The Impact of Weight Gain During HIV Treatment on Risk of Pre-diabetes, Diabetes Mellitus, Cardiovascular Disease, and Mortality

Shejil Kumar, Katherine Samaras, Shejil Kumar, Katherine Samaras

Abstract

Since the introduction of combined antiretroviral therapy (cART) and more effective treatments for AIDS, there has been a dramatic shift from the weight loss and wasting that characterised HIV/AIDS (and still does in countries where cART is not readily available or is initiated late) to healthy weight, or even overweight and obesity at rates mirroring those seen in the general population. These trends are attributable to several factors, including the "return to health" weight gain with reversal of the catabolic effects of HIV-infection following cART-initiation, strategies for earlier cART-initiation in the course of HIV-infection which have prevented many people living with HIV-infection from developing wasting, in addition to exposure to the modern obesogenic environment. Older cART regimens were associated with increased risk of body fat partitioning disorders (lipodystrophy) and cardiometabolic complications including atherothrombotic cardiovascular disease (CVD) and diabetes mellitus. Whilst cART now avoids those medications implicated in causing lipodystrophy, long-term cardiometabolic data on more modern cART regimens are lacking. Longitudinal studies show increased rates of incident CVD and diabetes mellitus with weight gain in treated HIV-infection. Abdominal fat gain, weight gain, and rising body mass index (BMI) in the short-term during HIV treatment was found to increase incident diabetes risk. Rising BMI was associated with increased risk of incident CVD, however the relationship varied depending on pre-cART BMI category. In contrast, a protective association with mortality is evident, predominantly in the underweight and in resource-poor settings, where weight gain reflects access to cART and virological suppression. The question of how to best evaluate, manage (and perhaps constrain) weight gain during HIV treatment is of clinical relevance, especially in the current climate of increasingly widespread cART use, rising overweight, and obesity prevalence and growing metabolic and cardiovascular disease burden in people living with HIV-infection. Large prospective studies to further characterise the relationship between weight gain during HIV treatment and risk of diabetes, CVD and mortality are required.

Keywords: HIV; cART; cardiovascular disease (CVD); diabetes; mortality; obesity; weight gain.

Figures

Figure 1
Figure 1
The intersection of the modern obesity epidemic and historical changes in HIV-infection prescription and timing and their contribution to weight gain and redistribution during HIV treatment.

References

    1. Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harbor Perspect Med. (2011) 1:a006841. 10.1101/cshperspect.a006841
    1. UNAIDS Fact Sheet—Latest Statistics on the Status of the AIDS Epidemic (2018). Available online at: (Accessed March 29, 2018).
    1. Lohse N. The road to success. Long-term prognosis for persons living with HIV in Denmark—Time trends and risk factors. Danish Med J. (2016) 63:B5210.
    1. Sabin CA. Do people with HIV infection have a normal life expectancy in the era of combination antiretroviral therapy? BMC Med. (2013) 11:251. 10.1186/1741-7015-11-251
    1. WHO Guideline on When to Start Antiretroviral Therapy and on Pre-exposure Prophylaxis for HIV (2015). Available online at: (Accessed March 29, 2018).
    1. UNAIDS . 90-90-90: Treatment for All (2018). Available online at: (Accessed March 29, 2018).
    1. Hontelez JA, de Vlas SJ, Tanser F, Bakker R, Barnighausen T, Newell ML, et al. . The impact of the new WHO antiretroviral treatment guidelines on HIV epidemic dynamics and cost in South Africa. PLoS ONE (2011) 6:e21919. 10.1371/journal.pone.0021919
    1. Department WHOHA. New WHO Recommendations: Antiretroviral Therapy for Adults and Adolescents (2018). Available online at: (Accessed April 13, 2018).
