Metabolic complications and treatment of perinatally HIV-infected children and adolescents

Journal of the International AIDS Society

Volumn 16, Issue , 2013, Pages

  Barlow Mosha, Linda ^a   Eckard, Allison Ross ^b   McComsey, Grace A ^c   Musoke, Philippa M ^a,d  

^a JHU Research Collaboration   (Uganda)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c CASE WESTERN RESERVE UNIVERSITY   (United States)

^d MAKERERE UNIVERSITY   (Uganda)

Author keywords

Adolescents; Antiretroviral therapy; Cardiovascular disease; Children; HIV; Metabolic complications

Indexed keywords

DIDANOSINE; PROTEINASE INHIBITOR; STAVUDINE; VITAMIN D; ZIDOVUDINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

ADOLESCENT HEALTH; ADULTHOOD; BODY FAT DISTRIBUTION; BONE DENSITY; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHILDHOOD; CLINICAL FEATURE; DEPRESSION; DIAGNOSTIC PROCEDURE; DYSLIPIDEMIA; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INSULIN RESISTANCE; LACTIC ACIDOSIS; LIPODYSTROPHY; MENTAL HEALTH; METABOLIC DISORDER; OSTEOLYSIS; OSTEOPENIA; OSTEOPOROSIS; PATHOGENESIS; PATIENT COMPLIANCE; PREVALENCE; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; SELF CONCEPT; TREATMENT INDICATION; VITAMIN D DEFICIENCY; ADOLESCENT; ADOLESCENTS; ANTIRETROVIRAL THERAPY; CHEMICALLY INDUCED DISORDER; CHILD; HUMAN IMMUNODEFICIENCY VIRUS; METABOLIC COMPLICATIONS; PATHOLOGY;

ADOLESCENTS; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR DISEASE; CHILDREN; HIV; METABOLIC COMPLICATIONS;

ADOLESCENT; ANTI-HIV AGENTS; CHILD; HIV INFECTIONS; HUMANS; METABOLIC DISEASES;

EID: 84887284990     PISSN: None     EISSN: 17582652     Source Type: Journal    
DOI: 10.7448/IAS.16.1.18600     Document Type: Review

References (174)

1. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338(13):853-60.
2. Sutcliffe CG, van Dijk JH, Bolton C, Persaud D, Moss WJ. Effectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa. Lancet Infect Dis. 2008;8(8):477-89.
3. Gibb DM, Duong T, Tookey PA, Sharland M, Tudor-Williams G, Novelli V, et al. Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland. Brit Med J. 2003;327(7422):1019.
4. Tsiodras S, Mantzoros C, Hammer S, Samore M. Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy: a 5-year cohort study. Arch Intern Med. 2000;160(13):2050-6.
5. European Paediatric Lipodystrophy Group. Antiretroviral therapy, fat redistribution and hyperlipidaemia in HIV-infected children in Europe. AIDS. 2004;1810:1443-51.
6. Carter RJ, Wiener J, Abrams EJ, Farley J, Nesheim S, Palumbo P, et al. Dyslipidemia among perinatally HIV-infected children enrolled in the PACTS-HOPE cohort, 1999-2004: a longitudinal analysis. J Acquir Immune Defic Syndr. 2006;41(4):453-60.
7. McComsey GA, Leonard E. Metabolic complications of HIV therapy in children. AIDS. 2004;18(13):1753-68.
8. Dapena M, Jimenez B, Noguera-Julian A, Soler-Palacin P, Fortuny C, Lahoz R, et al. Metabolic disorders in vertically HIV-infected children: future adults at risk for cardiovascular disease. J Pediatr Endocrinol Metab. 2012;25(5,6):529-35.
9. Aldrovandi GM, Lindsey JC, Jacobson DL, Zadzilka A, Sheeran E, Moye J, et al. Morphologic and metabolic abnormalities in vertically HIV-infected children and youth. AIDS. 2009;23(6):661-72.
10. World Health Organization. Antiretroviral therapy for HIV infection in infants and children Recommendations for a public health approach. Geneva, Switzerland: World Health Organization, 2010.
11. Mallewa JE, Wilkins E, Vilar J, Mallewa M, Doran D, Back D, et al. HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options. J Antimicrob Chemother. 2008;62(4):648-60.
12. Arpadi S, Shiau S, Strehlau R, Martens L, Patel F, Coovadia A, et al. Metabolic abnormalities and body composition of HIV-infected children on Lopinavir or Nevirapine-based antiretroviral therapy. Arch Dis Child. 2013;98:258-64.
13. Eckard AR, Tangpricha V, Seydafkan S, O'Riordan MA, Storer N, Labbato D, et al. The relationship between vitamin D status and HIV-related complications in HIV-infected children and young adults. Pediatr Infect Dis J. 2013. [Epub ahead of print].
14. Walker Harris V, Brown TT. Bone loss in the HIV-infected patient: evidence, clinical implications, and treatment strategies. J Infect Dis. 2012;205(Suppl 3):S391-8.
15. Mora S, Zamproni I, Beccio S, Bianchi R, Giacomet V, Vigano A. Longitudinal changes of bone mineral density and metabolism in antiretroviral-treated human immunodeficiency virus-infected children. J Clin Endocrinol Metab. 2004;89(1):24-8.
16. Musoke PM, Fergusson P. Severe malnutrition and metabolic complications of HIV-infected children in the antiretroviral era: clinical care and management in resource-limited settings. Am J Clin Nutr. 2011;94(6):1716S-20.
17. Wedekind CA, Pugatch D. Lipodystrophy syndrome in children infected with human immunodeficiency virus. Pharmacotherapy. 2001;21(7):861-6.
18. Aurpibul L, Puthanakit T, Lee B, Mangklabruks A, Sirisanthana T, Sirisanthana V. Lipodystrophy and metabolic changes in HIV-infected children on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Antivir Ther. 2007;12(8):1247-54.
19. Ene L, Goetghebuer T, Hainaut M, Peltier A, Toppet V, Levy J. Prevalence of lipodystrophy in HIV-infected children: a cross-sectional study. Eur J Pediatr. 2007;166(1):13-21.
20. Alam N, Cortina-Borja M, Goetghebuer T, Marczynska M, Vigano A, Thorne C. Body fat abnormality in HIV-infected children and adolescents living in Europe: prevalence and risk factors. J Acquir Immune Defic Syndr. 2012;59(3):314-24.
21. Kinabo GD, Sprengers M, Msuya LJ, Shayo AM, van Asten H, Dolmans WM, et al. Prevalence of Lipodystrophy in HIV-infected children in Tanzania on highly active antiretroviral therapy. Pediatr Infect Dis J. 2013;32(1):39-44.
22. Piloya T, Bakeera-Kitaka S, Kekitiinwa A, Kamya MR. Lipodystrophy among HIV-infected children and adolescents on highly active antiretroviral therapy in Uganda: a cross sectional study. J Int AIDS Soc. 2012;15(2):17427.
23. Kakuda TN, Brundage RC, Anderson PL, Fletcher CV. Nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity as an etiology for lipodystrophy. AIDS. 1999;13(16):2311-2.
24. Brinkman K, Smeitink JA, Romijn JA, Reiss P. Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. Lancet. 1999;354(9184):1112-5.
25. Walker UA, Brinkman K. NRTI induced mitochondrial toxicity as a mechanism for HAART related lipodystrophy: fact or fiction? HIV Med. 2001;2(3):163-5.
26. Walker UA. Update on mitochondrial toxicity: where are we now? J HIV Ther. 2003;8(2):32-5.
27. Cossarizza A, Pinti M, Moretti L, Bricalli D, Bianchi R, Troiano L, et al. Mitochondrial functionality and mitochondrial DNA content in lymphocytes of vertically infected human immunodeficiency virus-positive children with highly active antiretroviral therapy-related lipodystrophy. J Infect Dis. 2002;185(3):299-305.
28. Cossarizza A, Moyle G. Antiretroviral nucleoside and nucleotide analogues and mitochondria. AIDS. 2004;18(2):137-51.
29. Oh J, Hegele RA. HIV-associated dyslipidaemia: pathogenesis and treatment. Lancet Infect Dis. 2007;7(12):787-96.
30. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998;12(7):F51-8.
31. Bockhorst JL, Ksseiry I, Toye M, Chipkin SR, Stechenberg BW, Fisher DJ, et al. Evidence of human immunodeficiency virus-associated lipodystrophy syndrome in children treated with protease inhibitors. Pediatr Infect Dis J. 2003;22(5):463-5.
32. Alves C, Oliveira AC, Brites C. Lipodystrophic syndrome in children and adolescents infected with the human immunodeficiency virus. Braz J Infect Dis. 2008;12(4):342-8.
33. Barbaro G. Visceral fat as target of highly active antiretroviral therapy-associated metabolic syndrome. Curr Pharm Des. 2007;13(21):2208-13.
34. Zanone Poma B, Riva A, Nasi M, Cicconi P, Broggini V, Lepri AC, et al. Genetic polymorphisms differently influencing the emergence of atrophy and fat accumulation in HIV-related lipodystrophy. AIDS. 2008;22(14):1769-78.
35. Taylor P, Worrell C, Steinberg SM, Hazra R, Jankelevich S, Wood LV, et al. Natural history of lipid abnormalities and fat redistribution among human immunodeficiency virus-infected children receiving long-term, protease inhibitor-containing, highly active antiretroviral therapy regimens. Pediatrics. 2004;114(2):235-42.
36. McComsey GA, Walker UA. Role of mitochondria in HIV lipoatrophy: insight into pathogenesis and potential therapies. Mitochondrion. 2004;4(2,3):111-8.
37. Innes S, Levin L, Cotton M. Lipodystrophy syndrome in HIV-infected children on haart. South Afr J HIV Med. 2009;10(4):76-80.
38. Innes S, Cotton MF, Haubrich R, Conradie MM, van Niekerk M, Edson C, et al. High prevalence of lipoatrophy in pre-pubertal South African children on antiretroviral therapy: a cross-sectional study. BMC Pediatr. 2012;12:183.
39. Resino S, Micheloud D, Larru B, Bellon JM, Leon JA, Resino R, et al. Immunological recovery and metabolic disorders in severe immunodeficiency HIV type 1-infected children on highly active antiretroviral therapy. AIDS Res Hum Retroviruses. 2008;24(12):1477-84.
40. Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005;352(1):48-62.
41. Grunfeld C, Kotler DP, Hamadeh R, Tierney A, Wang J, Pierson RN. Hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med. 1989;86(1):27-31.
42. Jolliffe CJ, Janssen I. Distribution of lipoproteins by age and gender in adolescents. Circulation. 2006;114(10):1056-62.
43. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents; National Heart, Lung, and Blood Institute. Pediatrics. 2011;128(Suppl 5):S213-56.
44. Hickman TB, Briefel RR, Carroll MD, Rifkind BM, Cleeman JI, Maurer KR, et al. Distributions and trends of serum lipid levels among United States children and adolescents ages 4-19 years: data from the Third National Health and Nutrition Examination Survey. Prev Med. 1998;27(6):879-90.
45. Sax PE, Kumar P. Tolerability and safety of HIV protease inhibitors in adults. J Acquir Immune Defic Syndr. 2004;37(1):1111-24.
46. Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JM, Miller MD, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. J Am Med Assoc. 2004;292(2):191-201.
47. Cheseaux JJ, Jotterand V, Aebi C, Gnehm H, Kind C, Nadal D, et al. Hyperlipidemia in HIV-infected children treated with protease inhibitors: relevance for cardiovascular diseases. J Acquir Immune Defic Syndr. 2002;30(3):288-93.
48. Bitnun A, Sochett E, Babyn P, Holowka S, Stephens D, Read S, et al. Serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor-treated and naive HIV-infected children. AIDS. 2003;17(9):1319-27.
49. Bitnun A, Sochett E, Dick PT, To T, Jefferies C, Babyn P, et al. Insulin sensitivity and beta-cell function in protease inhibitor-treated and - naive human immunodeficiency virus-infected children. J Clin Endocrinol Metab. 2005;90(1):168-74.
50. Vigano A, Cerini C, Pattarino G, Fasan S, Zuccotti GV. Metabolic complications associated with antiretroviral therapy in HIV-infected and HIV-exposed uninfected paediatric patients. Expert Opin Drug Saf. 2010;9(3):431-45.
51. Melvin AJ, Lennon S, Mohan KM, Purnell JQ. Metabolic abnormalities in HIV type 1-infected children treated and not treated with protease inhibitors. AIDS Res Hum Retroviruses. 2001;17(12):1117-23.
52. Lainka E, Oezbek S, Falck M, Ndagijimana J, Niehues T. Marked dyslipidemia in human immunodeficiency virus-infected children on protease inhibitor-containing antiretroviral therapy. Pediatrics. 2002;110(5):56.
53. Jaquet D, Levine M, Ortega-Rodriguez E, Faye A, Polak M, Vilmer E, et al. Clinical and metabolic presentation of the lipodystrophic syndrome in HIV-infected children. AIDS. 2000;14(14):2123-8.
54. Vigano A, Zuccotti GV, Cerini C, Stucchi S, Puzzovio M, Giacomet V, et al. Lipodystrophy, insulin resistance, and adiponectin concentration in HIV-infected children and adolescents. Curr HIV Res. 2011;9(5):321-6.
55. Chantry CJ, Hughes MD, Alvero C, Cervia JS, Meyer WA 3rd, Hodge J, et al. Lipid and glucose alterations in HIV-infected children beginning or changing antiretroviral therapy. Pediatrics. 2008;122(1):e129-38.
56. Vigano A, Brambilla P, Pattarino G, Stucchi S, Fasan S, Raimondi C, et al. Long-term evaluation of glucose homeostasis in a cohort of HAART-treated HIV-infected children: a longitudinal, observational cohort study. Clin Drug Investig. 2009;29(2):101-9.
57. Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang JM, et al. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS. 1999;13(13):1659-67.
58. Brambilla P, Bricalli D, Sala N, Renzetti F, Manzoni P, Vanzulli A, et al. Highly active antiretroviral-treated HIV-infected children show fat distribution changes even in absence of lipodystrophy. AIDS. 2001;15(18):2415-22.
59. Borai A, Livingstone C, Ferns GA. The biochemical assessment of insulin resistance. Ann Clin Biochem. 2007;44(Pt 4):324-42.
60. Yeckel CW, Weiss R, Dziura J, Taksali SE, Dufour S, Burgert TS, et al. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab. 2004;89(3):1096-101.
61. Arpadi SM, Cuff PA, Horlick M, Wang J, Kotler DP. Lipodystrophy in HIV-infected children is associated with high viral load and low CD4+ -lymphocyte count and CD4+ -lymphocyte percentage at baseline and use of protease inhibitors and stavudine. J Acquir Immune Defic Syndr. 2001;27(1):30-4.
62. Vigano A, Mora S, Testolin C, Beccio S, Schneider L, Bricalli D, et al. Increased lipodystrophy is associated with increased exposure to highly active antiretroviral therapy in HIV-infected children. J Acquir Immune Defic Syndr. 2003;32(5):482-9.
63. Lakshmy R, Gupta R, Prabhakaran D, Snehi U, Reddy KS. Utility of dried blood spots for measurement of cholesterol and triglycerides in a surveillance study. J Diabetes Sci Technol. 2010;4(2):258-62.
64. Vigano A, Brambilla P, Cafarelli L, Giacomet V, Borgonovo S, Zamproni I, et al. Normalization of fat accrual in lipoatrophic, HIV-infected children switched from stavudine to tenofovir and from protease inhibitor to efavirenz. Antivir Ther. 2007;12(3):297-302.
65. Gonzalez-Tome MI, Amador JT, Pena MJ, Gomez ML, Conejo PR, Fontelos PM. Outcome of protease inhibitor substitution with nevirapine in HIV-1 infected children. BMC Infect Dis. 2008;8:144.
66. Vigano A, Mora S, Brambilla P, Schneider L, Merlo M, Monti LD, et al. Impaired growth hormone secretion correlates with visceral adiposity in highly active antiretroviral treated HIV-infected adolescents. AIDS. 2003;17(10):1435-41.
67. Vigano A, Mora S, Manzoni P, Schneider L, Beretta S, Molinaro M, et al. Effects of recombinant growth hormone on visceral fat accumulation: pilot study in human immunodeficiency virus-infected adolescents. J Clin Endocrinol Metab. 2005;90(7):4075-80.
68. Dollfus C, Blanche S, Trocme N, Funck-Brentano I, Bonnet F, Levan P. Correction of facial lipoatrophy using autologous fat transplants in HIV-infected adolescents. HIV Med. 2009;10(5):263-8.
69. Hultman CS, McPhail LE, Donaldson JH, Wohl DA. Surgical management of HIV-associated lipodystrophy: role of ultrasonic-assisted liposuction and suction-assisted lipectomy in the treatment of lipohypertrophy. Ann Plast Surg. 2007;58(3):255-63.
70. Moyle GJ. Plastic surgical approaches for HIV-associated lipoatrophy. Curr HIV/AIDS Rep. 2005;2(3):127-31.
71. Mobius U, Lubach-Ruitman M, Castro-Frenzel B, Stoll M, Esser S, Voigt E, et al. Switching to atazanavir improves metabolic disorders in antiretroviral-experienced patients with severe hyperlipidemia. J Acquir Immune Defic Syndr. 2005;39(2):174-80.
72. McComsey G, Bhumbra N, Ma JF, Rathore M, Alvarez A. Impact of protease inhibitor substitution with efavirenz in HIV-infected children: results of the first pediatric switch study. Pediatrics. 2003;111(3):275-81.
73. Vigano A, Aldrovandi GM, Giacomet V, Merlo M, Martelli L, Beretta S, et al. Improvement in dyslipidaemia after switching stavudine to tenofovir and replacing protease inhibitors with efavirenz in HIV-infected children. Antivir Ther. 2005;10(8):917-24.
74. Guffanti M, Caumo A, Galli L, Bigoloni A, Galli A, Dagba G, et al. Switching to unboosted atazanavir improves glucose tolerance in highly pretreated HIV-1 infected subjects. Eur J Endocrinol. 2007;156(4):503-9.
75. Obel N, Thomsen HF, Kronborg G, Larsen CS, Hildebrandt PR, Sorensen HT, et al. Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study. Clin Infect Dis. 2007;44(12):1625-31.
76. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007;92(7):2506-12.
77. McComsey GA, O'Riordan M, Hazen SL, El-Bejjani D, Bhatt S, Brennan ML, et al. Increased carotid intima media thickness and cardiac biomarkers in HIV infected children. AIDS. 2007;21(8):921-7.
78. Farley J, Gona P, Crain M, Cervia J, Oleske J, Seage G, et al. Prevalence of elevated cholesterol and associated risk factors among perinatally HIV-infected children (4-19 years old) in Pediatric AIDS Clinical Trials Group 219C. J Acquir Immune Defic Syndr. 2005;38(4):480-7.
79. Tassiopoulos K, Williams PL, Seage GR 3rd, Crain M, Oleske J, Farley J. Association of hypercholesterolemia incidence with antiretroviral treatment, including protease inhibitors, among perinatally HIV-infected children. J Acquir Immune Defic Syndr. 2008;47(5):607-14.
80. Jacobson DL, Williams P, Tassiopoulos K, Melvin A, Hazra R, Farley J. Clinical management and follow-up of hypercholesterolemia among perinatally HIV-infected children enrolled in the PACTG 219C study. J Acquir Immune Defic Syndr. 2011;57(5):413-20.
81. Ross AC, O'Riordan MA, Storer N, Dogra V, McComsey GA. Heightened inflammation is linked to carotid intima-media thickness and endothelial activation in HIV-infected children. Atherosclerosis. 2010;211(2):492-8.
82. Miller TI, Borkowsky W, DiMeglio LA, Dooley L, Geffner ME, Hazra R, et al. Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children. HIV Med. 2012;13(5):264-75.
83. Ross AC, Storer N, O'Riordan MA, Dogra V, McComsey GA. Longitudinal changes in carotid intima-media thickness and cardiovascular risk factors in human immunodeficiency virus-infected children and young adults compared with healthy controls. Pediatr Infect Dis J. 2010;29(7):634-8.
84. Kaplan RC, Sinclair E, Landay AL, Lurain N, Sharrett AR, Gange SJ, et al. T cell activation predicts carotid artery stiffness among HIV-infected women. Atherosclerosis. 2011;217(1):207-13.
85. Kaplan RC, Sinclair E, Landay AL, Lurain N, Sharrett AR, Gange SJ, et al. T cell activation and senescence predict subclinical carotid artery disease in HIV-infected women. J Infect Dis. 2011;203(4):452-63.
86. Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. J Acquir Immune Defic Syndr. 2009;51(3):268-73.
87. Longenecker C, Funderburg N, Jiang Y, Debanne S, Storer N, Labbato D, et al. Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals. HIV Med. 2013 Jan 18. doi: 10.1111/hiv.12013. [Epub ahead of print].
88. Ross AC, Rizk N, O'Riordan MA, Dogra V, El-Bejjani D, Storer N, et al. Relationship between inflammatory markers, endothelial activation markers, and carotid intima-media thickness in HIV-infected patients receiving antiretroviral therapy. Clin Infect Dis. 2009;49(7):1119-27.
89. Terai M, Ohishi M, Ito N, Takagi T, Tatara Y, Kaibe M, et al. Comparison of arterial functional evaluations as a predictor of cardiovascular events in hypertensive patients: the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study. Hypertens Res. 2008;31(6):1135-45.
90. Kullo IJ, Malik AR. Arterial ultrasonography and tonometry as adjuncts to cardiovascular risk stratification. J Am Coll Cardiol. 2007;49(13):1413-26.
91. Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, Bos ML, Schalekamp MA, et al. Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation. 2006;113(5):657-63.
92. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999; 99(18):2434-9.
93. Shokawa T, Imazu M, Yamamoto H, Toyofuku M, Tasaki N, Okimoto T, et al. Pulse wave velocity predicts cardiovascular mortality: findings from the Hawaii- Los Angeles-Hiroshima study. Circ J. 2005;69(3):259-64.
94. Willum-Hansen T, Staessen JA, Torp-Pedersen C, Rasmussen S, Thijs L, Ibsen H, et al. Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation. 2006;113(5):664-70.
95. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588-605.
96. Giuliano Ide C, de Freitas SF, de Souza M, Caramelli B. Subclinic atherosclerosis and cardiovascular risk factors in HIV-infected children: PERI study. Coron Artery Dis. 2008;19(3):167-72.
97. Charakida M, Donald AE, Green H, Storry C, Clapson M, Caslake M, et al. Early structural and functional changes of the vasculature in HIV-infected children: impact of disease and antiretroviral therapy. Circulation. 2005;112(1):103-9.
98. Vigano A, Bedogni G, Cerini C, Meroni L, Giacomet V, Stucchi S, et al. Both HIV-infection and long-term antiretroviral therapy are associated with increased common carotid intima-media thickness in HIV-infected adolescents and young adults. Curr HIV Res. 2010;8(5):411-7.
99. Fernhall B, Agiovlasitis S. Arterial function in youth: window into cardiovascular risk. J Appl Physiol. 2008;105(1):325-33.
100. Sass C, Herbeth B, Chapet O, Siest G, Visvikis S, Zannad F. Intima-media thickness and diameter of carotid and femoral arteries in children, adolescents and adults from the Stanislas cohort: effect of age, sex, anthropometry and blood pressure. J Hypertens. 1998;16(11):1593-602.
101. Jourdan C, Wuhl E, Litwin M, Fahr K, Trelewicz J, Jobs K, et al. Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens. 2005;23(9):1707-15.
102. Charakida M, Loukogeorgakis SP, Okorie MI, Masi S, Halcox JP, Deanfield JE, et al. Increased arterial stiffness in HIV-infected children: risk factors and antiretroviral therapy. Antivir Ther. 2009;14(8):1075-9.
103. Calza L, Manfredi R, Chiodo F. Hyperlactataemia and lactic acidosis in HIV-infected patients receiving antiretroviral therapy. Clin Nutr. 2005;24(1):5-15.
104. Kakuda TN. Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin Ther. 2000;22(6):685-708.
105. Members of Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for use of Antiretroviral agents in Pediatric HIV infection. 2012 [cited 17 February 2013]; Available from: http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf.
106. Lactic Acidosis International Group. Risk factors for lactic acidosis and severe hyperlactataemia in HIV-1-infected adults exposed to antiretroviral therapy. AIDS. 2007;21(18):2455-64.
107. Menezes CN, Maskew M, Sanne I, Crowther NJ, Raal FJ. A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects. BMC Infect Dis. 2011;11:244.
108. Rey C, Prieto S, Medina A, Perez C, Concha A, Menendez S. Fatal lactic acidosis during antiretroviral therapy. Pediatr Crit Care Med. 2003;4(4):485-7.
109. Shah I. Lactic acidosis in HIV infected children due to antiretroviral therapy. Indian Pediatr. 2005;42(10):1051-2.
110. Palmer M, Chersich M, Moultrie H, Kuhn L, Fairlie L, Meyers T. Frequency of stavudine substitution due to toxicity in children receiving antiretroviral treatment in Soweto, South Africa. AIDS. 2012 Nov 19. [Epub ahead of print].
111. Carter RW, Singh J, Archambault C, Arrieta A. Severe lactic acidosis in association with reverse transcriptase inhibitors with potential response to L-carnitine in a pediatric HIV-positive patient. AIDS Patient Care STDS. 2004;18(3):131-4.
112. Noguera A, Fortuny C, Sanchez E, Artuch R, Vilaseca MA, Munoz-Almagro C, et al. Hyperlactatemia in human immunodeficiency virus-infected children receiving antiretroviral treatment. Pediatr Infect Dis J. 2003;22(9):778-82.
113. Desai N, Mathur M,Weedon J. Lactate levels in children with HIV/AIDS on highly active antiretroviral therapy. AIDS. 2003;17(10):1565-8.
114. Claas GJ, Julg B, Goebel FD, Bogner J. Metabolic and anthropometric changes one year after switching from didanosine/stavudine to tenofovir in HIV-infected patients. Eur J Med Res. 2007;12(2):54-60.
115. Moren C, Noguera-Julian A, Garrabou G, Catalan M, Rovira N, Tobias E, et al. Mitochondrial evolution in HIV-infected children receiving first- or second-generation nucleoside analogues. J Acquir Immune Defic Syndr. 2012;60(2):111-6.
116. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS. 2006;20(17):2165-74.
117. McComsey GA, Tebas P, Shane E, Yin MT, Overton ET, Huang JS, et al. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. 2010;51(8):937-46.
118. Paccou J, Viget N, Legrout-Gerot I, Yazdanpanah Y, Cortet B. Bone loss in patients with HIV infection. Joint Bone Spine. 2009;76(6):637-41.
119. Triant VA, Brown TT, Lee H, Grinspoon SK. Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab. 2008;93(9):3499-504.
120. McKay HA, Bailey DA, Mirwald RL, Davison KS, Faulkner RA. Peak bone mineral accrual and age at menarche in adolescent girls: a 6-year longitudinal study. J Pediatr. 1998;133(5):682-7.
121. Gordon CM, Bachrach LK, Carpenter TO, Crabtree N, El-Hajj Fuleihan G, Kutilek S, et al. Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom. 2008;11(1):43-58.
122. Schtscherbyna A, Pinheiro MF, Mendonca LM, Gouveia C, Luiz RR, Machado ES, et al. Factors associated with low bone mineral density in a Brazilian cohort of vertically HIV-infected adolescents. Int J Infect Dis. 2012;16(12):e872-8.
123. Gafni RI, Hazra R, Reynolds JC, Maldarelli F, Tullio AN, DeCarlo E, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics. 2006;118(3):e711-8.
124. O'Brien KO, Razavi M, Henderson RA, Caballero B, Ellis KJ. Bone mineral content in girls perinatally infected with HIV. Am J Clin Nutr. 2001;73(4):821-6.
125. Jacobson DL, Lindsey JC, Gordon CM, Moye J, Hardin DS, Mulligan K, et al. Total body and spinal bone mineral density across Tanner stage in perinatally HIV-infected and uninfected children and youth in PACTG 1045. AIDS. 2010;24(5):687-96.
126. Puthanakit T, Saksawad R, Bunupuradah T, Wittawatmongkol O, Chuanjaroen T, Ubolyam S, et al. Prevalence and risk factors of low bone mineral density among perinatally HIV-infected Thai adolescents receiving antiretroviral therapy. J Acquir Immune Defic Syndr. 2012;61(4):477-83.
127. Jacobson DL, Spiegelman D, Duggan C,Weinberg GA, Bechard L, Furuta L, et al. Predictors of bone mineral density in human immunodeficiency virus-1 infected children. J Pediatr Gastroenterol Nutr. 2005;41(3):339-46.
128. Arpadi SM, Horlick M, Thornton J, Cuff PA, Wang J, Kotler DP. Bone mineral content is lower in prepubertal HIV-infected children. J Acquir Immune Defic Syndr. 2002;29(5):450-4.
129. Soyka LA, Fairfield WP, Klibanski A. Clinical review 117: hormonal determinants and disorders of peak bone mass in children. J Clin Endocrinol Metab. 2000;85(11):3951-63.
130. DiMeglio LA, Wang J, Siberry GK, Miller TL, Geffner ME, Hazra R, et al. Bone mineral density in children and adolescents with perinatal HIV infection. AIDS. 2013;27(2):211-20.
131. Theintz G, Buchs B, Rizzoli R, Slosman D, Clavien H, Sizonenko PC, et al. Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J Clin Endocrinol Metab. 1992;75(4):1060-5.
132. Hansen MA, Overgaard K, Riis BJ, Christiansen C. Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study. Brit Med J. 1991;303(6808):961-4.
133. Rizzoli R, Bonjour JP. Determinants of peak bone mass and mechanisms of bone loss. Osteoporos Int. 1999;9(Suppl 2):S17-23.
134. de Martino M, Tovo PA, Galli L, Gabiano C, Chiarelli F, Zappa M, et al. Puberty in perinatal HIV-1 infection: a multicentre longitudinal study of 212 children. AIDS. 2001;15(12):1527-34.
135. Finkelstein JS, Klibanski A, Neer RM. A longitudinal evaluation of bone mineral density in adult men with histories of delayed puberty. J Clin Endocrinol Metab. 1996;81(3):1152-5.
136. Siberry GK, Li H, Jacobson D. Fracture risk by HIV infection status in perinatally HIV-exposed children. AIDS Res Hum Retroviruses. 2012;28(3):247-50.
137. Duvivier C, Kolta S, Assoumou L, Ghosn J, Rozenberg S, Murphy RL, et al. Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS. 2009;23(7):817-24.
138. McComsey GA, Kitch D, Daar ES, Tierney C, Jahed NC, Tebas P, et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: AIDS Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203(12):1791-801.
139. Brown TT, McComsey GA, King MS, Qaqish RB, Bernstein BM, da Silva BA. Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. J Acquir Immune Defic Syndr. 2009;51(5):554-61.
140. Mora S, Sala N, Bricalli D, Zuin G, Chiumello G, Vigano A. Bone mineral loss through increased bone turnover in HIV-infected children treated with highly active antiretroviral therapy. AIDS. 2001;15(14):1823-9.
141. Hazra R, Gafni RI, Maldarelli F, Balis FM, Tullio AN, DeCarlo E, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics. 2005;116(6):846-54.
142. Purdy JB, Gafni RI, Reynolds JC, Zeichner S, Hazra R. Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus. J Pediatr. 2008;152(4):582-4.
143. Jones S, Restrepo D, Kasowitz A, Korenstein D,Wallenstein S, Schneider A, et al. Risk factors for decreased bone density and effects of HIV on bone in the elderly. Osteoporos Int. 2008;19(7):913-8.
144. Giacomet V, Mora S, Martelli L, Merlo M, Sciannamblo M, Vigano A. A 12-month treatment with tenofovir does not impair bone mineral accrual in HIV-infected children. J Acquir Immune Defic Syndr. 2005;40(4):448-50.
145. Vigano A, Zuccotti GV, Puzzovio M, Pivetti V, Zamproni I, Cerini C, et al. Tenofovir disoproxil fumarate and bone mineral density: a 60-month longitudinal study in a cohort of HIV-infected youths. Antivir Ther. 2010;15(7):1053-8.
146. Della Negra M, de Carvalho AP, de Aquino MZ, da Silva MT, Pinto J, White K, et al. A randomized study of tenofovir disoproxil fumarate in treatment-experienced HIV-1 infected adolescents. Pediatr Infect Dis J. 2012;31(5):469-73.
147. Stellbrink HJ, Orkin C, Arribas JR, Compston J, Gerstoft J, Van Wijngaerden E, et al. Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis. 2010;51(8):963-72.
148. Martin A, Bloch M, Amin J, Baker D, Cooper DA, Emery S, et al. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-Lamivudine: a randomized, 96-week trial. Clin Infect Dis. 2009;49(10):1591-601.
