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The paradox of improved antiretroviral therapy in HIV: potential for nutritional modulation?

Published online by Cambridge University Press:  28 February 2007

Lisa J. Ware  and
S. A. Wootton
Lisa J. Ware*
Affiliation:
Institute of Human Nutrition, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
S. A. Wootton
Affiliation:
Institute of Human Nutrition, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
*
*Corresponding Author: Lisa Ware, present address SHS International Ltd, 100 Wavertree Boulevard, Liverpool L7 9PT, UK, fax +44 (0)151 228 2650, email [email protected]
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Abstract

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Chronic infection with HIV type 1 is associated with alterations in macronutrient metabolism, specifically elevated plasma lipids, glucose and reduced insulin sensitivity. These alterations are most severe in patients at the later stages of AIDS, indicating a relationship with disease progression. Recently, a metabolic syndrome, termed lipodystrophy, has been described in successfully-treated HIV patients in whom the altered macronutrient metabolism of HIV infection appears to be amplified markedly, with concurrent alterations in adipose tissue patterning. This syndrome presents a paradox, as before the development of highly-active antiretroviral therapy (HAART) the most severe perturbations in metabolism were observed in the sickest patients. Now, the patients that respond well to therapy are showing metabolic perturbations much greater than those seen before. The implications of this syndrome are that, whilst life expectancy may be increased by reducing viral load, there are concomitant increases in the risk of cardiovascular disease, diabetes and pancreatitis within this patient population. The aetiology of the syndrome remains unclear. In a collaborative trial with the Chelsea and Westminster Hospital in London we have used stable-isotope-labelled fatty acids to examine the hypothesis that treatment with HAART causes a delayed clearance of dietary lipid from the circulation, resulting in the retention of lipid within plasma and the downstream changes in insulin and glucose homeostasis. This hypothesis would indicate a role for low-fat diets, exercise and drugs that reduce plasma lipid or insulin resistance, in modulating the response to antiretroviral therapy in HIV infection.

Keywords

LipodystrophyHIVMetabolismLipidsStable isotopes
Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 61 , Issue 1 , February 2002 , pp. 131 - 136
Copyright
Copyright © The Nutrition Society 2002

