Tuberculosis (TB)-associated immune reconstitution inflammatory syndrome in TB-HIV co-infected patients in Malaysia: prevalence, risk factors, and treatment outcomes
Hong Yien Tan A , Yean Kong Yong A , Sin How Lim A , Sasheela Ponnampalavanar A B , Sharifah F. S. Omar A B , Yong Kek Pang A C , Adeeba Kamarulzaman A B , Patricia Price G , Suzanne M. Crowe D E F and Martyn A. French G H I
+ Author Affiliations
- Author Affiliations
A Centre of Excellence for Research in AIDS (CERiA), Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
B Infectious Disease Unit, Department of Medicine, University of Malaya Medical Centre, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
C Respiratory Unit, Department of Medicine, University of Malaya Medical Centre, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
D Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, Vic. 3004, Australia.
E Infectious Diseases Unit, The Alfred Hospital, 55 Commercial Road, Melbourne, Vic. 3004, Australia.
F Department of Infectious Diseases, Monash University, Wellington Road, Clayton, Vic. 3800, Australia.
G Translational Immunology Unit, School of Pathology and Laboratory Medicine, University of Western Australia, Level 2, Medical Research Foundation Building, Rear 50 Murray Street, Perth, WA 6000, Australia.
H Department of Clinical Immunology, Royal Perth Hospital, 197 Wellington Street, Perth, WA 6000, Australia.
I Corresponding author. Email: martyn.french@uwa.edu.au
Sexual Health 11(6) 532-539 https://doi.org/10.1071/SH14093
Submitted: 3 June 2014 Accepted: 14 August 2014 Published: 9 September 2014
Abstract
Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication of antiretroviral therapy (ART) in countries with high rates of endemic TB, but data from South-East Asia are incomplete. Identification of prevalence, risk factors and treatment outcomes of TB-IRIS in Malaysia was sought. Methods: A 3-year retrospective study was conducted among TB-HIV co-infected patients treated at the University of Malaya Medical Centre. Simple and adjusted logistic regressions were used to identify the predictors for TB-IRIS while Cox regression was used to assess the influence of TB-IRIS on long-term CD4 T-cell recovery. Results: One hundred and fifty-three TB-HIV patients were enrolled, of whom 106 had received both anti-TB treatment (ATT) and ART. The median (IQR) baseline CD4 T-cell count was 52 cells μL–1 (13–130 cells μL–1). Nine of 96 patients (9.4%) developed paradoxical TB-IRIS and eight developed unmasking TB-IRIS, at a median (IQR) time of 27 (12–64) and 19 (14–65) days, respectively. In adjusted logistic regression analysis, only disseminated TB was predictive of TB-IRIS [OR: 10.7 (95% CI: 1.2–94.3), P = 0.032]. Mortality rates were similar for TB-IRIS (n = 1, 5.9%) and non-TB-IRIS (n = 5, 5.7%) patients and CD4 T-cell recovery post-ART was not different between the two groups (P = 0.363). Conclusion: Disseminated TB was a strong independent predictor of TB-IRIS in Malaysian HIV-TB patients after commencing ART. This finding underscores the role of a high pathogen load in the pathogenesis of TB-IRIS; so interventions that reduce pathogen load before ART may benefit HIV patients with disseminated TB.
Additional keywords: antiretroviral therapy, antituberculosis treatment.
References
[1] World Health Organization (WHO). Global tuberculosis report. Available online at: http://www.who.int/tb/publications/global_report/en/ [verified 26 September 2013].[2] World Health Organization (WHO). Tuberculosis country profiles. Malaysia. Available at: www.who.int/tb/data [verified 26 September 2013].
[3] French MA. HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis 2009; 48 101–7.
| HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal.Crossref | GoogleScholarGoogle Scholar | 19025493PubMed |
[4] Malaysia Health Technology Assessment Section (MaHTAS) MDD, Ministry of Health Malaysia. Clinical practice guidelines. Management of tuberculosis. Putrajaya, Malaysia: MaHTAS; 2012.
[5] World Health Organization (WHO). Guidelines for treatment of tuberculosis, 4th edn. Geneva: WHO; 2010.
[6] Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, et al Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis 2008; 8 516–23.
| Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings.Crossref | GoogleScholarGoogle Scholar | 18652998PubMed |
[7] Haddow LJ, Easterbrook PJ, Mosam A, Khanyile NG, Parboosing R, Moodley P, 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.
| Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort.Crossref | GoogleScholarGoogle Scholar | 19788360PubMed |
[8] Lawn SD, Wilkinson RJ, Lipman MC, Wood R. Immune reconstitution and “unmasking” of tuberculosis during antiretroviral therapy. Am J Respir Crit Care Med 2008; 177 680–5.
| Immune reconstitution and “unmasking” of tuberculosis during antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar | 18202347PubMed |
[9] Breton G, Duval X, Estellat C, Poaletti X, Bonnet D, Mvondo Mvondo D, 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.
| Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar | 15578375PubMed |
[10] 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; 158 157–61.
| Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1czisFaqug%3D%3D&md5=dc61d8a09144c03059ef90bfde4e2fc2CAS | 9655723PubMed |
[11] Breen RA, Smith CJ, Bettinson H, Dart S, Bannister B, Johnson MA, et al Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection. Thorax 2004; 59 704–7.
| Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2cznvFCltw%3D%3D&md5=d6b05ba699cdd6d1482fff9bef583facCAS | 15282393PubMed |
[12] 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.
| 15918332PubMed |
[13] 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 2007; 21 335–41.
| Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa.Crossref | GoogleScholarGoogle Scholar | 17255740PubMed |
[14] De D, Sarkar RN, Phaujdar S, Bhattacharyya K, Pal HK. Incidence and risk factors of immune reconstitution inflammatory syndrome in HIV-TB coinfected patients. Braz J Infect Dis 2011; 15 553–9.
| Incidence and risk factors of immune reconstitution inflammatory syndrome in HIV-TB coinfected patients.Crossref | GoogleScholarGoogle Scholar |
[15] Serra FC, Hadad D, Orofino RL, Marinho F, Lourenco C, Morgado M, et al Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro. Braz J Infect Dis 2007; 11 462–5.
| Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro.Crossref | GoogleScholarGoogle Scholar | 17962870PubMed |
[16] 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 2012; 9 17
| Tuberculosis associated immune reconstitution inflammatory syndrome in patients infected with HIV: meningitis a potentially life threatening manifestation.Crossref | GoogleScholarGoogle Scholar | 22620862PubMed |
[17] Umphonsathien W, Sungkanuparph S. Early initiation of antiretroviral therapy in HIV/Tuberculosis co-infection and immune reconstitution inflammatory syndrome. J Infect Dis Antimicrob Agents 2011; 28 15–23.
[18] 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.
| Immune reconstitution inflammatory syndrome of tuberculosis among HIV-infected patients receiving antituberculous and antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar | 16487593PubMed |
[19] Aramaki M, Silachamroon U, Desakorn V, Maek-A-nantawat W, Waiwaruwut J, Jutiwarakun K, et al Immune reconstitution inflammatory syndrome in adult human immunodeficiency virus-infected patients in Thailand. Southeast Asian J Trop Med Public Health 2010; 41 138–45.
| 20578492PubMed |
[20] Baalwa J, Mayanja-Kizza H, Kamya MR, John L, Kambugu A, Colebunders R. Worsening and unmasking of tuberculosis in HIV-1 infected patients after initiating highly active anti-retroviral therapy in Uganda. Afr Health Sci 2008; 8 190–5.
| 19357749PubMed |
[21] Chang CC, Crane M, Zhou J, Mina M, Post JJ, Cameron BA, et al HIV and co-infections. Immunol Rev 2013; 254 114–42.
| HIV and co-infections.Crossref | GoogleScholarGoogle Scholar | 23772618PubMed |
[22] Oliver BG, Elliott JH, Price P, Phillips M, Saphonn V, Vun MC, et al Mediators of innate and adaptive immune responses differentially affect immune restoration disease associated with Mycobacterium tuberculosis in HIV patients beginning antiretroviral therapy. J Infect Dis 2010; 202 1728–37.
| Mediators of innate and adaptive immune responses differentially affect immune restoration disease associated with Mycobacterium tuberculosis in HIV patients beginning antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhs1entLfP&md5=0157432546814c130f07edc4335ec1edCAS | 20977362PubMed |
[23] Vignesh R, Kumarasamy N, Lim A, Solomon S, Murugavel KG, Balakrishnan P, et al TB-IRIS after initiation of antiretroviral therapy is associated with expansion of pre-existent Th1 responses against Mycobacterium tuberculosis antigens. J Acquir Immune Defic Syndr 2013; 64 241–8.
| TB-IRIS after initiation of antiretroviral therapy is associated with expansion of pre-existent Th1 responses against Mycobacterium tuberculosis antigens.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhs1CitrbM&md5=eeaea6291db38811a19b24e1e1ce3fe2CAS | 23774879PubMed |
[24] Elliott JH, Vohith K, Saramony S, Savuth C, Dara C, Sarim C, et al Immunopathogenesis and diagnosis of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome during early antiretroviral therapy. J Infect Dis 2009; 200 1736–45.
| Immunopathogenesis and diagnosis of tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome during early antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFOlsrrI&md5=f072609ae73182be370bae82b6179252CAS | 19874177PubMed |
[25] Oliver BG, Elliott JH, Price P, Phillips M, Cooper DA, French MA. Tuberculosis after commencing antiretroviral therapy for HIV infection is associated with elevated CXCL9 and CXCL10 responses to Mycobacterium tuberculosis antigens. J Acquir Immune Defic Syndr 2012; 61 287–92.
| Tuberculosis after commencing antiretroviral therapy for HIV infection is associated with elevated CXCL9 and CXCL10 responses to Mycobacterium tuberculosis antigens.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsFOltLbO&md5=eaf402525d3e2c3c90643e304d4ef6b9CAS | 22732467PubMed |
[26] Martin-Blondel G, Mars LT, Liblau RS. Pathogenesis of the immune reconstitution inflammatory syndrome in HIV-infected patients. Curr Opin Infect Dis 2012; 25 312–20.
| Pathogenesis of the immune reconstitution inflammatory syndrome in HIV-infected patients.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XmsFKqsL0%3D&md5=f94ca5e310c7627f590df83627b2da8bCAS | 22562000PubMed |
[27] Narendran G, Andrade BB, Porter BO, Chandrasekhar C, Venkatesan P, Menon PA, 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 2013; 8 e63541
| 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.Crossref | GoogleScholarGoogle Scholar | 23691062PubMed |
[28] Manabe YC, Kesavan AK, Lopez-Molina J, Hatem CL, Brooks M, Fujiwara R, et al The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome. Tuberculosis (Edinb) 2008; 88 187–96.
| The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXnt1egtbc%3D&md5=1ca4de6e1004de902d9c6b3c0997d900CAS | 18068491PubMed |
[29] Conesa-Botella A, Loembe MM, Manabe YC, Worodria W, Mazakpwe D, Luzinda K, et al Urinary lipoarabinomannan as predictor for the tuberculosis immune reconstitution inflammatory syndrome. J Acquir Immune Defic Syndr 2011; 58 463–8.
| Urinary lipoarabinomannan as predictor for the tuberculosis immune reconstitution inflammatory syndrome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsVCksbbJ&md5=fb127f384d618c3a08b538b15fe3d071CAS | 21963941PubMed |
[30] Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, et al Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med 2010; 362 697–706.
| Timing of initiation of antiretroviral drugs during tuberculosis therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXisFOqsrs%3D&md5=19f61aa00fccd895237fa66b5b9a573cCAS | 20181971PubMed |
[31] Gupta P, Vijayan VK, Bansal SK. Changes in protein profile of erythrocyte membrane in bronchial asthma. J Asthma 2012; 49 129–33.
| Changes in protein profile of erythrocyte membrane in bronchial asthma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XitFGls7o%3D&md5=c55c24059331ae47dbf322b22e6e316fCAS | 22277105PubMed |
[32] Manosuthi W, Mankatitham W, Lueangniyomkul A, Thongyen S, Likanonsakul S, Suwanvattana P, et al TIME Study Team 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 2012; 60 377–83.
| Time to initiate antiretroviral therapy between 4 weeks and 12 weeks of tuberculosis treatment in HIV-infected patients: results from the TIME study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVWjsL7J&md5=17aa3872f50a658d0e720f765bfd61b1CAS | 22592586PubMed |
[33] Koenig SP, Riviere C, Leger P, Joseph P, Severe P, Parker K, et al High mortality among patients with AIDS who received a diagnosis of tuberculosis in the first 3 months of antiretroviral therapy. Clin Infect Dis 2009; 48 829–31.
| High mortality among patients with AIDS who received a diagnosis of tuberculosis in the first 3 months of antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar | 19207078PubMed |
[34] French MA. Immune reconstitution inflammatory syndrome: immune restoration disease 20 years on. Med J Aust 2012; 196 318–21.
| Immune reconstitution inflammatory syndrome: immune restoration disease 20 years on.Crossref | GoogleScholarGoogle Scholar | 22432669PubMed |
[35] Kumarasamy N, Venkatesh KK, Vignesh R, Devaleenal B, Poongulali S, Yepthomi T, 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. 2013; 12 28–31.
| 1:STN:280:DC%2BC3s%2FgtFyluw%3D%3D&md5=809f355a8d96da7e3f8cc77d8d2700b7CAS | 23011868PubMed |
