Metabolic abnormalities in adult HIV infected population on antiretroviral medication in Malaysia: a cross-sectional survey

BMC Public Health

Suzana Sahar¹  Christopher Lee Kwok Choong²  Roslee Rajikan¹  Nazisa Hejazi¹ 

[1] Dietetics Program, School of Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 50300, Malaysia;Jabatan Perubatan Am, Hospital Sungai Buloh, Jalan Hospital Sungai Buloh, Selangor, Darul Ehsan, 47000, Malaysia

关键词: Malaysia;    HIV positive;    Dyslipidemia;    Cardiovascular disease;    Protease inhibitor;    ARV medication;    Fasting plasma glucose;    Metabolic abnormalities;    Lipid disorders;   

Others  :  1161924
DOI  :  10.1186/1471-2458-13-758

 received in 2013-02-15, accepted in 2013-07-31,  发布年份 2013

【 摘 要 】

Background

In the current two decades, dyslipidemia and increased blood glucose as metabolic abnormalities are the most common health threats with a high incidence among HIV/AIDS patients on antiretroviral (ARV) treatment. Scientific investigations and reports on lipid and glucose disorders among HIV infected communities are inadequate especially in those developing such as Malaysia. This cross-sectional survey was mainly aimed to evaluate the prevalence of metabolic abnormalities and associated risk factors among HIV infected population patients on ARV medication.

Methods

In a single reference health center in Malaysia, 2739 adult HIV positive patients on antiretroviral therapy (ART) were studied cross-sectionally using medical records. Besides demographic variables and associated health disorders, those factors which can change the lipid and glucose levels were collected. Logistic Regression was used to find the potential risk factors (p < 0.05).

Results

Majority of the studied population were male (81.1%) and aged between 30–49 (68.6%). Mean CD4 count was 474.25 (cells/mm³) while undetectable RNA viral load was common among 83.3 (%) of subjects. Among 1,583 patients with the recent blood lipid and glucose tests, increased levels of triglyceride (TG) and total cholesterol (TC) were frequently prevalent in half of the population as 59 (%) and 54.2 (%) while 28.7 (%), 35.1 (%) and 38.2 (%) had declined level of high-density lipoprotein (HDL), raised low-density lipoprotein (LDL) and fasting plasma glucose (FPG) which were less common. Dyslipidemia was common in 82.3 (%) of the subjects. Notably, medication with protease inhibitor (PI) was a potential risk for elevated triglyceride (odds ratio (OR) = 2.309, 95% confidence interval (CI) = 1.605–3.324, P = 0.001), high TC (OR = 1.561, 95% CI = 1.123–2.169, P = 0.008) and low HDL (OR = 1.449, 95% CI = 1.037–2.024, P = 0.029). As lifestyle factor, alcohol consumption results as significant risk factor for raised TG (OR = 2.653, 95% CI = 1.353–5.202, P = 0.004). Also having hepatitis raised risk of high FPG level (OR = 1.630, 95% CI = 1.197-2.220, P = 0.002) in this sample population.

Conclusions

Dyslipidemia is highly common in Malaysian HIV subjects receiving ARV medication. Lifestyle modification, changing PI and switch to other ARV regimen can help in reduction of these abnormalities. Also suitable strategies and plans are necessary to prevent cardiovascular diseases in future.

