IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME IN HIV INFECTION

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Abstract

Antiretroviral therapy (ART) leads to suppression of HIV replication, contributes to increase in the number of CD4-lymphocytes count and  partial restoration or activation of the immune system. The  consequence is a reduction of incidence of opportunistic diseases,  increase in the duration and quality of life of people living with HIV  (PLHIV). However, in some patients with severe immunosuppression, this may be accompanied by a worsening of the condition and risks  of formation of the immune reconstitution inflammatory syndrome  (IRIS), which manifests itself in the development of new or  previously treated opportunistic, secondary and exacerbating non- infectious diseases against a virologically effective ART. The  frequency of the development of IRIS varies widely, in cases of  tuberculosis-associated manifestation it can reach 50%. Risk factors  for the development of IRIS are low initial CD4-lymphocyte count  and a high load of HIV RNA in the blood, the presence of  opportunistic infections during the initiation of ART. Discussed terminology issues, other possible risk factors for the  development of the syndrome, regularities of the pathological process are considered. Epidemiological statistics of  IRIS, pathogenetic bases, variants of clinical and laboratory  manifestations of complications are given. The criteria for diagnosis  of the syndrome, as well as the necessary conditions for its  occurrence, are considered. Particular attention is paid to the most  common opportunistic infections that cause the manifestation of  IRIS, the peculiarities and polymorphism of clinical manifestations  and the prevention of their occurrence. Currently, there is an  increasing incidence of HIV infection in the late stages. Laboratory  and clinical differences in the manifestations of acquired  immunodeficiency syndrome (AIDS) and IRIS have been sanctified. In view of the blurring of the diagnostic criteria, in the  Russian Federation specialists rarely expose IRIS to clinical or pathological diagnoses, therefore it is rather difficult to trace the  frequency of occurrence of this condition. Clinical and laboratory  manifestations are systematized, which allows to formulate this  diagnosis on the basis of their totality. Prevention of IRIS is the  prudent prescription of antiretroviral drugs. It is neces sary to  conduct a qualitative and timely diagnosis of concomitant diseases of infectious and non-infectious nature before the initiation of ART and  during treatment, the appointment of effective etiotropic therapy for  opportunistic and secon dary infections. In order to improve the  prognosis of HIV infection, preferably early onset of ART with stable  CD4-lym phocyte counts and low HIV RNA levels in the blood.

About the authors

E. V. Boeva

Pavlov First State Medical University

St. Petersburg Paster Institute

Author for correspondence.
Email: kathrine.boeva@gmail.com

Resident of the Department of Socially Significant Infections, First Pavlov State Medical University,  St. Petersburg, Russian Federation; Infectious Disease  Doctor, Head of Department of Chronic Viral Infection in  North-West District Center for Prevention and Control of  AIDS, St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation

197101, Russian Federation, St. Petersburg, Mira str., 14

Phone: +7 911 792-91-94

Russian Federation

N. A. Belyakov

Pavlov First State Medical University

St. Petersburg Paster Institute

Email: fake@neicon.ru

PhD, MD (Medicine), Professor, RAS Full Member, Head of  the Department of Socially Significant Infections, First Pavlov State Medical University, St. Petersburg,  Russian Federation; Chief Researcher of the Institute of  Experimental Medicine, St. Petersburg, Russian Federation;  Head of North-West District Center for Prevention and  Control of AIDS, St. Petersburg Pasteur Institute, St. Petersburg, Russian Federation