    1. Doherty M, Ford N, Vitoria M, Weiler G, Hirnschall G. The 2013 WHO guidelines for antiretroviral therapy: evidence-based recommendations to face new epidemic realities. Curr Opin HIV AIDS (2013) 8:528–34. 10.1097/COH.0000000000000008
    1. Dutta A, Barker C, Kallarakal A. The HIV treatment gap: estimates of the financial resources needed versus available for scale-up of antiretroviral therapy in 97 countries from 2015 to 2020. PLoS Med. (2015) 12:e1001907. 10.1371/journal.pmed.1001907
    1. Hill A, Pozniak A. HIV treatment cascades: how can all countries reach the UNAIDS 90-90-90 target? AIDS (2015) 29:2523–5. 10.1097/QAD.0000000000000864
    1. Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet (1998) 351:1881–3. 10.1016/S0140-6736(98)03391-1
    1. Nansseu JR, Bigna JJ, Kaze AD, Noubiap JJ. Incidence and risk factors for prediabetes and diabetes mellitus among HIV infected adults on antiretroviral therapy: systematic review and meta-analysis. Epidemiology (2018) 29:431–41. 10.1097/EDE.0000000000000815
    1. Friis-Moller N, Sabin CA, Weber R, d'Arminio Monforte A, El-Sadr WM, Reiss P, et al. . Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. (2003) 349:1993–2003. 10.1056/NEJMoa030218
    1. Mallon PW, Unemori P, Sedwell R, Morey A, Rafferty M, Williams K, et al. . In vivo, nucleoside reverse-transcriptase inhibitors alter expression of both mitochondrial and lipid metabolism genes in the absence of depletion of mitochondrial DNA. J Infect Dis. (2005) 191:1686–96. 10.1086/429697
    1. Tate T, Willig AL, Willig JH, Raper JL, Moneyham L, Kempf MC, et al. . HIV infection and obesity: where did all the wasting go? Antiviral Ther. (2012) 17:1281–9. 10.3851/IMP2348
    1. Yuh B, Tate J, Butt AA, Crothers K, Freiberg M, Leaf D, et al. . Weight change after antiretroviral therapy and mortality. Clin Infect Dis. (2015) 60:1852–9. 10.1093/cid/civ192
    1. Dulloo AG, Jacquet J, Seydoux J, Montani JP. The thrifty ‘catch-up fat' phenotype: its impact on insulin sensitivity during growth trajectories to obesity and metabolic syndrome. Int J Obes. (2006) 30 (Suppl. 4):S23–35. 10.1038/sj.ijo.0803516
    1. Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, et al. . Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr. (2000) 23:35–43. 10.1097/00126334-200001010-00005
    1. Koethe JR, Jenkins CA, Lau B, Shepherd BE, Justice AC, Tate JP, et al. . Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada. AIDS Res Hum Retroviruses (2016) 32:50–8. 10.1089/aid.2015.0147
    1. Crum-Cianflone N, Tejidor R, Medina S, Barahona I, Ganesan A. Obesity among patients with HIV: the latest epidemic. AIDS Patient Care STDs (2008) 22:925–30. 10.1089/apc.2008.0082
    1. Crum-Cianflone N, Roediger MP, Eberly L, Headd M, Marconi V, Ganesan A, et al. . Increasing rates of obesity among HIV-infected persons during the HIV epidemic. PLoS ONE (2010) 5:e10106. 10.1371/journal.pone.0010106
    1. Pernerstorfer-Schoen H, Schindler K, Parschalk B, Schindl A, Thoeny-Lampert S, Wunderer K, et al. . Beneficial effects of protease inhibitors on body composition and energy expenditure: a comparison between HIV-infected and AIDS patients. AIDS (1999) 13:2389–96. 10.1097/00002030-199912030-00010