【 授权许可】

   
2013 Hejazi et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]The Joint United Nations Programme on HIV/AIDS: Global report: UNAIDS report on the global AIDS epidemic. 2012. http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/20121120_unaids_global_report_2012_with_annexes_en.pdf webcite. Accessed 10 November 2013.
• [2]Ministry of Health, Malaysia: Global AIDS Response 2012 Progress Report. Reporting Period: January 2010-december 2011. Putrajaya: Ministry of Health Malaysia; 2012.
• [3]World Bank: Countryclassification. http://data.worldbank.org/country/malaysia webcite. Accessed 10 November 2012
• [4]World Health Organization, The Joint United Nations Programme on HIV/AIDS and The United Nations Children’s Fund: Global HIV/AIDS response: epidemic update and health sector progress towards universal access: progress report 2011. Geneva: World Health Organization; 2011.
• [5]World Health Organization: Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. – 2010 rev. Geneva: World Health Organization; 2010.
• [6]Srivanich N, Ngarmukos C, Sungkanuparph S: Prevalence of and risk factors for pre-diabetes in HIV-1-infected patients in Bangkok, Thailand. JIAPAC 2010, 9(6):358-361.
• [7]Idiculla J, Ravindra’n GD, D’Souza J, Singh G, Furruqh S: Diabetes mellitus, insulin resistance, and metabolic syndrome in HIV-positive patients in South India. Int J Gen Med 2011, 4:73.
• [8]Sinxadi PZ, McIlleron HM, Dave JA, Smith PJ, Levitt NS, Maartens G: Association of lopinavir concentrations and plasma lipid or glucose concentrations in HIV-infected South Africans. AIDS Res Ther 2012, 9(1):32. BioMed Central Full Text
• [9]Wu PY, Hung CC, Liu WC, Hsieh CY, Sun HY, Lu CL, Chien KL: Metabolic syndrome among HIV-infected Taiwanese patients in the era of highly active antiretroviral therapy: prevalence and associated factors. J Antimicrob Chemother 2012, 67(4):1001-1009.
• [10]Butt AA, Fultz SL, Kwoh CK, Kelley D, Skanderson M, Justice AC: Risk of diabetes in HIV infected veterans pre‒and post‒HAART and the role of HCV coinfection. Hepatology 2004, 40(1):115-119.
• [11]Samaras K, Wand H, Law M, Emery S, Cooper D, Carr A: Prevalence of metabolic syndrome in HIV-infected patients receiving highly active antiretroviral therapy using international diabetes foundation and adult treatment panel III criteria associations with insulin resistance, disturbed body fat compartmentalization, elevated C-reactive protein, and hypoadiponectinemia. Diabetes Care 2007, 30(1):113-119.
• [12]De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, Phillips A: Incidence and risk factors for new-onset diabetes in HIV-infected patients the data collection on adverse events of anti-HIV drugs (D: A: D) study. Diabetes Care 2008, 31(6):1224-1229.
• [13]Capeau J, Bouteloup V, Katlama C, Bastard JP, Guiyedi V, Salmon-Ceron D, Chêne G: Ten-year diabetes incidence in 1046 HIV-infected patients started on a combination antiretroviral treatment. AIDS 2012, 26(3):303.
• [14]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.
• [15]Hiransuthikul N, Hiransuthikul P, Kanasook Y: Lipid profiles of Thai adult HIV-infected patients receiving protease inhibitors. Southeast Asian J Trop Med Public Health 2007, 38(1):69-77.
• [16]Manuthu EM, Joshi MD, Lule GN, Karari E: Prevalence of dyslipidemia and dysglycaemia in HIV infected patients. E AFR MED J 2008, 85(1):10-17.
• [17]Yone EWP, Kengne AP, Ashuntantang G, Betyoumin AF, Ngogang J: Dyslipidaemia in HIV-1-infected patients receiving protease inhibitors after initial treatment with first-line-based non-nucleoside reverse transcriptase inhibitors: a cross-sectional study. BMJ open 2012, 2(4):1-5.