References

Batterham, M, Garsia, R & Greenop, P (2000) Dietary intake, serum lipids, insulin resistance and body composition in the era of HAART 'Diet FRS Study'. AIDS 14, 1839–1843.Google Scholar
Bell, SJ, Chavali, S, Bistrian, B, Connolly, CA, Utsonomiya, T & Forse, RA (1996) Dietary fish oil and cytokine production during HIV infection. Journal of Parenteral and Enteral Nutrition 20, 43–49.Google Scholar
Brinkman, K, Hofstede, H, Burger, D, Smeitinik, J & Koopmans, P (1998) Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 12, 1735–1744.CrossRefGoogle ScholarPubMed
Brinkman, K, Smeitinik, J, Romjin, J & Reiss, P (1999) Mitochondrial toxicity induced by nucleoside-analogue reverse transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. Lancet 354, 1112–1115.CrossRefGoogle ScholarPubMed
Calder, PC (1996) Effects of fatty acids and dietary lipids on cells of the immune system. Proceedings of the Nutrition Society 55, 127–150.Google Scholar
Carr, A & Cooper, D (2000) Adverse effects of antiretroviral therapy. Lancet 356, 1423–1430.Google Scholar
Carr, A, Samaras, K, Chisholm, D & Cooper, D (1998) Pathogenesis of HIV-1 protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 352, 1881–1883.Google Scholar
Carr, A, Samaras, K, Thorisdottir, A, Kauffman, G, Chisholm, D & Cooper, D (1999) Diagnosis, prediction and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 353, 2093–2099.Google Scholar
Christeff, N, Lortholary, O, Casassus, P, Thobie, N, Dalle, M, Veyssier, P, Guillevin, L & Nunez, E (1995) Serum lipid concentration with reference to the clinical and immunological status of HIV infected men. Annales de Médecine Interne 146, 490–495.Google Scholar
Cloyd, MW (1991) Perturbation of host-cell membrane is a primary mechanism of HIV cytopathology. Virology 181, 500–511.CrossRefGoogle ScholarPubMed
Constans, J, Pellegrin, J & Peuchant, E (1994) Plasma lipids in HIV-infected patients: a prospective study in 95 patients. European Journal of Clinical Investigation 24, 416–420.Google Scholar
Constans, J, Peuchant, E & Pellegrin, J (1995) Fatty acids and plasma antioxidants in HIV-positive patients: correlation with nutritional and immunological status. Clinical Biochemistry 28, 421–426.Google Scholar
Endres, S (1993) Messengers and mediators: interactions among lipids, eicosanoids and cytokines. American Journal of Clinical Nutrition 57, 7895–8005.CrossRefGoogle ScholarPubMed
Endres, S, Ghorbani, R, Kelley, VE, Georgilis, K, Lonnemann, G, van der Meer, JMW, Cannon, JG, Rogers, TS, Klempner, MS, Weber, PC, Schaeffer, EJ, Wolff, SM & Dinarello, CA (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumour necrosis factor by mononuclear cells. New England Journal of Medicine 320, 265–271.Google Scholar
Feingold, K, Adi, S, Staprins, I, Moser, A, Neese, R, Verdier, JA, Doerrler, W & Grunfeld, C (1990) Diet affects the mechanisms by which TNF stimulates hepatic triglyceride production. American Journal of Physiology 259, E177–E184.Google Scholar
Fernandez-Miranda, C, Pulido, F & Carrillo, JL (1998) Lipoprotein alterations in patients with HIV infection: relation with cellular and humoral immune markers. Clinica Chimica Acta 274, 63–70.Google Scholar
Frayn, K, Shadid, S, Hamlani, R, Humphreys, S, Clark, ML, Fielding, BA, Boland, O & Coppack, SW (1994) Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition. American Journal of Physiology 266, E308–E317.Google Scholar
Gazzard, B (editor) (1999) Weight loss and diarrhoea. In Chelsea and Westminster Hospital AIDS Care Handbook, pp. 201–214. London: Mediscript Ltd.Google Scholar
Gomez-Sirvent, JL, Alonso-Socas, MM, Santolaria-Fernandez, FJ, Gonzalez-Reimers, CE, Rodriguez-Moreno, F & Essardas-Daryanani, H (1994) Prognostic value of triglyceride levels in early HIV infection. AIDS 8, 1740–1741.Google Scholar
Grunfeld, C & Feingold, K (1991) The metabolic effects of tumour necrosis factor and other cytokines. Biotherapy 3, 143–158.Google Scholar
Grunfeld, C & Feingold, K (1992) Metabolic disturbances and wasting in AIDS. New England Journal of Medicine 327, 329–335.Google Scholar
Grunfeld, C, Kotler, D & Shigenaga, (1991) Circulating IFN-alpha and hypertriglyceridaemia in AIDS. American Journal of Medicine 90, 154–162.Google Scholar
Grunfeld, C, Pang, M, Doerrler, W, Shigenaga, J, Jensen, P & Feingold, K (1992) Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Journal of Clinical Endocrinology and Metabolism 74, 1045–1052.Google Scholar
Hellerstein, M, Grunfield, C, Wu, K, Christiansen, M, Kaempfer, S, Kletke, C & Shackleton, C (1993) Increased de novo hepatic lipogenesis in HIV infection. Journal of Clinical Endocrinology and Metabolism 76, 559–565.Google Scholar
Hommes, M, Romjin, J, Endert, E & Sauerwein, H (1991) Resting energy expenditure and substrate oxidation in HIV-infected asymptomatic men: HIV affects host metabolism in the early asymptomatic stage. American Journal of Clinical Nutrition 54, 311–315.Google Scholar