    1. Carbonnel F, Maslo C, Beaugerie L, Carrat F, Wirbel E, Aussel C, et al. . Effect of indinavir on HIV-related wasting. AIDS (1998) 12:1777–84. 10.1097/00002030-199814000-00009
    1. Silva M, Skolnik PR, Gorbach SL, Spiegelman D, Wilson IB, Fernandez-DiFranco MG, et al. . The effect of protease inhibitors on weight and body composition in HIV-infected patients. AIDS (1998) 12:1645–51. 10.1097/00002030-199813000-00012
    1. McDermott AY, Terrin N, Wanke C, Skinner S, Tchetgen E, Shevitz AH. CD4+ cell count, viral load, and highly active antiretroviral therapy use are independent predictors of body composition alterations in HIV-infected adults: a longitudinal study. Clin Infect Dis. (2005) 41:1662–70. 10.1086/498022
    1. Jones CY, Hogan JW, Snyder B, Klein RS, Rompalo A, Schuman P, et al. . Overweight and human immunodeficiency virus (HIV) progression in women: associations HIV disease progression and changes in body mass index in women in the HIV epidemiology research study cohort. Clin Infect Dis. (2003) 37 (Suppl. 2):S69–80. 10.1086/375889
    1. Taylor BS, Liang Y, Garduno LS, Walter EA, Gerardi MB, Anstead GM, et al. . High risk of obesity and weight gain for HIV-infected uninsured minorities. J Acquir Immune Defic Syndr. (2014) 65:e33–40. 10.1097/QAI.0000000000000010
    1. Lakey W, Yang LY, Yancy W, Chow SC, Hicks C. Short communication: from wasting to obesity: initial antiretroviral therapy and weight gain in HIV-infected persons. AIDS Res Hum Retroviruses (2013) 29:435–40. 10.1089/aid.2012.0234
    1. Bares SH, Smeaton LM, Xu A, Godfrey C, McComsey GA. HIV-infected women gain more weight than HIV-infected men following the initiation of antiretroviral therapy. J Women's Health (2018) 27:1162–9. 10.1089/jwh.2017.6717
    1. Mave V, Erlandson KM, Gupte N, Balagopal A, Asmuth DM, Campbell TB, et al. . Inflammation and change in body weight with antiretroviral therapy initiation in a multinational cohort of HIV-infected adults. J Infect Dis. (2016) 214:65–72. 10.1093/infdis/jiw096
    1. Shikuma CM, Zackin R, Sattler F, Mildvan D, Nyangweso P, Alston B, et al. . Changes in weight and lean body mass during highly active antiretroviral therapy. Clin Infect Dis. (2004) 39:1223–30. 10.1086/424665
    1. Erlandson KM, Kitch D, Tierney C, Sax PE, Daar ES, Tebas P, et al. . Weight and lean body mass change with antiretroviral initiation and impact on bone mineral density. AIDS (2013) 27:2069–79. 10.1097/QAD.0b013e328361d25d
    1. Achhra AC, Mocroft A, Reiss P, Sabin C, Ryom L, de Wit S, et al. . Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study. HIV Med. (2016) 17:255–68. 10.1111/hiv.12294
    1. Falutz J. Management of fat accumulation in patients with HIV infection. Curr HIV/AIDS Rep. (2011) 8:200–8. 10.1007/s11904-011-0087-3
    1. da Cunha J, Maselli LM, Stern AC, Spada C, Bydlowski SP. Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: old and new drugs. World J Virol. (2015) 4:56–77. 10.5501/wjv.v4.i2.56
    1. Paruthi J, Gill N, Mantzoros CS. Adipokines in the HIV/HAART-associated lipodystrophy syndrome. Metabolism (2013) 62:1199–205. 10.1016/j.metabol.2013.04.014
    1. Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. (2005) 352:48–62. 10.1056/NEJMra041811