Russian Federation

References

  1. Азовцева О.В., Архипов Г.С., Архипова Е.И. Сравнительный анализ причин смертности ВИЧ-инфицированных больных // ВИЧ-инфекция и иммуносупресии. 2015. Т. 7, № 4. С. 86–91. [Azovtseva O.V., Arhipov G.S., Arkhipova E.I. A comparative analysis of causes of death in HIV infected patients. VICh-infektsiya i immunosupressii = HIV Infection and Immunosuppressive Disorders, 2015, vol. 7, no. 4, pp. 86–91. doi: 10.22328/2077-9828-2015-7-4-86-91 (In Russ.)]
  2. Белов Б.С., Белова О.Л. ВИЧ-инфекция: ревматологические аспекты // Русский медицинский журнал. 2008. Т. 16, № 24. С. 1615–1618. [Belov B.S., Belova O.L. HIV- infection: rheumatological aspects. Russkii meditsinskii zhurnal = Russian Medical Journal, 2008, vol. 16, no. 24, pp. 1615–1618. (In Russ.)]
  3. Битнева А.М., Козлова Т.П., Савинцева Е.В. Особенности начала и течения синдрома восстановления иммунитета у больных туберкулезом легких // Проблемные науки. 2017. № 6 (19). С. 104–105. [Bitnyova A.M., Kozlova T.P., Savintseva E.V. Features of the onset and course of the immune reconstitution inflammatory syndrome in patients with pulmonary tuberculosis. Problemnye nauki = Problem Sciences, 2017, no. 6 (19), pp. 104– 105. (In Russ.)]
  4. Бойко А.В. Синдром восстановления иммунного ответа у больных с ко-инфекцией туберкулез/ВИЧ/СПИД // Вестник Совета молодых ученых и специалистов Челябинской области. 2014. № 5 (7). С. 5–7. [Bojko A.V. Immune reconstitution inflammatory syndrome in patients with co-infection tuberculosis/HIV/AIDS. Vestnik Soveta molodyh uchjonyh i specialistov Cheljabinskoj oblasti = Bulletin of Council of Young Scientists and Specialists of Chelyabinsk Region, 2014, no. 5 (7), pp. 5–7. (In Russ.)]
  5. ВИЧ 2014/2015. Под ред. Хоффман К., Рокштро Ю.К. Гамбург: Medizin Fokus, 2015. 755 с. [VICh 2014/2015. Pod red. Hoffman K., Rokshtro Ju.K. [HIV 2014/2015. Eds. Hoffman K., Rokshtro Ju.K.]. Hamburg: Medizin Fokus, 2015. 755 p.]
  6. Загдын З.М. Профилактическое лечение туберкулеза среди больных ВИЧ-инфекцией // ВИЧ-инфекция и иммуносупресии. 2014. Т. 6, № 4. С. 17–23. [Zagdyn Z.M. Preventive TB treatment in HIV patients. VICh-infektsiya i immunosupressii = HIV Infection and Immunosuppressive Disorders, 2014, vol. 6, no. 4, pp. 17–23. doi: 10.22328/2077-9828- 2014-6-4-17-23 (In Russ.)]
  7. Захарова Н.Г., Дворак С.И., Плавинский С.Л. Причины неблагоприятных исходов у больных с ВИЧ-инфекцией, принимавших ВААРТ. Часть 1 // ВИЧ-инфекция и иммуносупрессии. 2015. Т. 7, № 3. С. 48–54. [Zakharova N.G., Dvorak S.I., Plavinski S.L. The causes of unfavorable out-comes amoung patients taking HAART. Part 1. VICh-infektsiya i immunosupressii = HIV Infection and Immunosuppressive Disorders, 2015, vol. 7, no. 3, pp. 48–54. (In Russ.)]
  8. Зимина В.Н., Васильева И.А., Батыров Ф.А. Острое развитие туберкулеза внутригрудных лимфатических узлов как проявления синдрома восстановления иммунитета у больных с ВИЧ-инфекцией // Туберкулез и болезни легких. 2010. Т. 87, № 4. С. 58–60. [Zimina V.N., Vasilieva I.A., Batyrov F.A. Acute development of tuberculosis of intrathoracic lymph nodes as manifestations of immune reconstitution inflammatory syndrome in patients with HIV infection. Tuberkulez i bolezni legkih = Tuberculosis and Lung Diseases, 2010, vol. 87, no. 4, pp. 58–60. (In Russ.)]