Jahoor, F, Jackson, AA, Gazzard, B, Phillips, G, Sharpstone, D, Frazer, M & Heird, W (1999) Erythrocyte glutathione deficiency in symptom-free HIV infection is associated with decreased synthesis rate. American Journal of Physiology 276, E205–E211.Google Scholar
Klein, A, Bruser, B, Bast, M & Rachlis, A (1992) Progress of HIV infection and changes in the lipid membrane structure of CD4+ cells. AIDS 6, 332–333.Google Scholar
Koppel, K (2000) Serum lipid levels associated with increased risk for cardiovascular disease is associated with highly active antiretroviral therapy (HAART) in HIV-1 infection. International Journal of STD and AIDS 11, 451–455.CrossRefGoogle ScholarPubMed
Kotler, D & Heymsfield, S (1998) HIV Infection: a model chronic illness for studying wasting diseases. American Journal of Clinical Nutrition 68, 519–520.Google Scholar
Mallal, S, John, M, Moore, C, James, I & McKinnon, E (2000) Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. AIDS 14, 1309–1316.Google Scholar
Mercie, P (2000) Atherogen lipid profile in HIV-1 infected patients with lipodystrophy syndrome. European Journal of Internal Medicine 11, 257–263.Google Scholar
Meydani, SN, Endres, S, Woods, MM, Goldin, BR, Soo, C, Morrill-Labrode, A, Dinarello, C & Gorbach, SL (1991) Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. Journal of Nutrition 121, 547–555.Google Scholar
Meyer, L, Rabaud, C, Ziegler, O, May, T & Drouin, P (1998) Protease inhibitors, diabetes mellitus and blood lipids. Diabetes Metabolism 24, 547–549.Google ScholarPubMed
Mulligan, K, Grunfeld, C, Hellerstein, M, Neese, R & Schambelan, M (1993) Anabolic effects of recombinant human growth hormone in patients with wasting associated with HIV infection. Journal of Clinical Endocrinology and Metabolism 77, 956–962.Google Scholar
Noor, MA, Lo, JC, Mulligan, K, Shwarz, JM, Halvorsen, RA, Schambelan, M & Grunfeld, C (2001) Absent HIV infection, Indinavir causes insulin resistance. AIDS 15, 11–18.Google Scholar
Nunez, E & Christeff, N (1994) Steroid hormone, cytokine, lipid and metabolic disturbances in HIV infection. Baillieres Clinical Endocrinology and Metabolism 8, 803–824.Google Scholar
Pacht, ER, Diaz, P, Clanton, T, Hart, J & Gaadek, JE (1997) Serum vitamin E decreases in HIV-seropositive subjects over time. Journal of Laboratory and Clinical Medicine 130, 293–296.Google Scholar
Purnell, J, Zambon, A, Knopp, R et al. (1999) Effect of Ritonavir on lipids and post-heparin lipase activities in normal subjects. AIDS 14, 51–57.Google Scholar
Roubenouff, R, Weiss, L, McDermott, A, Heflin, T, Cloutier, G, Wood, M & Gorbach, S (1999) A pilot study of exercise training to reduce trunk fat in adults with HIV-associated fat redistribution. AIDS 13, 1373–1375.Google Scholar
Sappey, C, Leclercq, P, Coudray, C, Faure, P, Micoud, M & Favier, A (1994) Vitamin, trace element and peroxide status in HIV seropositive patients: asymptomatic patients present a severe beta-carotene deficiency. Clinica Chimica Acta 230, 35–42.Google Scholar
Silva, M, Skolnik, PR, Gorbach, SL, Spiegelman, D, Wilson, IB, Fernandez-Di Franco, MG & Knox, TA (1998) The effect of protease inhibitors on weight and body composition in HIV-infected patients. AIDS 12, 1645–1651.CrossRefGoogle ScholarPubMed
Sullivan, AK, Feher, MD, Nelson, MR & Gazzard, BG (1998) Marked hypertriglyceridaemia associated with ritonavir therapy. AIDS 12, 1393–1395.Google Scholar
Taskinen, MR (1995) Insulin resistance and lipoprotein metabolism. Current Opinion in Lipidology 6, 153–160.Google Scholar
Terrence Higgins Trust (2001) Terrence Higgins Trust factsheet. http://www.tht.org.uk/facts.htm.Google Scholar
Tikkanen, MJ, Ojala, J & Helve, E (1992) Long term use of Lovastatin in different types of hyperlipidaemia. Atherosclerosis 97, S27–S32.Google Scholar
Turcotte, L, Srivastava, A & Chiasson, J (1997) Fasting increases plasma membrane fatty acid-binding protein in red skeletal muscle. Molecular and Cellular Biochemistry 166, 153–158.CrossRefGoogle ScholarPubMed
Ware, LJ, Morlese, J, Burdge, G, Jackson, AA, Gazzard, B & Wooton, SA (2000) Differences in postprandial lipid metabolism in patients with PI-associated and NRTI-associated lipodystrophy. Antiviral Therapy 5, Suppl. 5, 13.Google Scholar
Ware, LJ, Morlese, J, Gazzard, B, Burdge, GC, Jackson, AA & Wooton, SA (2001) Highly active anti-retroviral therapy (HAART) in HIV-1 positive men increases the retention time of dietary lipid within the circulation. Proceedings of the Nutrition Society 60, 31A.Google Scholar
Xiang, S, Cianflone, K, Kalant, D & Sniderman, A (1999) Differential binding of triglyceride-rich lipoproteins to lipoprotein lipase. Journal of Lipid Research 40, 1655–1662.Google Scholar
Yarasheski, K, Tebas, P & Stanerson, B (2001) Resistance exercise training reduces hypertriglyceridaemia in HIV-infected men treated with antiviral therapy. Journal of Applied Physiology 90, 133–138.Google Scholar