Paradoxical TB-IRIS in HIV-infected adults: a systematic review and meta-analysis

Papers of special note have been highlighted as: • of interest

References

• 1 World Health Organization: Global tuberculosis report 2013. World Health Organization. http://apps.who.int/iris/bitstream.
  Google Scholar
• 2 World Health Organization: Consolidated guidelines on general HIV care and the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. http://apps.who.int/iris/bitstream/10665.
  Google Scholar
• 3 Gutierrez JP, Johns B, Adam T et al. Achieving the WHO/UNAIDS antiretroviral treatment 3 by 5 goal: what will it cost? Lancet 364(9428), 63–64 (2004).
  MedlineGoogle Scholar
• 4 Sun HY, Singh N. Immune reconstitution inflammatory syndrome in non-HIV immunocompromised patients. Curr. Opin. Infect. Dis. 22(4), 394–402 (2009).
  Medline CASGoogle Scholar
• 5 Lai RP, Nakiwala JK, Meintjes G, Wilkinson RJ. The immunopathogenesis of the HIV tuberculosis immune reconstitution inflammatory syndrome. Eur. J. Immunol. 43(8), 1995–2002 (2013).
  Medline CASGoogle Scholar
• 6 French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS 18(12), 1615–1627 (2004).
  Medline CASGoogle Scholar
• 7 Shelburne S, Hamill RJ. The immune reconstitution inflammatory syndrome. AIDS Rev. 5(2), 67–79 (2003).
  MedlineGoogle Scholar
• 8 French MA, Mallal SA, Dawkins RL. Zidovudine-induced restoration of cell-mediated immunity to mycobacteria in immunodeficient HIV-infected patients. AIDS 6(11), 1293–1298 (1992).
  Medline CASGoogle Scholar
• 9 Meintjes G, Wilkinson KA, Rangaka MX et al. Type 1 helper T cells and FoxP3-positive T cells in HIV–tuberculosis-associated immune reconstitution inflammatory syndrome. Am. J. Respir. Crit. Care Med. 178(10), 1083–1089 (2008).
  Medline CASGoogle Scholar
• 10 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. 8(8), 516–523 (2008).
  MedlineGoogle Scholar
• 11 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. 40(9), 1368–1371 (2005).
  MedlineGoogle Scholar
• 12 Narendran G, Andrade BB, Porter BO et al. Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in HIV patients with culture confirmed pulmonary tuberculosis in India and the potential role of IL-6 in prediction. PLoS ONE 8(5), e63541 (2013).• This observational study from India reported the highest incidence of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in the literature (54%), with median time of onset 11 days after starting antiretroviral therapy. Most patients were treated with corticosteroids. Two patients died due to CNS TB-IRIS.
  MedlineGoogle Scholar
• 13 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. 158(1), 157–161 (1998).• First cohort study to report cases of paradoxical TB-IRIS in 1998 (n = 12, incidence 36%). In certain TB-IRIS patients the clinical syndrome was accompanied by conversion of tuberculin skin test from negative to strongly positive.
  Medline CASGoogle Scholar
• 14 Lawn SD, Myer L, Bekker LG, Wood R. Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa. AIDS 21(3), 335–341 (2007).
  MedlineGoogle Scholar
• 15 Naidoo K, Yende-Zuma N, Padayatchi N et al. The immune reconstitution inflammatory syndrome after antiretroviral therapy initiation in patients with tuberculosis: findings from the SAPiT trial. Ann. Intern. Med. 157(5), 313–324 (2012).• Secondary analysis of the SAPiT trial that was focussed on TB-IRIS the investigators reported that those patients with HIV-associated TB who started antiretroviral therapy in the first 4 weeks of TB treatment had more frequent TB-IRIS, that was more severe and with longer symptom duration than those randomised to start later.
  MedlineGoogle Scholar
• 16 UNAIDS. The Gap Report UNAIDS. www.unaids.org/en/resources/campaigns.
  Google Scholar
• 17 Boulle A, Van Cutsem G, Hilderbrand K et al. Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. AIDS 24(4), 563–572 (2010).
  MedlineGoogle Scholar
• 18 Avila D, Althoff K, Mugglin C et al. Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries. J. Acquir. Immune Defic. Syndr. 65(1), e8–16 (2014).
  MedlineGoogle Scholar
• 19 Abdool Karim SS, Naidoo K, Grobler A et al. Integration of antiretroviral therapy with tuberculosis treatment. N. Engl. J. Med. 365(16), 1492–1501 (2011).
  Medline CASGoogle Scholar
• 20 Blanc F, Sok T, Laureillard D et al. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N. Engl. J. Med. 365(16), 1471–1481 (2011).