• [18]Friis-Moller N, Weber R, Reiss P, Thiébaut R, Kirk O, Monforte ADA, Lundgren JD: Cardiovascular disease risk factors in HIV patients-association with antiretroviral therapy:Results from the DAD study. Aids 2003, 17(8):1179-1193.
• [19]Tadewos A, Addis Z, Ambachew H, Banerjee S: Prevalence of dyslipidemia among HIV-infected patients using first-line highly active antiretroviral therapy in Southern Ethiopia: a cross-sectional comparative group study. AIDS Res Ther 2012, 9(1):31. BioMed Central Full Text
• [20]Fontas E, Van Leth F, Sabin CA, Friis-Møller N, Rickenbach M, DA Monforte A, Reiss P: Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect Dis 2004, 189(6):1056-1074.
• [21]Carr A, Samaras K, Chisholm DJ, Cooper DA: Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1998, 351(9119):1881.
• [22]Carr A: HIV protease inhibitor-related lipodystrophy syndrome. Clin Infect Dis 2000, 30(Supplement 2):S135-S142.
• [23]Currier JS, Lundgren JD, Carr A, Klein D, Sabin CA, Sax PE, Smieja M: Epidemiological evidence for cardiovascular disease in HIV-infected patients and relationship to highly active antiretroviral therapy. Circulation 2008, 118(2):e29-e35.
• [24]Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, Dobs AS: Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med 2005, 165(10):1179.
• [25]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):2506-2512.
• [26]MacInnes A, Lazzarin A, Di Perri G, Sierra-Madero JG, Aberg J, Heera J, Valdez H: Maraviroc can improve lipid profiles in dyslipidemic patients with HIV: results from the MERIT trial. HCT 2011, 12(1):24-36.
• [27]Friis-Moller N, Sabin CA, Weber R, D’ArminioMonforte A, El-Sadr WM, Reiss P, Lundgren JD: Combination antiretroviral therapy and the risk of myocardial infarction. New Engl J Med 2003, 349(21):1993-2003.
• [28]Biron A, Bobin-Dubigeon C, Volteau C, Piroth L, Perré P, Leport C, Biron C: Metabolic syndrome in French HIV-infected patients: prevalence and predictive factors after 3 years of antiretroviral therapy. AIDS Res Hum Retroviruses 2012, 28(12):1672-1678.
• [29]Mallon PW, Wand H, Law M, Miller J, Cooper DA, Carr A: Buffalo hump seen in HIV-associated lipodystrophy is associated with hyperinsulinemia but not dyslipidemia. JAIDS 2005, 38(2):156-162.
• [30]Law MG, Friis‒Moller N, El-Sadr WM, Weber R, Reiss P, d’ArminioMonforte A, Lundgren JD: The use of the Framingham equation to predict myocardial infarctions in HIV‒infected patients: comparison with observed events in the D: A: D Study. HIV Med 2006, 7(4):218-230.
• [31]Achhra AC, Amin J, Hoy J, Tanuma J, Sirisanthana T, Nolan D, Giles M: Differences in lipid measurements by antiretroviral regimen exposure in cohorts from Asia and Australia. AIDS Res Ther 2012, 2012:1-9.
• [32]Estrada V, Bernardino JI, Casado JL, Domingo P, Masiá M, Iribarren JA, Santos J: Prevalence of cardiovascular risk factors in Spanish HIV-infected patients on antiretroviral therapy.The CORONATOR Study [Abstract]. In Proceedings of the XIX International AIDS Conference 22–27 July 2012. Washingtone DC; http://pag.aids2012.org/Abstracts.aspx?AID=15438 webcite
• [33]Kerr SJ, Duncombe C, Avihingsanon A, Ananworanich J, Boyd M, Sopa B, Ruxrungtham K: Dyslipidemia in an Asian population after treatment for two years with protease inhibitor-containing regimens. JIAPAC 2007, 6(1):36-46.