    1. Sattler FR. Pathogenesis and treatment of lipodystrophy: what clinicians need to know. Top HIV Med. (2008) 16:127–33.
    1. Esfahani M, Movahedian A, Baranchi M, Goodarzi MT. Adiponectin: an adipokine with protective features against metabolic syndrome. Iran J Basic Med Sci. (2015) 18:430–42. 10.22038/ijbms.2015.4404
    1. Freitas P, Carvalho D, Santos AC, Madureira AJ, Martinez E, Pereira J, et al. . Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome. BMC Infect Dis. (2014) 14:347. 10.1186/1471-2334-14-347
    1. Kosmiski LA, Bacchetti P, Kotler DP, Heymsfield SB, Lewis CE, Shlipak MG, et al. . Relationship of fat distribution with adipokines in human immunodeficiency virus infection. J Clin Endocrinol Metab. (2008) 93:216–24. 10.1210/jc.2007-1155
    1. Morimoto HK, Simao AN, de Almeida ER, Ueda LT, Oliveira SR, de Oliveira NB, et al. . Role of metabolic syndrome and antiretroviral therapy in adiponectin levels and oxidative stress in HIV-1 infected patients. Nutrition (2014) 30:1324–30. 10.1016/j.nut.2014.03.017
    1. Moure R, Domingo P, Gallego-Escuredo JM, Villarroya J, Gutierrez Mdel M, Mateo MG, et al. . Impact of elvitegravir on human adipocytes: alterations in differentiation, gene expression and release of adipokines and cytokines. Antiviral Res. (2016) 132:59–65. 10.1016/j.antiviral.2016.05.013
    1. Guaraldi G, Stentarelli C, Zona S, Santoro A. HIV-associated lipodystrophy: impact of antiretroviral therapy. Drugs (2013) 73:1431–50. 10.1007/s40265-013-0108-1
    1. Taramasso L, Ricci E, Menzaghi B, Orofino G, Passerini S, Madeddu G, et al. . Weight gain: a possible side effect of all antiretrovirals. Open Forum Infect Dis. (2017) 4:ofx239. 10.1093/ofid/ofx239
    1. Bigoloni A, Gianotti N, Spagnuolo V, Galli L, Nozza S, Cossarini F, et al. . Long-term glucose tolerance in highly experienced HIV-infected patients receiving nucleoside analogue-sparing regimens. AIDS (2012) 26:1837–40. 10.1097/QAD.0b013e32835705dd
    1. Cooper DA, Cordery DV, Reiss P, Henry K, Nelson M, O'Hearn M, et al. . The effects of enfuvirtide therapy on body composition and metabolic parameters over 48 weeks in the TORO body imaging substudy. HIV Med. (2011) 12:31–9. 10.1111/j.1468-1293.2010.00845.x
    1. Zhao H, Goetz MB. Complications of HIV infection in an ageing population: challenges in managing older patients on long-term combination antiretroviral therapy. J Antimicrob Chemother. (2011) 66:1210–4. 10.1093/jac/dkr058
    1. Kirk JB, Goetz MB. Human immunodeficiency virus in an aging population, a complication of success. J Am Geriatr Soc. (2009) 57:2129–38. 10.1111/j.1532-5415.2009.02494.x
    1. Amorosa V, Synnestvedt M, Gross R, Friedman H, MacGregor RR, Gudonis D, et al. . A tale of 2 epidemics: the intersection between obesity and HIV infection in Philadelphia. J Acquir Immune Defic Syndr. (2005) 39:557–61.
    1. Vance DE, Mugavero M, Willig J, Raper JL, Saag MS. Aging with HIV: a cross-sectional study of comorbidity prevalence and clinical characteristics across decades of life. J Assoc Nurses AIDS Care (2011) 22:17–25. 10.1016/j.jana.2010.04.002
    1. Patel AV, Hildebrand JS, Gapstur SM. Body mass index and all-cause mortality in a large prospective cohort of white and black U.S. adults. PLoS ONE (2014) 9:e109153. 10.1371/journal.pone.0109153
    1. Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology (2007) 132:2087–102. 10.1053/j.gastro.2007.03.052
    1. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA (2013) 309:71–82. 10.1001/jama.2012.113905
    1. Reaven GM. Insulin resistance: the link between obesity and cardiovascular disease. Med Clin N Am. (2011) 95:875–92. 10.1016/j.mcna.2011.06.002
    1. Lake JE. The fat of the matter: obesity and visceral adiposity in treated HIV infection. Curr HIV/AIDS Rep. (2017) 14:211–9. 10.1007/s11904-017-0368-6
