Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Immune reconstitution inflammatory syndrome

INTRODUCTION

The term "immune reconstitution inflammatory syndrome" (IRIS) describes a collection of inflammatory disorders associated with paradoxical worsening of preexisting infectious processes following the initiation of highly active antiretroviral therapy (HAART) in HIV-infected individuals [1-6]. Preexisting infections in individuals with IRIS may have been previously diagnosed and treated or they may be subclinical and later unmasked by the host's regained capacity to mount an inflammatory response [7].

If immune function improves rapidly following the commencement of HAART, systemic or local inflammatory reactions may occur at the site or sites of the preexisting infection. This inflammatory reaction is usually self-limited, especially if the preexisting infection is effectively treated. However, long-term sequelae and fatal outcomes may rarely occur, particularly when neurologic structures are involved.

This topic reviews the immunobiology, pathogenesis, clinical features, and management of IRIS. Since the clinical features are strongly linked with type and location of preexisting infection, IRIS associated with preexisting mycobacterial, cryptococcal, cytomegalovirus, Pneumocystis jirovecii, and JC virus infection will be discussed as separate entities even though the basic mechanism of illness is similar. In the absence of well-performed clinical trials, our recommendations for managing IRIS are based on clinical experience, case reports, case series, and expert opinion.

Initiation of HAART is discussed separately. (See "Selecting antiretroviral regimens for the treatment naive HIV-infected patient".)

TERMS

Many synonyms exist for IRIS [2,8,9]:

                        

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2014. | This topic last updated: Mar 22, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. DeSimone JA, Pomerantz RJ, Babinchak TJ. Inflammatory reactions in HIV-1-infected persons after initiation of highly active antiretroviral therapy. Ann Intern Med 2000; 133:447.
  2. French MA, Lenzo N, John M, et al. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med 2000; 1:107.
  3. Shelburne SA 3rd, Hamill RJ, Rodriguez-Barradas MC, et al. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine (Baltimore) 2002; 81:213.
  4. Michelet C, Arvieux C, François C, et al. Opportunistic infections occurring during highly active antiretroviral treatment. AIDS 1998; 12:1815.
  5. Hirsch HH, Kaufmann G, Sendi P, Battegay M. Immune reconstitution in HIV-infected patients. Clin Infect Dis 2004; 38:1159.
  6. Shelburne SA, Montes M, Hamill RJ. Immune reconstitution inflammatory syndrome: more answers, more questions. J Antimicrob Chemother 2006; 57:167.
  7. French MA. HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis 2009; 48:101.
  8. Cheng VC, Yuen KY, Chan WM, et al. Immunorestitution disease involving the innate and adaptive response. Clin Infect Dis 2000; 30:882.
  9. Cooney EL. Clinical indicators of immune restoration following highly active antiretroviral therapy. Clin Infect Dis 2002; 34:224.
  10. Campbell IA, Dyson AJ. Lymph node tuberculosis: a comparison of various methods of treatment. Tubercle 1977; 58:171.
  11. Chambers ST, Hendrickse WA, Record C, et al. Paradoxical expansion of intracranial tuberculomas during chemotherapy. Lancet 1984; 2:181.
  12. Smith H. Paradoxical responses during the chemotherapy of tuberculosis. J Infect 1987; 15:1.
  13. Garcia Vidal C, Rodríguez Fernández S, Martínez Lacasa J, et al. Paradoxical response to antituberculous therapy in infliximab-treated patients with disseminated tuberculosis. Clin Infect Dis 2005; 40:756.
  14. Sansonetti P, Lagrange PH. The immunology of leprosy: speculations on the leprosy spectrum. Rev Infect Dis 1981; 3:422.
  15. Singh N, Lortholary O, Alexander BD, et al. An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients. Clin Infect Dis 2005; 40:1756.
  16. Cadena J, Thompson GR 3rd, Ho TT, et al. Immune reconstitution inflammatory syndrome after cessation of the tumor necrosis factor alpha blocker adalimumab in cryptococcal pneumonia. Diagn Microbiol Infect Dis 2009; 64:327.
  17. Pakker NG, Notermans DW, de Boer RJ, et al. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med 1998; 4:208.
  18. Notermans DW, Pakker NG, Hamann D, et al. Immune reconstitution after 2 years of successful potent antiretroviral therapy in previously untreated human immunodeficiency virus type 1-infected adults. J Infect Dis 1999; 180:1050.
  19. Autran B, Carcelain G, Li TS, et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 1997; 277:112.
  20. Markert ML, Alvarez-McLeod AP, Sempowski GD, et al. Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy. AIDS Res Hum Retroviruses 2001; 17:1635.
  21. Franco JM, Rubio A, Martínez-Moya M, et al. T-cell repopulation and thymic volume in HIV-1-infected adult patients after highly active antiretroviral therapy. Blood 2002; 99:3702.
  22. Sempowski GD, Haynes BF. Immune reconstitution in patients with HIV infection. Annu Rev Med 2002; 53:269.
  23. Lederman MM, Connick E, Landay A, et al. Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect Dis 1998; 178:70.
  24. Antonelli LR, Mahnke Y, Hodge JN, et al. Elevated frequencies of highly activated CD4+ T cells in HIV+ patients developing immune reconstitution inflammatory syndrome. Blood 2010; 116:3818.
  25. Haddow LJ, Easterbrook PJ, Mosam A, et al. Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort. Clin Infect Dis 2009; 49:1424.
  26. Grant PM, Komarow L, Andersen J, et al. Risk factor analyses for immune reconstitution inflammatory syndrome in a randomized study of early vs. deferred ART during an opportunistic infection. PLoS One 2010; 5:e11416.
  27. Ratnam I, Chiu C, Kandala NB, Easterbrook PJ. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1-infected cohort. Clin Infect Dis 2006; 42:418.
  28. Manabe YC, Campbell JD, Sydnor E, Moore RD. Immune reconstitution inflammatory syndrome: risk factors and treatment implications. J Acquir Immune Defic Syndr 2007; 46:456.
  29. Jabs DA, Van Natta ML, Kempen JH, et al. Characteristics of patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Am J Ophthalmol 2002; 133:48.
  30. Breton G, Duval X, Estellat C, et al. Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy. Clin Infect Dis 2004; 39:1709.
  31. Murdoch DM, Venter WD, Feldman C, Van Rie A. Incidence and risk factors for the immune reconstitution inflammatory syndrome in HIV patients in South Africa: a prospective study. AIDS 2008; 22:601.
  32. Müller M, Wandel S, Colebunders R, et al. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. Lancet Infect Dis 2010; 10:251.
  33. Nolan RC, Chidlow G, French MA. Parvovirus B19 encephalitis presenting as immune restoration disease after highly active antiretroviral therapy for human immunodeficiency virus infection. Clin Infect Dis 2003; 36:1191.
  34. Breton G, Adle-Biassette H, Therby A, et al. Immune reconstitution inflammatory syndrome in HIV-infected patients with disseminated histoplasmosis. AIDS 2006; 20:119.
  35. van Hal SJ, Kotsiou G. An HIV-positive man with generalized rash. Clin Infect Dis 2005; 40:113, 182.
  36. Couppié P, Abel S, Voinchet H, et al. Immune reconstitution inflammatory syndrome associated with HIV and leprosy. Arch Dermatol 2004; 140:997.
  37. Lawn SD, Wood C, Lockwood DN. Borderline tuberculoid leprosy: an immune reconstitution phenomenon in a human immunodeficiency virus-infected person. Clin Infect Dis 2003; 36:e5.
  38. Menezes VM, Sales AM, Illarramendi X, et al. Leprosy reaction as a manifestation of immune reconstitution inflammatory syndrome: a case series of a Brazilian cohort. AIDS 2009; 23:641.
  39. Puthanakit T, Oberdorfer P, Punjaisee S, et al. Immune reconstitution syndrome due to bacillus Calmette-Guérin after initiation of antiretroviral therapy in children with HIV infection. Clin Infect Dis 2005; 41:1049.
  40. Gupta S, Mathur P, Maskey D, et al. Immune restoration syndrome with disseminated Penicillium marneffei and cytomegalovirus co-infections in an AIDS patient. AIDS Res Ther 2007; 4:21.
  41. de Silva S, Walsh J, Brown M. Symptomatic Schistosoma mansoni infection as an immune restoration phenomenon in a patient receiving antiretroviral therapy. Clin Infect Dis 2006; 42:303.
  42. Shelburne SA, Visnegarwala F, Darcourt J, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005; 19:399.
  43. Connick E, Kane MA, White IE, et al. Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma during potent antiretroviral therapy. Clin Infect Dis 2004; 39:1852.
  44. Bower M, Nelson M, Young AM, et al. Immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma. J Clin Oncol 2005; 23:5224.
  45. Cheng VC, Ho PL, Lee RA, et al. Clinical spectrum of paradoxical deterioration during antituberculosis therapy in non-HIV-infected patients. Eur J Clin Microbiol Infect Dis 2002; 21:803.
  46. Manabe YC, Breen R, Perti T, et al. Unmasked tuberculosis and tuberculosis immune reconstitution inflammatory disease: a disease spectrum after initiation of antiretroviral therapy. J Infect Dis 2009; 199:437.
  47. Hawkey CR, Yap T, Pereira J, et al. Characterization and management of paradoxical upgrading reactions in HIV-uninfected patients with lymph node tuberculosis. Clin Infect Dis 2005; 40:1368.
  48. Dheda K, Lampe FC, Johnson MA, Lipman MC. Outcome of HIV-associated tuberculosis in the era of highly active antiretroviral therapy. J Infect Dis 2004; 190:1670.
  49. Matthay RA, Neff TA, Iseman MD. Tuberculous pleural effusions developing during chemotherapy for pulmonary tuberculosis. Am Rev Respir Dis 1974; 109:469.
  50. Al-Majed SA. Study of paradoxical response to chemotherapy in tuberculous pleural effusion. Respir Med 1996; 90:211.
  51. Price P, Murdoch DM, Agarwal U, et al. Immune restoration diseases reflect diverse immunopathological mechanisms. Clin Microbiol Rev 2009; 22:651.
  52. Afghani B, Lieberman JM. Paradoxical enlargement or development of intracranial tuberculomas during therapy: case report and review. Clin Infect Dis 1994; 19:1092.
  53. Nicolls DJ, King M, Holland D, et al. Intracranial tuberculomas developing while on therapy for pulmonary tuberculosis. Lancet Infect Dis 2005; 5:795.
  54. Pepper DJ, Marais S, Maartens G, et al. Neurologic manifestations of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome: a case series. Clin Infect Dis 2009; 48:e96.
  55. Rooney JJ Jr, Crocco JA, Kramer S, Lyons HA. Further observations on tuberculin reactions in active tuberculosis. Am J Med 1976; 60:517.
  56. Dooley DP, Carpenter JL, Rademacher S. Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature. Clin Infect Dis 1997; 25:872.
  57. Kaplan JE, Benson C, Holmes KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009; 58:1.
  58. Chien JW, Johnson JL. Paradoxical reactions in HIV and pulmonary TB. Chest 1998; 114:933.
  59. John M, French MA. Exacerbation of the inflammatory response to Mycobacterium tuberculosis after antiretroviral therapy. Med J Aust 1998; 169:473.
  60. Navas E, Martín-Dávila P, Moreno L, et al. Paradoxical reactions of tuberculosis in patients with the acquired immunodeficiency syndrome who are treated with highly active antiretroviral therapy. Arch Intern Med 2002; 162:97.
  61. Narita M, Ashkin D, Hollender ES, Pitchenik AE. Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS. Am J Respir Crit Care Med 1998; 158:157.
  62. Fishman JE, Saraf-Lavi E, Narita M, et al. Pulmonary tuberculosis in AIDS patients: transient chest radiographic worsening after initiation of antiretroviral therapy. AJR Am J Roentgenol 2000; 174:43.
  63. Kumarasamy N, Chaguturu S, Mayer KH, et al. Incidence of immune reconstitution syndrome in HIV/tuberculosis-coinfected patients after initiation of generic antiretroviral therapy in India. J Acquir Immune Defic Syndr 2004; 37:1574.
  64. Hill AR, Mateo F, Hudak A. Transient exacerbation of tuberculous lymphadenitis during chemotherapy in patients with AIDS. Clin Infect Dis 1994; 19:774.
  65. Furrer H, Malinverni R. Systemic inflammatory reaction after starting highly active antiretroviral therapy in AIDS patients treated for extrapulmonary tuberculosis. Am J Med 1999; 106:371.
  66. Guex AC, Bucher HC, Demartines N, et al. Inflammatory bowel perforation during immune restoration after one year of antiretroviral and antituberculous therapy in an HIV-1-infected patient: report of a case. Dis Colon Rectum 2002; 45:977.
  67. Jehle AW, Khanna N, Sigle JP, et al. Acute renal failure on immune reconstitution in an HIV-positive patient with miliary tuberculosis. Clin Infect Dis 2004; 38:e32.
  68. Cabié A, Abel S, Brebion A, et al. Mycobacterial lymphadenitis after initiation of highly active antiretroviral therapy. Eur J Clin Microbiol Infect Dis 1998; 17:812.
  69. Race EM, Adelson-Mitty J, Kriegel GR, et al. Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease. Lancet 1998; 351:252.
  70. Phillips P, Bonner S, Gataric N, et al. Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: spectrum of disease and long-term follow-up. Clin Infect Dis 2005; 41:1483.
  71. Lawn SD, Bekker LG, Miller RF. Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals. Lancet Infect Dis 2005; 5:361.
  72. Dworkin MS, Fratkin MD. Mycobacterium avium complex lymph node abscess after use of highly active antiretroviral therapy in a patient with AIDS. Arch Intern Med 1998; 158:1828.
  73. Murray R, Mallal S, Heath C, French M. Cerebral mycobacterium avium infection in an HIV-infected patient following immune reconstitution and cessation of therapy for disseminated mycobacterium avium complex infection. Eur J Clin Microbiol Infect Dis 2001; 20:199.
  74. Cinti SK, Kaul DR, Sax PE, et al. Recurrence of Mycobacterium avium infection in patients receiving highly active antiretroviral therapy and antimycobacterial agents. Clin Infect Dis 2000; 30:511.
  75. Hill AR, Premkumar S, Brustein S, et al. Disseminated tuberculosis in the acquired immunodeficiency syndrome era. Am Rev Respir Dis 1991; 144:1164.
  76. Skiest DJ, Hester LJ, Hardy RD. Cryptococcal immune reconstitution inflammatory syndrome: report of four cases in three patients and review of the literature. J Infect 2005; 51:e289.
  77. Lortholary O, Fontanet A, Mémain N, et al. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS 2005; 19:1043.
  78. Sungkanuparph S, Jongwutiwes U, Kiertiburanakul S. Timing of cryptococcal immune reconstitution inflammatory syndrome after antiretroviral therapy in patients with AIDS and cryptococcal meningitis. J Acquir Immune Defic Syndr 2007; 45:595.
  79. Woods ML 2nd, MacGinley R, Eisen DP, Allworth AM. HIV combination therapy: partial immune restitution unmasking latent cryptococcal infection. AIDS 1998; 12:1491.
  80. Boulware DR, Bonham SC, Meya DB, et al. Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is associated with subsequent immune reconstitution inflammatory syndrome. J Infect Dis 2010; 202:962.
  81. Shelburne SA 3rd, Darcourt J, White AC Jr, et al. The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis 2005; 40:1049.
  82. Singh N, Perfect JR. Immune reconstitution syndrome associated with opportunistic mycoses. Lancet Infect Dis 2007; 7:395.
  83. Jenny-Avital ER, Abadi M. Immune reconstitution cryptococcosis after initiation of successful highly active antiretroviral therapy. Clin Infect Dis 2002; 35:e128.
  84. Blanche P, Gombert B, Ginsburg C, et al. HIV combination therapy: immune restitution causing cryptococcal lymphadenitis dramatically improved by anti-inflammatory therapy. Scand J Infect Dis 1998; 30:615.
  85. Wright ME, Suzman DL, Csaky KG, et al. Extensive retinal neovascularization as a late finding in human immunodeficiency virus-infected patients with immune recovery uveitis. Clin Infect Dis 2003; 36:1063.
  86. Karavellas MP, Plummer DJ, Macdonald JC, et al. Incidence of immune recovery vitritis in cytomegalovirus retinitis patients following institution of successful highly active antiretroviral therapy. J Infect Dis 1999; 179:697.
  87. Wohl DA, Kendall MA, Owens S, et al. The safety of discontinuation of maintenance therapy for cytomegalovirus (CMV) retinitis and incidence of immune recovery uveitis following potent antiretroviral therapy. HIV Clin Trials 2005; 6:136.
  88. Jacobson MA, Zegans M, Pavan PR, et al. Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy. Lancet 1997; 349:1443.
  89. Karavellas MP, Song M, Macdonald JC, Freeman WR. Long-term posterior and anterior segment complications of immune recovery uveitis associated with cytomegalovirus retinitis. Am J Ophthalmol 2000; 130:57.
  90. Miller RF, Shaw PJ, Williams IG. Immune reconstitution CMV pneumonitis. Sex Transm Infect 2000; 76:60.
  91. Gilquin J, Piketty C, Thomas V, et al. Acute cytomegalovirus infection in AIDS patients with CD4 counts above 100 x 10(6) cells/l following combination antiretroviral therapy including protease inhibitors. AIDS 1997; 11:1659.
  92. Gallant JE, Moore RD, Richman DD, et al. Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group. J Infect Dis 1992; 166:1223.
  93. Cinque P, Bossolasco S, Brambilla AM, et al. The effect of highly active antiretroviral therapy-induced immune reconstitution on development and outcome of progressive multifocal leukoencephalopathy: study of 43 cases with review of the literature. J Neurovirol 2003; 9 Suppl 1:73.
  94. Collazos J, Mayo J, Martínez E, Blanco MS. Contrast-enhancing progressive multifocal leukoencephalopathy as an immune reconstitution event in AIDS patients. AIDS 1999; 13:1426.
  95. Berenguer J, Miralles P, Arrizabalaga J, et al. Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy. Clin Infect Dis 2003; 36:1047.
  96. Hoffmann C, Horst HA, Albrecht H, Schlote W. Progressive multifocal leucoencephalopathy with unusual inflammatory response during antiretroviral treatment. J Neurol Neurosurg Psychiatry 2003; 74:1142.
  97. Vendrely A, Bienvenu B, Gasnault J, et al. Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy. Acta Neuropathol 2005; 109:449.
  98. Safdar A, Rubocki RJ, Horvath JA, et al. Fatal immune restoration disease in human immunodeficiency virus type 1-infected patients with progressive multifocal leukoencephalopathy: impact of antiretroviral therapy-associated immune reconstitution. Clin Infect Dis 2002; 35:1250.
  99. Barry SM, Lipman MC, Deery AR, et al. Immune reconstitution pneumonitis following Pneumocystis carinii pneumonia in HIV-infected subjects. HIV Med 2002; 3:207.
  100. Koval CE, Gigliotti F, Nevins D, Demeter LM. Immune reconstitution syndrome after successful treatment of Pneumocystis carinii pneumonia in a man with human immunodeficiency virus type 1 infection. Clin Infect Dis 2002; 35:491.
  101. Wislez M, Bergot E, Antoine M, et al. Acute respiratory failure following HAART introduction in patients treated for Pneumocystis carinii pneumonia. Am J Respir Crit Care Med 2001; 164:847.
  102. Martínez E, Gatell J, Morán Y, et al. High incidence of herpes zoster in patients with AIDS soon after therapy with protease inhibitors. Clin Infect Dis 1998; 27:1510.
  103. Carr A, Cooper DA. Restoration of immunity to chronic hepatitis B infection in HIV-infected patient on protease inhibitor. Lancet 1997; 349:995.
  104. Drake A, Mijch A, Sasadeusz J. Immune reconstitution hepatitis in HIV and hepatitis B coinfection, despite lamivudine therapy as part of HAART. Clin Infect Dis 2004; 39:129.
  105. John M, Flexman J, French MA. Hepatitis C virus-associated hepatitis following treatment of HIV-infected patients with HIV protease inhibitors: an immune restoration disease? AIDS 1998; 12:2289.
  106. Rutschmann OT, Negro F, Hirschel B, et al. Impact of treatment with human immunodeficiency virus (HIV) protease inhibitors on hepatitis C viremia in patients coinfected with HIV. J Infect Dis 1998; 177:783.
  107. Zylberberg H, Pialoux G, Carnot F, et al. Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy. Clin Infect Dis 1998; 27:1255.
  108. Monsuez JJ, Vittecoq D, Musset L, et al. Arthralgias and cryoglobulinemia during protease inhibitor therapy in a patient infected with human immunodeficiency virus and hepatitis C virus. Arthritis Rheum 1998; 41:740.
  109. Posada-Vergara MP, Lindoso JA, Tolezano JE, et al. Tegumentary leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome in 2 patients with AIDS. J Infect Dis 2005; 192:1819.
  110. Clutter D, Kambugu A, Orem J, et al. Kaposi's Sarcoma-associated IRIS in Africa: Initial findings from a prospective evaluation. Presented at the 16th Annual Conference on Retroviruses and Opportunistic Infections, Montreal, Canada February 8-11th, 2009; abstract #31.
  111. Crane HM, Deubner H, Huang JC, et al. Fatal Kaposi's sarcoma-associated immune reconstitution following HAART initiation. Int J STD AIDS 2005; 16:80.
  112. Achenbach CJ, Harrington RD, Dhanireddy S, et al. Paradoxical immune reconstitution inflammatory syndrome in HIV-infected patients treated with combination antiretroviral therapy after AIDS-defining opportunistic infection. Clin Infect Dis 2012; 54:424.
  113. Gomez V, Smith PR, Burack J, et al. Sarcoidosis after antiretroviral therapy in a patient with acquired immunodeficiency syndrome. Clin Infect Dis 2000; 31:1278.
  114. Lenner R, Bregman Z, Teirstein AS, DePalo L. Recurrent pulmonary sarcoidosis in HIV-infected patients receiving highly active antiretroviral therapy. Chest 2001; 119:978.
  115. Naccache JM, Antoine M, Wislez M, et al. Sarcoid-like pulmonary disorder in human immunodeficiency virus-infected patients receiving antiretroviral therapy. Am J Respir Crit Care Med 1999; 159:2009.
  116. Gilquin J, Viard JP, Jubault V, et al. Delayed occurrence of Graves' disease after immune restoration with HAART. Highly active antiretroviral therapy. Lancet 1998; 352:1907.
  117. Jubault V, Penfornis A, Schillo F, et al. Sequential occurrence of thyroid autoantibodies and Graves' disease after immune restoration in severely immunocompromised human immunodeficiency virus-1-infected patients. J Clin Endocrinol Metab 2000; 85:4254.
  118. Chen F, Day SL, Metcalfe RA, et al. Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease. Medicine (Baltimore) 2005; 84:98.
  119. Zolopa A, Andersen J, Powderly W, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One 2009; 4:e5575.
  120. Castelnuovo B, Manabe YC, Kiragga A, et al. Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort. Clin Infect Dis 2009; 49:965.
  121. Thompson MA, Aberg JA, Cahn P, et al. Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel. JAMA 2010; 304:321.
  122. http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=7&ClassID=1 (Accessed on September 20, 2010).
  123. Burman WJ. Issues in the management of HIV-related tuberculosis. Clin Chest Med 2005; 26:283.
  124. McGovern B. What drives hepatitis B virus-related hepatic flares? Virus, T cells--or a bit of both? Clin Infect Dis 2004; 39:133.