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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Self-citation
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Background
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de Alencastro, P. R. (2012) · Journal of AIDS & Clinical Research · doi:10.4172/2155-6113.1000182 · Cited by 9
The Effects of Fetal and Childhood Exposure to Antiretroviral Agents
Mas, C. M. (2012) · Journal of AIDS & Clinical Research · doi:10.4172/2155-6113.s2-001 · Cited by 9
Zidovudine Induces Visceral Mitochondrial Toxicity and Intra-Abdominal Fat Gain in a Rodent Model of Lipodystrophy
Walker, U. A., Lebrecht, D., Reichard, W., Kirschner, J., Bissé, E., Iversen, L. V., Venhoff, A. C., & Venhoff, N. (2013) · Antiviral Therapy · doi:10.3851/imp2758 · Cited by 9
“The pathogenesis of fat loss and lipoaccumulation was initially mainly associated with different risk factors, with lipoatrophy being predominantly associated with thymidine analogue treatment and the fat gain mainly with protease inhibitors (PIs) [5,6].”
Background
Lower Concentrations of Circulating Medium and Long-Chain Acylcarnitines Characterize Insulin Resistance in Persons with HIV
Bailin, S. S., Jenkins, C. A., Petucci, C. J., Culver, J. A., Shepherd, B. E., Fessel, J. P., Hulgan, T., & Koethe, J. R. (2018) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2017.0314 · Cited by 9
Systemic Circulation
Cheung, Y. (2009) · Elsevier eBooks · doi:10.1016/b978-0-443-11851-7.00006-9 · Cited by 10
Modulation of adipose inflammation by cellular retinoic acid-binding protein 1
Wei, C.-W., Nhieu, J., Lin, Y., & Wei, L. (2022) · International Journal of Obesity · doi:10.1038/s41366-022-01175-3 · Cited by 9
Pathophysiology of the HIV-Associated Lipodystrophy Syndrome
Fève, B., Glorian, M., & Hadri, K. E. (2004) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2004.2.274 · Cited by 9
Alopecia associated with ritonavir-boosted atazanavir therapy
Torres, H. A., Barnett, B. J., & Arduino, R. C. (2007) · AIDS · doi:10.1097/qad.0b013e3281532b42 · Cited by 9
Protease inhibitor related type III hyperlipoproteinaemia is common and not associated with apolipoprotein-E E2/E2 phenotype
Shahmanesh, M. (2001) · Sexually Transmitted Infections · doi:10.1136/sti.77.4.283 · Cited by 9
STRATEGIES OF ANTIRETROVIRAL THERAPY IN ADULTS
Itani, S., & Bartlett, J. A. (1999) · Urologic Clinics of North America · doi:10.1016/s0094-0143(05)70221-4 · Cited by 9
Effect of antiretroviral therapy on inflammatory markers of endothelial dysfunction in HIV treatment‐Naïve infected patients
Marín, J. A. M., Méndez‐Cruz, R., Arroyo-Anduiza, C. I., Marín, L. A. M., Gaytán‐Martínez, J., & Asbún‐Bojalil, J. (2013) · Journal of Medical Virology · doi:10.1002/jmv.23624 · Cited by 9
“The possibility that HAART directly induces endothelial activation has been documented recently [Carr et al., 1998; Zhong et al., 2002].”
Background
Hyperlipidemia in children with HIV infection: an emerging problem
Kamin, D., & Hadigan, C. M. (2003) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.1.1.143 · Cited by 9
HIV and Liver Diseases: Recent Clinical Advances
Cengız, C., Park, J. S., Saraf, N., & Dieterich, D. T. (2005) · Clinics in Liver Disease · doi:10.1016/j.cld.2005.07.009 · Cited by 9
“PIs are associated with lipoatrophy, truncal–abdominal fat deposition, hyperlipidemia, insulin resistance, and subsequent fatty liver, contributing to their hepatotoxicity [71].”
Background
HIV Infection, Antiretroviral Therapy and Cardiovascular Risk
Bárbaro, G. (2002) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1177/174182670200900511 · Cited by 9
Nevirapine plus efavirenz plus didanosine: a simple, safe, and effective once-daily regimen for patients with HIV infection.
Jordan, W. C., Jefferson, R., Yemofio, F., Tolbert, L., Conlon, V., Carroll, H., Green, D. C., Green, A., & Green, R. (2003) · PubMed Central · Cited by 9
Lipodystrophy in Patients with HIV-1 Infection: Effect of Stopping Protease Inhibitors on Tnf-α and Tnf-Receptor Levels, and on Metabolic Parameters
Maher, B., Lloyd, J., Wilkins, E. G. L., Fraser, W. D., Back, D. J., Park, B. K., & Pirmohamed, M. (2004) · Antiviral Therapy · doi:10.1177/135965350400900601 · Cited by 9
“Particular attention has focused on the lipodystrophy (LD) syndrome, which is characterized by both progressive fat wasting and intra-abdominal or localized fat accumulation, in addition to metabolic abnormalities such as dyslipidaemia and insulin resistance [3].”
Background
Barraquer-Simons lipodystrophy, Raynaud's phenomenon and cutaneous vasculitis
Porter, W. M., O'Gorman-Lalor, O., Lane, R. J. M., Francis, N., & Bunker, C. B. (2000) · Clinical and Experimental Dermatology · doi:10.1046/j.1365-2230.2000.00641.x · Cited by 9
Interleukin 2 Treatment for HIV Infection
Blankson, J. N. (2000) · JAMA · doi:10.1001/jama.284.2.236 · Cited by 9
Efficacy and Safety of a Quadruple Combination Combivir + Abacavir + Efavirenz Regimen in Antiretroviral Treatment–Naive HIV-1–Infected Adults: La Francilienne
de Truchis, P., Force, G., Welker, Y., Mechali, D., Pulik, M., Chemlal, K., Rouveix, É., Devidas, A., Praindhui, D., & Mamet, J.-P. (2002) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200210010-00008 · Cited by 9
Body habitus changes, metabolic abnormalities, osteopenia and cardiovascular risk in patients treated for human immunodeficiency virus infection.
