [54] and indinavir with the retinoic acid pathway [55].”
Background
Goals and milestones during treatment of HIV-1 infection with antiretroviral therapy: a pathogenesis-based perspective
Louie, M. J., & Markowitz, M. H. (2002) · Antiviral Research · doi:10.1016/s0166-3542(02)00022-0 · Cited by 36
Novel strategies for targeting the dimerization interface of HIV protease with cross‐linked interfacial peptides
Bowman, M. J., & Chmielewski, J. A. (2002) · Biopolymers · doi:10.1002/bip.10232 · Cited by 36
A Risk-Benefit Assessment of HIV Protease Inhibitors
Moyle, G. J., & Gazzard, B. (1999) · Drug Safety · doi:10.2165/00002018-199920040-00002 · Cited by 36
Human Immunodeficiency Virus Protease Inhibitors
Rana, K. Z., & Dudley, M. N. (1999) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.19.1.35.30513 · Cited by 36
“It is unclear how protease inhibitors interfere with such processes, but it is hypothesized that they may bind to specific binding proteins involved with retinoic acid metabolism critical in adipocyte function, and may also interfere with the CYP3A enzyme within these cells.(59) By interfering with these processes, fa…”
Background
Prevalence of lipodystrophy in Thai-HIV infected patients.
Puttawong, S., Prasithsirikul, W., & Vadcharavivad, S. (2004) · PubMed · Cited by 35
DNA immunization in combination with effective antiretroviral drug therapy controls viral rebound and prevents simian AIDS after treatment is discontinued
FULLER, D. H., Rajakumar, P. A., Wu, M. S., McMahon, C. W., Shipley, T., Fuller, J. T., Bazmi, A., Trichel, A. M., Allen, T. M., Mothé, B. R., et al. (2006) · Virology · doi:10.1016/j.virol.2005.12.008 · Cited by 34
Cutaneous effects of highly active antiretroviral therapy in HIV-infected patients
Kong, H. H., & Myers, S. A. (2005) · Dermatologic Therapy · doi:10.1111/j.1529-8019.2005.05004.x · Cited by 35
“Other than discontinuation of the suspected antiretroviral agent, therapies used in lipodystrophy in HIV patients include liposuction, fat transfer, medications such as metformin (81), implants, and fillers.”
Background
Molecular basis of partial lipodystrophy and prospects for therapy
Hegele, R. A. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(01)01930-x · Cited by 35
Syndrome of body fat redistribution in HIV‐1‐infected patients: relationships to cortisol and catecholamines
Renard, É., Fabre, J., Paris, F., Reynes, J., & Bringer, J. (1999) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1999.00777.x · Cited by 35
“Fax :þ33 4 67 04 13 56; E-mail: renard.amtim@wanadoo.fr described in HIV-infected patients, mostly males showing a low viral load, while HIV protease inhibitors were widely used in antiretroviral therapy (Hengelet al., 1997; Miller et al., 1998; Carr et al., 1998a).”
Background
Latent dysbetalipoproteinaemia precipitated by HIV-protease inhibitors
Lister, R., Youle, M. S., Nair, D. R., WINDER, A. F., & Rustin, M. H. A. (1999) · The Lancet · doi:10.1016/s0140-6736(99)01449-x · Cited by 35
The Bile Acid Sensor FXR Protects against Dyslipidemia and Aortic Plaques Development Induced by the HIV Protease Inhibitor Ritonavir in Mice
Mencarelli, A., Cipriani, S., Renga, B., Francisci, D., Palladino, G., Distrutti, E., Baldelli, F., & Fiorucci, S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013238 · Cited by 34
CRABP1 in Non-Canonical Activities of Retinoic Acid in Health and Diseases
Nhieu, J., Lin, Y., & Wei, L. (2022) · Nutrients · doi:10.3390/nu14071528 · Cited by 34
“proposed that the toxic effects on adipose and metabolism associated with the use of HIV-1 protease inhibitors were, in part, due to these inhibitors’ direct binding and inhibiting CRABP1 function [98].”
