Drugs & Aging

, Volume 19, Issue 9, pp 647–669

HIV Disease and Advanced Age

An Increasing Therapeutic Challenge
Review Article


The mean age of patients at both first HIV detection and AIDS diagnosis is progressively rising over time. However, reliable epidemiological estimates, clinical data or controlled therapeutic and outcome figures are lacking for elderly patients, especially with regard to laboratory and clinical response to antiretroviral therapy, treatment tolerability, drug-drug interactions, short- and long-term toxicity, and interactions with underlying illnesses and concurrent pharmacological treatment. In fact, the large majority of randomised, controlled trials evaluating and comparing new antiretroviral drugs or anti-HIV therapeutic strategies, as well as antimicrobial treatment or chemoprophylaxis of HIV-related complications, either excluded patients with advanced age and/or concurrent disorders or did not offer substudies or detailed data analysis focusing on older patients compared with younger ones. The life expectancy of HIV-infected persons receiving highly active antiretroviral therapy (HAART) is now extended (approaching that of the general population), so that the definition of AIDS has lost its epidemiological and clinical significance thanks to the immune reconstitution resulting from potent antiretroviral therapy. However, an ever-increasing number of individuals aged ≥50 years with HIV infection is expected in the coming years, as a result of both increased survival of patients with treated disease and delayed recognition of individuals with occult HIV disease. The limited data available about combined antiretroviral therapy in the elderly seem to show an overlapping virological success rate but a slower and blunted immune recovery compared with younger patients. Thymic output, however, seems somewhat preserved even in adulthood and may contribute to the reconstitution of most of the quantitative and functional T cell abnormalities caused by HIV disease. More attention must be paid to underlying end-organ disorders, as well as expected pharmacological interactions and combined drug toxicity that may interfere with HAART efficacy and patients’ compliance with recommended regimens and could lead to increased adverse effects. The available guidelines for antiretroviral treatment and therapy and prophylaxis of AIDS-related illnesses should be regularly updated and should include problems related to HIV disease in an aging population. Specific trials or substudies focusing on older people are warranted to obtain controlled data on all issues of antiretroviral therapy in the elderly, including time and mode of initiation, and modification and salvage HAART regimens. Antiretroviral drug dosage adjustment to take into account underlying pathological conditions or other pharmacological treatments is another emerging issue.


  1. 1.
    El Sadr W, Gettler J. Unrecognized human immunodeficiency virus infection in the elderly. Arch Intern Med 1994; 155: 184–6Google Scholar
  2. 2.
    Woolery WA. Occult HIV infection: diagnosis and treatment of older patients. Geriatrics 1997; 52: 51–61PubMedGoogle Scholar
  3. 3.
    Bachus MA. HIV and the older adult. J Gerontol Nurs 1998; 24: 41–6PubMedGoogle Scholar
  4. 4.
    Manfredi R, Calza L, Chiodo F. Lack of change in the distribution of AIDS-defining opportunistic diseases and the related degree of immunodeficiency during the periods before and after the introduction of highly active antiretroviral therapy. Eur J Clin Microbiol Infect Dis 2001; 20: 410–3PubMedGoogle Scholar
  5. 5.
    Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis 2000; 30Suppl. 1: S5–14PubMedCrossRefGoogle Scholar
  6. 6.
    Butt AA, Dascomb KK, DeSalvo KB, et al. Human immunodeficiency virus infection in elderly patients. South Med J 2001; 94: 397–400PubMedGoogle Scholar
  7. 7.
    Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency viras infection. N Engl J Med 1998; 338: 853–60PubMedCrossRefGoogle Scholar
  8. 8.
    Powderly WG, Landay A, Lederman MM. Recovery of the immune system with antiretroviral therapy: the end of opportunism? JAMA 1998; 280: 72–7PubMedCrossRefGoogle Scholar
  9. 9.
    Whitman S, Murphy J, Cohen M, et al. Marked declines in HIV-related mortality in Chicago in women, African Americans, Hispanics, young adults and injection drug users from 1995–1997. Arch Intern Med 2000; 163: 365–9CrossRefGoogle Scholar
  10. 10.
    Manfredi R, Ragazzini I, Zucchini A, et al. How long may perinatally-acquired human immunodeficiency virus infection last asymptomatically? Pediatr Infect Dis J 1995; 14: 821–2PubMedCrossRefGoogle Scholar
  11. 11.
    Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morb Mortal Wkly Rep 1994; 41: 1–9Google Scholar
  12. 12.
    Centers for Disease Control and Prevention. HIV/AIDS surveillance report. 1999; 11: 16–25Google Scholar
  13. 13.
