Current HIV/AIDS Reports

, Volume 11, Issue 1, pp 35–44 | Cite as

Metabolic Consequences of HIV: Pathogenic Insights

HIV Pathogenesis and Treatment (AL Landay, Section Editor)

Abstract

With the advances in antiretroviral therapy (ART), HIV infection has been transformed into a chronic medical condition that can be effectively managed like diabetes or hypertension. For HIV care providers, the focus of care for many patients has shifted from prevention of opportunistic infection and AIDS-related conditions to age-related cardiometabolic comorbidities, including cardiovascular disease, diabetes, obesity, and frailty. Numerous reports have highlighted that these diseases are occurring at an earlier age among HIV-infected persons. However, there is an ongoing debate regarding the role of HIV infection, ART, and other factors that may underlie the accelerated occurrence of these diseases. Herein, we review the epidemiology of the US HIV epidemic with regards to several metabolic comorbidities and address mechanisms that likely contribute to the current nature of HIV disease.

Keywords

HIV AIDS Metabolism Inflammation Frailty Cardiovascular disease Diabetes Mitochondria Pathogenesis HIV pathogenesis Antiretroviral therapy (ART) Chronic medical condition 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Amanda L. Willig, and E. Turner Overton declare that they have no conflict of interest

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Palella Jr FJ, 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(1):27–34.PubMedCrossRefGoogle Scholar
  2. 2.•
    Tate T, Willig AL, Willig JH, Raper JL, Moneyham L, Kempf MC, et al. HIV infection and obesity: where did all the wasting go? Antivir Ther. 2012;17(7):1281–9. This study evaluated 681 patients over a two-year time period. They observed a high rate of overweight/obesity prevalence at ART initiation (44%), and a 20% increase in overweight/obesity at two years, with only a modest contribution of ART therapy to weight gain. PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Vance DE, Mugavero M, Willig J, Raper JL, Aging SMS, With HIV. A Cross-Sectional Study of Comorbidity Prevalence and Clinical Characteristics Across Decades of Life. J Assoc Nurses AIDS Care. 2011;22(1):17–25.PubMedCrossRefGoogle Scholar
  4. 4.
    Mugavero MJ, Amico KR, Horn T, Thompson MA. The state of engagement in HIV care in the United States: from cascade to continuum to control. Clin Infect Dis Off Publ Infect Dis Soc Am. 2013;57(8):1164–71.CrossRefGoogle Scholar
  5. 5.
    Warriner AH, Mugavero MJ. Bone changes and fracture risk in individuals infected with HIV. Curr Rheumatol Rep. 2010;12(3):163–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Desquilbet L, Jacobson LP, Fried LP, Phair JP, Jamieson BD, Holloway M, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci. 2007;62(11):1279–86.PubMedCrossRefGoogle Scholar
  7. 7.
    Terzian AS, Holman S, Nathwani N, Robison E, Weber K, Young M, et al. Factors associated with preclinical disability and frailty among HIV-infected and HIV-uninfected women in the era of cART. J Womens Health (Larchmt). 2009;18(12):1965–74.CrossRefGoogle Scholar
  8. 8.
    Schafer I, von Leitner EC, Schon G, Koller D, Hansen H, Kolonko T, et al. Multimorbidity patterns in the elderly: a new approach of disease clustering identifies complex interrelations between chronic conditions. PLoS ONE. 2010;5(12):e15941.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Wolff JL, Starfield B, Anderson G. Prevalence, expenditures, and complications of multiple chronic conditions in the elderly. Arch Intern Med. 2002;162(20):2269–76.PubMedCrossRefGoogle Scholar
  10. 10.•
    Kim DJ, Westfall AO, Chamot E, Willig AL, Mugavero MJ, Ritchie C, et al. Multimorbidity patterns in HIV-infected patients: the role of obesity in chronic disease clustering. J Acquir Immune Defic Syndr. 2012;61(5):600–5. This study investigated multimorbidity among over 1800 HIV-infected participants. They found that obesity was associated with increasing odds of multimorbidity, and that three distinct multimorbidity clusters could be identified using exploratory factor analysis: 1) metabolic, 2) behavioral, and 3) substance use. PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.•
    Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis Off Publ Infect Dis Soc Am. 2011;53(11):1120–6. This case–control study observed that noninfectious comorbidities and polypathology (multimorbidity) occur more often and at a 10-year earlier time frame among HIV-infected patients than in the general population. CrossRefGoogle Scholar
  12. 12.