  9. Зимина В.Н., Кравченко А.В., Зюзя Ю.Р., Васильева И.А. Диагностика и лечение туберкулеза в сочетании с ВИЧ-инфекцией. М.: ГЭОТАР-Медиа, 2015. 240 с. [Zimina V.N., Kravchenko A.V., Zyuzya Yu.R., Vasil’eva I.A. Diagnostika i leche nie tuberkuleza v sochetanii s VICh-infektsiei [Diagnostics and treatment of tuberculosis in combination with HIV infection]. Moscow: GEOTAR-Media, 2015. 240 p.]
  10. Корж Е.В. Современные взгляды на антиретровирусную терапию у больных с ко-инфекцией туберкулез/ВИЧ // Туберкулез, легочные болезни, ВИЧ-инфекция. 2012. № 1 (8). С. 115–121. [Korzh E.V. Modern opinions at antiretroviral therapy in patients with the tuberсulosis/HIV cо-infection. Tuberkulez, legochnye bolezni, VICh-infekcija = Tuberculosis, pulmonary diseases, HIV infection, 2012, no. 1 (8), pp. 115–121. (In Russ.)]
  11. Леонова О.Н., Степанова Е.В., Беляков Н.А. Тяжелые и коморбидные состояния у больных с ВИЧ-инфекцией // ВИЧ-инфекция и иммуносупрессии. 2017. Т. 9, № 1, С. 55– 62. [Leonova O.N., Stepanova Y.V., Belyakov N.A. Severe and comorbid conditions in HIV patients: an analysis of adverse outcomes. VICh-infektsiya i immunosupressii = HIV Infection and Immunosuppressive Disorders, 2017, vol. 9, no. 1, pp. 55–62. doi: 10.22328/2077-9828- 2017-9-1-55-64 (In Russ.)]
  12. Маркелов Ю.М., Пахомова Е.В., Рожкова И.И. Особенности распространения и летальность больных с сочетанной инфекцией ВИЧ+ТБ в Карелии // ВИЧ-инфекция и иммуносупресии. 2016. Т. 8, № 3. С. 65–73. [Markelov Yu.M., Pahomova E.V., Rozhkova I.I. Distribution and mortality patterns in patients co-infected with HIV and TB in Karelia. VIChinfektsiya i immunosupressii = HIV Infection and Immunosuppressive Disorders, 2016, vol. 8, no. 3, pp. 65–73. doi: 10.22328/2077-9828-2016-8-3-65-73 (In Russ.)]
  13. Матиевская Н.В. Воспалительный синдром восстановления иммунитета у ВИЧ-инфицированных пациентов: факторы риска, клинические проявления, исходы, профилактика // Вестник Балтийского Федерального Университета им. И. Канта. Серия: естественные и медицинские науки. 2012. № 7. С. 44–51. [Matiyevskaya N.V. Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients: risk factors, clinical features, outcomes, prevention. Vestnik Baltijskogo Federal’nogo Universiteta im. I. Kanta. Serija: estestvennye i medicinskie nauki = Bulletin of the Baltic Federal University I. Kant. Series: Natural and Medical Sciences, 2012, no. 7, pp. 44–51. (In Russ.)]
  14. Мусатов В.Б., Яковлев А.А., Савченко М.А., Соколова О.И. Летальные исходы у ВИЧ-инфицированных больных, имеющих неопределяемую вирусную нагрузку на фоне антиретровирусной терапии // Инфекционные болезни: новости, мнения, обучение. 2017. № 4 (21). С. 67–71. [Musatov V.B., Yakovlev A.A., Savchenko M.A., Sokolova O.I. Lethal outcomes in HIV positive patients with undetectable viral load on antiretroviral therapy. Infekcionnye bolezni: novosti, mnenija, obuchenie = Infectious diseases: news, opinions, training, 2017, no. 4 (21), pp. 67–71. (In Russ.)]
  15. Покровский В.В. ВИЧ-инфекция и СПИД: национальное руководство. М.: ГЭОТАР-Медиа, 2013. 608 с. [Pokrovskiy V.V. VICh-infektsiya i SPID: nacional’noe rukovodstvo [HIV infection and AIDS: national guidance]. Moscow: GEOTAR-Media, 2013. 608 p.]
