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

Carr, Andrew; Samaras, Katherine; Chisholm, Donald J; Cooper, David A

doi:10.1016/s0140-6736(98)03391-1

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

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?

Acquired lipodystrophy can be seen in patients with HIV infection being treated with highly active antiretroviral therapy.
“Acquired lipodystrophy can be seen in patients with HIV infection who are being treated with highly active antiretroviral therapy (99).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [99]

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 · see citing works
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 3,533 · see citing works
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 · see citing works
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 2,858 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
HIV-1 protease inhibitors. A review for clinicians
Deeks, S. G. (1997) · JAMA · doi:10.1001/jama.277.2.145 · Cited by 686 · see citing works
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 · see citing works
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 598 · see citing works
“Buffalo hump” in men with HIV-1 infection
Lo, J. C.-M., Mulligan, K. M., Tai, V., Algren, H. A., & Schambelan, M. (1998) · The Lancet · doi:10.1016/s0140-6736(97)11443-x · Cited by 565 · see citing works
Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation.
Adams, M., Montague, C. T., Prins, J. B., Holder, J. C., Smith, S. A., Sanders, L., Digby, J., Sewter, C. P., Lazar, M. A., Chatterjee, K., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119870 · Cited by 516 · see citing works
Regulation of Adipose Cell Number in Man
Prins, J. B., & O'rahilly, S. (1997) · Clinical Science · doi:10.1042/cs0920003 · Cited by 406 · see citing works
Retinoic acid biosynthesis and metabolism
Napoli, J. L. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.9.8801182 · Cited by 378 · see citing works
Inhibition of Hepatic Chylomicron Remnant Uptake by Gene Transfer of a Receptor Antagonist
Willnow, T. E., Sheng, Z., Ishibashi, S., & Herz, J. (1994) · Science · doi:10.1126/science.7515194 · Cited by 301 · see citing works
Indinavir-associated lipodystrophy
Viraben, R., & Aquilina, C. (1998) · AIDS · doi:10.1097/00002030-199806000-00001 · Cited by 280 · see citing works
HIV-1 protease inhibitors.
Deeks, S. G., Smith, M. D., Holodniy, M., & Kahn, J. S. (1997) · PubMed · doi:10.1001/jama.1997.03540260059037 · Cited by 156 · see citing works
Effects of nonesterified fatty acid availability on tissue-specific glucose utilization in rats in vivo.
Jenkins, A. B., Storlien, L. H., Chisholm, D. J., & Kraegen, E. W. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113586 · Cited by 119 · see citing works
Self-citation
Hypertrophy of the Breasts in a Patient Treated with Indinavir
Herry, I., Bernard, L., de Truchis, P., & Perronne, C. (1997) · Clinical Infectious Diseases · doi:10.1086/597649 · Cited by 117 · see citing works
Regulation of Metabolism by Retinoic Acid and Its Nuclear Receptors
Pfahl, M., & Chytil, F. (1996) · Annual Review of Nutrition · doi:10.1146/annurev.nu.16.070196.001353 · Cited by 110 · see citing works
Structure/Function of Cytoplasmic Vitamin A-Binding Proteins
Li, E., & Norris, A. W. (1996) · Annual Review of Nutrition · doi:10.1146/annurev.nu.16.070196.001225 · Cited by 103 · see citing works
The LDL-receptor-related protein ??? portrait of a multifunctional receptor
Herz, J. (1993) · Current Opinion in Lipidology · doi:10.1097/00041433-199304000-00006 · Cited by 77 · see citing works
Crystal Structure of Cellular Retinoic Acid Binding Protein I Shows Increased Access to the Binding Cavity due to Formation of an Intermolecular β-Sheet
Thompson, J. R., Bratt, J. M., & Banaszak, L. J. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0509 · Cited by 59 · see citing works
The non-genetic determinants of central adiposity*
Samaras, K., & Campbell, L. (1997) · International Journal of Obesity · doi:10.1038/sj.ijo.0800502 · Cited by 46 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents
(1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-128-12_part_2-199806151-00003 · Cited by 5,197 · see citing works
Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: acohort study