Background
Long-Term Treatment with Lopinavir-Ritonavir Induces a Reduction in Peripheral Adipose Depots in Mice
Prot, M., Héripret, L., Cardot‐Leccia, N., Perrin, C., Aouadi, M., Lavrut, T., Garraffo, R., Dellamonica, P., Durant, J., MARCHAND‐BRUSTEL, Y. L., et al. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00625-06 · Cited by 34
Effect of Protease Inhibitor Therapy on Glucose Intolerance in Pregnancy
Tang, J. H., Sheffield, J. S., Grimes, J., McElwee, B. S., Roberts, S. W., Laibl, V. R., McIntire, D. D., & Wendel, G. D. (2006) · Obstetrics and Gynecology · doi:10.1097/01.aog.0000207657.94360.78 · Cited by 34
“001 Prepregnancy 44 (47) 57 (74) Pregnancy 50 (53) 20 (26) AIDS diagnosis 13 (14) 6 (8) .”
A pilot study of the safety and efficacy of cholestin in treating HIV-related dyslipidemia
Keithley, J. K., Swanson, B. A., Sha, B. E., Zeller, J. M., Kessler, H. A., & Smith, K. Y. (2002) · Nutrition · doi:10.1016/s0899-9007(01)00688-8 · Cited by 33
Novel functions of PXR in cardiometabolic disease
Zhou, C. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.02.015 · Cited by 35
Treatment of Kaposiʼs sarcoma—an update
Toschi, E., Sgadari, C., Monini, P., Barillari, G., Bacigalupo, I., Palladino, C., Baccarini, S., Carlei, D., Grosso, M. G., Sirianni, M. C., et al. (2002) · Anti-Cancer Drugs · doi:10.1097/00001813-200211000-00001 · Cited by 33
The metabolic syndrome in HIV
Worm, S. W., & Lundgren, J. D. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.10.018 · Cited by 33
Treatment of human immunodeficiency virus-associated facial lipoatrophy with lipofilling and submalar silicone implants
Mori, A., Russo, G. L., Agostini, T., Pattarino, J., Vichi, F., & Dini, M. (2006) · Journal of Plastic Reconstructive & Aesthetic Surgery · doi:10.1016/j.bjps.2005.12.047 · Cited by 33
Adipocyte metabolism and the metabolic syndrome
Stears, A. J., & Byrne, C. D. (2001) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2001.00151.x · Cited by 33
Relationship between Muscle Activity of the Frontalis and the Associated Brow Displacement
Pennock, J. D., Johnson, P. C., Manders, E. K., VanSwearingen, J. M., & Guyuron, B. (1999) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-199911000-00029 · Cited by 33
Medication-induced hyperglycemia and diabetes mellitus: a review of current literature and practical management strategies
Jain, A. B., & Lai, V. (2024) · Diabetes Therapy · doi:10.1007/s13300-024-01628-0 · Cited by 32
“Carr et al. also report that PIs impair chylomicron uptake in the liver as well as triglyceride clearance resulting in central fat deposition and insulin resistance [82].”
Background
HIV-Associated Cervicodorsal Lipodystrophy: Etiology and Management
Gold, D. R., & Annino, D. J. (2005) · The Laryngoscope · doi:10.1097/01.mlg.0000161838.22766.88 · Cited by 32
“One theory by Carr et al.4 highlights the observed temporal relationship between the prolonged use of protease inhibitors, especially Indinavir, and the development of fat metabolic disorders.”