    1. Shuter J, Chang CJ, Klein RS. Prevalence and predictive value of overweight in an urban HIV care clinic. J Acquir Immune Defic Syndr. (2001) 26:291–7. 10.1097/00042560-200103010-00013
    1. Blashill AJ, Mayer KH, Crane HM, Grasso C, Safren SA. Body mass index, immune status, and virological control in HIV-infected men who have sex with men. J Int Assoc Providers AIDS Care (2013) 12:319–24. 10.1177/2325957413488182
    1. Shor-Posner G, Campa A, Zhang G, Persaud N, Miguez-Burbano MJ, Quesada J, et al. . When obesity is desirable: a longitudinal study of the Miami HIV-1-infected drug abusers (MIDAS) cohort. J Acquir Immune Defic Syndr. (2000) 23:81–8. 10.1097/00126334-200001010-00011
    1. Sharma A, Hoover DR, Shi Q, Gustafson D, Plankey MW, Hershow RC, et al. . Relationship between body mass index and mortality in HIV-infected HAART users in the women's interagency HIV study. PLoS ONE (2015) 10:e0143740. 10.1371/journal.pone.0143740
    1. Crum-Cianflone NF, Roediger M, Eberly LE, Vyas K, Landrum ML, Ganesan A, et al. . Obesity among HIV-infected persons: impact of weight on CD4 cell count. AIDS (2010) 24:1069–72. 10.1097/QAD.0b013e328337fe01
    1. Koethe JR, Jenkins CA, Shepherd BE, Stinnette SE, Sterling TR. An optimal body mass index range associated with improved immune reconstitution among HIV-infected adults initiating antiretroviral therapy. Clin Infect Dis. (2011) 53:952–60. 10.1093/cid/cir606
    1. Womack J, Tien PC, Feldman J, Shin JH, Fennie K, Anastos K, et al. . Obesity and immune cell counts in women. Metabolism (2007) 56:998–1004. 10.1016/j.metabol.2007.03.008
    1. Quach LA, Wanke CA, Schmid CH, Gorbach SL, Mwamburi DM, Mayer KH, et al. . Drug use and other risk factors related to lower body mass index among HIV-infected individuals. Drug Alcohol Depend. (2008) 95:30–6. 10.1016/j.drugalcdep.2007.12.004
    1. McMahon CN, Petoumenos K, Hesse K, Carr A, Cooper DA, Samaras K. High rates of incident diabetes and prediabetes are evident in men with treated HIV followed for 11 years. AIDS (2018) 32:451–9. 10.1097/QAD.0000000000001709
    1. Herrin M, Tate JP, Akgun KM, Butt AA, Crothers K, Freiberg MS, et al. . Weight gain and incident diabetes among HIV-infected veterans initiating antiretroviral therapy compared with uninfected individuals. J Acquir Immune Defic Syndr. (2016) 73:228–36. 10.1097/QAI.0000000000001071
    1. Madec Y, Szumilin E, Genevier C, Ferradini L, Balkan S, Pujades M, et al. . Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries. AIDS (2009) 23:853–61. 10.1097/QAD.0b013e32832913ee
    1. Sudfeld CR, Isanaka S, Mugusi FM, Aboud S, Wang M, Chalamilla GE, et al. . Weight change at 1 mo of antiretroviral therapy and its association with subsequent mortality, morbidity, and CD4 T cell reconstitution in a Tanzanian HIV-infected adult cohort. Am J Clin Nutr. (2013) 97:1278–87. 10.3945/ajcn.112.053728
    1. Koethe JR, Lukusa A, Giganti MJ, Chi BH, Nyirenda CK, Limbada MI, et al. . Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia. J Acquir Immune Defic Syndr. (2010) 53:507–13. 10.1097/QAI.0b013e3181b32baf
    1. Samaras K. The burden of diabetes and hyperlipidemia in treated HIV infection and approaches for cardiometabolic care. Curr HIV/AIDS Rep. (2012) 9:206–17. 10.1007/s11904-012-0124-x
    1. Samaras K. Prevalence and pathogenesis of diabetes mellitus in HIV-1 infection treated with combined antiretroviral therapy. J Acquir Immune Defic Syndr. (2009) 50:499–505. 10.1097/QAI.0b013e31819c291b
    1. Slama L, Palella FJ, Jr., Abraham AG, Li X, Vigouroux C, Pialoux G, et al. . Inaccuracy of haemoglobin A1c among HIV-infected men: effects of CD4 cell count, antiretroviral therapies and haematological parameters. J Antimicrob Chemother. (2014) 69:3360–7. 10.1093/jac/dku295
    1. Seang S, Lake JE, Tian F, Anastos K, Cohen MH, Tien PC. Oral Glucose Tolerance Testing identifies HIV+ infected women with Diabetes Mellitus (DM) not captured by standard DM definition. J AIDS Clin Res. (2016) 7:545 10.4172/2155-6113.1000545