Carr, A. D., Samaras, K., Þórisdóttir, A. S., Kaufmann, G. R., Chisholm, D. J., & Cooper, D. A. (1999) · The Lancet · doi:10.1016/s0140-6736(98)08468-2 · Cited by 1,490 · see citing works
Self-citation
Lipid-induced insulin resistance: unravelling the mechanism
Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60408-4 · Cited by 1,189 · see citing works
British HIV Association guidelines for the treatment of HIV‐1‐infected adults with antiretroviral therapy 2008
Gazzard, B., & on behalf of the BHIVA Treatment Guidelines Writing Group (2008) · HIV Medicine · doi:10.1111/j.1468-1293.2008.00636.x · Cited by 1,089 · see citing works
Adverse effects of antiretroviral therapy
Carr, A. D., & Cooper, D. A. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02854-3 · Cited by 1,062 · see citing works
Self-citation
Efavirenz plus Zidovudine and Lamivudine, Efavirenz plus Indinavir, and Indinavir plus Zidovudine and Lamivudine in the Treatment of HIV-1 Infection in Adults
Staszewski, S., Morales-Ramirez, J. O., Tashima, K. T., Rachlis, A., Skiest, D. J., Stanford, J., Stryker, R., Johnson, P. C., Labriola, D., Farina, D., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912163412501 · Cited by 993 · see citing works
Consistent Viral Evolutionary Changes Associated with the Progression of Human Immunodeficiency Virus Type 1 Infection
Shankarappa, R., Margolick, J. B., Gange, S. J., Rodrigo, A. G., Upchurch, D., Farzadegan, H., Gupta, P., Rinaldo, C. R., Learn, G. H., He, X., et al. (1999) · Journal of Virology · doi:10.1128/jvi.73.12.10489-10502.1999 · Cited by 926 · see citing works
Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study
Ledergerber, B., Egger, M., Opravil, M., Telenti, A., Hirschel, B. J., Battegay, M., Vernazza, P., Sudre, P., Flepp, M., Furrer, H., et al. (1999) · The Lancet · doi:10.1016/s0140-6736(99)01122-8 · Cited by 906 · see citing works
Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline
Berglund, L., Brunzell, J. D., Goldberg, A. C., Goldberg, I. J., Sacks, F., Murad, M. H., & Stalenhoef, A. F. H. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3213 · Cited by 887 · see citing works
“Other conditions Acquired lipodystrophy can be seen in patients with HIV infection who are being treated with highly active antiretroviral therapy (99).”
Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy
Brinkman, K., Smeitink, J. A. M., Romijn, J. A., & Reiss, P. (1999) · The Lancet · doi:10.1016/s0140-6736(99)06102-4 · Cited by 863 · see citing works
HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression
Davey, R. T., Bhat, N., Yoder, C. P., Chun, T., Metcalf, J. A., Dewar, R. L., Natarajan, V., Lempicki, R. A., Adelsberger, J. W., Miller, K. D., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15109 · Cited by 837 · see citing works
Human Body Composition: In Vivo Methods
Ellis, K. J. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.2.649 · Cited by 826 · see citing works
“Recently, the observation of a significant increase of a lipodystrophylike syndrome in human immunodeficience virus-positive subjects has been confirmed using MRI examinations (40, 152, 202, 330).”
Background
Life without white fat: a transgenic mousePreprint
Moitra, J., Mason, M. M., Olive, M., Krylov, D. Y., Gavrilova, O., Marcus‐Samuels, B., Feigenbaum, L., Lee, E., Aoyama, T., Eckhaus, M., et al. (1998) · Genes & Development · doi:10.1101/gad.12.20.3168 · Cited by 776 · see citing works
“Lipodystrophic diabetes was recently recognized as a complication of protease inhibitor treatment of HIV infection (Carr et al. 1998).”
Background
Metabolic Abnormalities and Cardiovascular Disease Risk Factors in Adults with Human Immunodeficiency Virus Infection and Lipodystrophy
Hadigan, C. M., Meigs, J. B., Corcoran, C. P., Rietschel, P., Piecuch, S., Basgoz, N. O., Davis, B., Sax, P. E., Stanley, T. L., Wilson, P. W. F., et al. (2001) · Clinical Infectious Diseases · doi:10.1086/317541 · Cited by 679 · see citing works
ATUALIZAÇÃO DA DIRETRIZ BRASILEIRA DE DISLIPIDEMIAS E PREVENÇÃO DA ATEROSCLEROSE - 2017
Faludi, A., Izar, M. C. D. O., Saraiva, J., Chacra, A., Bianco, H. T., Neto, A. A., Bertolami, A., Pereira, A., Lottenberg, A., Sposito, A. C., et al. (2017) · Arquivos Brasileiros de Cardiologia · doi:10.5935/abc.20170121 · Cited by 660 · see citing works