Background
The Pharmacogenetics of Antiretroviral Therapy: A Review of Studies to Date
Quirk, E. K., McLeod, H. L., & Powderly, W. G. (2004) · Clinical Infectious Diseases · doi:10.1086/421557 · Cited by 32
Coronary heart disease associated with the use of human immunodeficiency virus (HTV)‐1 protease inhibitors: Report of four cases and review
Duong, M., Buisson, M., Cottin, Y., Piroth, L., L’Huillier, I., Grappin, M., Chavanet, P., Wolff, J., & Portier, H. (2001) · Clinical Cardiology · doi:10.1002/clc.4960241011 · Cited by 32
Low lipolytic enzyme activity in patients with severe hypertriglyceridemia on highly active antiretroviral therapy
Baril, L., Beucler, I., Valantin, M., Bruckert, É., Bonnefont‐Rousselot, D., Coutellier, A., Caumes, É., Katlama, C., & Bricaire, F. (2001) · AIDS · doi:10.1097/00002030-200102160-00016 · Cited by 32
Vascular Endothelial Toxicity Induced by HIV Protease Inhibitor: Evidence of Oxidant-Related Dysfunction and Apoptosis
Baliga, R. S., Liu, C., Hoyt, D. G., Chaves, A., & Bauer, J. A. (2004) · Cardiovascular Toxicology · doi:10.1385/ct:4:2:199 · Cited by 31
Metabolic Complications Associated with the Use of Highly Active Antiretroviral Therapy in HIV-1–Infected Adults
Monier, P. L., & Wilcox, R. D. (2004) · The American Journal of the Medical Sciences · doi:10.1097/00000441-200407000-00007 · Cited by 31
Insulin resistance and associated factors among HIV-infected patients in sub-Saharan Africa: a cross sectional study from Cameroon
Noumegni, S. R., Nansseu, J. R., Moor, V. J. A., Bigna, J. J., Assah, F. K., Guewo‐Fokeng, M., Leumi, S., Katte, J.-C. N., Dehayem, M. Y., Kengne, A. P., et al. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0543-1 · Cited by 31
“These metabolic abnormalities seem to be more preponderant among patients on ART, especially those on protease inhibitors-containing regimen [5, 6].”
Evaluation of the Risk Factors Associated with Lipodystrophy Development in a Cohort of HIV-Positive Patients
Seminari, E. M., Tinelli, C., Minoli, L., Sacchi, P., Filice, G., Zocchetti, C., Meneghetti, G., Bruno, R., & Maserati, R. (2002) · Antiviral Therapy · doi:10.1177/135965350200700306 · Cited by 31
“Available data seem to indicate two classes of drugs, NRTIs and PIs, as the most likely culprits for this manifestation [2,3,5,8].”
Background
Longer‐Term Immunologic Effects and Side Effects of Successful Antiretroviral Therapy
Schooley, R. T. (1999) · Clinical Infectious Diseases · doi:10.1086/520139 · Cited by 31
Current strategies in the treatment of HIV infection
Cohen, O. J., & Fauci, A. S. (2002) · Disease-a-Month · doi:10.1067/mda.2002.124659 · Cited by 30
Body-Fat Abnormalities in Patients With HIV: Progress and Challenges
Bedimo, R. (2008) · Journal of the International Association of Physicians in AIDS Care · doi:10.1177/1545109708328931 · Cited by 30
Myocardial infarction risk in HIV-infected patients: epidemiology, pathogenesis, and clinical management
Calza, L., Manfredi, R., & Verucchi, G. (2010) · AIDS · doi:10.1097/qad.0b013e328337afdf · Cited by 30
“binding protein type 1 (CRABP-1), which is critical for maturation and proliferation of adipocytes, and the LDLreceptor-related protein (LRP), an hepatic cell receptor which cleaves fatty acids from circulating triglycerides [94,95].”
Background
Chondrocalcinosis and Gitelman's syndrome. A new association?
Cobeta-Garcia, J. C., GASCON, A., IGLESIAS, E., & Estopiñán, V. (1998) · Annals of the Rheumatic Diseases · doi:10.1136/ard.57.12.748 · Cited by 30
Insulin resistance in HIV-infected patients: relationship with pro-inflammatory cytokines released by peripheral leukocytes
Limone, P. P. (2003) · Journal of Infection · doi:10.1016/s0163-4453(03)00055-0 · Cited by 30

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