149. Zuccotti G, Vigano A, Gabiano C, Giacomet V, Mignone F, Stucchi S, et al. Antiretroviral therapy and bone mineral measurements in HIV-infected youths. Bone. 2010;46(6):1633-8.
150. Pitukcheewanont P, Safani D, Church J, Gilsanz V. Bone measures in HIV-1 infected children and adolescents: disparity between quantitative computed tomography and dual-energy X-ray absorptiometry measurements. Osteoporos Int. 2005;16(11):1393-6.
151. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. J Am Med Assoc. 2005;293(18):2257-64.
152. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997;337(10):670-6.
153. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669-83.
154. El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, et al. Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab. 2006;91(2):405-12.
155. Winzenberg TM, Powell S, Shaw KA, Jones G. Vitamin D supplementation for improving bone mineral density in children. Cochrane Database Syst Rev. 2010;(10):CD006944.
156. Paul TV, Asha HS, Thomas N, Seshadri MS, Rupali P, Abraham OC, et al. Hypovitaminosis D and bone mineral density in human immunodeficiency virus-infected men from India, with or without antiretroviral therapy. Endocr Pract. 2010;16(4):547-53.
157. Hileman CLD, Storer N, McComsey GA. Bone Mineral Density (BMD), vitamin D levels and inflamation markers in antiretroviral-naive HIV infected and un-infected adults (absract# 880). 19th Conference on Retroviruses and Opportunistics Infections; Seattle, WA: CROI; 2012. [cited 2013 Feb 16].
158. Dolan SE, Kanter JR, Grinspoon S. Longitudinal analysis of bone density in human immunodeficiency virus-infected women. J Clin Endocrinol Metab. 2006;91(8):2938-45.
159. Havens PL, Stephensen CB, Hazra R, Flynn PM, Wilson CM, Rutledge B, et al. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial. Clin Infect Dis. 2012;54(7):1013-25.
160. Mondy K, Yarasheski K, Powderly WG, Whyte M, Claxton S, De Marco D, et al. Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals. Clin Infect Dis. 2003;36(4):482-90.
161. Dao CN, Patel P, Overton ET, Rhame F, Pals SL, Johnson C, et al. Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D Levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population. Clin Infect Dis. 2011;52(3):396-405.
162. Arpadi S, McMahon D, Abrams E, Mahrukh B, Purswani M, Engelson E, et al. 2-year bone mass accrual in HIV+ children and adolescents after bi-monthly supplementation with oral cholecalciferol and calcium (abstract #707). 18th Conference on Retroviruses and Opportunistic Infections; Boston, MA: CROI; 2011. [cited 2013 Feb 16].
163. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81.
164. Ross AC, Judd S, Kumari M, Hileman C, Storer N, Labbato D, et al. Vitamin D is linked to carotid intima-media thickness and immune reconstitution in HIV-positive individuals. Antivir Ther. 2011;16(4):555-63.
165. Eckard AR, Judd SE, Ziegler TR, Camacho-Gonzalez AF, Fitzpatrick AM, Hadley GR, et al. Risk factors for vitamin D deficiency and relationship with cardiac biomarkers, inflammation and immune restoration in HIV-infected youth. Antivir Ther. 2012;17(6):1069-78.
166. Rutstein R, Downes A, Zemel B, Schall J, Stallings V. Vitamin D status in children and young adults with perinatally acquired HIV infection. Clin Nutr. 2011;30(5):624-8.
167. Stephensen CB, Marquis GS, Kruzich LA, Douglas SD, Aldrovandi GM, Wilson CM. Vitamin D status in adolescents and young adults with HIV infection. Am J Clin Nutr. 2006;83(5):1135-41.
168. Atkinson SBL, Patel D, Monrose C, Tudor-Williams G, Foster C. Vitamin D deficiency in children with perinatally acquired HIV-1 infection living in the UK (abstract P159). 16th Conference of British HIV Association 2010; Manchester, UK: British HIV Association; 2010. [cited 2013 Feb 16].
169. Havens PL, Mulligan K, Hazra R, Flynn P, Rutledge B, Van Loan MD, et al. Serum 25-hydroxyvitamin D response to vitamin D3 supplementation 50,000 IU monthly in youth with HIV-1 infection. J Clin Endocrinol Metab. 2012;97(11):400413.
170. Institute of Medicine (US). Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press, 2011.
171. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-30.
172. Brown TT, McComsey GA. Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D. Antivir Ther. 2010;15(3):425-9.
173. Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarasheski KE, Dusso AS. HIV-protease inhibitors impair vitamin D bioactivation to 1, 25-dihydroxyvitamin D. AIDS. 2003;17(4):513-20.
174. Longenecker CT, Hileman CO, Carman TL, Ross AC, Seydafkan S, Brown TT, et al. Vitamin D supplementation and endothelial function in vitamin D deficient HIV-infected patients: a randomized placebo-controlled trial. Antivir Ther. 2012;17(4):613-21.