Cirelli, A., Cirelli, G., Balsamo, G., Masciangelo, R., Stasolla, A., & Marini, M. (2003) · PubMed · Cited by 9
Lipid Abnormalities During Saquinavir Soft-Gel–Based Highly Active Antiretroviral Therapy
Moyle, G. J., & Baldwin, C. (1999) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-199908150-00011 · Cited by 9
Lipid Abnormalities During Saquinavir Soft-Gel–Based Highly Active Antiretroviral Therapy
Moyle, G. J., & Baldwin, C. (1999) · Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology · doi:10.1097/00042560-199908150-00011 · Cited by 9
Unilateral Atrophy of the Cheek
Gaβling, V., Douglas, T., Wiltfang, J., & Warnke, P. H. (2009) · Journal of Craniofacial Surgery · doi:10.1097/scs.0b013e31819b96c9 · Cited by 8
Evaluation of Oral Antiretroviral Drugs in Mice With Metabolic and Neurologic Complications
Tsai, F., Ho, M., Lai, C., Chou, C.-H., Li, J., Cheng, C., Wu, Y., Liu, X., Tsang, H., Lin, T., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01004 · Cited by 8
“ART drugs may bind to the LDL receptor-related protein (LRP), thereby inhibiting the function of the LRP-Lpl complex (the cleavage of fatty acids from plasma triglycerides) (Carr et al., 1998; Matoga et al., 2017).”
Background
Comparison of Tolerability and Impact on Metabolic Profiles of Antiretroviral Regimens Containing Darunavir/Ritonavir or Darunavir/Cobicistat in Romanian HIV Infected Patients
Marin, R.-C., Ţiţ, D. M., Săndulescu, O., Streinu‐Cercel, A., & BUNGAU, S. G. (2021) · Biomedicines · doi:10.3390/biomedicines9080987 · Cited by 8
“Studies before do not established exactly how the disorders in lipid metabolism are influenced by ART, but it seems that the PIs binds to proteins involved in the regulation of lipid metabolism, low-density lipoprotein-receptor protein (LRP) and cytoplasmic retinoic acid binding protein type 1 (CRABP1), which are 60%…”
Background
Circulating MicroRNAs as a Tool for Diagnosis of Liver Disease Progression in People Living with HIV-1
Martı́nez, M. Á., Tural, C., & Franco, S. (2022) · Viruses · doi:10.3390/v14061118 · Cited by 9
“Remarkably, protease inhibitors, which have been associated with insulin resistance and obesity [31], do not show a significant risk for liver fibrosis [30].”
Background
Altered adipose tissue macrophage populations in people with HIV on integrase inhibitor-containing antiretroviral therapy
Vakili, S., Paneru, B., Guerrier, C. M., Miller, J., Baumrin, E., Forrestel, A. K., Lynn, K., Frank, I., Re, V. L., Collman, R. G., et al. (2022) · AIDS · doi:10.1097/qad.0000000000003278 · Cited by 8
“metabolic effects [10], they are used with decreasing frequency.”
Background
Bilateral Lipomastia in Men: A Side Effect of Highly Active Antiretroviral Therapy
Deonarain, J., Ramdial, P. K., & Singh, B. (2008) · International Journal of Surgical Pathology · doi:10.1177/1066896907307037 · Cited by 8
“The first pathogenetic proposal on HLS addressed the sequence homologies between the PIs and human proteins involved in the regulation of lipid metabolism.(10) The interference of PIs with these proteins and the inhibition of cytochrome P450 3A enzymes were hypothesized to induce apoptosis of peripheral adipocytes, st…”
Background
Hospitalization due to Adverse Drug Reactions and Drug Interactions before and after HAART
Foisy, M., Gough, K. A., Quan, C., Harris, K., Ibañez, D., & Phillips, A. A. (2000) · Canadian Journal of Infectious Diseases and Medical Microbiology · doi:10.1155/2000/123046 · Cited by 8
Subcorneal pustular dermatosis in a patient with AIDS
Calista, D. (2003) · Journal of the European Academy of Dermatology and Venereology · doi:10.1046/j.1468-3083.2003.00614_6.x · Cited by 8
Xenobiotic pregnane X receptor promotes neointimal formation in balloon‐injured rat carotid arteries
Zhang, M., Zhang, Z., Xie, X., Yao, Q., Liu, J., Lai, B., Xiao, L., & Wang, N. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27215 · Cited by 8
Modern trends in lipomodeling
El-Sabbagh, A. H. (2017) · Europe PMC (PubMed Central) · doi:10.3205/iprs000108 · Cited by 8
“Fat depots redistribution in the HIV-associated lipodystrophy includes visceral fat accumulation in the abdomen, subcutaneous fat accumulation in breasts and in the cervical and dorsal area (buffalo hump) with fat wasting in the legs, arms, buttocks, and face [102], [103].”
Background
Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids
Ponte, C. M. M., Castelo, M. H. C. G., & Montenegro, R. M. (2009) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302009000800012 · Cited by 8
Les désordres lipidiques des patients atteints d’affections causées par le VIH
Chanu, B., & Valensi, P. E. (2005) · La Presse Médicale · doi:10.1016/s0755-4982(05)84124-7 · Cited by 8

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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