  Medline CASGoogle Scholar
• 21 Havlir DV, Kendall MA, Ive P et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N. Engl. J. Med. 365(16), 1482–1491 (2011).
  Medline CASGoogle Scholar
• 22 Müller 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. 10(4), 251–261 (2010).
  MedlineGoogle Scholar
• 23 Pedral-Sampaio DB, Alves CR, Netto EM, Brites C, Oliveira AS, Badaro R. Efficacy and safety of efavirenz in HIV patients on rifampin for tuberculosis. Brazil. J. Infect. Dis. 8(3), 211–216 (2004).
  Medline CASGoogle Scholar
• 24 Luetkemeyer AF, Kendall MA, Nyirenda M et al. Tuberculosis immune reconstitution inflammatory syndrome in A5221 STRIDE: timing, severity, and implications for HIV-TB programs. J. Acquir. Immune Defic. Syndr. 65(4), 423–428 (2014).• Secondary analysis of the multinational STRIDE trial that focussed specifically on TB-IRIS. Participants with HIV-associated TB were randomised to start antiretroviral therapy within 2 weeks versus 8–12 weeks after starting TB treatment. In those patients with CD4 <50 cells/µl the risk of TB-IRIS was four-fold higher in those who started ART earlier, but an increased risk associated with early antiretroviral therapy was not seen in those with CD4 ≥50 cells/µl.
  Medline CASGoogle Scholar
• 25 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. 37(5), 1574–1576 (2004).
  Medline CASGoogle Scholar
• 26 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. 6(1), 71–75 (2002).
  Medline CASGoogle Scholar
• 27 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. 162(1), 97–99 (2002).
  MedlineGoogle Scholar
• 28 Breen RA, Smith CJ, Bettinson H et al. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection. Thorax 59(8), 704–707 (2004).
  Medline CASGoogle Scholar
• 29 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. 39(11), 1709–1712 (2004).
  MedlineGoogle Scholar
• 30 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. (Lond.) 10(3), 417–422 (2005).
  MedlineGoogle Scholar
• 31 Shelburne SA, Visnegarwala F, Darcourt J et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 19(4), 399–406 (2005).
  MedlineGoogle Scholar
• 32 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. 53(6), 357–363 (2006).
  MedlineGoogle Scholar
• 33 Puljiz I, Begovac J. Tuberculosis in HIV-infected patients in Croatia between 1986 and 2005. Coll. Antropol. 30(2), 53–58 (2006).
  MedlineGoogle Scholar
• 34 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. 11(12), 1282–1289 (2007).
  Medline CASGoogle Scholar
• 35 Serra FC, Hadad D, Orofino RL et al. Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro. Brazil. J. Infect. Dis. 11(5), 462–465 (2007).
  MedlineGoogle Scholar
• 36 Tansuphasawadikul S, Saito W, Kim J et al. Outcomes in HIV-infected patients on antiretroviral therapy with tuberculosis. Southeast Asian J. Trop. Med. Public Health 38(6), 1053–1060 (2007).
  MedlineGoogle Scholar
• 37 van Oosterhout JJ, Kumwenda JJ, Beadsworth M et al. Nevirapine-based antiretroviral therapy started early in the course of tuberculosis treatment in adult Malawians. Antivir. Ther. (Lond.) 12(4), 515 (2007).
  Medline CASGoogle Scholar
• 38 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. 8(8), 516–523 (2008).
  MedlineGoogle Scholar
• 39 Baalwa J, Mayanja-Kizza H, Kamya MR, John L, Kambugu A, Colebunders R. Short report: worsening and unmasking of tuberculosis in HIV-1 infected patients after initiating highly active anti-retroviral therapy in Uganda. Afr. Health Sci. 8(3), 190–195 (2008).
  MedlineGoogle Scholar
• 40 Manosuthi W, Van Tieu H, Mankatitham W et al. Clinical case definition and manifestations of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS 23(18), 2467–2471 (2009).
  MedlineGoogle Scholar
• 41 Tieu HV, Ananworanich J, Avihingsanon A et al. Immunologic markers as predictors of tuberculosis-associated immune reconstitution inflammatory syndrome in HIV and tuberculosis coinfected persons in Thailand. AIDS Res. Hum. Retroviruses 25(11), 1083–1089 (2009).
  Medline CASGoogle Scholar
• 42 Eshun-Wilson I, Havers F, Nachega JB et al. Evaluation of paradoxical TB-associated IRIS with the use of standardized case definitions for resource-limited settings. J. Int. Assoc. Physicians. AIDS. Care. (Chic.) 9(2), 104–108 (2010).
  MedlineGoogle Scholar
• 43 Sharma SK, Dhooria S, Barwad P et al. A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case-definition. Indian J. Med. Res. 131, 804–808 (2010).
  MedlineGoogle Scholar
• 44 Dibyendu D, Sarkar RN, Phaujdar S, Bhattacharyya K, Pal HK. Incidence and risk factors of immune reconstitution inflammatory syndrome in HIV-TB coinfected patients. Brazil. J. Infect. Dis. 15(6), 553–559 (2011).
  MedlineGoogle Scholar
• 45 Karmakar S, Sharma SK, Vashishtha R et al. Clinical characteristics of tuberculosis-associated immune reconstitution inflammatory syndrome in north Indian population of HIV/AIDS patients receiving HAART. Clin. Dev. Immunol. 2011, 239021_1–239021_9 (2011).
  Google Scholar
• 46 Letang E, Miró JM, Nhampossa T et al. Incidence and predictors of immune reconstitution inflammatory syndrome in a rural area of Mozambique. PLoS ONE 6(2), e16946 (2011).
  Medline CASGoogle Scholar
• 47 Lorent N, Sebatunzi O, Mukeshimana G, Van den Ende J, Clerinx J. Incidence and risk factors of serious adverse events during antituberculous treatment in Rwanda: a prospective cohort study. PLoS ONE 6(5), e19566 (2011).
  Medline CASGoogle Scholar
• 48 Ali K, Klotz SA. The immune reconstitution inflammatory syndrome with tuberculosis: a common problem in Ethiopian HIV-infected patients beginning antiretroviral therapy. J. Int. Assoc. Physicians AIDS Care (Chic.) 11(3), 198–202 (2012).
  MedlineGoogle Scholar
• 49 Agarwal U, Kumar A, Behera D, French MA, Price P. Tuberculosis associated immune reconstitution inflammatory syndrome in patients infected with HIV: meningitis a potentially life threatening manifestation. AIDS Res. Ther. 9(1), 17 (2012).
  MedlineGoogle Scholar
• 50 Haddow LJ, Moosa MS, Mosam A, Moodley P, Parboosing R, Easterbrook PJ. Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa. PLoS ONE 7(11), e40623 (2012).
  Medline CASGoogle Scholar
• 51 Kumarasamy N, Venkatesh KK, Vignesh R et al. Clinical outcomes among HIV/tuberculosis-coinfected patients developing immune reconstitution inflammatory syndrome after HAART initiation in South India. J. Int. Assoc. Provid. AIDS Care 12(1), 28–31 (2013).
  Medline CASGoogle Scholar
• 52 Limmahakhun S, Chaiwarith R, Nuntachit N, Sirisanthana T, Supparatpinyo K. Treatment outcomes of patients co-infected with tuberculosis and HIV at Chiang Mai University Hospital, Thailand. Int. J. STD AIDS 23(6), 414–418 (2012).
  Medline CASGoogle Scholar
• 53 Manosuthi W, Mankatitham W, Lueangniyomkul A et al. Time to initiate antiretroviral therapy between 4 weeks and 12 weeks of tuberculosis treatment in HIV-infected patients: results from the TIME study. J. Acquir. Immune Defic. Syndr. 60(4), 377–383 (2012).• Randomised trial conducted in Thailand (n = 156) participants with HIV-associated TB were randomised to initiate antiretroviral therapy 4 versus 12 weeks after commencing TB treatment. The incidence of TB-IRIS was higher in the 4-week arm.
  Medline CASGoogle Scholar
• 54 Worodria W, Menten J, Massinga-Loembe M et al. Clinical spectrum, risk factors and outcome of immune reconstitution inflammatory syndrome in patients with tuberculosis-HIV coinfection. Antivir. Ther. 17(5), 841–848 (2012).
  MedlineGoogle Scholar
• 55 Laureillard D, Marcy O, Madec Y et al. Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome after early initiation of antiretroviral therapy in a randomized clinical trial. AIDS 27(16), 2577–2586 (2013).• Focussed on the incidence and risk factors for TB-IRIS in the CAMELIA trial that was conducted in Cambodia among patients with HIV-associated TB and generally very low CD4 counts. The most common TB-IRIS features were lymphadenitis and fever. The cumulative incidence of TB-IRIS was more than double in those who started antiretroviral therapy 2 weeks after TB treatment versus 8 weeks.
  Medline CASGoogle Scholar
• 56 Marais S, Meintjes G, Pepper DJ et al. Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome. Clin. Infect. Dis. 56(3), 450–460 (2013).
  Medline CASGoogle Scholar
• 57 van der Plas H, Meintjes G, Schutz C et al. Complications of antiretroviral therapy initiation in hospitalised patients with HIV-associated tuberculosis. PLoS ONE 8(2), e54145 (2013).
  Medline CASGoogle Scholar
• 58 Bonnet M, Baudin E, Jani IV et al. Incidence of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome and impact on patient outcome. PLoS ONE 8(12), e84585 (2013).
  MedlineGoogle Scholar
• 59 Abdool Karim SS, Naidoo K, Grobler A et al. Timing of initiation of antiretroviral drugsduring tuberculosis therapy. N. Engl. J. Med. 362(8), 697–706 (2010).
  Medline CASGoogle Scholar
• 60 Karmakar S, Sharma SK, Vashishtha R et al. Clinical characteristics of tuberculosis-associated immune reconstitution inflammatory syndrome in north Indian population of HIV/AIDS patients receiving HAART. Clin. Dev. Immunol. 2011, 239021_1–239021_9 (2011).
  Google Scholar
• 61 Breen RA, Smith CJ, Bettinson H et al. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection. Thorax 59(8), 704–707 (2004).
  Medline CASGoogle Scholar
• 62 Sharma SK, Dhooria S, Barwad P et al. A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case-definition. Indian J Med Res. 131, 804–808 (2010).
  MedlineGoogle Scholar
• 63 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. 52(11), 1374–1383 (2011).
  MedlineGoogle Scholar
• 64 Shelburne Iii SA, Hamill RJ, Rodriguez-Barradas MC et al. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine 81(3), 213–227 (2002).
  MedlineGoogle Scholar
• 65 Shao HJ, Crump JA, Ramadhani HO et al. Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania. AIDS Res. Hum. Retroviruses 25(12), 1277–1285 (2009).
  Medline CASGoogle Scholar
• 66 Affandi JS, Kumar M, Agarwal U, Singh S, Price P. The search for a genetic factor associating with immune restoration disease in HIV patients co-infected with Mycobacterium tuberculosis. Dis. Markers 34(6), 445–449 (2013).
  Medline CASGoogle Scholar
• 67 Conesa-Botella A, Meintjes G, Coussens AK et al. Corticosteroid therapy, vitamin D status, and inflammatory cytokine profile in the HIV-tuberculosis immune reconstitution inflammatory syndrome. Clin. Infect. Dis. 55(7), 1004–1011 (2012).
  Medline CASGoogle Scholar
• 68 Price P, Haddow LJ, Affandi J et al. Short communication: plasma levels of vitamin D in HIV patients initiating antiretroviral therapy do not predict immune restoration disease associated with Mycobacterium tuberculosis. AIDS Res. Hum. Retroviruses 28(10), 1216–1219 (2012).
  Medline CASGoogle Scholar
• 69 Nansera D, Graziano FM, Friedman DJ, Bobbs MK, Jones AN, Hansen KE. Vitamin D and calcium levels in Ugandan adults with human immunodeficiency virus and tuberculosis. Int. J. Tuberc. Lung Dis. 15(11), 1522–1527, i (2011).
  Medline CASGoogle Scholar
• 70 Conesa-Botella A, Loembe MM, Manabe YC et al. Urinary lipoarabinomannan as predictor for the tuberculosis immune reconstitution inflammatory syndrome. J. Acquir. Immune Defic. Syndr. 58(5), 463–468 (2011).
  Medline CASGoogle Scholar
• 71 LawnSD, Edwards DJ, Kranzer K,Vogt M, Bekker LG, Wood R. Urine lipoarabinomannanassay for tuberculosis screening before antiretroviral therapy diagnostic yieldand association with immune reconstitution disease. AIDS 23(14), 1875–1880 (2009).
  MedlineGoogle Scholar
• 72 Meintjes G, Scriven J, Marais S. Management of the immune reconstitution inflammatory syndrome. Current HIV/AIDS Reports 9(3), 238–250 (2012).
  MedlineGoogle Scholar
• 73 Breton G, Bourgarit A, Pavy S et al. Treatment for tuberculosis-associated immune reconstitution inflammatory syndrome in 34 HIV-infected patients. Int. J. Tuberc. Lung Dis. 16(10), 1365–1370 (2012).• Cohort study from France that reported on the outcomes of 34 patients with TB-IRIS managed with a variety of strategies: no treatment, corticosteroids, antiretroviral interruption or simultaneous corticosteroids and antiretroviral interruption.
  Medline CASGoogle Scholar
• 74 Kaplan JE, Benson C, Holmes K et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. MMWR Recomm. Rep. 58(RR-4), 1–207 (2009).
  Google Scholar
• 75 Meintjes G, Wilkinson RJ, Morroni C et al. Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS 24(15), 2381–2390 (2010).• Only randomised controlled trial published to date that evaluated a treatment for paradoxical TB-IRIS. Patients diagnosed with TB-IRIS were randomised to receive prednisone or placebo for 4 weeks. Those who received prednisone had significantly reduced duration of hospitalization and outpatient therapeutic procedures, the composite primary end point.
  Medline CASGoogle Scholar