    Guaraldi GZ, S.; Stentarelli C; et al. Aging with HIV versus HIV seroconversion at older age: a diverse population with distinct comorbidity profiles. 4th International Workshop on HIV and Aging; Baltimore, MD2013.Google Scholar
  13. 13.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Durand M, Sheehy O, Baril JG, Lelorier J, Tremblay CL. Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case–control study using Quebec's public health insurance database. J Acquir Immune Defic Syndr. 2011;57(3):245–53.PubMedCrossRefGoogle Scholar
  15. 15.
    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(22):2283–96.PubMedCrossRefGoogle Scholar
  16. 16.
    Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5(10):e203.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Baker JV, Henry WK, Patel P, Bush TJ, Conley LJ, Mack WJ, et al. Progression of carotid intima-media thickness in a contemporary human immunodeficiency virus cohort. Clin Infect Dis Off Publ Infect Dis Soc Am. 2011;53(8):826–35.CrossRefGoogle Scholar
  18. 18.•
    Yarasheski KE, Laciny E, Overton ET, Reeds DN, Harrod M, Baldwin S, et al. 18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors. J Inflamm (Lond). 2012;9(1):26. This study confirmed carotid artery 18FDG PET-CT imaging as an effective technique to observe differences between HIV-infected adults versus controls in vascular inflammation and early atherosclerosis. CrossRefGoogle Scholar
  19. 19.•
    Zanni MV, Abbara S, Lo J, Wai B, Hark D, Marmarelis E, et al. Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men. AIDS. 2013;27(8):1263–72. This study observed a significantly greater presence of vulnerable plaques - low attenuation plaque and high-risk 3-feature plaque – in HIV-infected patients that may partly explain the high rates of myocardial infarction and sudden cardiac death in this population. PubMedCrossRefGoogle Scholar
  20. 20.
    Friis-Moller N, Weber R, Reiss P, Thiebaut R, Kirk O, d’Arminio Monforte A, et al. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study. AIDS. 2003;17(8):1179–93.PubMedCrossRefGoogle Scholar
  21. 21.
    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 5152 s. J Am Coll Cardiol. 2008;52(7):569–76.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Kitagawa T, Yamamoto H, Horiguchi J, Ohhashi N, Tadehara F, Shokawa T, et al. Characterization of noncalcified coronary plaques and identification of culprit lesions in patients with acute coronary syndrome by 64-slice computed tomography. JACC Cardiovasc Imaging. 2009;2(2):153–60.PubMedCrossRefGoogle Scholar
  23. 23.
    Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, et al. 18 F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med. 2009;50(10):1611–20.PubMedCrossRefGoogle Scholar
  24. 24.
    Hsue PY, Scherzer R, Hunt PW, Schnell A, Bolger AF, Kalapus SC et al. Carotid Intima-Media Thickness Progression in HIV-Infected Adults Occurs Preferentially at the Carotid Bifurcation and Is Predicted by Inflammation. Journal of the American Heart Association. 2012;1(2):1–12.Google Scholar
  25. 25.
    Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005;165(10):1179–84.PubMedCrossRefGoogle Scholar
  26. 26.
    Adeyemi OM, Livak B, Orsi J, Glesby MJ, Villacres MC, Weber KM, et al. Vitamin D and insulin resistance in non-diabetic women's interagency HIV study participants. AIDS Patient Care STDs. 2013;27(6):320–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Grunfeld C, Rimland D, Gibert CL, Powderly WG, Sidney S, Shlipak MG, et al. Association of upper trunk and visceral adipose tissue volume with insulin resistance in control and HIV-infected subjects in the FRAM study. J Acquir Immune Defic Syndr. 2007;46(3):283–90.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, et al. 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):1224–9.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Kino T, Gragerov A, Slobodskaya O, Tsopanomichalou M, Chrousos GP, Pavlakis GN. Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces transcription of the HIV-1 and glucocorticoid-responsive promoters by binding directly to p300/CBP coactivators. J Virol. 2002;76(19):9724–34.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Shrivastav S, Kino T, Cunningham T, Ichijo T, Schubert U, Heinklein P, et al. Human immunodeficiency virus (HIV)-1 viral protein R suppresses transcriptional activity of peroxisome proliferator-activated receptor gamma and inhibits adipocyte differentiation: implications for HIV-associated lipodystrophy. Mol Endocrinol. 2008;22(2):234–47.PubMedCrossRefGoogle Scholar
  31. 31.
    Meininger G, Hadigan C, Laposata M, Brown J, Rabe J, Louca J, et al. Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution. Metab Clin Exp. 2002;51(2):260–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Overton ETT, P, Ryan, R, Coate B, Perniciaro, A, Dayaram, YK, De La Rosa, G, Baugh, B. Once daily Darunavir/Ritonavir (DRV/r) versus Atazanavir/Ritonavir (ATV/r) on insulin sensitivity in HIV-infected persons over 48 weeks. Poster Presentation 53rd ICAAC. 2013;September 10–13,2013. Denver, CO:Abstract #2147.Google Scholar
  33. 33.
    Reeds DC, WT, Patterson, BW, Overton, T, Yarasheski, KE, Klein, S. Metabolic benefits of weight loss are blunted in obese, HIV-infected women. Obesity. 2011;19 (S1):S112.Google Scholar
  34. 34.
    Han JH, Crane HM, Bellamy SL, Frank I, Cardillo S, Bisson GP, et al. HIV infection and glycemic response to newly initiated diabetic medical therapy. AIDS. 2012;26(16):2087–95.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.•
    Brown TT, Tassiopoulos K, Bosch RJ, Shikuma C, McComsey GA. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care. 2010;33(10):2244–9. This retrospective study identified a relationship between diabetes risk and sTNFR1, sTNFR2 and hs-CRP among HIV-infected patients with and without a diabetes diagnosis. PubMedCrossRefGoogle Scholar
  36. 36.
    Hansen AB, Gerstoft J, Kronborg G, Larsen CS, Pedersen C, Pedersen G, et al. Incidence of low and high-energy fractures in persons with and without HIV infection: a Danish population-based cohort study. AIDS. 2012;26(3):285–93.PubMedCrossRefGoogle Scholar
  37. 37.
    Womack JA, Goulet JL, Gibert C, Brandt CA, Skanderson M, Gulanski B, et al. Physiologic frailty and fragility fracture in HIV-infected male veterans. Clin Infect Dis Off Publ Infect Dis Soc Am. 2013;56(10):1498–504.CrossRefGoogle Scholar
  38. 38.
    Yin MT, Kendall MA, Wu X, Tassiopoulos K, Hochberg M, Huang JS, et al. Fractures after antiretroviral initiation. AIDS. 2012;26(17):2175–84.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.•
    Yin MT, Lund E, Shah J, Zhang CA, Foca M, Neu N et al. Lower peak bone mass and abnormal trabecular and cortical microarchitecture in young men infected with HIV early in life. Aids. 2013 Sep 25. [Epub ahead of print].Google Scholar
  40. 40.
    Tanchaweng SP, T.; Saksawad, R.; Brukesawan, C.; Maleesantharn, A.; Chokephaibulkit, K. Longitudinal study of bone mineral density and vitamin D levels among perinatally HIV-infected Thai adolescents on long-term antiretroviral therapy. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention. 2013;June 30-July 3, 2013. Kuala Lumpur:Abstract MOPDB0103.Google Scholar
  41. 41.
    Grant PM, Kitch D, McComsey GA, Dube MP, Haubrich R, Huang J, et al. Low Baseline CD4+ Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation. Clin Infect Dis Off Publ Infect Dis Soc Am. 2013;57(10):1483–8.CrossRefGoogle Scholar
  42. 42.
    Titanji KV, A.; Sheth, A.; Lennox, J.; Weitzmann, N.; Ofotokun, I. B cell dysregulation promotes HIV-induced bone loss. Conference on Retroviruses and Opportunistic Infections. 2013;March 3–6, 2013. Atlanta, GA:Abstract 821.Google Scholar
  43. 43.•
    Hernandez-Vallejo SJ, Beaupere C, Larghero J, Capeau J, Lagathu C. HIV protease inhibitors induce senescence and alter osteoblastic potential of human bone marrow mesenchymal stem cells: beneficial effect of pravastatin. Aging Cell. 2013. doi:  10.1111/acel.12119.
  44. 44.
    Althoff KN, Jacobson LP, Cranston RD, Detels R, Phair JP, Li X et al. Age, Comorbidities, and AIDS Predict a Frailty Phenotype in Men Who Have Sex With Men. The journals of gerontology Series A, Biological sciences and medical sciences. 2013. Oct 14. [Epub ahead of print].Google Scholar
  45. 45.
    Onen NF, Agbebi A, Shacham E, Stamm KE, Onen AR, Overton ET. Frailty among HIV-infected persons in an urban outpatient care setting. J Infect. 2009;59(5):346–52.PubMedCrossRefGoogle Scholar
  46. 46.
    McMillan GJ, Hubbard RE. Frailty in older inpatients: what physicians need to know. QJM Mon J Assoc Phys. 2012;105(11):1059–65.Google Scholar
  47. 47.
    Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, et al. Proinflammatory Cytokines, Aging, and Age-Related Diseases. J Am Med Dir Assoc. 2013;14(12):877–82.Google Scholar
  48. 48.•
    Erlandson KM, Allshouse AA, Jankowski CM, Lee EJ, Rufner KM, Palmer BE, et al. Association of functional impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy. J Infect Dis. 2013;208(2):249–59. This study found that functional impairment following ART initiation is associated with higher CD8+ t-cell activation and higher IL-6 levels. PubMedCrossRefGoogle Scholar
  49. 49.•
    Reekie J, Gatell JM, Yust I, Bakowska E, Rakhmanova A, Losso M, et al. Fatal and nonfatal AIDS and non-AIDS events in HIV-1-positive individuals with high CD4 cell counts according to viral load strata. AIDS. 2011;25(18):2259–68. This study showed that, among patients with CD4+ t-cell counts > 350 cells/mul, uncontrolled viral replication was associated with increased incidence of AIDS. PubMedCrossRefGoogle Scholar
  50. 50.
    Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA J Am Med Assoc. 2012;308(4):387–402.CrossRefGoogle Scholar
  51. 51.
    Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev. 2009;8(1):18–30.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Howcroft TK, Campisi J, Louis GB, Smith MT, Wise B, Wyss-Coray T, et al. The role of inflammation in age-related disease. Aging (Albany NY). 2013;5(1):84–93.Google Scholar
  53. 53.
    Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Investig. 2013;123(3):966–72.PubMedCrossRefGoogle Scholar
  54. 54.
    Khan N, Shariff N, Cobbold M, Bruton R, Ainsworth JA, Sinclair AJ, et al. Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol. 2002;169(4):1984–92.PubMedGoogle Scholar
  55. 55.
    Pathai S, Bajillan H, Landay AL, High KP. Is HIV a Model of Accelerated or Accentuated Aging? The journals of gerontology Series A, Biological sciences and medical sciences. 2013.Google Scholar
  56. 56.
    Scholer A, Hugues S, Boissonnas A, Fetler L, Amigorena S. Intercellular adhesion molecule-1-dependent stable interactions between T cells and dendritic cells determine CD8+ T cell memory. Immunity. 2008;28(2):258–70.PubMedCrossRefGoogle Scholar
  57. 57.
    Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71.PubMedCrossRefGoogle Scholar
  58. 58.
    Gordon SN, Cervasi B, Odorizzi P, Silverman R, Aberra F, Ginsberg G, et al. Disruption of intestinal CD4+ T cell homeostasis is a key marker of systemic CD4+ T cell activation in HIV-infected individuals. J Immunol. 2010;185(9):5169–79.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Li Q, Estes JD, Duan L, Jessurun J, Pambuccian S, Forster C, et al. Simian immunodeficiency virus-induced intestinal cell apoptosis is the underlying mechanism of the regenerative enteropathy of early infection. J Infect Dis. 2008;197(3):420–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Lederman MM, Calabrese L, Funderburg NT, Clagett B, Medvik K, Bonilla H, et al. Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis. 2011;204(8):1217–26.PubMedCrossRefGoogle Scholar
  61. 61.
    Robbins GK, Spritzler JG, Chan ES, Asmuth DM, Gandhi RT, Rodriguez BA, et al. Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384. Clin Infect Dis Off Publ Infect Dis Soc Am. 2009;48(3):350–61.CrossRefGoogle Scholar
  62. 62.
    Ellis CL, Ma ZM, Mann SK, Li CS, Wu J, Knight TH, et al. Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation. J Acquir Immune Defic Syndr. 2011;57(5):363–70.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Gori A, Tincati C, Rizzardini G, Torti C, Quirino T, Haarman M, et al. Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis. J Clin Microbiol. 2008;46(2):757–8.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, et al. Dysbiosis of the gut microbiota is associated with hiv disease progression and tryptophan catabolism. Sci Transl Med. 2013;5(193):193ra91.PubMedCrossRefGoogle Scholar
  65. 65.
    van der Velde AE. Reverse cholesterol transport: from classical view to new insights. World J Gastroenterol WJG. 2010;16(47):5908–15.Google Scholar
  66. 66.
    Huang CY, Chiang SF, Lin TY, Chiou SH, Chow KC. HIV-1 Vpr triggers mitochondrial destruction by impairing Mfn2-mediated ER-mitochondria interaction. PLoS ONE. 2012;7(3):e33657.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Pearce EL, Poffenberger MC, Chang CH, Jones RG. Fueling immunity: insights into metabolism and lymphocyte function. Science. 2013;342(6155):1242454.PubMedCrossRefGoogle Scholar
  68. 68.
    Leow MK, Addy CL, Mantzoros CS. Clinical review 159: Human immunodeficiency virus/highly active antiretroviral therapy-associated metabolic syndrome: clinical presentation, pathophysiology, and therapeutic strategies. J Clin Endocrinol Metab. 2003;88(5):1961–76.PubMedCrossRefGoogle Scholar
  69. 69.
    Joy T, Keogh HM, Hadigan C, Dolan SE, Fitch K, Liebau J, et al. Relation of body composition to body mass index in HIV-infected patients with metabolic abnormalities. J Acquir Immune Defic Syndr. 2008;47(2):174–84.PubMedCrossRefGoogle Scholar
  70. 70.
    Grunfeld C, Saag M, Cofrancesco Jr J, Lewis CE, Kronmal R, Heymsfield S, et al. Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy. AIDS. 2010;24(11):1717–26.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Koethe JR, Hulgan T, Niswender K. Adipose Tissue and Immune Function: A Review of Evidence Relevant to HIV Infection. J Infect Dis. 2013;208(8):1194–201.PubMedCrossRefGoogle Scholar
  72. 72.
    Grunfeld C, Pang M, Shimizu L, Shigenaga JK, Jensen P, Feingold KR. Resting energy expenditure, caloric intake, and short-term weight change in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Am J Clin Nutr. 1992;55(2):455–60.PubMedGoogle Scholar
  73. 73.
    Melchior JC, Raguin G, Boulier A, Bouvet E, Rigaud D, Matheron S, et al. Resting energy expenditure in human immunodeficiency virus-infected patients: comparison between patients with and without secondary infections. Am J Clin Nutr. 1993;57(5):614–9.PubMedGoogle Scholar
  74. 74.
    Mittelsteadt AL, Hileman CO, Harris SR, Payne KM, Gripshover BM, McComsey GA. Effects of HIV and antiretroviral therapy on resting energy expenditure in adult HIV-infected women-a matched, prospective, cross-sectional study. J Acad Nutr Diet. 2013;113(8):1037–43.PubMedCrossRefGoogle Scholar
  75. 75.
    Kosmiski LA, Sage-El A, Kealey EH, Bessesen DH. Brown fat activity is not apparent in subjects with HIV lipodystrophy and increased resting energy expenditure. Obesity. 2011;19(10):2096–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Tesoriero JM, Gieryic SM, Carrascal A, Lavigne HE. Smoking among HIV positive New Yorkers: prevalence, frequency, and opportunities for cessation. AIDS Behav. 2010;14(4):824–35.PubMedCrossRefGoogle Scholar
  77. 77.
    (CDC) CfDCaP. Vital signs: current cigarette smoking among sdults aged > 18 years with mental illnes - United States, 2990–2011. Morb Mortal Wkly Rep. 2013;62(5):81–7.Google Scholar
  78. 78.
    Feldman JG, Minkoff H, Schneider MF, Gange SJ, Cohen M, Watts DH, et al. Association of cigarette smoking with HIV prognosis among women in the HAART era: a report from the women's interagency HIV study. Am J Publ Health. 2006;96(6):1060–5.CrossRefGoogle Scholar
  79. 79.
    Grubb JR, Overton ET, Presti R, Onen NF. Reply to Ganesan et al. J Infect Dis. 2012;205(3):518–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Kalichman SC, Cherry C, Amaral C, White D, Kalichman MO, Pope H, et al. Health and treatment implications of food insufficiency among people living with HIV/AIDS, Atlanta, Georgia. J Urban Health. 2010;87(4):631–41.PubMedCrossRefGoogle Scholar
  81. 81.
    Weiser SD, Bangsberg DR, Kegeles S, Ragland K, Kushel MB, Frongillo EA. Food insecurity among homeless and marginally housed individuals living with HIV/AIDS in San Francisco. AIDS Behav. 2009;13(5):841–8.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Anema A, Vogenthaler N, Frongillo EA, Kadiyala S, Weiser SD. Food insecurity and HIV/AIDS: current knowledge, gaps, and research priorities. Curr HIV/AIDS Rep. 2009;6(4):224–31.PubMedCrossRefGoogle Scholar
  83. 83.
    Weiser SD, Fernandes KA, Brandson EK, Lima VD, Anema A, Bangsberg DR, et al. The association between food insecurity and mortality among HIV-infected individuals on HAART. J Acquir Immune Defic Syndr. 2009;52(3):342–9.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Stradling C, Chen YF, Russell T, Connock M, Thomas GN, Taheri S. The effects of dietary intervention on HIV dyslipidaemia: a systematic review and meta-analysis. PLoS ONE. 2012;7(6):e38121.PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Viskovic K, Rutherford GW, Sudario G, Stemberger L, Brnic Z, Begovac J. Ultrasound measurements of carotid intima-media thickness and plaque in HIV-infected patients on the Mediterranean diet. Croat Med J. 2013;54(4):330–8.PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    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(4):e10106.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Bogers RP, Bemelmans WJ, Hoogenveen RT, Boshuizen HC, Woodward M, Knekt P, et al. Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med. 2007;167(16):1720–8.PubMedCrossRefGoogle Scholar
  88. 88.
    Greenfield JR, Samaras K, Jenkins AB, Kelly PJ, Spector TD, Gallimore JR, et al. Obesity is an important determinant of baseline serum C-reactive protein concentration in monozygotic twins, independent of genetic influences. Circulation. 2004;109(24):3022–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Crum-Cianflone NF, Roediger M, Eberly LE, Ganesan A, Weintrob A, Johnson E, et al. Impact of weight on immune cell counts among HIV-infected persons. Clin Vaccine Immunol CVI. 2011;18(6):940–6.CrossRefGoogle Scholar
  90. 90.
    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 Off Publ Infect Dis Soc Am. 2011;53(9):952–60.CrossRefGoogle Scholar
  91. 91.
    Womack J, Tien PC, Feldman J, Shin JH, Fennie K, Anastos K, et al. Obesity and immune cell counts in women. Metab Clin Exp. 2007;56(7):998–1004.PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    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(5):319–24.CrossRefGoogle Scholar
  93. 93.
    Engelson ES, Agin D, Kenya S, Werber-Zion G, Luty B, Albu JB, et al. Body composition and metabolic effects of a diet and exercise weight loss regimen on obese, HIV-infected women. Metab Clin Exp. 2006;55(10):1327–36.PubMedCrossRefGoogle Scholar
  94. 94.
    Phelan JA, Mulligan R, Nelson E, Brunelle J, Alves ME, Navazesh M, et al. Dental caries in HIV-seropositive women. J Dent Res. 2004;83(11):869–73.PubMedCrossRefGoogle Scholar
  95. 95.
    Davoodi P, Hamian M, Nourbaksh R, Ahmadi MF. Oral Manifestations Related To CD4 Lymphocyte Count in HIV-Positive Patients. J Dent Res Dent Clin Dent Prospects. 2010;4(4):115–9.PubMedCentralPubMedGoogle Scholar
  96. 96.
    Nittayananta W, Talungchit S, Jaruratanasirikul S, Silpapojakul K, Chayakul P, Nilmanat A, et al. Effects of long-term use of HAART on oral health status of HIV-infected subjects. J Oral Pathol Med. 2010;39(5):397–406.PubMedCentralPubMedGoogle Scholar
  97. 97.
    McLachlan JL, Sloan AJ, Smith AJ, Landini G, Cooper PR. S100 and cytokine expression in caries. Infect Immun. 2004;72(7):4102–8.PubMedCentralPubMedCrossRefGoogle Scholar
  98. 98.
    Graham CS, Baden LR, Yu E, Mrus JM, Carnie J, Heeren T, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Inf Dis Off Publ Infect Dis Soc Am. 2001;33(4):562–9.CrossRefGoogle Scholar
  99. 99.
    Bonacini M. Alcohol use among patients with HIV infection. Ann Hepatol. 2011;10(4):502–7.PubMedGoogle Scholar
  100. 100.
    Chaudhry AA, Sulkowski MS, Chander G, Moore RD. Hazardous drinking is associated with an elevated aspartate aminotransferase to platelet ratio index in an urban HIV-infected clinical cohort. HIV Med. 2009;10(3):133–42.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Balagopal A, Philp FH, Astemborski J, Block TM, Mehta A, Long R, et al. Human immunodeficiency virus-related microbial translocation and progression of hepatitis C. Gastroenterology. 2008;135(1):226–33.PubMedCentralPubMedCrossRefGoogle Scholar
  102. 102.
    Joshi D, O'Grady J, Dieterich D, Gazzard B, Agarwal K. Increasing burden of liver disease in patients with HIV infection. Lancet. 2011;377(9772):1198–209.PubMedCrossRefGoogle Scholar
  103. 103.
    Lin W, Weinberg EM, Tai AW, Peng LF, Brockman MA, Kim KA, et al. HIV increases HCV replication in a TGF-beta1-dependent manner. Gastroenterology. 2008;134(3):803–11.PubMedCrossRefGoogle Scholar
  104. 104.
    Morse CG, Voss JG, Rakocevic G, McLaughlin M, Vinton CL, Huber C, et al. HIV infection and antiretroviral therapy have divergent effects on mitochondria in adipose tissue. J Infect Dis. 2012;205(12):1778–87.PubMedCrossRefGoogle Scholar
  105. 105.
    Bhargava A, Raghuram GV, Pathak N, Varshney S, Jatawa SK, Jain D, et al. Occult hepatitis C virus elicits mitochondrial oxidative stress in lymphocytes and triggers PI3-kinase-mediated DNA damage response. Free Radic Biol Med. 2011;51(9):1806–14.PubMedCrossRefGoogle Scholar
  106. 106.•
    Chapplain JM, Tattevin P, Guyader D, Begue JM, Beillot J, Turlin B, et al. Mitochondrial abnormalities in patients with HIV-HCV co-infection as compared to patients with HCV mono-infection. HIV Clin Trials. 2011;12(1):54–60. This study showed that HCV infection is independently associated with liver mitochondrial dysfunction in HIV-infected patients. PubMedCrossRefGoogle Scholar
  107. 107.
    Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359–407.PubMedCentralPubMedCrossRefGoogle Scholar
  108. 108.•
    Hatano H, Yukl SA, Ferre AL, Graf EH, Somsouk M, Sinclair E, et al. Prospective Antiretroviral Treatment of Asymptomatic, HIV-1 Infected Controllers. PLoS Pathog. 2013;9(10):e1003691. This study showed that HIV replication continues in elite controllers with low levels of plasma HIV RNA, and that this subset of patients may benefit from initiation of ART to control chronic, systemic inflammation. PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Division of Infectious Diseases. UAB Center for AIDS ResearchUniversity of Alabama School of MedicineBirminghamUSA
  2. 2.Division of Infectious DiseasesUniversity of Alabama School of MedicineBirminghamUSA

Personalised recommendations