  16. Рахманова А.Г., Яковлев А.А., Дмитриева М.И., Виноградова Т.Н., Козлов А.А. Анализ причин смерти ВИЧ-инфицированных в 2008–2010 гг. По материалам клинической инфекционной больницы им. С.П. Боткина, Санкт-Петербург // Казанский медицинский журнал. 2012. Т. 93, № 3. С. 522–526. [Rakhmanova A.G., Yakovlev A.A., Dmitrieva M.I., Vinogradova T.N., Kozlov A.A. Analysis of the causes of death in HIV-infected individuals in 2008–2010 according to the data of the Clinical Infectious Disease Hospital named after S.P. Botkin, St. Petersburg. Kazanskij medicinskij zhurnal = Kazan Medical Journal, 2012, vol. 93, no. 3, pp. 522–526. (In Russ.)]
  17. Симбирцев А.С. Иммунопатогенез и перспективы иммуномодулирующей терапии ВИЧ-инфекции. Часть 1. Общие вопросы иммунологии и ВИЧ1 // ВИЧ-инфекция и иммуносупресии. 2017. Т. 9, № 1. С. 22–35. [Simbirtsev A.S. Immunopathogenesis of and prospects for immunomodulatory therapy for HIV infection. Part 1. The general aspects of immunology and HIV. VICh-infektsiya i immunosupressii = HIV Infection and Immunosuppressive Disorders, 2017, vol. 9, no. 1, pp. 22–35. doi: 10.22328/2077-9828-2017-9-1-22-35 (In Russ.)]
  18. Степанова Е.В. Герпесвирусные заболевания и ВИЧ-инфекция. СПб.: Балтийский медицинский образовательный центр, 2009. 60 с. [Stepanova E.V. Gerpesvirusnye zabolevaniya i VICh-infektsiya [Herpesvirus and HIV infection]. St. Petersburg: Baltic Medical Education Center, 2009. 60 p.]
  19. Степанова Е.В., Леонова О.Н., Пантелеева О.В. Причины тяжелого течения и смертей у больных с ВИЧ и коинфекцией // ВИЧ-инфекция и иммуносупрессии. 2014. Т. 6, № 4. С. 115–117. [Stepanova E.V., Leonova O.N., Panteleeva O.V. Causes of severe course and death in patients with HIV and co-infection. VICh-infektsiya i immunosupressii = HIV Infection and Immunosuppressive Disorders, 2014, vol. 6, no. 4, pp. 115–117. (In Russ.)]
  20. Тищенко Т.В., Цыркунов В.М. Воспалительный синдром восстановления иммунитета у ВИЧ-инфицированных пациентов: клинико-морфологические аспекты // Здравоохранение (Минск). 2017. № 10. С. 5–11. [Tishchenko G.V., Tsyrkunov V.M. Immune reconstitution inflammatory syndrome in HIV-infected patients: clinical and morphological aspects. Zdravoohranenie (Minsk) = Health (Minsk), 2017, no. 10, pp. 5–11. (In Russ.)]
  21. Улюкин И.М. ВИЧ-инфекция: особенности восстановления иммунной системы на фоне специфической терапии туберкулеза // Клиническая патофизиология. 2017. Т. 23, № 2. С. 29–33. [Uliukin I.M. HIV-infection: features of immune reconstitution on the background of specific therapy of tuberculosis. Klinicheskaja patofiziologija = Clinical Pathophysiology, 2017, vol. 23, no. 2, pp. 29–33. (In Russ.)]
  22. Черенько С.А., Матвеева С.Л. Причины нарушения тиреоидного гомеостаза при ко-инфекции туберкулез/ВИЧ // Туберкулез, легочные болезни, ВИЧ-инфекция. 2014. № 1 (16). С. 8–12. [Chereniko S.A., Matveeva S.L. Causes of thyroid dysfunction of homeostasis in co-infection with tuberculosis/HIV. Tuberkulez, legochnye bolezni, VICh-infekcija = Tuberculosis, Lung Diseases, HIV Infection, 2014, no. 1 (16), pp. 8–12. (In Russ.)]
  23. Шеломов А.С., Степанова Е.В., Леонова О.Н., Смирнова Н.Л. Оппортунистические заболевания как причины поражения центральной нервной системы у больных ВИЧ- инфекцией // Журнал инфектологии. 2016. Т. 8, № 3. С. 107–115. [Shelomov A.S., Stepanova E.V., Leonova O.N., Smirnova N.L. Opportunistic diseases as the cause of damage to the central nervous system in patients with HIV-infection. Zhurnal infektologii = Infectology Journal, 2016, vol. 8, no. 3, pp. 107–115. (In Russ.)]
  24. Шмидт Т.Е. Прогрессирующая мультифокальная лейкоэнцефалопатия и другие неврологические проявления реактивации вируса JC // Неврологический журнал. 2014. Т. 19, № 4. С. 4–10. [Shmidt T.E. Progressive multifocal leukoencephalopathy and other neurological symptoms of JC virus reactivation. Nevrologicheskij zhurnal = Neurological Journal, 2014, vol. 19, no. 4, pp. 4–10. (In Russ.)]
  25. Яковлев А.А., Мусатов В.Б., Савченко М.А. Причины летальных исходов у ВИЧ-инфицированных пациентов, получающих антиретровирусную терапию // ВИЧ- инфекция и иммуносупрессии. 2015. Т. 7, № 1. С. 84–88. [Yakovlev A.A., Musatov V.B., Savchenko M.A. Causes of death amoung HIV infected patients receiving antiretroviral therapy. VICh-infektsiya i immunosupressii = HIV Infection and Immunosuppressive Disorders, 2015, vol. 7, no. 1, pp. 84–88. doi: 10.22328/2077-9828-2015-7-1-84-89 (In Russ.)]
  26. Bicanic T., Meintjes G., Rebe K., Williams A., Loyse A., Wood R., Hayes M., Jaffar S., Harrison T. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J. Acquir. Immune Defic. Syndr., 2009, vol. 51, no. 2, pp. 130–134. doi: 10.1097/QAI.0b013e3181a56f2e
  27. Boulware D.R., Meya D.B., Bergemann T.L., Wiesner D.L., Rhein J., Musubire A., Lee S.J., Kambugu A., Janoff E.N., Bohjanen P.R. Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study. PLoS Med., 2010, vol. 7, no. 12: e1000384. doi: 10.1371/journal.pmed.100038
  28. Crum N.F., Ganesan A., Johns S.T., Wallace M.R. Graves disease: an increasingly recognized immune reconstitution syndrome. AIDS, 2006, vol. 20, no. 3, pp. 466–469. doi: 10.1097/01.aids.0000196173.42680.5f
  29. Dunić I., Djurković-Djaković O., Vesić S., Zerjav S., Jevtović D. Herpes zoster as an immune restoration disease in AIDS patients during therapy including protease inhibitors. Int. J. STD AIDS, 2005, vol. 16, no. 7, pp. 475–478. doi: 10.1258/0956462054308404
  30. French M.A. Immune reconstitution inflammatory syndrome: a reappraisal. Clin. Infect. Dis., 2009, vol. 48, iss. 1, pp. 101–107. doi: 10.1086/595006
  31. French M.A., Price P., Stone S.F. Immune restoration disease after antiretroviral therapy. AIDS, 2004, vol. 18, no. 12, pp. 1615–1627.
  32. George V., Harrison L., Roach M., Li X.D., Tierney C., Fischl M.A., Aberg J., Tebas P., Asmuth D.M., Pollard R.B., Godfrey C., Pahwa S. Associations of plasma cytokine and microbial translocation biomarkers with immune reconstitution inflammatory syndrome. J. Infect. Dis., 2017, vol. 216, no. 9, pp. 1159–1163. doi: 10.1093/infdis/jix460
  33. Gopal R., Rapaka R.R., Kolls J.K. Immune reconstitution inflammatory syndrome associated with pulmonary pathogens. Eur. Respir. Rev., 2017, vol. 26, no. 143: e160042. doi: 10.1183/16000617.0042-2016
  34. Haddow L.J., Moosa M.Y., Easterbrook P.J. Validation of a published case definition for tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS, 2010, vol. 24, iss. 1, pp. 103–108. doi: 10.1097/QAD.0b013e32832ec1f4