    Aggiornamento dei casi di AIDS notificati in Italia al 30 giugno 2000. Notiziario dell’Istituto Superiore di Sanità 2000; 13: 1–12Google Scholar
  14. 14.
    Operskalski EA, Stram DO, Lee H, et al. Human immunodeficiency type 1 infection: relationship of risk group and age to rate of progression to AIDS. J Infect Dis 1995; 172: 648–55PubMedCrossRefGoogle Scholar
  15. 15.
    Chaisson RE, Keraly JC, Moore RD. Race, sex, drag use, and progression of human immunodeficiency virus disease. N Engl J Med 1995; 333: 751–6PubMedCrossRefGoogle Scholar
  16. 16.
    Soriano V, Castilla J, Gomez-Cano M, et al. The decline in CD4+ T lymphocytes as a function of the duration of HIV infection, age at seroconversion, and viral load. J Infect 1998; 36: 307–11PubMedCrossRefGoogle Scholar
  17. 17.
    Alioum A, Leroy V, Commenges D, et al. Effect of gender, age, transmission category, and antiretroviral therapy on the progression of human immunodeficiency virus infection using multistate Markov models. Epidemiology 1998; 9: 605–12PubMedCrossRefGoogle Scholar
  18. 18.
    Adler WH, Nagel JE. Acquired immunodeficiency syndrome in the elderly. Drags Aging 1994; 4: 410–6CrossRefGoogle Scholar
  19. 19.
    Keller MJ, Hausdorff JM, Kyne L, et al. Is age a negative prognostic indicator in HIV infection or AIDS? Aging 1999; 11: 35–8PubMedGoogle Scholar
  20. 20.
    Adler WH, Baskar PV, Chrest FJ, et al. HIV infection and aging: mechanisms to explain the accelerated rate of progression in the older patient. Mech Ageing Dev 1997; 96: 137–55PubMedCrossRefGoogle Scholar
  21. 21.
    Belanger F, Meyer L, Carré N, et al. Influence of age at infection on human immunodeficiency virus disease progression to different clinical endpoints: the SEROCO Cohort (1988–1994). Int J Epidemiol 1997; 26: 1340–5PubMedCrossRefGoogle Scholar
  22. 22.
    Easterbrook PJ, Yu LM, Goetghebeur E, et al. Ten-year trends in CD4 cell counts at HIV and AIDS diagnosis in a London HIV clinic. AIDS 2000; 14: 561–71PubMedCrossRefGoogle Scholar
  23. 23.
    Law MG, De Winter L, McDonald A, et al. AIDS diagnoses at higher CD4 counts in Australia following the introduction of highly active antiretroviral treatment. AIDS 1999; 13: 263–9PubMedCrossRefGoogle Scholar
  24. 24.
    Ledergerber B, Egger M, Erard V, et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy. The Swiss HIV Cohort Study. JAMA 1999; 282: 2220–6PubMedCrossRefGoogle Scholar
  25. 25.
    Mussini C, Pezzotti P, Govoni A, et al. Discontinuation of primary prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency type 1-infected patients: the changes in opportunistic prophylaxis study. J Infect Dis 2000; 181: 1635–42PubMedCrossRefGoogle Scholar
  26. 26.
    USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency viras. Clin Infect Dis 2000; 30Suppl. 1: S29–65Google Scholar
  27. 27.
    Weverling GJ, Mocroft A, Ledergerber B, et al. Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection. Euro SIDA Study Group. Lancet 1999; 353: 1293–8PubMedCrossRefGoogle Scholar
  28. 28.
    Manfredi R, Pieri F, Pileri SA, et al. The changing face of AIDS-related opportunism: cryptococcosis in the highly active antiretroviral therapy (HAART) era: case reports and literature review. Mycopathologia 1999; 148: 73–8PubMedCrossRefGoogle Scholar
  29. 29.
    Michelet C, Arvieux C, François C,et al. Opportunistic infections occurring during highly active antiretroviral treatment. AIDS 1998; 12: 1815–22PubMedCrossRefGoogle Scholar
  30. 30.
    Gebo KA, Diener-West M, Moore RD. Hospitalization rates in an urban cohort after the introduction of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2001; 27: 143–52PubMedGoogle Scholar
  31. 31.
    Manfredi R, Chiodo F. Features of AIDS and AIDS-defining diseases during the highly active antiretroviral therapy (HAART) era, compared with the pre-HAART period: a case-control study. Sex Transm Infect 2000; 76: 145–6PubMedCrossRefGoogle Scholar
  32. 32.