Cardiovascular and Cerebrovascular Events in Patients Treated for Human Immunodeficiency Virus Infection
Bozzette, S. A., Ake, C. F., Tam, H. K., Chang, S. W., & Louis, T. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022048 · Cited by 626 · see citing works
The Challenge of Viral Reservoirs in HIV-1 Infection
Blankson, J. N., Persaud, D., & Siliciano, R. F. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104024 · Cited by 623 · see citing works
Atherogenic Dyslipidemia in HIV-Infected Individuals Treated With Protease Inhibitors
Périard, D., Telenti, A., Sudre, P., Cheseaux, J., Halfon, P., Reymond, M. J., Marcovina, S. M., Glauser, M. P., NICOD, P. H., Darioli, R., et al. (1999) · Circulation · doi:10.1161/01.cir.100.7.700 · Cited by 603 · see citing works
The Mechanism of Insulin Resistance Caused by HIV Protease Inhibitor Therapy
Murata, H., Hruz, P. W., & Mueckler, M. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000228200 · Cited by 579 · see citing works
A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy
Saint-Marc, T., Partisani, M., Poizot‐Martin, I., Bruno, F., Rouvière, O., Lang, J.-M., Gastaut, J., & Touraine, J. L. (1999) · AIDS · doi:10.1097/00002030-199909100-00009 · Cited by 579 · see citing works
Hyperlipidemia and Insulin Resistance Are Induced by Protease Inhibitors Independent of Changes in Body Composition in Patients With HIV Infection
Mulligan, K. M., Grünfeld, C., Tai, V., Algren, H. A., Pang, M., Chernoff, D., Lo, J. C.-M., & Schambelan, M. (2000) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200001010-00005 · Cited by 516 · see citing works
Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors
Behrens, G. M. N., Dejam, A., Schmidt, H., Balks, H. J., Brabant, G. E., Körner, T., Stoll, M., & Schmidt, R. E. (1999) · AIDS · doi:10.1097/00002030-199907090-00001 · Cited by 515 · see citing works
Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection
Mallal, S. A., John, M., Moore, C., JAMES, I. R., & McKinnon, E. (2000) · AIDS · doi:10.1097/00002030-200007070-00002 · Cited by 509 · see citing works
“The lipodystrophy syndrome was ascribed to a unique cumulative toxicity of HIV protease inhibitor (PI) therapy [2,4] having been noted only 2 years after the introduction of PI into routine”
Background
Medical significance of peroxisome proliferator-activated receptors
Vamecq, J., & Latruffe, N. (1999) · The Lancet · doi:10.1016/s0140-6736(98)10364-1 · Cited by 463 · see citing works
Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study
Martínez, E., Mocroft, A., García-Viejo, M. A., Pérez-Cuevas, J. B., Blanco, J. L., Mallolas, J., Bianchi, L., Conget, I., Blanch, J., Phillips, A. N., et al. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04056-3 · Cited by 456 · see citing works
Effects of Protease Inhibitors on Hyperglycemia, Hyperlipidemia, and Lipodystrophy
Tsiodras, S., Mantzoros, C. S., Hammer, S., & Samore, M. H. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.13.2050 · Cited by 452 · see citing works
“With regard to the cause of the lipodystrophy, it has been speculated that interference of PIs with apoptosis and impaired differentiation of peripheral adipocytes but relative sparing of intra-abdominal adipocytes is the underlying mechanism.(28) The occurrence of hyperlipidemia as the primary metabolic change may co…”
Background
Fat distribution and metabolic changes in patients with HIV infection
Safrin, S., & Grünfeld, C. (1999) · AIDS · doi:10.1097/00002030-199912240-00002 · Cited by 358 · see citing works
Adverse effects of antiretroviral therapy for HIV infection.
Montessori, V., Press, N., Harris, M., Akagi, L., & Montaner, J. S. G. (2004) · Europe PMC (PubMed Central) · Cited by 355 · see citing works
Procedure, applications, and outcomes of autologous fat grafting
Simonacci, F., Bertozzi, N., Grieco, M. P., Grignaffini, E., & Raposio, E. (2017) · Annals of Medicine and Surgery · doi:10.1016/j.amsu.2017.06.059 · Cited by 344 · see citing works
Metformin in the Treatment of HIV Lipodystrophy Syndrome: A Randomized Controlled Trial
Hadigan, C., Corcoran, C., Basgoz, N., Davis, B., Sax, P., & Grinspoon, S. (2000) · JAMA · doi:10.1001/jama.284.4.472 · Cited by 357 · see citing works
“Glucose (120 min), mg/dL 138 (12) 140 (7) 7 (10) −2 (8) .”