• [34]Domigos H, Cunha RVD, Paniago AMM, Martins DM, Elkhoury EB, Souza ASD: Metabolic effects associated to the highly active antiretroviral therapy (HAART) in AIDS patients. Braz J Infect Dis 2009, 13(2):130-136.
• [35]Armstrong C, Liu E, Grinspoon S, Okuma J, Spiegelman D, Guerino C, Hawkins C: Dyslipidemia in an HIV-positive, antiretroviral treatment-naïve population in Dar es Salaam, Tanzania. J Acquir Immune Defic Syndr 2011, 57(2):141.
• [36]Julius H, Basu D, Ricci E, Wing J, KusariBasu J, Pocaterra D, Bonfanti P: The burden of metabolic diseases amongst HIV positive patients on HAART attending the Johannesburg Hospital. Curr HIV Res 2012, 9(4):247-252.
• [37]Omech B, Sempa J, Castelnuovo B, Opio K, Otim M, Mayanja-Kizza H, Manabe YC: Prevalence of HIV-associated metabolic abnormalities among patients taking first-line antiretroviral therapy in Uganda. ISRN AIDS 2012, 2012:1-6.
• [38]Pharm SPMI: Prevalence of lipodystrophy in Thai-HIV infected patients. J Med Assoc Thai 2004, 87(6):605-611.
• [39]Homsanit M, Nelson KE, Sonjai A, Anekthananon T, Suwanagool S, Cofrancesco J Jr: Body shape and metabolic abnormalities in Thai HIV-infected patients. AIDS Res Hum Retroviruses 2007, 23(11):1314-1321.
• [40]Mankhatitham W, Luaengniyomkul A, Manosuthi W: Lipid profile changes in Thai HIV and tuberculosis co-infected patients receiving non-nucleoside reverse transcriptase inhibitors-based antiretroviral therapy. Journal of the Medical Association of Thailand. Chotmaihetthangphaet 2012, 95(2):163.
• [41]Pujari SN, Dravid A, Naik E, Bhagat S, Tash K, Nadler JP, Sinnott JT: Lipodystrophy and dyslipidemia among patients taking first-line, World Health Organization-recommended highly active antiretroviral therapy regimens in Western India. JAIDS 2005, 39(2):199-202.
• [42]Padmapriyadarsini C, Kumar SR, Terrin N, Narendran G, Menon PA, Ramachandran G, Swaminathan S: Dyslipidemia among HIV-infected patients with tuberculosis taking once-daily nonnucleoside reverse-transcriptase inhibitor–based antiretroviral therapy in India. Clin Infect Dis 2011, 52(4):540-546.
• [43]Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of LDL-cholesterol. Clin Chem 1972, 18(6):499-515.
• [44]National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation 2001, 106:3143-3421.
• [45]Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant D, Conference Participants: Definition of metabolic syndrome: report of the national, heart, lung, and blood institute/american heart association conference on scientific issues related to definition. Circulation 2004, 109:433-438.
• [46]Grundy SM, Cleeman JI, Daniels SR: Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement. Circulation 2005, 112(17):2735-2752.
• [47]Centre for Disease Control and Prevention (CDC): Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992, 41(RR-17):1-19.
• [48]Saag MS, Holodniy M, Kuritzkes DR: HIV viral load markers in clinical practice: recommendations of an International AIDS Society-USA Expert Panel. Nat Med 1996, 2:625-629.
• [49]SPSS 16.0: Statistical package for the social sciences 16.0. Chicago, Illinois: SPSS Inc; 2007.
• [50]Chuapai Y, Kiertiburanakul S, Malathum K, Sungkanuparph S: Lipodystrophy and dyslipidemia in human immunodeficiency virus-infected Thai patients receiving antiretroviral therapy. J Med Assoc Thai 2007, 90(3):452-458.
• [51]Carpentier A, Patterson BW, Uffelman KD, Salit I, Lewis GF: Mechanism of highly active anti-retroviral therapy-induced hyperlipidemia in HIV-infected individuals. Atherosclerosis 2005, 178(1):165-172.