    Mezzaroma I, Carlesimo M, Pinter E, et al. Clinical and immunological response without decrease in virus load in patients with AIDS after 24 months of highly active antiretroviral therapy. Clin Infect Dis 1999; 29: 1423–30PubMedCrossRefGoogle Scholar
  33. 33.
    Samet JH, Freedberg KA, Savetsky JB, et al. Understanding delay to medical care for HIV infection: the long-term non-presenter. AIDS 2001; 15: 77–85PubMedCrossRefGoogle Scholar
  34. 34.
    Manfredi R, Azzimondi G, Rinaldi R, et al. Syndrome of recurrent transient neurological deficits in patients with HIV infection [letter]. AIDS Res Hum Retrovirases 1996; 12: 1583CrossRefGoogle Scholar
  35. 35.
    Rinaldi R, Manfredi R, Azzimondi TG, et al. Recurrent “migrainelike” episodes in patients with HIV disease. Headache 1997; 37: 443–8PubMedCrossRefGoogle Scholar
  36. 36.
    Manfredi R, Chiodo F. Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drags, and role of hypolipidaemic therapy with bezafibrate. J Infect 2001; 42: 181–8PubMedCrossRefGoogle Scholar
  37. 37.
    Calza L, Manfredi R, Mastroianni A, et al. Osteonecrosis and highly active antiretroviral therapy during HIV infection: report of a series and literature review. AIDS Patient Care STDS 2001; 15: 385–9PubMedCrossRefGoogle Scholar
  38. 38.
    Manfredi R. Management of dyslipidemia in patients with HIV disease. Clin Microbiol Infect 2000; 6: 579–84PubMedCrossRefGoogle Scholar
  39. 39.
    Puoti M, Spinetti A, Ghezzi A, et al. Mortality for liver disease in patients with HIV infection: a cohort study. J Acquir Immune Defic Syndr 2000; 24: 211–7PubMedGoogle Scholar
  40. 40.
    Manfredi R, Mastroianni A, Coronado O, et al. Therapeutic and diagnostic procedures in hospitalized AIDS patients with terminal illness. AIDS Care 1996; 8: 373–6PubMedCrossRefGoogle Scholar
  41. 41.
    Manfredi R, Fiacchi P, Riolo U, et al. Terapia antiretrovirale nell’infezione da HIV. Effetti indotti dall’introduzione di nuovi farmaci sulla spesa sanitaria 1994–1999. Recenti Prog Med 2000; 91: 425–9PubMedGoogle Scholar
  42. 42.
    Beck EJ, Miners AH, Tolley K. The cost of HIV treatment and care: a global review. Pharmacoeconomics 2001; 19: 13–39PubMedCrossRefGoogle Scholar
  43. 43.
    Chaix C, Grenier-Sennelier C, Clevenbergh P, et al. Economic evaluation of drag resistance genotyping for the adaptation of treatment in HIV-infected patients in the VIRADAPT study. J Acquir Immune Defic Syndr 2000; 24: 227–31PubMedGoogle Scholar
  44. 44.
    Freedberg KA, Losina E, Weinstein MC, et al. The cost effectiveness of combination antiretroviral therapy for HIV disease. N Engl J Med 2001; 344: 824–31PubMedCrossRefGoogle Scholar
  45. 45.
    Horn CK, Dodds R, Scott GR. Antiretroviral therapy in HIV infection: are we using resources appropriately and cost effectively? Int J STD AIDS 1999; 10: 689–91PubMedCrossRefGoogle Scholar
  46. 46.
    Mole L, Ockrim K, Holodniy M. Decreased medical expenditures for care of HIV-seropositive patients. The impact of highly active antiretroviral therapy at a US Veterans Affairs Medical Center. Pharmacoeconomics 1999; 16: 307–15PubMedCrossRefGoogle Scholar
  47. 47.
    Moore RD. Cost effectiveness of combination HIV therapy: three years later. Pharmacoeconomics 2000; 17: 325–30PubMedCrossRefGoogle Scholar
  48. 48.
    Sendi PP, Bucher HC, Harr T, et al. Cost effectiveness of highly active antiretroviral therapy in HIV-infected patients. The Swiss HIV Cohort Study. AIDS 1999; 13: 1115–22PubMedCrossRefGoogle Scholar
  49. 49.
    Carpenter CCJ, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA 2000; 283: 381–90PubMedCrossRefGoogle Scholar
  50. 50.
    Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS) and the Henry J. Kaiser Family Foundation. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. 2001 Feb 5: 1–104Google Scholar
  51. 51.
    Manfredi R, Chiodo F. First-line nevirapine in combination with nucleoside analogues compared with nevirapine added to a salvage HAART. Infection 2000; 28: 167–70PubMedCrossRefGoogle Scholar
  52. 52.
    Manfredi R, Calza L, Chiodo F. Dual nucleoside analogue treatment in the era of highly active antiretroviral therapy (HAART): a single-centre cross-sectional survey. J Anti-microb Chemother 2001; 48: 299–302Google Scholar
  53. 53.
    Friedland GH, Williams A. Attaining higher goals in HIV treatment: the central importance of adherence. AIDS 1999; 13 Suppl. 1: S61–72PubMedGoogle Scholar
  54. 54.
    Harrington M, Carpenter CC. Hit HIV-1 hard, but only when necessary. Lancet 2000; 355: 2147–52PubMedCrossRefGoogle Scholar
  55. 55.
    Nieuwkerk PT, Reijers MHE, Weigel HM, et al. Quality of life in maintenance vs prolonged induction therapy for HIV. JAMA 2000; 284: 178–9PubMedCrossRefGoogle Scholar
  56. 56.
    Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133: 21–30PubMedGoogle Scholar
  57. 57.
    Bart PA, Rizzardi GP, Tambussi G, et al. Immunological and virological responses in HIV-1-infected adults at early stage of established infection treated with highly active antiretroviral therapy. AIDS 2000; 14: 1887–97PubMedCrossRefGoogle Scholar
  58. 58.
    Chaisson RE, Keruly JC, Moore RD. Association of initial CD4 cell count and viral load with response to highly active antiretroviral therapy. JAMA 2000; 284: 3128–9PubMedCrossRefGoogle Scholar
  59. 59.
    Working Group on Antiretroviral Therapy and Medical Management of HIV-infected Children convened by the National Pediatric and Family HIV Resource Center (NPHRC), the Health Resources and Services Administration (HRSA), and the National Institutes of Health (NIH). Guidelines for the use of antiretroviral agents in Pediatric HIV infection, 2000 Jan 7: 1–59Google Scholar
  60. 60.
    Balotta C, Violin M, Monno L, et al. Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multi-center cohort of HIV-1-infected Italian patients with virologic failure. J Acquir Immune Defic Syndr 2000; 24: 232–40PubMedGoogle Scholar
  61. 61.
    Lorenzi P, Opravil M, Hirschel B, et al. Impact of drug resistance mutations on virologic response to salvage therapy. AIDS 1999; 13: F17–21PubMedCrossRefGoogle Scholar
  62. 62.
    Andrews L, Friedland G. Progress in HIV therapeutics and the challenge of adherence to antiretroviral therapy. Infect Dis Clin North Am 2000; 14: 901–28PubMedCrossRefGoogle Scholar
  63. 63.
    Manfredi R, Chiodo F. Limits of deep salvage antiretroviral therapy with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated patients with HIV disease. Int J Antimicrob Agents 2001; 17: 511–6PubMedCrossRefGoogle Scholar
  64. 64.
    Deeks SG, Hecht FM, Swanson M, et al. HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy. AIDS 1999; 13: F35–43PubMedCrossRefGoogle Scholar
  65. 65.
    Deeks SG, Hellmann NS, Grant RM, et al. Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome. J Infect Dis 1999; 179: 1375–81PubMedCrossRefGoogle Scholar
  66. 66.
    Falloon J. Salvage antiretroviral therapy. AIDS 2000; 14Suppl. 3: S209–17PubMedGoogle Scholar
  67. 67.
    Gisolf EH, Jurriaans S, Pelgrom J, et al. The effect of treatment intensification in HIV-infection: a study comparing treatment with ritonavir/saquinavir and ritonavir/saquinavir/stavudine. AIDS 2000; 14: 405–13PubMedCrossRefGoogle Scholar
  68. 68.
    Khanna N, Klimkait T, Schiffer V, et al. Salvage therapy with abacavir plus a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor in heavily pre-treated HIV-1 infected patients. AIDS 2000; 14: 791–9PubMedCrossRefGoogle Scholar
  69. 69.
    Palmer S, Shafer RW, Merigan TC. Highly drug-resistant HIV-1 clinical isolates are cross-resistant to many antiretroviral compounds in current clinical development. AIDS 1999; 13: 661–7PubMedCrossRefGoogle Scholar
  70. 70.
    Paolucci S, Baldanti F, Maserati R, et al. Quantification of the impact of HIV-1 reverse transcriptase and protease mutations on the efficacy of rescue HAART. Antiviral Res 2000; 45: 101–14PubMedCrossRefGoogle Scholar
  71. 71.
    Piketty C, Race E, Castiel P, et al. Efficacy of a five-drug combination including ritonavir, saquinavir and efavirenz in patients who failed on a conventional triple-drug regimen: phenotypic resistance to protease inhibitors predicts outcome of therapy. AIDS 1999; 13: F71–7PubMedCrossRefGoogle Scholar
  72. 72.
    Shulman NS, Zolopa AR, Passaro DJ, et al. Efavirenz- and adefovir dipivoxil-based salvage therapy in highly treatment-experienced patients: clinical and genotypic predictors of virologic response. J Acquir Immune Defic Syndr 2000; 23: 221–6PubMedGoogle Scholar
  73. 73.
    Heeney JL, Hahn BH. Vaccines and immunology: elucidating immunity to HIV-1 and current prospects for AIDS vaccine development. AIDS 2000; 14Suppl. 3: S125–7PubMedGoogle Scholar
  74. 74.
    Schultz J, Dollenmaier G, Moiling K. Update on antiviral DNA vaccine research (1998–2000). Intervirology 2000; 43: 197–217PubMedCrossRefGoogle Scholar
  75. 75.
    Fessel J, Follansbee S, Hurley L, et al. Does use of potent anti retroviral therapy differ by health care setting? JAMA 1999; 281: 1696–7PubMedCrossRefGoogle Scholar
  76. 76.
    Kumaranayake L, Watts C. Economic costs of HIV/AIDS prevention activities in sub-Saharan Africa. AIDS 2000; 14Suppl. 3: S239–52PubMedGoogle Scholar
  77. 77.
    Drug Topics Red Book. 103rd ed. Montvale (NJ), United States: Thomson Medical Economics, 1999Google Scholar
  78. 78.
    Gebo KA, Chaisson RE, Folkemer JG, et al. Costs of HIV medical care in the era of highly active antiretroviral therapy. AIDS 1999; 13: 963–9PubMedCrossRefGoogle Scholar
  79. 79.
    Cook J, Dasbach D, Coplan P, et al. Modeling the long-term outcomes and costs of HIV antiretroviral therapy using HIVRNA levels: application to a clinical trial. AIDS Res Hum Retroviruses 1999; 15: 599–608CrossRefGoogle Scholar
  80. 80.
    Haynes BF, Hale LP, Weinhold KJ, et al. Analysis of the adult thymus in reconstruction of T lymphocytes in HIV-1 infection. J Clin Invest 1999; 103: 453–6PubMedCrossRefGoogle Scholar
  81. 81.
    Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998; 396: 690–5PubMedCrossRefGoogle Scholar
  82. 82.
    Beltz L. Thymic involution and HIV progression [letter]. Immunol Today 1999; 20: 429PubMedCrossRefGoogle Scholar
  83. 83.
    Poulin JF, Sékaly RP. Function of the thymus in HIV-infected adults [letter]. JAMA 1999; 282: 219PubMedCrossRefGoogle Scholar
  84. 84.
    Manfredi R, Chiodo F. A case-control study of virological and immunological effects of highly active antiretroviral therapy in HIV-infected patients with advanced age. AIDS 2000; 14: 1475–7PubMedCrossRefGoogle Scholar
  85. 85.
    Goetz MB, Boscardin WJ, Wiley D, et al. Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning highly active antiretroviral therapy. AIDS 2001; 15: 1576–9PubMedCrossRefGoogle Scholar
  86. 86.
    Pakker NG, Kroon EDMB, Roos MTL, et al. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. AIDS1999; 13: 203–12PubMedCrossRefGoogle Scholar
  87. 87.
    Operskalski EA, Mosley JW, Busch MP, et al. Influences of age, viral load, and CD4+ count on the rate of progression of HIV-1 infection to AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 15: 243–4PubMedCrossRefGoogle Scholar
  88. 88.
    Goetz MB. Editorial response between virological, immunologic, and clinical outcomes of therapy with protease inhibitors among human immunodeficiency virus-infected patients. Clin Infect Dis 1999; 29: 1431–4PubMedCrossRefGoogle Scholar
  89. 89.
    Deeks SG, Barbour JD, Martin JN, et al. Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection. J Infect Dis 2000; 181: 946–53PubMedCrossRefGoogle Scholar
  90. 90.
    Zhang L, Lewin SR, Markowitz M, et al. Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J Exp Med 1999; 190: 725–32PubMedCrossRefGoogle Scholar
  91. 91.
    Smith KY, Valdez H, Landay A, et al. Thymic size and lymphocyte restoration in patients with human immunodeficiency virus infection after 48 weeks of zidovudine, lamivudine andritonavir therapy. J Infect Dis 2000; 181: 141–7PubMedCrossRefGoogle Scholar
  92. 92.
    Markert ML, Hicks CB, Bartlett JA, et al. Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection. AIDS Res Hum Retroviruses 2000; 16: 403–13PubMedCrossRefGoogle Scholar
  93. 93.
    Douek DC, Koup RA, McFarland RD, et al. Effect of HIV on thymic function before and after antiretroviral therapy in children. J Infect Dis 2000; 181: 1479–82PubMedCrossRefGoogle Scholar
  94. 94.
    Kitchen SG, Killian S, Giorgi JV, et al. Functional reconstitution of thymopoiesis after human immunodeficiency virus infection. J Virol 2000; 74: 2943–8PubMedCrossRefGoogle Scholar
  95. 95.
    Gibb DM, Newberry A, Klein N, et al. Immune repopulation after HAART in previously untreated HIV-1-infected children. Lancet 2000; 355: 1331–2PubMedCrossRefGoogle Scholar
  96. 96.
    Viganò A, Vella S, Principi N, et al. Thymus volume correlates with the progression of vertical HIV infection. AIDS 1999; 13: F29–34PubMedCrossRefGoogle Scholar
  97. 97.
    Viganò A, Vella S, Saresella M, et al. Early immune reconstitution after potent antiretroviral therapy in HIV-infected children correlates with the increase in thymus volume. AIDS 2000; 14: 251–61PubMedCrossRefGoogle Scholar
  98. 98.
    Douek DC, Koup RA. Evidence for thymic function in the elderly. Vaccine 2000; 18: 1638–41PubMedCrossRefGoogle Scholar
  99. 99.
    George AJT, Ritter MA. Thymic involution with ageing: obsolescence or good housekeeping? Immunol Today 1996; 17: 267–72PubMedCrossRefGoogle Scholar
  100. 100.
    Rezza G. Determinants of progression to AIDS in HIV-infected individuals: an update from the Italian Seroconversion Study. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 17Suppl. 1: S13–6PubMedCrossRefGoogle Scholar
  101. 101.
    Paredes R, Mocroft A, Kirk O, et al. Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe: results from the EuroSIDA study. Arch Intern Med 2000; 160: 1123–32PubMedCrossRefGoogle Scholar
  102. 102.
    D’Arminio Monforte A, Testori V, Adozni F, et al. CD4 cell counts at the third month of HAART may predict clinical failure. AIDS 1999; 13: 1669–76PubMedCrossRefGoogle Scholar
  103. 103.
    Descamps D, Flandre P, Calvez V, et al. Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. JAMA 2000; 283: 205–11PubMedCrossRefGoogle Scholar
  104. 104.
    Floridia M, Bucciardini R, Ricciardulli D, et al. A randomized, double-blind trial on the use of a triple combination including nevirapine, a non-nucleoside reverse transcriptase HIV inhibitor, in antiretroviral-naive patients with advanced disease. J Acquir Immune Defic Syndr Hum Retrovirol 1999; 20: 11–9PubMedCrossRefGoogle Scholar
  105. 105.
    Floridia M, Tomino C, Bucciardini R, et al. A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection. AIDS Res Hum Retroviruses 2000; 16: 1809–20PubMedCrossRefGoogle Scholar
  106. 106.
    Grabar S, Pradier C, Le Corfec, et al. Factors associated with clinical and virological failure in patients receiving a triple therapy including a protease inhibitor. AIDS 2000; 14: 141–9PubMedCrossRefGoogle Scholar
  107. 107.
    Gulick RM, Mellors JW, Havlir D, et al. Treatment with in dinavir, zidovudine and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 1997; 337: 725–33CrossRefGoogle Scholar
  108. 108.
    Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions. Ann Intern Med 1999; 131: 81–7PubMedGoogle Scholar
  109. 109.
    Murphy RL, Brun S, Hicks C, et al. ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-week results. AIDS 2001; 15: 1–9CrossRefGoogle Scholar
  110. 110.
    Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med 1999; 341: 1865–73PubMedCrossRefGoogle Scholar
  111. 111.
    Casado JL, Perez-Elías MJ, Antela A, et al. Predictors of long-term response to protease inhibitors therapy in a cohort of HIV-infected patients. AIDS 1998; 12: F131–5PubMedCrossRefGoogle Scholar
  112. 112.
    Wit WNM, Van Leeuwen R, Weverling GJ, et al. Outcome and predictors of failure of highly active antiretroviral therapy: one-year follow-up of a cohort of human odeficiency virus type 1-infected persons. J Infect Dis 1999; 179: 790–8PubMedCrossRefGoogle Scholar
  113. 113.
    Mocroft A, Youle M, Moore A, et al. Reasons for modification and discontinuation of antiretroviral therapy: results from a single treatment centre. AIDS 2001; 15: 185–94PubMedCrossRefGoogle Scholar
  114. 114.
    Manfredi R, Chiodo F. Switch of protease inhibitor-containing HAART in routine clinical practice: a four-year prospective observational study. Int J STD AIDS 2001; 12: 84–8PubMedCrossRefGoogle Scholar
  115. 115.
    Manfredi R, Chiodo F. Substitution of protease inhibitors during treatment of patients with human immunodeficiency virus infection: frequency, mode, reasons, and mid-term outcome. J Antimicrob Chemother 2000; 45: 261–3PubMedCrossRefGoogle Scholar
  116. 116.
    Manfredi R, Calza L, Chiodo F. Gynecomastia associated with highly active antiretroviral therapy. Ann Pharmacother 2001; 35: 438–9PubMedCrossRefGoogle Scholar
  117. 117.
    Barreiro P, Soriano V, Blanco F, et al. Risks and benefits of replacing protease inhibitors by nevirapine in HIV-infected subjects under long-term successful triple combination therapy. AIDS 2000; 14: 807–12PubMedCrossRefGoogle Scholar
  118. 118.
    Manfredi R, Chiodo F. Switch to an antiretroviral treatment of expected lower potency after effective highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2000; 23: 95–8PubMedGoogle Scholar
  119. 119.
    Martinez E, Conget I, Lozano L, et al. Reversion of metabolic abnormalities after switching from HIV-1 protease inhibitors to nevirapine. AIDS1999; 13: 805–10PubMedCrossRefGoogle Scholar
  120. 120.
    Pialoux G, Raffi F, Brun-Vezinet F, et al. A randomized trial of three maintenance regimens given after three months of induction therapy with zidovudine, lamivudine, and indinavir in previously untreated HIV-1-infected patients. N Engl J Med 1998; 339: 1269–76PubMedCrossRefGoogle Scholar
  121. 121.
    Chesney MA. Factors affecting adherence to antiretroviral therapy. Clin Infect Dis 2000; 30Suppl. 2: S171–6PubMedCrossRefGoogle Scholar
  122. 122.
    Catucci M, Venturi G, Romano L, et al. Development and significance of the HIV-1 reverse transcriptase M184V mutation during combination therapy with lamivudine, zidovudine, and protease inhibitors. J Acquir Immune Defic Syndr 1999; 21: 203–8PubMedCrossRefGoogle Scholar
  123. 123.
    Casado JL, Hertogs K, Ruiz L, et al. Non-nucleoside reverse transcriptase inhibitor resistance among patients failing a nevirapine plus protease inhibitor-containing regimen. AIDS 2000; 14: Fl–7CrossRefGoogle Scholar
  124. 124.
    Durant J, Clevenbergh P, Halfon P, et al. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet 1999; 353: 2195–9PubMedCrossRefGoogle Scholar
  125. 125.
    Erickson JW, Gulnick SV, Markowitz M. Protease inhibitors: resistance, cross-resistance, fitness and the choice of initial and salvage therapies. AIDS 1999; 13Suppl. A: S189–204PubMedGoogle Scholar
  126. 126.
    Harrigan PR, Côte HCF. Clinical utility of testing human immunodeficiency virus for drug resistance. Clin Infect Dis 2000; 30Suppl. 2: S117–22PubMedCrossRefGoogle Scholar
  127. 127.
    Havlir DV, Hellmann NS, Petropoulos CJ, et al. Drug susceptibility in HIV infection after viral rebound in patients receiving avir-containing regimens. JAMA 2000; 283: 229–34PubMedCrossRefGoogle Scholar
  128. 128.
    Call SA, Saag MS, Westfall AO, et al. Phenotypic drug susceptibility testing predicts long-term virologic suppression better than treatment history in patients with human immunodeficiency virus infection. J Infect Dis 2001; 183: 401–8PubMedCrossRefGoogle Scholar
  129. 129.
    Max B, Sherer R. Management of the adverse effects of antiretroviral therapy and medication adherence. Clin Infect Dis 2000; 30Suppl. 2: S96–116PubMedCrossRefGoogle Scholar
  130. 130.
    Wutoh AK, Brown CM, Kumoji EK, et al. Antiretroviral adherence and use of alternative therapies and older HIV-infected adults. J Natl Med Assoc 2001; 93: 243–50PubMedGoogle Scholar
  131. 131.
    Manfredi R, Chiodo F. The effects of alternative treatments for HIV disease on recommended pharmacological regimens. Int J Antimicrob Agents 2000; 13: 281–5PubMedCrossRefGoogle Scholar
  132. 132.
    Von Giesen HJ, Hefter H, Jablonowski H, et al. Stavudine and the peripheral nerve in HIV-1 infected patients. J Neurol 1999; 246: 211–7CrossRefGoogle Scholar
  133. 133.
    Brinkman K, Smeitink JA, Romijn JA, et al. Mitochondrial toxicity induced by nucleoside analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral therapy-related lipodystrophy. Lancet 1999; 354: 112–5CrossRefGoogle Scholar
  134. 134.
    Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12: F51–8PubMedCrossRefGoogle Scholar
  135. 135.
    Christeff N, Melchior JC, De Truchis P, et al. Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations. AIDS 1999; 13: 2251–60PubMedCrossRefGoogle Scholar
  136. 136.
    Graham NM. Metabolic disorders among HIV-infected patients treated with protease inhibitors: a review. J Acquir Immune Defic Syndr 2000; 25Suppl. 1: S4–11PubMedGoogle Scholar
  137. 137.
    Hadigan C, Meigs JB, Corcoran C, et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001; 32: 130–9PubMedCrossRefGoogle Scholar
  138. 138.
    Mann M, Piazza-Hepp T, Koller E, et al. Unusual distribution of body fat in AIDS patients: a review of adverse events reported to the Food and Drug Administration. AIDS Patient Care STDS 1999; 13: 287–95PubMedCrossRefGoogle Scholar
  139. 139.
    Mauss S. HIV-associated lipodystrophy syndrome. AIDS 2000; 14Suppl. 3: S197–207PubMedGoogle Scholar
  140. 140.
    Périard D, Telenti A, Sudre P, et al. Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. Circulation 1999; 100: 700–5PubMedCrossRefGoogle Scholar
  141. 141.
    Saint-Marc T, Partisani M, Poizot-Martin I, et al. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS 1999; 13: 1659–67PubMedCrossRefGoogle Scholar
  142. 142.
    Saint-Marc T, Partisani M, Poizot-Martin I, et al. Fat redistribution evaluated by computed tomography and metabolic abnormalities in patients undergoing antiretroviral therapy: preliminary results of the LIPOCO study. AIDS 2000; 14: 37–49PubMedCrossRefGoogle Scholar
  143. 143.
    Tantisiriwat W, Tebas P, Polish LB, et al. Elevated lactate levels in hospitalized persons with HIV infection. AIDS Res Hum Retroviruses 2001; 17: 195–201PubMedCrossRefGoogle Scholar
  144. 144.
    Tebas P, Powderly WG, Claxton S, et al. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS 2000; 14: F63–7PubMedCrossRefGoogle Scholar
  145. 145.
    Yanovski JA, Miller KN, Kino T, et al. Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. J Clin Endocrinol Metab 1999; 84: 1925–31PubMedCrossRefGoogle Scholar
  146. 146.
    Kakuda TN, Brundage RC, Anderson PL, et al. Nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity as an etiology for lipodystrophy. AIDS 1999; 13: 2311–2PubMedCrossRefGoogle Scholar
  147. 147.
    Miller KD, Cameron M, Wood LV, et al. Lactic acidosis and hepatic steatosis associated with use of stavudine administration: report of four cases. Ann Intern Med 2000; 133: 192–6PubMedGoogle Scholar
  148. 148.
    Mulligan K, Grunfeld C, Tai VW, 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: 35–43PubMedGoogle Scholar
  149. 149.
    Henry K, Melroe H, Huebesch J, et al. Atorvastatin and gemfibrozil for protease-inhibitor-related lipid abnormalities. Lancet 1998; 352: 1031–2PubMedCrossRefGoogle Scholar
  150. 150.
    Dubé MP, Sprecher D, Keith Henry W, et al. Preliminary guide lines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: recommendations of the Adults AIDS Clinical Trial Group Cardiovascular Disease Focus Group. Clin Infect Dis 2000; 31: 1216–24PubMedCrossRefGoogle Scholar
  151. 151.
    Murphy RL, Sommadossi JP, Lamson M, et al. Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1. J Infect Dis 1999; 179: 1116–23PubMedCrossRefGoogle Scholar
  152. 152.
    Zablotsky DL. Overlooked, ignored and forgotten: older women at risk for HIV infection and AIDS. Res Aging 1998; 20: 760–6CrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  1. 1.Department of Clinical and Experimental Medicine, Division of Infectious DiseasesUniversity of Bologna, S. Orsola HospitalBolognaItaly

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