Fat Distribution in Men With HIV Infection
(FRAM), F. T. S. O. F. R. A. M. C. I. H. I. (2005) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/01.qai.0000182230.47819.aa · Cited by 327 · see citing works
Prevalence of Metabolic Syndrome in HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy Using International Diabetes Foundation and Adult Treatment Panel III Criteria
Samaras, K., Wand, H. C., Law, M. G., Emery, S., Cooper, D. A., & Carr, A. D. (2006) · Diabetes Care · doi:10.2337/dc06-1075 · Cited by 310 · see citing works
Self-citation
The HIV Protease Inhibitor Indinavir Impairs Sterol Regulatory Element-Binding Protein-1 Intranuclear Localization, Inhibits Preadipocyte Differentiation, and Induces Insulin Resistance
Caron, M., Auclair, M., Vigouroux, C., Glorian, M., Forest, C. D., & Capeau, J. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1378 · Cited by 310 · see citing works
“(2) proposed a From the (1)Institut National de la Santé et de la Recherche Médicale (INSERM) U 402, Faculté de Médecine Saint-Antoine; and (2)INSERM U 530, Centre Universitaire des Saints Pères, Paris, France.”
Background
HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma
Sgadari, C., Barillari, G., Toschi, E., Carlei, D., Bacigalupo, I., Baccarini, S., Palladino, C., Leone, P., Bugarini, R., Malavasi, L., et al. (2002) · Nature Medicine · doi:10.1038/nm0302-225 · Cited by 308 · see citing works
Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy
Gervasoni, C., Ridolfo, A. L., Trifirò, G., Santambrogio, S., Norbiato, G., Musicco, M., Clerici, M., Galli, M., & Moroni, M. (1999) · AIDS · doi:10.1097/00002030-199903110-00004 · Cited by 297 · see citing works
Abacavir-Lamivudine-Zidovudine vs Indinavir-Lamivudine-Zidovudine in Antiretroviral-Naive HIV-Infected Adults<SUBTITLE>A Randomized Equivalence Trial</SUBTITLE>
Staszewski, S. (2001) · JAMA · doi:10.1001/jama.285.9.1155 · Cited by 277 · see citing works
HIV lipodystrophy
Carr, A. D. (2003) · AIDS · doi:10.1097/00002030-200304001-00017 · Cited by 274 · see citing works
Self-citation
Subcutaneous fat in normal and diseased states
Avram, M. M., Avram, A. S., & James, W. D. (2007) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2006.06.022 · Cited by 266 · see citing works
Factors Associated with the Incidence of Type 2 Diabetes Mellitus in HIV-Infected Participants in the Swiss HIV Cohort Study
Ledergerber, B., Furrer, H., Rickenbach, M., Lehmann, R., Elzi, L., Hirschel, B. J., Cavassini, M. L., Bernasconi, E., Schmid, P., Egger, M., et al. (2007) · Clinical Infectious Diseases · doi:10.1086/518619 · Cited by 261 · see citing works
HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: A potential mechanism for protease inhibitor-induced hyperlipidemia
Liang, J.-S., Distler, O., Cooper, D. A., Jamil, H., Deckelbaum, R. J., Ginsberg, H. N., & Sturley, S. L. (2001) · Nature Medicine · doi:10.1038/nm1201-1327 · Cited by 260 · see citing works
Self-citation
Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database
Heath, K., Hogg, R. S., Chan, K., Harris, M., Montessori, V., O’Shaughnessy, M. V., & Montaner, J. S. G. (2001) · AIDS · doi:10.1097/00002030-200101260-00013 · Cited by 250 · see citing works
“Others have reported similar [41,42] or higher [4,43] rates of prevalent morphological changes, whereas most clinical studies [4,24,43] Table 4.”
Result
Premature lesions of the carotid vessels in HIV-1-infected patients treated with protease inhibitors
Maggi, P., Serio, G., Epifani, G., Fiorentino, G., Saracino, A., Fico, C., Perilli, F., Lillo, A., Ferraro, S., Gargiulo, M., et al. (2000) · AIDS · doi:10.1097/00002030-200011100-00001 · Cited by 240 · see citing works
Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy
Domingo, P., Matías‐Guiu, X., Pujol, R. M., Francia, E., Lagarda, E., Sambeat, M. A., & Vázquez, G. (1999) · AIDS · doi:10.1097/00002030-199911120-00008 · Cited by 232 · see citing works
Lipodystrophy in Human Immunodeficiency Virus-Infected Patients
Chen, D., Misra, A., & Garg, A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020794 · Cited by 229 · see citing works
Results of a Phase 2 Clinical Trial at 48 Weeks (AI424-007): A Dose-Ranging, Safety, and Efficacy Comparative Trial of Atazanavir at Three Doses in Combination with Didanosine and Stavudine in Antiretroviral-Naive Subjects
Sanne, I., Piliero, P. J., Squires, K., Thiry, A., & Schnittman, S. (2003) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200301010-00004 · Cited by 226 · see citing works
Regulation of Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Adipose Tissue: Tissue-Specific Induction by Cytokines*
Tomlinson, J. W., Moore, J., Cooper, M. S., Bujalska, I., Shahmanesh, M., Burt, C., Strain, A., Hewison, M., & Stewart, P. M. (2001) · Endocrinology · doi:10.1210/endo.142.5.8168 · Cited by 222 · see citing works
Hypoadiponectinemia Is Associated with Insulin Resistance, Hypertriglyceridemia, and Fat Redistribution in Human Immunodeficiency Virus-Infected Patients Treated with Highly Active Antiretroviral Therapy
Addy, C., Gavrila, A., Tsiodras, S., Brodovicz, K. G., Karchmer, A. W., & Mantzoros, C. S. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020795 · Cited by 219 · see citing works
Cardiovascular Manifestations of HIV Infection
Bárbaro, G. (2002) · Circulation · doi:10.1161/01.cir.0000031704.78200.59 · Cited by 218 · see citing works
HIV Protease Inhibitor Induces Fatty Acid and Sterol Biosynthesis in Liver and Adipose Tissues Due to the Accumulation of Activated Sterol Regulatory Element-binding Proteins in the Nucleus
Riddle, T. M., Kuhel, D. G., Woollett, L. A., Fichtenbaum, C. J., & Hui, D. Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104557200 · Cited by 216 · see citing works
The science behind autologous fat grafting
Bellini, E., Grieco, M. P., & Raposio, E. (2017) · Annals of Medicine and Surgery · doi:10.1016/j.amsu.2017.11.001 · Cited by 209 · see citing works
HIV Protease Inhibitor-Related Lipodystrophy Syndrome
Carr, A. D. (2000) · Clinical Infectious Diseases · doi:10.1086/313854 · Cited by 209 · see citing works
Self-citation
Metabolic Effects of Rosiglitazone in HIV Lipodystrophy
Hadigan, C. M., Yawetz, S., Thomas, A., Havers, F. P., Sax, P. E., & Grinspoon, S. K. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-140-10-200405180-00008 · Cited by 207 · see citing works
Atorvastatin and gemfibrozil for protease-inhibitor-related lipid abnormalities
Henry, K., Melroe, H., Huebesch, J., Hermundson, J., & Simpson, J. (1998) · The Lancet · doi:10.1016/s0140-6736(98)00022-1 · Cited by 204 · see citing works
Incidence of and Risk Factors for Lipoatrophy (Abnormal Fat Loss) in Ambulatory HIV-1-Infected Patients
Lichtenstein, K. A., Delaney, K. M., Armon, C., Ward, D. J., Moorman, A. C., Wood, K. C., & Holmberg, S. D. (2003) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200301010-00007 · Cited by 203 · see citing works
Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis
Dillon, D., Gurdasani, D., Riha, J., Ekoru, K., Asiki, G., Mayanja, B. N., Levitt, N. S., Crowther, N. J., Nyirenda, M., Njelekela, M. A., et al. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dyt198 · Cited by 201 · see citing works
A Choline-Deficient Diet Exacerbates Fatty Liver but Attenuates Insulin Resistance and Glucose Intolerance in Mice Fed a High-Fat Diet
Raubenheimer, P. J., Nyirenda, M., & Walker, B. R. (2006) · Diabetes · doi:10.2337/db06-0097 · Cited by 199 · see citing works
Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects
Murphy, R. L., Sanne, I., Cahn, P. E., Phanuphak, P., Percival, L., Kelleher, T., & Giordano, M. (2003) · AIDS · doi:10.1097/00002030-200312050-00007 · Cited by 195 · see citing works
Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity
Moyle, G. J. (2000) · Clinical Therapeutics · doi:10.1016/s0149-2918(00)80064-8 · Cited by 192 · see citing works
Psychosocial impact of the lipodystrophy syndrome in HIV infection.
Collins, E. J., Wagner, C., & Walmsley, S. L. (2000) · PubMed · Cited by 192 · see citing works
Toxicity of antiretroviral therapy and implications for drug development
Carr, A. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1151 · Cited by 192 · see citing works
Self-citation
Fasting Hyperinsulinemia and Changes in Regional Body Composition in Human Immunodeficiency Virus-Infected Women1
Hadigan, C. M., Miller, K. K., Corcoran, C. P., Anderson, E. J., Basgoz, N. O., & Grinspoon, S. K. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.6.5738 · Cited by 186 · see citing works
Lipodystrophy in patients naive to HIV protease inhibitors
Madge, S., Loes, S. K., Mercey, D., Johnson, M. A., & Weller, I. V. D. (1999) · AIDS · doi:10.1097/00002030-199904160-00020 · Cited by 184 · see citing works
The Impact of Weight Gain During HIV Treatment on Risk of Pre-diabetes, Diabetes Mellitus, Cardiovascular Disease, and Mortality
Kumar, S., & Samaras, K. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00705 · Cited by 180 · see citing works
“Lipodystrophy is characterised by peripheral subcutaneous lipoatrophy and central/abdominal lipohypertrophy (12, 15) and has been shown to increase risk of diabetes (13) and myocardial infarction (14) in HIV-treated populations.”
BackgroundSelf-citation
HIV–Associated Lipodystrophy: Pathogenesis, Prognosis, Treatment, and Controversies
Koutkia, P., & Grinspoon, S. K. (2004) · Annual Review of Medicine · doi:10.1146/annurev.med.55.091902.104412 · Cited by 179 · see citing works
“Furthermore, sequence homology of the PIs to lipoprotein receptor-like protein (LRP) suggests a potential effect of the PI’s on lipid clearance, but the clinical importance of this observation remains unknown (23).”
Background
The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism
Zhou, C., Verma, S., & Blumberg, B. (2009) · Nuclear Receptor Signaling · doi:10.1621/nrs.07001 · Cited by 178 · see citing works
“Thus, SXR downregulation would reduce expression of CYP3A4, thereby increasing local estrogen levels and/or increasing sensitivity of estrogen receptor to estradiol [Cheng et al., 2001].”
Background
Alteration of tumor necrosis factor–α T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus–associated lipodystrophy syndrome
Ledru, É., Christeff, N., Patey, O., de Truchis, P., Melchior, J., & Gougeon, M. (2000) · Blood · doi:10.1182/blood.v95.10.3191 · Cited by 177 · see citing works
Clinical and metabolic presentation of the lipodystrophic syndrome in HIV-infected children
Jaquet, D., Lévine, M., Ortega-Rodriguez, E., Faye, A., Polak, M., VILMER, E., & Lévy‐Marchal, C. (2000) · AIDS · doi:10.1097/00002030-200009290-00008 · Cited by 174 · see citing works
Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection
van der Valk, M., Gisolf, E. H., Reiss, P., Wit, F. W. N. M., Japour, A. J., Weverling, G. J., & Danner, S. A. (2001) · AIDS · doi:10.1097/00002030-200105040-00005 · Cited by 175 · see citing works
Lipodystrophy, Metabolic Disorders, and Human Immunodeficiency Virus Infection: Aquitaine Cohort, France, 1999
Thiébaut, R., Daucourt, V., Mercié, P., Ekouévi, D. K., Malvy, D. J.-M., Morlat, P., Dupon, M., Neau, D., Farbos, S., Marimoutou, C., et al. (2000) · Clinical Infectious Diseases · doi:10.1086/317477 · Cited by 174 · see citing works
Early Structural and Functional Changes of the Vasculature in HIV-Infected Children
Charakida, M., Donald, A. E., Green, H., Storry, C., Clapson, M., CASLAKE, M. J., Dunn, D. T., Halcox, J., Gibb, D. M., Klein, N. J., et al. (2005) · Circulation · doi:10.1161/circulationaha.104.517144 · Cited by 171 · see citing works
Interactions Between Antiretroviral Drugs and Drugs Used for the Therapy of the Metabolic Complications Encountered During HIV Infection
Fichtenbaum, C. J., & Gerber, J. G. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241140-00004 · Cited by 167 · see citing works
Intracellular Pharmacokinetics of Antiretroviral Drugs in HIV-Infected Patients, and their Correlation with Drug Action
Bazzoli, C., Jullien, V., Tiec, C. L., Rey, E., Mentré, F., & Taburet, A. (2009) · Clinical Pharmacokinetics · doi:10.2165/11318110-000000000-00000 · Cited by 165 · see citing works
“For example, PIs could alter adipose tissue and lipid metabolism by inhibiting the heterodimeric nuclear receptor complex composed of peroxisome proliferator-activated receptor g and the retinoid X receptor, the cellular retinoic acid-binding protein, and the synthesis of cis-9-retinoic acid.([157]) PIs could also inh…”
Drug/Drug Interaction Between Lopinavir/Ritonavir and Rosuvastatin in Healthy Volunteers
Kiser, J. J., Gerber, J. G., Predhomme, J. A., Wolfe, P., Flynn, D. M., & Hoody, D. W. (2008) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e318160a542 · Cited by 159 · see citing works
HIV protease inhibitors block adipogenesis and increase lipolysis in vitro
Lenhard, J. M., Furfine, E. S., Jain, R. G., Ittoop, O. R. R., Orband‐Miller, L. A., Blanchard, S. G., Paulik, M. A., & Weiel, J. E. (2000) · Antiviral Research · doi:10.1016/s0166-3542(00)00102-9 · Cited by 160 · see citing works
“For example, PIs may interact with common proteins (proteases or cytochrome P450) in other tissues and this may neck and abdomen (Carr et al., 1998a; Lo et al., 1998; Miller et al., 1998; Walli et al., 1998).”