• [52]Shahmanesh M, Das S, Stolinski M, Shojaee-Moradie F, Jackson NC, Jefferson W, Umpleby AM: Antiretroviral treatment reduces very-low-density lipoprotein and intermediate-density lipoprotein apolipoprotein B fractional catabolic rate in human immunodeficiency virus-infected patients with mild dyslipidemia. Clin Endocrinol Metab 2005, 90(2):755-760.
• [53]Reeds DN, Yarasheski KE, Fontana L, Cade WT, Laciny E, DeMoss A, Klein S: Alterations in liver, muscle, and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia. Am J Physiol Endocrinol Metab 2006, 290(1):E47-E53.
• [54]Lenhard JM, Croom DK, Weiel JE, Winegar DA: HIV protease inhibitors stimulate hepatic triglyceride synthesis. Arterioscler Thromb Vasc Biol 2000, 20(12):2625-2629.
• [55]Petit JM, Duong M, Duvillard L, Florentin E, Portier H, Lizard G, Verges B: LDL‒receptors expression in HIV‒infected patients: relations to antiretroviral therapy, hormonal status, and presence of lipodystrophy. Am J Physiol EndocrinolMetab 2002, 32(5):354-359.
• [56]Hruz PW, Murata H, Mueckler M: Adverse metabolic consequences of HIV protease inhibitor therapy: the search for a central mechanism. Am J Physiol Endocrinol Metab 2001, 280(4):E549-E553.
• [57]Couteur L, David G, Cogger VC, Mccuskey RS, De Cabo RAFAEL, Smedsrod B, Fraser R: Age‒related changes in the liver sinusoidal endothelium. Ann N Y Acad Sci 2007, 1114(1):79-87.
• [58]Habib SS, Aslam M, Hameed W: Gender differences in Lipids and Lipoprotein (A) profiles in healthy individuals and patients with type 2 Diabetes Mellitus. Pak J Physiol 2005, 1:1-2.
• [59]Richter A, Pladevall M, Manjunath R, Lafata JE, Xi H, Simpkins J, Irish W: Patient characteristics and costs associated with dyslipidaemia and related conditions in HIV‒infected patients: a retrospective cohort study. HIV Med 2005, 6(2):79-90.
• [60]Foulkes AS, Woh DA, Frank I, Puleo E, Restine S, Megan LW: Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy. PLoS Med 2006, 3(3):0337-0347.
• [61]Gibert CL, Shlay JC, Sharma S, Bartsch G, Peng G, Grunfeld C: Racial differences in changes of metabolic parameters and body composition in antiretroviral therapy-naive persons initiating antiretroviral therapy. JAIDS 2009, 50(1):44-53.
• [62]Hejazi N, Lee MHS, Lin KG, Choong CLK: Factors associated with abdominal obesity among HIV-infected adults on antiretroviral therapy in Malaysia. GJHS 2010, 2(2):20.
• [63]Clerc O, Nanchen D, Cornuz J, Marques-Vidal P, Gmel G, Daeppen JB, Rodondi N: Alcohol drinking, the metabolic syndrome and diabetes in a population with high mean alcohol consumption. Diabetic Med 2010, 27(11):1241-1249.
• [64]Domingo P, Suarez-Lozano I, Teir R, Lozano F, Terrón A, Viciana P, Garrido M: Dyslipidemia and cardiovascular disease risk factor management in HIV-1-infected subjects treated with HAART in the Spanish VACH cohort. Open AIDS J 2008, 2:26.
• [65]Scott R, O’Brien R, Fulcher G, Pardy C, D’Emden M, Tse D, Keech A: Effects of fenofibrate treatment On cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome the fenofibrate intervention and event lowering in diabetes (FIELD) study. Diabetes Care 2009, 32(3):493-498.
• [66]Perlemuter G, Sabile A, Letteron P, Vona G, Topilco A, Chrétien Y, Bréchot C: Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. The FASEB J 2002, 16(2):185-194.
• [67]Marzouk D, Sass J, Bakr I, El Hosseiny M, Abdel-Hamid M, Rekacewicz C, Fontanet A: Metabolic and cardiovascular risk profiles and hepatitis C virus infection in rural Egypt. Gut 2007, 56(8):1105-1110.
• [68]Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, Koike K: Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 2004, 126(3):840-848.