  35. Jaffe H.W., De Stavola B.L., Carpenter L.M., Porter K., Cox D.R. Immune reconstitution and risk of Kaposi sarcoma and non-Hodgkin lymphoma in HIV-infected adults. AIDS, 2011, vol. 25, iss. 11, pp. 1395–1403. doi: 10.1097/QAD.0b013e3283489c8b
  36. Jagannathan P., Davis E., Jacobson M., Huang L. Life-threatening immune reconstitution inflammatory syndrome after Pneumocystis pneumonia: a cautionary case series. AIDS, 2009, vol. 23, iss. 13, pp. 1794–1796. doi: 10.1097/QAD.0b013e32832d9b20
  37. Jevtović D.J., Salemović D., Ranin J., Pesić I., Zerjav S., Djurković-Djaković O. The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV Med., 2005, vol. 6, iss. 2, pp. 140–143. doi: 10.1111/j.1468-1293.2005.00277.x
  38. Letang E., Almeida J.M., Miro J.M., Ayala E., White I.E., Carrilho C., Bastos R., Nhampossa T., Mendez C., Campbell T.B., Alonso P.L., Naniche D. Predictors of immune reconstitution inflammatory syndrome-associated with Kaposi sarcoma in Mozambique: a prospective study. J. Acquir. Immune Defic. Syndr., 2010, vol. 53, pp. 589–597. doi: 10.1097/QAI.0b013e3181bc476f
  39. McCombe J.A., Auer R.N., Maingat F.G., Houston S., Gill M.J., Power C. Neurologic immune reconstitution inflammatory syndrome in HIV/AIDS: outcome and epidemiology. Neurology, 2009, vol. 72, no. 9, pp. 835–841. doi: 10.1212/01.wnl.0000343854.80344.69
  40. Morbidity and Mortality Weekly Report. 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. Eds. Kaplan J.E., Benson C., Holmes K.H., Brooks J.T., Pau A., Masur H. 2009, 58 (RR04), pp. 1–198. URL: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5804a1.htm (15.05.2018)
  41. Murdoch D.M., Venter W.D.F., Rie A.V., Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res. Ther., 2007, vol. 4, no. 9, 10 p. doi: 10.1186/1742-6405-4-9
  42. Phillips P., Bonner S., Gataric N., Bai T., Wil-Cox P., Hogg R, O’Shaughnessy M., Montaner J. Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: spectrum of disease and long-term follow-up. Clin. Infect. Dis., 2005, vol. 41, iss. 10, pp. 1483–1497. doi: 10.1086/497269
  43. Sharma S.K, Dhooria S., Barwad P., Kad-Hiravan T., Ranjan S., Miglani S., Gupta D. A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case- definition. Indian J. Med. Res., 2010, vol. 131, pp. 804–808.
  44. Sharma S.K., Soneja M. HIV & immune reconstitution inflammatory syndrome (IRIS). Indian J. Med. Res., 2011, vol. 134, no. 6, pp. 866–877. doi: 10.4103/0971-5916.92632
  45. Shelburne S.A., Montes M., Hamill R.J. Immune reconstitution inflammatory syndrome: more answers, more questions. J. Antimicrob. Chemother., 2006, vol. 57, iss. 2, pp. 167–170. doi: 10.1093/jac/dki444
  46. Vendrely A., Bienvenu B., Gasnault J., Thiebault J.B., Salmon D., Gray F. Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy. Acta Neuropathol., 2005, vol. 109, iss. 4, pp. 449–455. doi: 10.1007/s00401-005-0983-y
  47. Walker N.F., Scriven J., Meintjes G., Wilkinson R.J. Immune reconstitution inflammatory syndrome in HIV-infected patients. HIV AIDS (Auckl.), 2015, vol. 7, pp. 49–64. doi: 10.2147/HIV.S42328
  48. Wiesner D.L., Boulware D.R. Cryptococcus-related immune reconstitution inflammatory syndrome (IRIS): pathogenesis and its clinical implications. Curr. Fungal Infect. Rep., 2011, vol. 5, no. 4, pp. 252–261. doi: 10.1007/s12281-011-0064-8

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