BackgroundResultInfluential
Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy
Langford, D., Letendre, S. L., Marcotte, T. D., Ellis, R. J., McCutchan, J. A., Grant, I., Mallory, M. E., Hansen, L. A., Archibald, S. L., Jernigan, T. L., et al. (2002) · AIDS · doi:10.1097/00002030-200205030-00008 · Cited by 160 · see citing works
“lipoprotein-receptor-related protein) and CRABP-1 (cytoplasmic retinoic acid binding protein type 1) [51].”
Background
Longitudinal Analysis of Bone Density in Human Immunodeficiency Virus-Infected Women
Dolan, S. E., Kanter, J. R., & Grinspoon, S. K. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0127 · Cited by 156 · see citing works
Endocrine and Metabolic Evaluation of Human Immunodeficiency Virus-Infected Patients with Evidence of Protease Inhibitor-Associated Lipodystrophy
Yanovski, J. A., Miller, K. D., Kino, T., Friedman, T. C., Chrousos, G. P., Tsigos, C., & Falloon, J. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.6.5740 · Cited by 156 · see citing works
Drug–Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors
Chauvin, B., Drouot, S., Barrail‐Tran, A., & Taburet, A. (2013) · Clinical Pharmacokinetics · doi:10.1007/s40262-013-0075-4 · Cited by 154 · see citing works
Metabolic complications associated with antiretroviral therapy
Jain, R. G., Furfine, E. S., Pedneault, L., White, A. J., & Lenhard, J. M. (2001) · Antiviral Research · doi:10.1016/s0166-3542(01)00148-6 · Cited by 150 · see citing works
Effects of Testosterone Supplementation on Whole Body and Regional Fat Mass and Distribution in Human Immunodeficiency Virus-Infected Men with Abdominal Obesity
Bhasin, S., Parker, R. A., Sattler, F. R., Haubrich, R., Alston, B., Umbleja, T., & Shikuma, C. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2060 · Cited by 149 · see citing works
Use of HIV protease inhibitors to block Kaposi's sarcoma and tumour growth
Sgadari, C., Monini, P., Barillari, G., & Ensoli, B. (2003) · The Lancet Oncology · doi:10.1016/s1470-2045(03)01192-6 · Cited by 148 · see citing works
Altered Myocellular and Abdominal Fat Partitioning Predict Disturbance in Insulin Action in HIV Protease Inhibitor-Related Lipodystrophy
Gan, S. K., Samaras, K., Thompson, C. H., Kraegen, E. W., Carr, A. D., Cooper, D. A., & Chisholm, D. J. (2002) · Diabetes · doi:10.2337/diabetes.51.11.3163 · Cited by 148 · see citing works
Self-citation
Fibrates, dyslipoproteinaemia and cardiovascular disease
Watts, G. F., & Dimmitt, S. B. (1999) · Current Opinion in Lipidology · doi:10.1097/00041433-199912000-00011 · Cited by 145 · see citing works
Prevalence and Pathogenesis of Diabetes Mellitus in HIV-1 Infection Treated With Combined Antiretroviral Therapy
Samaras, K. (2009) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e31819c291b · Cited by 146 · see citing works
Self-citation
Nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity as an etiology for lipodystrophy
Kakuda, T. N., Brundage, R. C., Anderson, P. L., & Fletcher, C. V. (1999) · AIDS · doi:10.1097/00002030-199911120-00019 · Cited by 144 · see citing works
Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations
Christeff, N., Melchior, J., de Truchis, P., Perronne, C., Nunez, E. A., & Gougeon, M. (1999) · AIDS · doi:10.1097/00002030-199911120-00007 · Cited by 142 · see citing works
Effects of metformin on insulin resistance and central adiposity in patients receiving effective protease inhibitor therapy
Saint-Marc, T., & Touraine, J. L. (1999) · AIDS · doi:10.1097/00002030-199905280-00023 · Cited by 142 · see citing works
HIV Protease Inhibitors Stimulate Hepatic Triglyceride Synthesis
Lenhard, J. M., Croom, D. K., Weiel, J. E., & Winegar, D. A. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.12.2625 · Cited by 140 · see citing works
Bile acid-activated receptors in the treatment of dyslipidemia and related disorders
Fiorucci, S., Cipriani, S., Baldelli, F., & Mencarelli, A. (2009) · Progress in Lipid Research · doi:10.1016/j.plipres.2009.11.001 · Cited by 138 · see citing works
HIV-associated dyslipidaemia: pathogenesis and treatment
Oh, J., & Hegele, R. A. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70287-6 · Cited by 137 · see citing works