    1. Coelho AR, Moreira FA, Santos AC, Silva-Pinto A, Sarmento A, Carvalho D, et al. . Diabetes mellitus in HIV-infected patients: fasting glucose, A1c, or oral glucose tolerance test—which method to choose for the diagnosis? BMC Infect Dis. (2018) 18:309. 10.1186/s12879-018-3221-7
    1. Petoumenos K, Worm SW, Fontas E, Weber R, De Wit S, Bruyand M, et al. . Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. J Int AIDS Soc. (2012) 15:17426. 10.7448/IAS.15.2.17426
    1. Willig AL, Overton ET. Metabolic complications and glucose metabolism in HIV infection: a review of the evidence. Curr HIV/AIDS Rep. (2016) 13:289–96. 10.1007/s11904-016-0330-z
    1. Kalra S, Agrawal N. Diabetes and HIV: current understanding and future perspectives. Curr Diab Rep. (2013) 13:419–27. 10.1007/s11892-013-0369-9
    1. Hruz PW. Molecular mechanisms for insulin resistance in treated HIV-infection. Best Pract Res Clin Endocrinol Metab. (2011) 25:459–68. 10.1016/j.beem.2010.10.017
    1. Brinkman K, ter Hofstede HJ, Burger DM, Smeitink JA, Koopmans PP. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS (1998) 12:1735–44. 10.1097/00002030-199814000-00004
    1. Noor MA, Seneviratne T, Aweeka FT, Lo JC, Schwarz JM, Mulligan K, et al. . Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study. AIDS (2002) 16:F1–8. 10.1097/00002030-200203290-00002
    1. Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem. (2000) 275:20251–4. 10.1074/jbc.C000228200
    1. Murata H, Hruz PW, Mueckler M. Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS (2002) 16:859–63. 10.1097/00002030-200204120-00005
    1. Hresko RC, Hruz PW. HIV protease inhibitors act as competitive inhibitors of the cytoplasmic glucose binding site of GLUTs with differing affinities for GLUT1 and GLUT4. PLoS ONE (2011) 6:e25237. 10.1371/journal.pone.0025237
    1. Hertel J, Struthers H, Horj CB, Hruz PW. A structural basis for the acute effects of HIV protease inhibitors on GLUT4 intrinsic activity. J Biol Chem. (2004) 279:55147–52. 10.1074/jbc.M410826200
    1. Eyawo O, Franco-Villalobos C, Hull MW, Nohpal A, Samji H, Sereda P, et al. . Changes in mortality rates and causes of death in a population-based cohort of persons living with and without HIV from 1996 to 2012. BMC Infect Dis. (2017) 17:174. 10.1186/s12879-017-2254-7
    1. Martinez E, Milinkovic A, Buira E, de Lazzari E, Leon A, Larrousse M, et al. . Incidence and causes of death in HIV-infected persons receiving highly active antiretroviral therapy compared with estimates for the general population of similar age and from the same geographical area. HIV Med. (2007) 8:251–8. 10.1111/j.1468-1293.2007.00468.x
    1. Weber R, Ruppik M, Rickenbach M, Spoerri A, Furrer H, Battegay M, et al. . Decreasing mortality and changing patterns of causes of death in the Swiss HIV Cohort Study. HIV Med. (2013) 14:195–207. 10.1111/j.1468-1293.2012.01051.x
    1. Yang CH, Huang YF, Hsiao CF, Yeh YL, Liou HR, Hung CC, et al. . Trends of mortality and causes of death among HIV-infected patients in Taiwan, 1984–2005. HIV Med. (2008) 9:535–43. 10.1111/j.1468-1293.2008.00600.x
    1. Palella FJ, Jr., Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, et al. . Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. (2006) 43:27–34. 10.1097/01.qai.0000233310.90484.16
    1. Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. . Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet (2014) 384:241–8. 10.1016/S0140-6736(14)60604-8
    1. Price J, Hoy J, Ridley E, Nyulasi I, Paul E, Woolley I. Changes in the prevalence of lipodystrophy, metabolic syndrome and cardiovascular disease risk in HIV-infected men. Sex Health (2015) 12:240–8. 10.1071/SH14084
    1. Rickerts V, Brodt H, Staszewski S, Stille W. Incidence of myocardial infarctions in HIV-infected patients between 1983 and 1998: the Frankfurt HIV-cohort study. Eur J Med Res. (2000) 5:329–33.
    1. Krentz HB, Kliewer G, Gill MJ. Changing mortality rates and causes of death for HIV-infected individuals living in Southern Alberta, Canada from 1984 to 2003. HIV Med. (2005) 6:99–106. 10.1111/j.1468-1293.2005.00271.x
    1. Rasmussen LD, May MT, Kronborg G, Larsen CS, Pedersen C, Gerstoft J, et al. . Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study. Lancet HIV (2015) 2:e288–98. 10.1016/S2352-3018(15)00077-6
    1. Worm SW, De Wit S, Weber R, Sabin CA, Reiss P, El-Sadr W, et al. . Diabetes mellitus, preexisting coronary heart disease, and the risk of subsequent coronary heart disease events in patients infected with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study). Circulation (2009) 119:805–11. 10.1161/CIRCULATIONAHA.108.790857
    1. 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) 92:2506–12. 10.1210/jc.2006-2190
    1. Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, et al. . Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population. AIDS (2010) 24:1228–30. 10.1097/QAD.0b013e328339192f
    1. 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) 44:1625–31. 10.1086/518285
    1. Freiberg MS, Chang CC, Kuller LH, Skanderson M, Lowy E, Kraemer KL, et al. . HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. (2013) 173:614–22. 10.1001/jamainternmed.2013.3728
    1. Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. J Acquir Immune Defic Syndr. (2009) 51:268–73. 10.1097/QAI.0b013e3181a9992c
    1. Drozd DR, Kitahata MM, Althoff KN, Zhang J, Gange SJ, Napravnik S, et al. . Increased risk of myocardial infarction in HIV-infected individuals in North America compared with the general population. J Acquir Immune Defic Syndr. (2017) 75:568–76. 10.1097/QAI.0000000000001450
    1. Currier JS, Taylor A, Boyd F, Dezii CM, Kawabata H, Burtcel B, et al. . Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr. (2003) 33:506–12. 10.1097/00126334-200308010-00012
    1. Saves M, Chene G, Ducimetiere P, Leport C, Le Moal G, Amouyel P, et al. . Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis. (2003) 37:292–8. 10.1086/375844
    1. Klein D, Hurley LB, Quesenberry CP, Jr., Sidney S. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acquir Immune Defic Syndr. (2002) 30:471–7. 10.1097/00126334-200208150-00002
    1. El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, et al. . CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. (2006) 355:2283–96. 10.1056/NEJMoa062360
    1. Lichtenstein KA, Armon C, Buchacz K, Chmiel JS, Buckner K, Tedaldi EM, et al. . Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study. Clin Infect Dis. (2010) 51:435–47. 10.1086/655144
    1. Vos AG, Idris NS, Barth RE, Klipstein-Grobusch K, Grobbee DE. Pro-inflammatory markers in relation to cardiovascular disease in HIV infection. A systematic review. PLoS ONE (2016) 11:e0147484. 10.1371/journal.pone.0147484
    1. Baker JV, Duprez D, Rapkin J, Hullsiek KH, Quick H, Grimm R, et al. . Untreated HIV infection and large and small artery elasticity. J Acquir Immune Defic Syndr. (2009) 52:25–31. 10.1097/qai.0b013e3181b02e6a
    1. Torriani FJ, Komarow L, Parker RA, Cotter BR, Currier JS, Dube MP, et al. . Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: the ACTG (AIDS Clinical Trials Group) Study 5152s. J Am Coll Cardiol. (2008) 52:569–76. 10.1016/j.jacc.2008.04.049
    1. Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, et al. . Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. (2007) 356:1723–35. 10.1056/NEJMoa062744
    1. Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, et al. . Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis. (2010) 201:318–30. 10.1086/649897
    1. Bavinger C, Bendavid E, Niehaus K, Olshen RA, Olkin I, Sundaram V, et al. . Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review. PLoS ONE (2013) 8:e59551. 10.1371/journal.pone.0059551
    1. Asztalos BF, Matera R, Horvath KV, Horan M, Tani M, Polak JF, et al. . Cardiovascular disease-risk markers in HIV patients. J AIDS Clin Res. (2014) 5. 10.4172/2155-6113.1000317
    1. Mercie P, Thiebaut R, Lavignolle V, Pellegrin JL, Yvorra-Vives MC, Morlat P, et al. . Evaluation of cardiovascular risk factors in HIV-1 infected patients using carotid intima-media thickness measurement. Ann Med. (2002) 34:55–63. 10.1080/078538902317338652
    1. Worm SW, Sabin CA, Reiss P, El-Sadr W, Monforte A, Pradier C, et al. Presence of the metabolic syndrome is not a better predictor of cardiovascular disease than the sum of its components in HIV-infected individuals: data collection on adverse events of anti-HIV drugs (D:A:D) study. Diab Care (2009) 32:474–80. 10.2337/dc08-1394
    1. Gelpi M, Afzal S, Lundgren J, Ronit A, Roen A, Mocroft A, et al. Higher risk of abdominal obesity, elevated LDL cholesterol and hypertriglyceridemia, but not of hypertension, in people living with HIV: results from the copenhagen comorbidity in HIV infection (COCOMO) study. Clin Infect Dis. (2018) 67:579–86. 10.1093/cid/ciy146
    1. Palenicek JP, Graham NM, He YD, Hoover DA, Oishi JS, Kingsley L, et al. . Weight loss prior to clinical AIDS as a predictor of survival. Multicenter AIDS Cohort Study Investigators. J Acquir Immune Defic Syndr Hum Retrovirol. (1995) 10:366–73. 10.1097/00042560-199511000-00009
    1. Wheeler DA, Gibert CL, Launer CA, Muurahainen N, Elion RA, Abrams DI, et al. . Weight loss as a predictor of survival and disease progression in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. (1998) 18:80–5. 10.1097/00042560-199805010-00012
    1. Tang AM, Forrester J, Spiegelman D, Knox TA, Tchetgen E, Gorbach SL. Weight loss and survival in HIV-positive patients in the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. (2002) 31:230–6. 10.1097/00126334-200210010-00014
    1. Okunade AA, Rubin RM, Okunade AK. Delayed effects of obese and overweight population conditions on all-cause adult mortality rate in the USA. Front Public Health (2016) 4:212. 10.3389/fpubh.2016.00212
    1. Hainer V, Aldhoon-Hainerova I. Obesity paradox does exist. Diab Care (2013) 36 (Suppl. 2):S276–81. 10.2337/dcS13-2023
    1. Blum A, Simsolo C, Sirchan R, Haiek S. “Obesity paradox” in chronic obstructive pulmonary disease. Israel Med Assoc J. (2011) 13:672–5.
    1. Uretsky S, Messerli FH, Bangalore S, Champion A, Cooper-Dehoff RM, Zhou Q, et al. . Obesity paradox in patients with hypertension and coronary artery disease. Am J Med. (2007) 120:863–70. 10.1016/j.amjmed.2007.05.011
    1. Curtis JP, Selter JG, Wang Y, Rathore SS, Jovin IS, Jadbabaie F, et al. . The obesity paradox: body mass index and outcomes in patients with heart failure. Arch Inter Med. (2005) 165:55–61. 10.1001/archinte.165.1.55
    1. Weiser SD, Young SL, Cohen CR, Kushel MB, Tsai AC, Tien PC, et al. . Conceptual framework for understanding the bidirectional links between food insecurity and HIV/AIDS. Am J Clin Nutr. (2011) 94:1729s−39s. 10.3945/ajcn.111.012070
    1. Scherzer R, Heymsfield SB, Lee D, Powderly WG, Tien PC, Bacchetti P, et al. . Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection. AIDS (2011) 25:1405–14. 10.1097/QAD.0b013e32834884e6

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe