Morbidity in older HIV-infected patients: Impact of long-term antiretroviral use

AIDS Reviews

Volumn 16, Issue 2, 2014, Pages 75-89

  Guaraldi, Giovanni ^a   Prakash, Manyu ^b   Moecklinghoff, Christiane ^c   Stellbrink, Hans Jürgen ^d  

^a UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^b Janssen   (United Kingdom)

^c Janssen   (Germany)

^d Infektionsmedizinisches Centrum Hamburg   (Germany)

Author keywords

Aging; Frailty; Multimorbidity

Indexed keywords

ABACAVIR; ABACAVIR PLUS LAMIVUDINE; ANTIRETROVIRUS AGENT; ATAZANAVIR; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; COBICISTAT; DIDANOSINE; DOLUTEGRAVIR; EFAVIRENZ; EMTRICITABINE; EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; ENFUVIRTIDE; INDINAVIR; INTEGRASE INHIBITOR; LAMIVUDINE; LAMIVUDINE PLUS ZIDOVUDINE; LOPINAVIR PLUS RITONAVIR; NEVIRAPINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; PROTEINASE INHIBITOR; RALTEGRAVIR; RILPIVIRINE; RITONAVIR; STAVUDINE; TENOFOVIR; TIPRANAVIR; UNINDEXED DRUG; VITAMIN D; ZALCITABINE; ZIDOVUDINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; AGING; ANGIOPLASTY; ATHEROSCLEROSIS; BONE DENSITY; BRAIN INFARCTION; CARDIOVASCULAR DISEASE; CENTRAL NERVOUS SYSTEM DISEASE; CHRONIC INFLAMMATION; COMORBIDITY; DIABETES MELLITUS; DOCTOR PATIENT RELATION; DRUG EFFICACY; DRUG TOLERABILITY; FRACTURE; FRAIL ELDERLY; HEART INFARCTION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HOLISTIC CARE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERTENSION; INFECTION RISK; KIDNEY FAILURE; LIFE EXPECTANCY; LIPODYSTROPHY; LIVER TOXICITY; LUNG EMBOLISM; MORBIDITY; NEPHROTOXICITY; NEUROTOXICITY; OSTEOPOROSIS; POLYPHARMACY; REVIEW; SENESCENCE; AGE; AGED; ANTIVIRAL RESISTANCE; DRUG INTERACTION; HIV INFECTIONS; IMMUNOLOGY; MIDDLE AGED; PATIENT COMPLIANCE; QUALITY OF LIFE; STATISTICS AND NUMERICAL DATA;

AGE FACTORS; AGED; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; COMORBIDITY; DRUG INTERACTIONS; DRUG RESISTANCE, VIRAL; FRAIL ELDERLY; HIV INFECTIONS; HUMANS; LIFE EXPECTANCY; MIDDLE AGED; PATIENT COMPLIANCE; PHYSICIAN-PATIENT RELATIONS; POLYPHARMACY; QUALITY OF LIFE;

EID: 84902243673     PISSN: 11396121     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (157)

1. Health Protection Agency. HIV in the United Kingdom: 2010 report. Available at: www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/HIV.
2. Centers for Disease Control and Prevention. February 2011. HIV Surveillance Report. Available at: http://www.cdc.gov/hiv/topics/surveillance/ resources/reports/.
3. Nakagawa F, Lodwick R, Smith C, et al. Projected life expectancy of people with HIV according to timing of diagnosis. AIDS. 2012;26:335-43.
4. Desai S, Landay A. Early immune senescence in HIV disease. Curr HIV/AIDS Rep. 2010;7:4-10.
5. BHIVA guidelines for the treatment of HIV-1 positive adults with antiretroviral therapy 2012. 30th April 2012. Available at: http://www.bhiva. org/TreatmentofHIV1-2012.aspx.
6. Desquilbet L, Jacobson L, Fried L, 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;62:1279-86. (Pubitemid 350287617)
7. Terzian A, Holman S, Nathwani N, et al. Factors associated with preclinical disability and frailty among HIV-infected and HIV-uninfected women in the era of cART. J Women's Health (Larchmt). 2009;18:1965-74.
8. Desquilbet L, Margolick J, Fried L, et al. Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men. J Acquir Immune Defic Syndr. 2009;50:299-306.
9. Desquilbet L, Jacobson L, Fried L, et al. A frailty-related phenotype before HAART initiation as an independent risk factor for AIDS or death after HAART among HIV-infected men. J Gerontol A Biol Sci Med Sci. 2011;66:1030-8.
10. Fried L, Tangen C, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146-57.
11. Onen N, Agbebi A, Shacham E, Stamm K, Onen A, Overton E. Frailty among HIV-infected persons in an urban outpatient care setting. J Infect. 2009;59:346-52.
12. Margolick J, Li X, Detels R, Phair J, Rinaldo C, Jacobson L, and the Multicenter AIDS Cohort Study. Earlier occurrence of the frailty phenotype in HIV+ men than in HIV- men: the MACS. 18th CROI, Boston, MA, USA. 2011. [Abstract 794].
13. Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. New Engl J Med. 2005;352:48-62. (Pubitemid 40075680)
14. Guaraldi G, Squillace N, Stentarelli C, et al. Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. Clin Infect Dis. 2008;47:250-7. (Pubitemid 351920629)
15. Guaraldi G, Stentarelli C, Zona S, et al. Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical atherosclerosis in human immunodeficiency virus infected subjects. Atherosclerosis. 2010;208:222-7.
16. Guaraldi G, Scaglioni R, Zona S, et al. Epicardial adipose tissue is an independent marker of cardiovascular risk in HIV-infected patients. AIDS. 2011;25:1199-205.
17. Guaraldi G, Zona S, Orlando G, et al. Progression of coronary artery calcium in men affected by human immunodeficiency virus infection. Int J Cardiovasc Imaging. 2012;28:935-41.
18. Guaraldi G, Baraboutis I. Evolving perspectives on HIV-associated lipodystrophy syndrome: moving from lipodystrophy to non-infectious HIV co-morbidities. J Antimicrob Chemother. 2009;64:437-40.
19. The HIV and aging consensus project: recommended treatment strategies for clinicians managing older patients with HIV. 2011. Available at: http://www.aahivm.org/Upload-Module/upload/HIV%20and%20Aging/ Aging%20report%20working%20document%20FINAL%2012.1.pdf.
20. Franceschi C, Capri M, Monti D, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev. 2007;128:92-105. (Pubitemid 46073065)
21. Macaulay R, Akbar A, Henson S. The role of the T cell in age-related inflammation. Age (Dordr). 2013;35:563-72.
22. Avelino-Silva V, Ho Y, Avelino-Silva T, Santos Sde S. Aging and HIV infection. Ageing Res Rev. 2011;10:163-72.
23. Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol. 2008;214:231-41. (Pubitemid 351160160)
24. Neuhaus J, Jacobs D, Baker J, et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis. 2010;201:1788-95.
25. Rodger A, Fox Z, Lundgren J, et al. Activation and coagulation biomarkers are independent predictors of the development of opportunistic disease in patients with HIV infection. J Infect Dis. 2009;200:973-83.
26. Kuller L, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008;5:e203.
27. Hunt P, Rodriguez B, Shive C, et al. Gut epithelial barrier dysfunction, inflammation, and coagulation predict higher mortality during treated HIV/AIDS. 19th CROI, Seattle, WA, USA. 2012. [Abstract 278].
28. Capeau J. Premature aging and premature age-related comorbidities in HIV-infected patients: facts and hypotheses. Clin Infect Dis. 2011;53:1127-9.
29. Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011;53:1120-6.
30. Hasse B, Ledergerber B, Egger M, et al. Aging and non-HIV-associated co-morbidity in HIV+ persons: The SHCS. 18th CROI, Boston, MA, USA. 2011. [Abstract 792].
31. Hasse B, Ledergerber B, Furrer H, et al. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis. 2011;53:1130-9.
32. Palella F, Baker R, Moorman A, 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. (Pubitemid 44306484)
33. Smit C, Geskus R, Walker S, et al. Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion. AIDS. 2006;20:741-9. (Pubitemid 43884302)
34. Justice A. HIV and aging: time for a new paradigm. Curr HIV/AIDS Rep. 2010;7:69-76.
35. Petoumenos K, Worm S. HIV infection, aging and cardiovascular disease: epidemiology and prevention. Sex Health. 2011;8:465-73.
36. Caron-Debarle M, Lagathu C, Boccara F, Vigouroux C, Capeau J. HIV-associated lipodystrophy: from fat injury to premature aging. Trends Mol Med. 2010;16:218-29.
37. Falutz J. HIV infection, body composition changes and related metabolic complications: contributing factors and evolving management strategies. Curr Opin Clin Nutr Metab Care. 2011;14:255-60.
38. Kaplan R, Sinclair E, Landay A, et al. T cell activation predicts carotid artery stiffness among HIV-infected women. Atherosclerosis. 2011;217:207-13.
39. Lagathu C, Bastard J, Auclair M, et al. Antiretroviral drugs with adverse effects on adipocyte lipid metabolism and survival alter the expression and secretion of proinflammatory cytokines and adiponectin in vitro. Antivir Ther. 2004;9:911-20. (Pubitemid 40040265)
40. Giralt M, Díaz-Delfín J, Gallego-Escuredo J, Villarroya J, Domingo P, Villarroya F. Lipotoxicity on the basis of metabolic syndrome and lipodystrophy in HIV-1-infected patients under antiretroviral treatment. Curr Pharm Des. 2010;16:3371-8.
41. Díaz-Delfín J, del Mar Gutiérrez M, Gallego-Escuredo J, et al. Effects of nevirapine and efavirenz on human adipocyte differentiation, gene expression, and release of adipokines and cytokines. Antiviral Res. 2011;91:112-19.
42. Wilkin A, Pozniak A, Morales-Ramirez J, et al. Long-term efficacy, safety, and tolerability of rilpivirine (RPV, TMC278) in HIV type 1-infected antiretroviral-naive patients: week 192 results from a phase IIb randomized trial. AIDS Res Hum Retroviruses. 2012;28:437-46.
43. Fätkenheuer G, Duvivier C, Rieger A, et al. Lipid profiles for etravirine versus efavirenz in treatment-naive patients in the randomized, double-blind SENSE trial. J Antimicrob Chemother. 2012;67:685-90.
44. Sankatsing R, Wit F, Vogel M, et al. Increased carotid intima-media thickness in HIV patients treated with protease inhibitors as compared to non-nucleoside reverse transcriptase inhibitors. Atherosclerosis. 2009;202:589-95.
45. Worm S, Sabin C, Weber R, 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.
46. Butt A, McGinnis K, Rodriguez-Barradas M, et al. HIV infection and the risk of diabetes mellitus. AIDS. 2009;23:1227-34.
47. Capeau J, Bouteloup V, Katlama C, et al. Ten-year diabetes incidence in 1046 HIV-infected patients started on a combination antiretroviral treatment. AIDS. 2012;26:303-14.
48. Ledergerber B, Furrer H, Rickenbach M, et al. Factors Associated with the Incidence of Type 2 Diabetes Mellitus in HIV-Infected Participants in the Swiss HIV Cohort Study. Clin Infect Dis. 2007;45:111-19. (Pubitemid 46984626)
49. Walli R, Goebel FD, Demant T. Impaired glucose tolerance and protease inhibitors. Ann Intern Med. 1998;129:837-8. (Pubitemid 28522823)
50. Lennox J, DeJesus E, Berger D, et al. Raltegravir versus efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J Acquir Immune Defic Syndr. 2010;55:39-48.
51. Martinez E, Larrousse M, Llibre J, et al. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS. 2010;24:1697-707.
52. Reynes J, Trinh R, Pulido F, et al. Lopinavir/ritonavir combined with raltegravir or tenofovir/emtricitabine in antiretroviral-naive subjects: 96-week results of the PROGRESS Study. AIDS Res Hum Retroviruses. 2013;29:256-65.
53. Ofotokun I, Sheth A, Sanford S, et al. A switch in therapy to a reverse transcriptase inhibitor sparing combination of lopinavir/ ritonavir and raltegravir in virologically suppressed HIV-infected patients: a pilot randomized trial to assess efficacy and safety profile: the KITE Study. AIDS Res Hum Retroviruses. 2012;28:1196-206.
54. SECOND-LINE Study Group; Boyd M, Kumarasamy N, Moore C, et al. Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, noninferiority study. Lancet. 2013;381:2091-9.
55. Rockstroh J, Lennox J, DeJesus E, Long-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatment-naive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRK. Clin Infect Dis. 2011;53:807-16.
56. Curran A, Martinez E, Saumoy M, et al. Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy. AIDS. 2012;26:475-81.
57. Martin A, Moore C, Mallon P, et al. HIV lipodystrophy in participants randomised to lopinavir/ritonavir (LPV/r) +2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI) or LPV/r + raltegravir as second-line antiretroviral therapy. PLoS One. 2013;8:e77138.
58. Stellbrink H, Reynes J, Lazzarin A, et al. SPRING-1 Team. Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study. AIDS. 2013;27:1771-8.
59. van Lunzen J, Maggiolo F, Arribas J, et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect Dis. 2012;12:111-8.
60. Raffi F, Rachlis A, Stellbrink H, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013;381:735-43.
61. Cahn P, Pozniak A, Mingrone H, et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382:700-8.
62. DeJesus E, Rockstroh J, Henry K, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012;379:2429-38.
63. MacInnes A, Lazzarin A, Di Perri G, et al. Maraviroc can improve lipid profiles in dyslipidemic patients with HIV: results from the MERIT trial. HIV Clin Trials. 2011;12:24-36.
64. Wyatt C, Arons R, Klotman P, et al. Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality. AIDS. 2006;20:561-5. (Pubitemid 43731600)
65. Mocroft A, Kirk O, Gatell J, et al. Chronic renal failure among HIV-1-infected patients. AIDS. 2007;21:1119-27. (Pubitemid 46763282)
66. Wyatt C, Winston J, Malvestutto C, et al. Chronic kidney disease in HIV infection: an urban epidemic. AIDS. 2007;21:2101-3. (Pubitemid 47462160)
67. Winston J, Deray G, Hawkins T, Szczech L, Wyatt C, Young B. Kidney disease in patients with HIV infection and AIDS. Clin Infect Dis. 2008;47:1449-57.
68. Naftalin C, Nathan B, Hamzah L, Post F. HIV-associated kidney disease in the context of an aging population. Sex Health. 2011;8:485-92.
69. Madeddu G, Quirino T, Carradori S, et al. Renal toxicity in HIV-infected patients receiving HAART including tenofovir. Infez Med. 2006;14:125-34. (Pubitemid 46207094)
70. Bruggeman L, Bark C, Kalayjian R. HIV and the Kidney. Curr Infect Dis Rep. 2009;11:479-85.
71. Wyatt C, Meliambro K, Klotman P. Recent progress in HIV-associated nephropathy. Annu Rev Med. 2012;63:147-59.
72. Fine D, Perazella M, Lucas G, Atta M. Renal disease in patients with HIV infection: epidemiology, pathogenesis and management. Drugs. 2008;68:963-80. (Pubitemid 351652924)
73. Plaisier E, Lescure F, Ronco P. Kidney and HIV infection. Presse Med. 2012;41:267-75.
74. Lucas G, Eustace J, Sozio S, et al. Highly active antiretroviral therapy and the incidence of HIV-1-associated nephropathy: a 12-year cohort study. AIDS. 2004;18:541-6. (Pubitemid 38365883)
75. Krawczyk C, Holmberg S, Moorman A, et al. Factors associated with chronic renal failure in HIV-infected ambulatory patients. AIDS. 2004;18:2171-8. (Pubitemid 39463682)
76. El-Sadr W, Lundgren J, Neaton J, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283-96. (Pubitemid 44837777)
77. Mocroft A, Wyatt C, Szczech L, et al. Interruption of antiretroviral therapy is associated with increased plasma cystatin C. AIDS. 2009;23:71-82.
78. Beversluis D, Reynolds S, Kityo C, et al. Greater renal function preservation is associated with continuous vs intermittent ART. 16th CROI, Montréal, Canada. 2009. [Abstract 742].
79. Kalayjian R, Franceschini N, Gupta S, et al. Suppression of HIV-1 replication by antiretroviral therapy improves renal function in persons with low CD4 cell counts and chronic kidney disease. AIDS. 2008;22:481-7. (Pubitemid 351317289)
80. Peters P, Moore D, Mermin J, et al. Antiretroviral therapy improves renal function among HIV-infected Ugandans. Kidney Int. 2008;74:925-9.
81. Reid A, Stohr W, Walker A, et al. Severe renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapy. Clin Infect Dis. 2008;46:1271-81. (Pubitemid 351589914)
82. Mauss S, Berger F, Schmutz G. Antiretroviral therapy with tenofovir is associated with mild renal dysfunction. AIDS. 2005;19:93-5. (Pubitemid 40111024)
83. Hall A, Hendry B, Nitsch D, Connolly J. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011;57:773-80.
84. Madeddu G, Bonfanti P, De Socio G, et al. Tenofovir renal safety in HIV-infected patients: results from the SCOLTA Project. Biomed Pharmacother. 2008;62:6-11.
85. Campbell L, Ibrahim F, Fisher M, Holt S, Hendry B, Post F. Spectrum of chronic kidney disease in HIV-infected patients. HIV Med. 2009;10:329-36.
86. Cooper R, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis. 2010;51:496-505.
87. Ryom L and the D:A:D study group. Exposure to ARV and the Risk of Renal Impairment among HIV+ Persons with Normal Baseline Renal Function: The D:A:D Study. 19th CROI, Seattle, WA, USA. 2012. [Abstract 865].
88. Gupta S, Mi D, Moe S, Dubé M, Liu Z. Effects of switching from efavirenz to raltegravir on endothelial function, bone mineral metabolism, inflammation, and renal function: a randomized, controlled trial. J Acquir Immune Defic Syndr. 2013;64:279-83.
89. Price J, Thio C. Liver disease in the HIV infected individual. Clin Gastroenterol Hepatol. 2010;8:1002-12.
90. Antiretroviral Therapy Cohort Collaboration. Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996-2006: collaborative analysis of 13 HIV cohort studies. Clin Infect Dis. 2010;50:1387-96.
91. Weber R, Sabin CA, Friis-Moller N, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006;166:1632-41. (Pubitemid 44232373)
92. Reisler R, Han C, Burman W, et al. Grade 4 events are as important as AIDS events in the era of HAART. J Acquir Immune Defic Syndr. 2003;34:379-86. (Pubitemid 37444465)
93. Kovari H, Weber R. Influence of antiretroviral therapy on liver disease. Curr Opin HIV AIDS. 2011;6:272-7.
94. Soriano V, Puoti M, Garcia-Gasco P, et al. Antiretroviral drugs and liver injury. AIDS. 2008;22:1-13. (Pubitemid 350301936)
95. Puoti M, Nasta P, Gatti F, et al. HIV-related liver disease: ARV drugs, coinfection, and other risk factors. J Int Assoc Physicians AIDS Care (Chic Ill). 2009;8:30-42.
96. Sulkowski M, Mehta S, Chaisson R, et al. Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir. AIDS. 2004;18:2277-84. (Pubitemid 39620220)
97. Torti C, Lapadula G, Antinori A, et al. Hyperbilirubinemia during atazanavir treatment in 2,404 patients in the Italian atazanavir expanded access program and MASTER Cohorts. Infection. 2009;37:244-9.
98. Maida I, Nunez M, Rios M, et al. Severe liver disease associated with prolonged exposure to antiretroviral drugs. J Acquir Immune Defic Syndr. 2006;42:177-82. (Pubitemid 43884712)
99. Kovari H, Ledergerber B, Peter U, et al. Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: a nested case-control study. Clin Infect Dis. 2009;49:626-35.
100. Blanco F, Barreiro P, Ryan P, et al. Risk factors for advanced liver fibrosis in HIV-infected individuals: role of antiretroviral drugs and insulin resistance. J Viral Hepat. 2011;18:11-16.
101. Martín-Carbonero L, Núñez M, González-Lahoz J, Soriano V. Incidence of liver injury after beginning antiretroviral therapy with efavirenz or nevirapine. HIV Clin Trials. 2003;4:115-20.
102. Cotter A, Mallon P. HIV infection and bone disease: implications for an aging population. Sex Health. 2011;8:493-501.
103. Ofotokun I, McIntosh E, Weitzmann M. HIV: inflammation and bone. Curr HIV/AIDS Rep. 2012;9:16-25.
104. Brown T, Qaqish R. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS. 2006;20:2165-74. (Pubitemid 44684707)
105. Ofotokun I, Weitzmann M. HIV and bone metabolism. Discov Med. 2011;11:385-93.
106. Childs K, Welz T, Samarawickrama A, Post F. Effects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patients. AIDS. 2012;26:253-62.
107. McComsey G, Kitch D, Daar E, 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;203:1791-801.
108. Duvivier C, Kolta S, Assoumou L, et al. Hippocampe study group. 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;23:817-24.
109. Qaqish R, Trinh R, Tian M, et al. Bone mineral density (BMD) analysis in antiretroviral (ART)-subjects taking lopinavir/ritonavir (LPV/r) combined with raltegravir (RAL) or tenofovir/emtricitabine (TDF/FTC) for 96 weeks in the PROGRESS study. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy. 2011. [Abstract TULBPE021].
110. Bloch M, Tong W, Hoy J, Baker D, Richardson R, Carr A. Improved low BMD and bone turnover markers with switch from tenofovir to raltegravir in virologically suppressed HIV-1+ adults at 48 weeks: The TROP Study. 19th CROI, Seattle, WA, USA. 2012. [Abstract 878].
111. Rockstroh J, DeJesus E, Henry K, et al. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013;62:483-6.
112. Tebas P, Kumar P, Hicks C, et al. 48 week bone marker changes with dolutegravir plus abacavir/lamivudine vs. tenofovir/emtricitabine/efavirenz: the SINGLE trial. 53rd ICAAC, 2013. Denver, Co, USA. [Abstract H-1461]
113. Focà E, Motta D, Borderi M, et al. Prospective evaluation of bone markers, parathormone and 1,25-(OH)2 vitamin D in HIV-positive patients after the initiation of tenofovir/emtricitabine with atazanavir/ritonavir or efavirenz. BMC Infect Dis. 2012;12:38.
114. Allavena C, Delpierre C, Rey D, et al. Effects of ARV on Vitamin D Concentration in HIV-infected Patients: A Large Prospective Cohort Analysis. 18th CROI. Boston, MA, USA. 2011. [Abstract 826].
115. Fox J, Peters B, Prakash M, Arribas J, Hill A, Moecklinghoff C. Improvement in vitamin D deficiency following antiretroviral regime change: Results from the MONET trial. AIDS Res Hum Retroviruses. 2011;27:29-34.
116. Viard J, Souberbielle J, Kirk O, et al. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study. AIDS. 2011;25:1305-15.
117. Wohl D, Doroana M, Orkin C, et al. Change in vitamin D levels smaller and risk of development of severe vitamin D deficiency lower among HIV-1-infected, treatment-naïve adults receiving TMC278 compared with EFV: 48-week results from the Phase III ECHO trial. 18th CROI. Boston, USA. 2011. [Abstract 79LB].
118. Cobb Scott J, Woods S, Carey C, et al. Neurocognitive Consequences of HIV Infection in Older Adults: An Evaluation of the "Cortical" Hypothesis. AIDS Behav. 2011;15:1187-96.
119. Langford T, Everall I, Masliah E. Current concepts in HIV neuropathogenesis: neuronal injury, white matter disease, and neurotrophic factors. In: Gendelman HE, Grant I, Everall IP, Lipton S, Swindells S, editors. The neurology of AIDS. 2. Oxford University Press; London: 2005:405-14.
120. Burke S, Barnes C. Neural plasticity in the ageing brain. Nat Rev Neurosci. 2006;7:30-40. (Pubitemid 41828929)
121. Jernigan T, Gamst A, Archibald S, et al. Effects of methamphetamine dependence and HIV infection on cerebral morphology. Am J Psychiatry. 2005;162:1461-72. (Pubitemid 41105560)
122. Ernst T, Chang L. Effect of aging on brain metabolism in antiretroviral-naive HIV patients. AIDS. 2004;18(Suppl 1):S61-7. (Pubitemid 38365907)
123. Gonzalez-Scarano F, Martín-García J. The neuropathogenesis of AIDS. Nat Rev Immunol. 2005;5:69-81.
124. Chang L, Lee P, Yiannoutsos C, et al. A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age. Neuroimage. 2004;23:1336-47. (Pubitemid 40260357)
125. Becker J, Maruca V, Kingsley L, et al. Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology. 2012;54:113-21.
126. Becker J, Lopez O, Dew M, Aizenstein H. Prevalence of cognitive disorders differs as a function of age in HIV virus infection. AIDS. 2004;18(Suppl 1):S11-18. (Pubitemid 38365901)
127. Valcour V, Shikuma C, Shiramizu B, et al. Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort. Neurology. 2004;63:822-7. (Pubitemid 39297641)
128. Valcour V, Shikuma C, Shiramizu B, et al. Age, apolipoprotein E4, and the risk of HIV dementia: the Hawaii Aging with HIV Cohort. J Neuroimmunol. 2004;157:197-202. (Pubitemid 39576655)
129. Larussa D, Lorenzini P, Cingolani A, et al. Highly active antiretroviral therapy reduces the age-associated risk of dementia in a cohort of older HIV-1-infected patients. AIDS Res Hum Retroviruses. 2006; 22:386-92. (Pubitemid 43787762)
130. Cherner M, Ellis R, Lazzaretto D, et al. Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings. AIDS. 2004; 18(Suppl 1):S27-34. (Pubitemid 38365903)
131. Kissel E, Pukay-Martin N, Bornstein R. The relationship between age and cognitive function in HIV-infected men. J Neuropsychiatry Clin Neurosci. 2005;17:180-4. (Pubitemid 41350604)
132. Sacktor N, Skolasky R, Selnes OA, et al. Neuropsychological test profile differences between young and old human immunodeficiency virus-positive individuals. J Neurovirol. 2007;13:203-9. (Pubitemid 47050646)
133. McCutchan J, Marquie-Beck J, Fitzsimons C, et al. Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder. Neurology. 2012;78:485-92.
134. Gannon P, Khan M, Kolson D. Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol. 2011; 24:275-83.
135. Schouten J, Cinque P, Gisslen M, Reiss P, Portegies P. HIV-1 infection and cognitive impairment in the cART era: a review. AIDS. 2011; 25:561-75.
136. Clark U, Cohen R. Brain dysfunction in the era of combination antiretroviral therapy: implications for the treatment of the aging population of HIV-infected individuals. Curr Opin Investig Drugs. 2010; 11:884-900.
137. Mothobi N, Brew B. Neurocognitive dysfunction in the highly active antiretroviral therapy era. Curr Opin Infect Dis. 2012;25:4-9.
138. Heaton R, Clifford D, Franklin D, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75:2087-96.
139. Bunupuradah T, Chetchotisakd P, Jirajariyavej S, et al. Neurocognitive impairments in patients using lopinavir/ritonavir monotherapy vs. lopinavir/ritonavir-based HAART. 19th CROI. Seattle, USA. 2012. [Abstract 479].
140. Ances B, Ortega M, Vaida F, Heaps J, Paul R. Independent effects of HIV, aging, and HAART on brain volumetric measures. J Acquir Immune Defic Syndr. 2012;59:469-77.
141. Lochet P, Peyrière H, Lotthé A, Mauboussin J, Delmas B, Reynes J. Long-term assessment of neuropsychiatric adverse reactions associated with efavirenz. HIV Med. 2003;4:62-6. (Pubitemid 37161538)
142. Cespedes M, Aberg J. Neuropsychiatric complications of antiretroviral therapy. Drug Saf. 2006;29:865-74. (Pubitemid 44511587)
143. Nelson M, Stellbrink H, Podzamczer D, et al. A comparison of neuropsychiatric adverse events during 12 weeks of treatment with etravirine and efavirenz in a treatment-naive, HIV-1-infected population. AIDS. 2011; 25:335-40.
144. Evans S, Ellis R, Chen H, et al. Peripheral neuropathy in HIV: prevalence and risk factors. AIDS. 2011;25:919-28.
145. Arenas-Pinto A, Bhaskaran K, Dunn D, Weller I. The risk of developing peripheral neuropathy induced by nucleoside reverse transcriptase inhibitors decreases over time: evidence from the Delta trial. Antivir Ther. 2008;13:289-95. (Pubitemid 351535380)
146. BHIVA for the routine investigation and monitoring of adult HIV-1-infected individuals 2011. Available at: http://www.bhiva.org/documents/ Guidelines/Monitoring/hiv-971-EV.pdf.
147. Department of Health and Social Services (DHHS). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf.
148. Nogueras M, Navarro G, Anton E, et al. Epidemiological and clinical features, response to HAART, and survival in HIV infected patients diagnosed at the age of 50 or more. BMC Infect Dis. 2006;6:159.
149. Bosch R, Bennett K, Collier A, Zackin R, Benson C. Pretreatment factors associated with 3-year (144-week) virologic and immunologic responses to potent antiretroviral therapy. J Acquir Immune Defic Syndr. 2007; 44:268-77. (Pubitemid 46328342)
150. Sabin C, Smith C, d'Arminio Monforte A, et al. Response to combination antiretroviral therapy: variation by age. AIDS. 2008;22:1463-73.
151. Althoff K, Justice A, Gange S, et al. Virologic and immunologic response to HAART, by age and regimen class. AIDS. 2010;24:2469-79.
152. Wellons M, Sanders L, Edwards L, Bartlett J, Heald A, Schmader K. HIV infection: treatment outcomes in older and younger adults. J Am Geriatr Soc. 2002;50:603-7. (Pubitemid 34298746)
153. Wutoh A, Elekwachi O, Clarke-Tasker V, Daftary M, Powell N, Campusano G. Assessment and predictors of antiretroviral adherence in older HIV-infected patients. J Acquir Immune Defic Syndr. 2003;33(Suppl 2): S106-14. (Pubitemid 36801608)
154. Silverberg M, Leyden W, Horberg M, DeLorenze G, Klein D, Quesenberry CP. Older age and the response to and tolerability of antiretroviral therapy. Arch Intern Med. 2007;167:684-91. (Pubitemid 46598461)
155. Sherr L, Lampe F, Clucas C, et al. Self-reported non-adherence to ART and virological outcome in a multiclinic UK study. AIDS Care. 2010;22:939-45.
156. Valantin M, Flandre P, Kolta S, et al. Fat tissue distribution changes in HIV-infected patients with viral suppression treated with CDRV/r monotherapy vs 2 NRTI + DRV/r in the MONOI-ANRS 136 randomized trial: results at 48 weeks. 17th CROI. San Francisco, CA, USA. 2010. [Abstract 721].
157. Guaraldi G, Zona S, Cossarizza A, et al. Impact of switching to darunavir/ ritonavir monotherapy vs triple-therapy on body fat redistribution and bone mass in virologically suppressed HIV-infected adults. The MONARCH randomized controlled trial. 13th European AIDS Clinical Society, Belgrade, Serbia. 2011. [Poster PE7.5/4].