A Randomized Clinical Trial Comparing Nelfinavir Or Nevirapine Associated to Zidovudine/Lamivudine in HIV-Infected Naive Patients (The Combine Study)
Podzamczer, D., Ferrer, E., Consiglio, E., Gatell, J. M., Pérez, P., Pérez, J. L., Luna, E., González, A., Pedrol, E., Lozano, L., et al. (2002) · Antiviral Therapy · doi:10.1177/135965350200700202 · Cited by 137 · see citing works
“Protease inhibitor (PI)-containing regimens are uncomfortable, and are associated with a considerable incidence of adverse effects – the most worrisome being the probable association between PIs and the occurrence of lipodystrophy and other metabolic disorders – making adherence difficult and negatively influencing pa…”
Background
Use of observational databases to evaluate the effectiveness of antiretroviral therapy for HIV infection: comparison of cohort studies with randomized trials
Phillips, A. N., Grabar, S., Tassie, J.-M., Costagliola, D. G., Lundgren, J. D., & Egger, M. (1999) · AIDS · doi:10.1097/00002030-199910220-00010 · Cited by 136 · see citing works
HIV Protease Inhibitor Ritonavir Induces Cytotoxicity of Human Endothelial Cells
Zhong, D.-S., Lu, X.-H., Conklin, B. S., Lin, P. H., Lumsden, A. B., Yao, Q. C., & Chen, C. (2002) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000034707.40046.02 · Cited by 135 · see citing works
The metabolic abnormalities associated with non-alcoholic fatty liver disease
Haque, M., & Sanyal, A. J. (2002) · Best Practice & Research Clinical Gastroenterology · doi:10.1053/bega.2002.0325 · Cited by 134 · see citing works
Effects of HIV protease inhibitor therapy on lipid metabolism
Hui, D. Y. (2003) · Progress in Lipid Research · doi:10.1016/s0163-7827(02)00046-2 · Cited by 133 · see citing works
Elevated blood pressure in subjects with lipodystrophy
Sattler, F. R., Qian, D., Louie, S. G., Johnson, D., Briggs, W., DeQuattro, V. L., & Dubé, M. P. (2001) · AIDS · doi:10.1097/00002030-200110190-00013 · Cited by 132 · see citing works
“used to treat HIV [22], but other reports suggest that individuals may develop these abnormalities despite never having received PI [7,8,9,10,23±26].”
Coronary Artery Disease and Human Immunodeficiency Virus Infection
Mayer, K. H., Passalaris, J. D., Sepkowitz, K. A., & Glesby, M. J. (2000) · Clinical Infectious Diseases · doi:10.1086/313995 · Cited by 132 · see citing works
Adipocytes Targets and Actors in the Pathogenesis of HIV-Associated Lipodystrophy and Metabolic Alterations
Gougeon, M., Pénicaud, L., Fromenty, B., Leclercq, P., Viard, J., & Capeau, J. (2004) · Antiviral Therapy · doi:10.1177/135965350400900206 · Cited by 129 · see citing works
Human Immunodeficiency Virus/Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome: Clinical Presentation, Pathophysiology, and Therapeutic Strategies
Leow, M. K., Addy, C., & Mantzoros, C. S. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021704 · Cited by 128 · see citing works
Peroxisome proliferator-activated receptors in cutaneous biology
Kuenzli, S., & Saurat, J. ‐. (2003) · British Journal of Dermatology · doi:10.1046/j.1365-2133.2003.05532.x · Cited by 128 · see citing works

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 · see citing works
Correspondence to:
Carr, A., & Carr, A. (2011)
Self-citation
Effects of HIV protease inhibitor therapy on lipid metabolism
Hui, D. Y. (2003) · Progress in Lipid Research · doi:10.1016/s0163-7827(02)00046-2 · Cited by 133 · see citing works
Human obesity and thinness, hyperlipidemia, hyperglycemia, and insulin resistance associated with HIV1 protease inhibitors Prevention by alternating several antiproteases in short sequences
Mathé, G. (1999) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(00)88101-9 · Cited by 10 · see citing works
HIV Protease Inhibitor-Related Lipodystrophy Syndrome
Carr, A. D. (2000) · Clinical Infectious Diseases · doi:10.1086/313854 · Cited by 209 · see citing works
Self-citation

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 › Emergency Medicine › 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

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks