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Management of the Immune Reconstitution Inflammatory Syndrome

  • Co-infections (C Benson, Section Editor)
  • Published:
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Abstract

The immune reconstitution inflammatory syndrome (IRIS) is a frequent early complication of antiretroviral therapy (ART) in patients with advanced HIV. Because there is no confirmatory diagnostic test, the diagnosis is based on clinical presentation and exclusion of alternative causes for deterioration, such as antimicrobial drug resistance. Opportunistic infection treatment should be optimized. Mild cases may require symptomatic therapy alone or nonsteroidal anti-inflammatory drugs. Corticosteroids have been used to treat more severe cases of IRIS associated with mycobacterial and fungal infections. There is evidence from a randomized controlled trial that prednisone reduces morbidity and improves symptoms in paradoxical tuberculosis (TB)-IRIS. Neurological TB-IRIS is potentially life-threatening; high-dose corticosteroids are indicated and ART interruption should be considered if level of consciousness is depressed. When considering corticosteroid treatment clinicians should be aware of their side effects and only use them when the diagnosis of IRIS is certain. In viral forms of IRIS corticosteroids are generally avoided.

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References

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

  1. 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;1:107–15.

    Article  PubMed  CAS  Google Scholar 

  2. 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;49:1424–32.

    Article  PubMed  Google Scholar 

  3. 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;42:418–27.

    Article  PubMed  CAS  Google Scholar 

  4. • Haddow LJ, Colebunders R, Meintjes G, et al. Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions. Lancet Infect Dis. 2010;10:791–802. Consenus case definitions for diagnosing cryptococcal IRIS proposed by the International Network for the Study of HIV-associated IRIS (INSHI).

    Article  PubMed  Google Scholar 

  5. Meintjes G, Lawn SD, Scano F, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis. 2008;8:516–23.

    Article  PubMed  Google Scholar 

  6. Burman W, Weis S, Vernon A, et al. Frequency, severity and duration of immune reconstitution events in HIV-related tuberculosis. Int J Tuberc Lung Dis. 2007;11:1282–9.

    PubMed  CAS  Google Scholar 

  7. •• Boulware DR, Meya DB, Bergemann TL, et al. Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study. PLoS Med. 2010;7:e1000384. A prospective cohort study conducted in Uganda of patients with CM. A total of 45 % developed paradoxical cryptococcal IRIS after starting ART. The risk of mortality was doubled in those who developed IRIS. A detailed analysis of biomarkers predictive of and associated with IRIS was performed.

    Article  PubMed  Google Scholar 

  8. Muller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10:251–61.

    Article  PubMed  Google Scholar 

  9. 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:e96–107.

    Article  PubMed  Google Scholar 

  10. • Lawn SD, Meintjes G. Pathogenesis and prevention of immune reconstitution disease during antiretroviral therapy. Expert Rev Anti Infect Ther. 2011;9:415–30. A recently published review article that covered the immunopathogenesis of IRIS and strategies to prevent both unmasking and paradoxical forms of IRIS. The review focused particularly on IRIS associated with mycobacterial infections, cryptococcosis, and CMV.

    Article  PubMed  CAS  Google Scholar 

  11. •• Meintjes G, Wilkinson RJ, Morroni C, et al. Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS. 2010;24:2381–90. The first clinical trial to assess a treatment for IRIS. A total of 110 patients with paradoxical TB-IRIS were enrolled in this randomised placebo-controlled trial of a 4-week course of prednisone. Prednisone resulted in reduction in hospitalization and outpatient therapeutic procedures without an excess of severe infections or metabolic complications.

    PubMed  CAS  Google Scholar 

  12. Lehloenya R, Meintjes G. Dermatologic manifestations of the immune reconstitution inflammatory syndrome. Dermatol Clin. 2006;24:549–70. vii.

    Article  PubMed  CAS  Google Scholar 

  13. Meintjes G, Rangaka MX, Maartens G, et al. Novel relationship between tuberculosis immune reconstitution inflammatory syndrome and antitubercular drug resistance. Clin Infect Dis. 2009;48:667–76.

    Article  PubMed  Google Scholar 

  14. Adcock IM. Glucocorticoid-regulated transcription factors. Pulm Pharmacol Ther. 2001;14:211–9.

    Article  PubMed  CAS  Google Scholar 

  15. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids–new mechanisms for old drugs. N Eng J Med. 2005;353:1711–23.

    Article  CAS  Google Scholar 

  16. Payne DN, Adcock IM. Molecular mechanisms of corticosteroid actions. Paediatr Respir Rev. 2001;2:145–50.

    Article  PubMed  CAS  Google Scholar 

  17. Zen M, Canova M, Campana C, et al. The kaleidoscope of glucorticoid effects on immune system. Autoimmun Rev. 2011;10:305–10.

    Article  PubMed  CAS  Google Scholar 

  18. Briel M, Bucher HC, Boscacci R, Furrer H. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection. Cochrane Database Syst Rev 2006:CD006150.

  19. Hakim JG, Ternouth I, Mushangi E, Siziya S, Robertson V, Malin A. Double blind randomised placebo controlled trial of adjunctive prednisolone in the treatment of effusive tuberculous pericarditis in HIV seropositive patients. Heart. 2000;84:183–8.

    Article  PubMed  CAS  Google Scholar 

  20. • Achenbach CJ, Harrington RD, Dhanireddy S, Crane HM, Casper C, Kitahata MM. Paradoxical immune reconstitution inflammatory syndrome in HIV-infected patients treated with combination antiretroviral therapy after AIDS-defining opportunistic infection. Clin Infect Dis. 2012;54:424–33. A retrospective cohort study of 196 patients who started ART after a diagnosis of an AIDS-defining OI in the US. A total of 11 % developed paradoxical IRIS. Treatment and outcome are reported. Morbidity and mortality were highest in those with visceral KS-IRIS.

    Article  PubMed  CAS  Google Scholar 

  21. 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;37:1574–6.

    Article  PubMed  CAS  Google Scholar 

  22. Manfredi R, Pieri F, Pileri SA, Chiodo F. The changing face of AIDS-related opportunism: cryptococcosis in the highly active antiretroviral therapy (HAART) era. Case reports and literature review. Mycopathologia. 1999;148:73–8.

    Article  PubMed  CAS  Google Scholar 

  23. Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H. 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;58:1–207.

    Google Scholar 

  24. Nelson MR, Katlama C, Montaner JS, et al. The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years. AIDS. 2007;21:1273–81.

    Article  PubMed  CAS  Google Scholar 

  25. Morelle J, Labriola L, Lambert M, Cosyns JP, Jouret F, Jadoul M. Tenofovir-related acute kidney injury and proximal tubule dysfunction precipitated by diclofenac: a case of drug-drug interaction. Clin Nephrol. 2009;71:567–70.

    PubMed  CAS  Google Scholar 

  26. Thwaites GE, Nguyen DB, Nguyen HD, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004;351:1741–51.

    Article  PubMed  CAS  Google Scholar 

  27. Strang JI, Kakaza HH, Gibson DG, Girling DJ, Nunn AJ, Fox W. Controlled trial of prednisolone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei. Lancet. 1987;2:1418–22.

    Article  PubMed  CAS  Google Scholar 

  28. Breen RA, Smith CJ, Bettinson H, et al. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection. Thorax. 2004;59:704–7.

    Article  PubMed  CAS  Google Scholar 

  29. McAllister WA, Thompson PJ, Al-Habet SM, Rogers HJ. Rifampicin reduces effectiveness and bioavailability of prednisolone. Br Med J (Clin Res Ed). 1983;286:923–5.

    Article  CAS  Google Scholar 

  30. Meintjes G, Skolimowska KH, Wilkinson KA, Matthews K, Tadokera R, Conesa-Botella A, Seldon R, Rangaka MX, Rebe K, Pepper DJ, Morroni C, Colebunders R, Maartens G, Wilkinson RJ. Corticosteroid modulated immune activation in the TB immune reconstitution inflammatory syndrome. Am J Respir Crit Care Med. 2012. doi:10.1164/rccm.201201-00940c.

  31. Michailidis C, Pozniak AL, Mandalia S, Basnayake S, Nelson MR, Gazzard BG. Clinical characteristics of IRIS syndrome in patients with HIV and tuberculosis. Antivir Ther. 2005;10:417–22.

    PubMed  Google Scholar 

  32. Olalla J, Pulido F, Rubio R, et al. Paradoxical responses in a cohort of HIV-1-infected patients with mycobacterial disease. Int J Tuberc Lung Dis. 2002;6:71–5.

    PubMed  CAS  Google Scholar 

  33. 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;39:1709–12.

    Article  PubMed  Google Scholar 

  34. Lawn SD, Wood R. Hepatic involvement with tuberculosis-associated immune reconstitution disease. AIDS. 2007;21:2362–3.

    Article  PubMed  Google Scholar 

  35. Meintjes G, Sonderup MW. A practical approach to the diagnosis and management of paradoxical tuberculosis immune reconstitution inflammatory syndrome. Contin Med Educ. 2011;29(10):410–7.

    Google Scholar 

  36. • Torok ME, Yen NT, Chau TT, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)–associated tuberculous meningitis. Clin Infect Dis. 2011;52:1374–83. This is the only published randomised controlled trial to compare early versus delayed ART in patients with HIV-associated TBM. Mortality was ~60 % and no different in the two arms of the trial (those who started ART within 7 days of TB treatment and those who started ART after 2 months of TB treatment). Participants in both arms of the trial received adjunctive dexamethasone for 6–8 weeks.

    Article  PubMed  Google Scholar 

  37. Asselman V, Thienemann F, Pepper DJ, et al. Central nervous system disorders after starting antiretroviral therapy in South Africa. AIDS. 2010;24:2871–6.

    Article  PubMed  Google Scholar 

  38. Torok ME, Kambugu A, Wright E. Immune reconstitution disease of the central nervous system. Curr Opin HIV AIDS. 2008;3:438–45.

    Article  PubMed  Google Scholar 

  39. Dautremer J, Pacanowski J, Girard PM, Lalande V, Sivignon F, Meynard JL. A new presentation of immune reconstitution inflammatory syndrome followed by a severe paradoxical reaction in an HIV-1-infected patient with tuberculous meningitis. AIDS. 2007;21:381–2.

    Article  PubMed  Google Scholar 

  40. Tuon FF, Mulatti GC, Pinto WP, de Siqueira Franca FO, Gryschek RC. Immune reconstitution inflammatory syndrome associated with disseminated mycobacterial infection in patients with AIDS. AIDS Patient Care STDS. 2007;21:527–32.

    Article  PubMed  Google Scholar 

  41. Lee CH, Lui CC, Liu JW. Immune reconstitution syndrome in a patient with AIDS with paradoxically deteriorating brain tuberculoma. AIDS Patient Care STDS. 2007;21:234–9.

    Article  PubMed  Google Scholar 

  42. Manosuthi W, Kiertiburanakul S, Phoorisri T, Sungkanuparph S. Immune reconstitution inflammatory syndrome of tuberculosis among HIV-infected patients receiving antituberculous and antiretroviral therapy. J Infect. 2006;53:357–63.

    Article  PubMed  Google Scholar 

  43. Rajeswaran G, Becker JL, Michailidis C, Pozniak AL, Padley SP. The radiology of IRIS (immune reconstitution inflammatory syndrome) in patients with mycobacterial tuberculosis and HIV co-infection: appearances in 11 patients. Clin Radiol. 2006;61:833–43.

    Article  PubMed  CAS  Google Scholar 

  44. Crump JA, Tyrer MJ, Lloyd-Owen SJ, Han LY, Lipman MC, Johnson MA. Miliary tuberculosis with paradoxical expansion of intracranial tuberculomas complicating human immunodeficiency virus infection in a patient receiving highly active antiretroviral therapy. Clin Infect Dis. 1998;26:1008–9.

    Article  PubMed  CAS  Google Scholar 

  45. Vidal JE, Cimerman S, Schiavon Nogueira R, et al. Paradoxical reaction during treatment of tuberculous brain abscess in a patient with AIDS. Rev Inst Med Trop Sao Paulo. 2003;45:177–8.

    Article  PubMed  Google Scholar 

  46. Lipman M, Breen R. Immune reconstitution inflammatory syndrome in HIV. Curr Opin Infect Dis. 2006;19:20–5.

    Article  PubMed  Google Scholar 

  47. World Health Organisation. Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent resource-constrained settings. Geneva: WHO Press; 2006.

  48. 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;41:1483–97.

    Article  PubMed  Google Scholar 

  49. Riddell J, Kaul DR, Karakousis PC, Gallant JE, Mitty J, Kazanjian PH. Mycobacterium avium complex immune reconstitution inflammatory syndrome: long term outcomes. J Transl Med. 2007;5:50.

    Article  PubMed  CAS  Google Scholar 

  50. Desimone Jr JA, Babinchak TJ, Kaulback KR, Pomerantz RJ. Treatment of Mycobacterium avium complex immune reconstitution disease in HIV-1-infected individuals. AIDS Patient Care STDS. 2003;17:617–22.

    Article  PubMed  Google Scholar 

  51. Benson CA, Williams PL, Currier JS, et al. A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome. Clin Infect Dis. 2003;37:1234–43.

    Article  PubMed  CAS  Google Scholar 

  52. Cinti SK, Kaul DR, Sax PE, Crane LR, Kazanjian PH. Recurrence of Mycobacterium avium infection in patients receiving highly active antiretroviral therapy and antimycobacterial agents. Clin Infect Dis. 2000;30:511–4.

    Article  PubMed  CAS  Google Scholar 

  53. Lee YC, Lu CL, Lai CC, Tseng YT, Sun HY, Hung CC. Mycobacterium avium complex infection-related immune reconstitution inflammatory syndrome of the central nervous system in an HIV-infected patient: Case report and review. J Microbiol Immunol Infect. 2012 Jan 6. [Epub ahead of print].

  54. Jenny-Avital ER. A patient with refractory disseminated Mycobacterium avium after immune-reconstitution localized MAC. AIDS Clin Care. 2003;15:24–6.

    PubMed  Google Scholar 

  55. Sungkanuparph S, Filler Scott G, Chetchotisakd P, et al. Cryptococcal immune reconstitution inflammatory syndrome after antiretroviral therapy in AIDS patients with cryptococcal meningitis: a prospective multicenter study. Clin Infect Dis. 2009;49:931–4.

    Article  PubMed  Google Scholar 

  56. Shelburne SA, Darcourt J, White AC, 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;40:1049–52.

    Article  PubMed  Google Scholar 

  57. • Bicanic T, Meintjes G, Rebe K, et al. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr. 2009;51:130–4. A prospective cohort study of CM patients in South Africa reporting an IRIS incidence of 17 %. IRIS management and patient outcomes are described. In this study CM-IRIS was not associated with excess mortality.

    Article  PubMed  CAS  Google Scholar 

  58. 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;202:962–70.

    Article  PubMed  CAS  Google Scholar 

  59. Lawn SD, Bekker L-G, Myer L, Orrell C, Wood R. Cryptococcocal immune reconstitution disease: a major cause of early mortality in a South African antiretroviral programme. AIDS. 2005;19:2050–2.

    Article  PubMed  Google Scholar 

  60. • Perfect John R, Dismukes William E, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin Infect Dis. 2010;50:291–322. The most recent Infectious Diseases Society of America guidelines for managing cryptococcal disease. These include recommendations on the management of elevated intracranial pressure in CM and use of corticosteroids in IRIS.

    Article  PubMed  CAS  Google Scholar 

  61. King MD, Perlino CA, Cinnamon J, Jernigan JA. Paradoxical recurrent meningitis following therapy of cryptococcal meningitis: an immune reconstitution syndrome after initiation of highly active antiretroviral therapy. Int J STD AIDS. 2002;13:724–6.

    Article  PubMed  Google Scholar 

  62. 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;19:1043–9.

    Article  PubMed  Google Scholar 

  63. Venkataramana A, Pardo CA, McArthur JC, et al. Immune reconstitution inflammatory syndrome in the CNS of HIV-infected patients. Neurology. 2006;67:383–8.

    Article  PubMed  CAS  Google Scholar 

  64. Scourfield A, Waters L, Tittle V, Martin T, Rockwood N, Gazzard B, Bower M, Nelson M. Azathioprine use as a novel treatment for cryptococcal immune reconstitution and inflammatory syndrome in HIV. 17th Annual Conference of the British HIV Association, Bournmouth, 2011, abstract P92.

  65. • Muller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10:251–61. A systematic review and meta-analysis of the incidence and mortality associated with IRIS. A total of 16 % of unselected patients who started ART developed any kind of IRIS. The highest incidence of paradoxical IRIS was in patients with CMV retinitis at ART initiation. IRIS was associated with 21 % mortality in CM.

    Article  PubMed  Google Scholar 

  66. • Stewart MW. Optimal management of cytomegalovirus retinitis in patients with AIDS. Clin Ophthalmol. 2010;4:285–99. A comprehensive review of the currently available treatments for CMV retinitis. Advantages and disadvantages of various treatment options as well as their use in different socioeconomic settings are discussed.

    Article  PubMed  Google Scholar 

  67. El-Bradey MH, Cheng L, Song MK, Torriani FJ, Freeman WR. Long-term results of treatment of macular complications in eyes with immune recovery uveitis using a graded treatment approach. Retina. 2004;24:376–82.

    Article  PubMed  Google Scholar 

  68. Karavellas MP, Azen SP, MacDonald JC, et al. Immune recovery vitritis and uveitis in AIDS: clinical predictors, sequelae, and treatment outcomes. Retina. 2001;21:1–9.

    Article  PubMed  CAS  Google Scholar 

  69. Henderson HW, Mitchell SM. Treatment of immune recovery vitritis with local steroids. Br J Ophthalmol. 1999;83:540–5.

    Article  PubMed  CAS  Google Scholar 

  70. Karavellas MP, Lowder CY, Macdonald C, Avila Jr CP, Freeman WR. Immune recovery vitritis associated with inactive cytomegalovirus retinitis: a new syndrome. Arch Ophthalmol. 1998;116:169–75.

    PubMed  CAS  Google Scholar 

  71. Arevalo JF, Mendoza AJ, Ferretti Y. Immune recovery uveitis in AIDS patients with cytomegalovirus retinitis treated with highly active antiretroviral therapy in Venezuela. Retina. 2003;23:495–502.

    Article  PubMed  Google Scholar 

  72. Zegans ME, Walton RC, Holland GN, O’Donnell JJ, Jacobson MA, Margolis TP. Transient vitreous inflammatory reactions associated with combination antiretroviral therapy in patients with AIDS and cytomegalovirus retinitis. Am J Ophthalmol. 1998;125:292–300.

    Article  PubMed  CAS  Google Scholar 

  73. Lin YC, Yang CH, Lin CP, et al. Cytomegalovirus retinitis and immune recovery uveitis in AIDS patients treated with highly active antiretroviral therapy in Taiwanese. Ocul Immunol Inflamm. 2008;16:83–7.

    Article  PubMed  CAS  Google Scholar 

  74. Morrison VL, Kozak I, LaBree LD, Azen SP, Kayicioglu OO, Freeman WR. Intravitreal triamcinolone acetonide for the treatment of immune recovery uveitis macular edema. Ophthalmology. 2007;114:334–9.

    Article  PubMed  Google Scholar 

  75. Sirimaharaj M, Robinson MR, Zhu M, et al. Intravitreal injection of triamcinolone acetonide for immune recovery uveitis. Retina. 2006;26:578–80.

    Article  PubMed  Google Scholar 

  76. Hu J, Coassin M, Stewart JM. Fluocinolone acetonide implant (Retisert) for chronic cystoid macular edema in two patients with AIDS and a history of cytomegalovirus retinitis. Ocul Immunol Inflamm. 2011;19:206–9.

    Article  PubMed  CAS  Google Scholar 

  77. Ufret-Vincenty RL, Singh RP, Lowder CY, Kaiser PK. Cytomegalovirus retinitis after fluocinolone acetonide (Retisert) implant. Am J Ophthalmol. 2007;143:334–5.

    Article  PubMed  Google Scholar 

  78. Dalessandro L, Bottaro E. Reactivation of CMV retinitis after treatment with subtenon corticosteroids for immune recovery uveitis in a patient with AIDS. Scand J Infect Dis. 2002;34:780–2.

    Article  PubMed  Google Scholar 

  79. Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 2010;9:425–37.

    Article  PubMed  CAS  Google Scholar 

  80. Harrison DM, Newsome SD, Skolasky RL, McArthur JC, Nath A. Immune reconstitution is not a prognostic factor in progressive multifocal leukoencephalopathy. J Neuroimmunol. 2011;238:81–6.

    Article  PubMed  CAS  Google Scholar 

  81. •• Tan K, Roda R, Ostrow L, McArthur J, Nath A. PML-IRIS in patients with HIV infection: clinical manifestations and treatment with steroids. Neurology. 2009;72:1458–64. A case series and retrospective review of the literature reporting 54 patients with PML-IRIS. The clinical manifestations and outcomes of patients treated with and without corticosteroids are reported.

    Article  PubMed  CAS  Google Scholar 

  82. Tantisiriwat W, Tebas P, Clifford DB, Powderly WG, Fichtenbaum CJ. Progressive multifocal leukoencephalopathy in patients with AIDS receiving highly active antiretroviral therapy. Clin Infect Dis. 1999;28:1152–4.

    Article  PubMed  CAS  Google Scholar 

  83. Thurnher MM, Post MJ, Rieger A, Kleibl-Popov C, Loewe C, Schindler E. Initial and follow-up MR imaging findings in AIDS-related progressive multifocal leukoencephalopathy treated with highly active antiretroviral therapy. Am J Neuroradiol. 2001;22:977–84.

    PubMed  CAS  Google Scholar 

  84. Falco V, Olmo M, del Saz SV, et al. Influence of HAART on the clinical course of HIV-1-infected patients with progressive multifocal leukoencephalopathy: results of an observational multicenter study. J Acquir Immune Defic Syndr. 2008;49:26–31.

    Article  PubMed  Google Scholar 

  85. Miralles P, Berenguer J, Lacruz C, et al. Inflammatory reactions in progressive multifocal leukoencephalopathy after highly active antiretroviral therapy. AIDS. 2001;15:1900–2.

    Article  PubMed  CAS  Google Scholar 

  86. Hoffmann C, Horst HA, Albrecht H, Schlote W. Progressive multifocal leucoencephalopathy with unusual inflammatory response during antiretroviral treatment. J Neurol Neurosurg Psychiatry. 2003;74:1142–4.

    Article  PubMed  CAS  Google Scholar 

  87. Marshall LJ, Major EO. Molecular regulation of JC virus tropism: insights into potential therapeutic targets for progressive multifocal leukoencephalopathy. J Neuroimmune Pharmacol. 2010;5:404–17.

    Article  PubMed  Google Scholar 

  88. Martinez JV, Mazziotti JV, Efron ED, et al. Immune reconstitution inflammatory syndrome associated with PML in AIDS: a treatable disorder. Neurology. 2006;67:1692–4.

    Article  PubMed  CAS  Google Scholar 

  89. • Berger JR. Steroids for PML-IRIS: a double-edged sword? Neurology. 2009;72:1454–5. An editorial that summarizes the pro’s and con’s of corticosteroid treatment for PML-IRIS.

    Article  PubMed  Google Scholar 

  90. Cinque P, Koralnik IJ, Gerevini S, Miro JM, Price RW. Progressive multifocal leukoencephalopathy in HIV-1 infection. Lancet Infect Dis. 2009;9:625–36.

    Article  PubMed  CAS  Google Scholar 

  91. Berger JR, Levy RM, Flomenhoft D, Dobbs M. Predictive factors for prolonged survival in acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy. Ann Neurol. 1998;44:341–9.

    Article  PubMed  CAS  Google Scholar 

  92. Kotecha N, George MJ, Smith TW, Corvi F, Litofsky NS. Enhancing progressive multifocal leukoencephalopathy: an indicator of improved immune status? Am J Med. 1998;105:541–3.

    Article  PubMed  CAS  Google Scholar 

  93. Du Pasquier RA, Koralnik IJ. Inflammatory reaction in progressive multifocal leukoencephalopathy: harmful or beneficial? J Neurovirol. 2003;9 Suppl 1:25–31.

    PubMed  Google Scholar 

  94. Cattelan AM, Calabrò ML, Gasperini P, et al. Acquired immunodeficiency syndrome-related Kaposi’s sarcoma regression after highly active antiretroviral therapy: biologic correlates of clinical outcome. J Natl Cancer Inst Monographs 2001;44–9.

  95. Bower M, Nelson M, Young AM, et al. Immune reconstitution inflammatory syndrome associated with Kaposi’s sarcoma. J Clin Oncol. 2005;23:5224–8.

    Article  PubMed  CAS  Google Scholar 

  96. Connick E, Kane MA, White IE, Ryder J, Campbell TB. Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma during potent antiretroviral therapy. Clin Infect Dis. 2004;39:1852–5.

    Article  PubMed  Google Scholar 

  97. Weir A, Wansbrough-Jones M. Mucosal Kaposi’s sarcoma following protease inhibitor therapy in an HIV-infected patient. AIDS. 1997;11:1895–6.

    Article  PubMed  CAS  Google Scholar 

  98. •• Letang E, Almeida JM, Miró JM, et al. Predictors of immune reconstitution inflammatory syndrome-associated with kaposi sarcoma in mozambique: a prospective study. J Acquir Immune Defic Syndr. 2010;53:589–97. A prospective cohort study conducted in Mozambique that reports the incidence, risk factors, management, and outcomes of KS-IRIS. The mortality in patients with KS-IRIS was 25 %.

    PubMed  CAS  Google Scholar 

  99. Leidner RS, Aboulafia DM. Recrudescent Kaposi’s sarcoma after initiation of HAART: a manifestation of immune reconstitution syndrome. AIDS Patient Care STDS. 2005;19:635–44.

    Article  PubMed  Google Scholar 

  100. Crane HM, Deubner H, Huang JC, Swanson PE, Harrington RD. Fatal Kaposi’s sarcoma-associated immune reconstitution following HAART initiation. Int J STD AIDS. 2005;16:80–3.

    Article  PubMed  Google Scholar 

  101. Volkow PF, Cornejo P, Zinser JW, Ormsby CE, Reyes-Terán G. Life-threatening exacerbation of Kaposi’s sarcoma after prednisone treatment for immune reconstitution inflammatory syndrome. AIDS. 2008;22:663–5.

    Article  PubMed  Google Scholar 

  102. Elliott AM, Luzze H, Quigley MA, et al. A randomized, double-blind, placebo-controlled trial of the use of prednisolone as an adjunct to treatment in HIV-1-associated pleural tuberculosis. J Infect Dis. 2004;190:869–78.

    Article  PubMed  CAS  Google Scholar 

  103. Gill PS, Loureiro C, Bernstein-Singer M, Rarick MU, Sattler F, Levine AM. Clinical effect of glucocorticoids on Kaposi sarcoma related to the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1989;110:937–40.

    PubMed  CAS  Google Scholar 

  104. Ueno T, Mitsuishi T, Kimura Y, et al. Immune reconstitution inflammatory syndrome associated with Kaposi’s sarcoma: successful treatment with interferon-alpha. Eur J Dermatol. 2007;17:539–40.

    PubMed  Google Scholar 

  105. den Brinker M, Wit FW, Wertheim-van Dillen PM, et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS. 2000;14:2895–902.

    Article  Google Scholar 

  106. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA. 2000;283:74–80.

    Article  PubMed  CAS  Google Scholar 

  107. Wit FWNM, Weverling GJ, Weel J, Jurriaans S, Lange JMA. Incidence of and risk factors for severe hepatotoxicity associated with antiretroviral combination therapy. J Infect Dis. 2002;186:23–31.

    Article  PubMed  CAS  Google Scholar 

  108. 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;39:129–32.

    Article  PubMed  Google Scholar 

  109. Murcia JM, Boix V, Merino E, Manso MI, Portilla J. Drug toxicity or syndrome of immune restoration causing fulminant cirrhosis after HAART-induced immune recovery. Eur J Clin Micro Infect Dis. 2002;21:153–5.

    Article  CAS  Google Scholar 

  110. Carr A, Cooper DA. Restoration of immunity to chronic hepatitis B infection in HIV-infected patient on protease inhibitor. Lancet. 1997;349:995–6.

    Article  PubMed  CAS  Google Scholar 

  111. Crane M, Matthews G, Lewin SR. Hepatitis virus immune restoration disease of the liver. Curr Opin HIV AIDS. 2008;3:446–52.

    Article  PubMed  Google Scholar 

  112. 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;12:2289–93.

    Article  PubMed  CAS  Google Scholar 

  113. Manegold C, Hannoun C, Wywiol A, et al. Reactivation of hepatitis B virus replication accompanied by acute hepatitis in patients receiving highly active antiretroviral therapy. Clin Infect Dis. 2001;32:144–8.

    Article  PubMed  CAS  Google Scholar 

  114. Rouanet I, Peyriere H, Mauboussin JM, Terrail N, Vincent D. Acute clinical hepatitis by immune restoration in a human immunodeficiency virus/hepatitis B virus co-infected patient receiving antiretroviral therapy. Eur J Gastroenterol Hepatol. 2003;15:95–7.

    Article  PubMed  Google Scholar 

  115. Velasco M, Moran A, Tellez MJ. Resolution of chronic hepatitis B after ritonavir treatment in an HIV-infected patient. N Eng J Med. 1999;340:1765–6.

    Article  CAS  Google Scholar 

  116. Nüesch R, Ananworanich J, Srasuebkul P, et al. Interruptions of tenofovir/emtricitabine-based antiretroviral therapy in patients with HIV/hepatitis B virus co-infection. AIDS. 2008;22:152–4.

    Article  PubMed  CAS  Google Scholar 

  117. Calabrese LH, Zein NN, Vassilopoulos D. Hepatitis B virus (HBV) reactivation with immunosuppressive therapy in rheumatic diseases: assessment and preventive strategies. Ann Rheum Dis. 2006;65:983–9.

    Article  PubMed  CAS  Google Scholar 

  118. Sagnelli E, Manzillo G, Maio G, et al. Serum levels of hepatitis B surface and core antigens during immunosuppressive treatment of HBsAg-positive chronic active hepatitis. Lancet. 1980;2:395–7.

    Article  PubMed  CAS  Google Scholar 

  119. McGee S, Hirschmann J. Use of corticosteroids in treating infectious diseases. Arch Intern Med. 2008;168:1034–46.

    Article  PubMed  CAS  Google Scholar 

  120. Baker JV, Boulware DR, Bohjanen PR. A case for treating high hepatitis B DNA levels before starting HIV therapy. AIDS. 2006;20:2402–3.

    Article  PubMed  Google Scholar 

  121. Hardwick C, White D, Morris E, Monteiro EF, Breen RA, Lipman M. Montelukast in the treatment of HIV associated immune reconstitution disease. Sex Transm Infect. 2006;82:513–4.

    Article  PubMed  CAS  Google Scholar 

  122. Marais S, Wilkinson RJ, Pepper DJ, Meintjes G. Management of patients with the immune reconstitution inflammatory syndrome. Curr HIV/AIDS Rep. 2009;6:162–71.

    Article  PubMed  Google Scholar 

  123. Tadokera R, Meintjes G, Skolimowska KH, et al. Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome. Eur Resp J. 2011;37:1248–59.

    Article  CAS  Google Scholar 

  124. Blackmore TK, Manning L, Taylor WJ, Wallis RS. Therapeutic use of infliximab in tuberculosis to control severe paradoxical reaction of the brain and lymph nodes. Clin Infect Dis. 2008;47:e83–5.

    Article  PubMed  CAS  Google Scholar 

  125. Hennigan S, Kavanaugh A. Interleukin-6 inhibitors in the treatment of rheumatoid arthritis. Ther Clin Risk Manag. 2008;4:767–75.

    PubMed  CAS  Google Scholar 

  126. Martin-Blondel G, Cuzin L, Delobel P, et al. Is maraviroc beneficial in paradoxical progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome management? AIDS. 2009;23:2545–6.

    Article  PubMed  Google Scholar 

  127. Sun HY, Singh N. Potential role of statins for the management of immune reconstitution syndrome. Med Hypotheses. 2011;76:307–10.

    Article  PubMed  CAS  Google Scholar 

  128. Gallant JE, Chaisson RE, Moore RD. The effect of adjunctive corticosteroids for the treatment of Pneumocystis carinii pneumonia on mortality and subsequent complications. Chest. 1998;114:1258–63.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

G. Meintjes was funded in part through a Fogarty International Center South African TB/AIDS Training Award (NIH/FIC 1U2RTW007373-01A1, U2RTW007370 ICORTA). J. Scriven, G. Meintjes and Suzaan Marais are funded by the Wellcome Trust.

Disclosure

Conflicts of interest: G. Meintjes is a senior clinical consultant for the Aid for AIDS Managed Care Group and has received a lecture fee paid by Sanofi-Aventis; J. Scriven: none; S. Marais: none.

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Authors and Affiliations

  1. Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa

    Graeme Meintjes, James Scriven & Suzaan Marais

  2. Division of Infectious Diseases and HIV Medicine, University of Cape Town, Cape Town, South Africa

    Graeme Meintjes

  3. GF Jooste Hospital, Cape Town, South Africa

    Graeme Meintjes

  4. Department of Medicine, Imperial College London, London, UK

    Graeme Meintjes

  5. Liverpool School of Tropical Medicine, Liverpool University, Liverpool, UK

    James Scriven

  6. Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Suzaan Marais

  7. Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa

    Graeme Meintjes, James Scriven & Suzaan Marais

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  1. Graeme Meintjes
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  2. James Scriven
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  3. Suzaan Marais
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Correspondence to Graeme Meintjes.

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Meintjes, G., Scriven, J. & Marais, S. Management of the Immune Reconstitution Inflammatory Syndrome. Curr HIV/AIDS Rep 9, 238–250 (2012). https://doi.org/10.1007/s11904-012-0129-5

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