|Year : 2017 | Volume
| Issue : 2 | Page : 279-281
Risk factors and frequency of tuberculosis-associated immune reconstitution inflammatory syndrome among HIV/Tuberculosis co-infected patients in Southern India
Ramachandran Vignesh1, Chinnambedu R Swathirajan2, Sunil S Solomon3, Esaki Muthu Shankar2, Kailapuri G Murugavel2
1 Infectious Diseases Laboratory, Y. R. Gaitonde Centre for AIDS Research and Education, Chennai, Tamil Nadu, India; Laboratory-based Department, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Malaysia
2 Infectious Diseases Laboratory, Y. R. Gaitonde Centre for AIDS Research and Education, Chennai, Tamil Nadu, India
3 Medical Centre, Y. R. Gaitonde Centre for AIDS Research and Education, Chennai, Tamil Nadu, India; Department of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, USA
|Date of Web Publication||5-Jul-2017|
Kailapuri G Murugavel
Infectious Diseases Laboratory, Y. R. Gaitonde Centre for AIDS Research and Education, 2nd Floor, Admin Building, VHS Hospital Campus, Rajiv Gandhi Salai, Taramani, Chennai - 600 113, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Immune reconstitution inflammatory syndrome (IRIS) continues to be a complication in HIV/tuberculosis (TB) co-infected patients initiating highly active antiretroviral therapy (HAART). The aim of this study was to evaluate the risk factors associated with developing IRIS to identify a possible biomarker to predict or diagnose IRIS in patients initiating HAART. A total of 175 HIV/TB co-infected patients initiating HAART were followed up longitudinally during September 2010 to May 2013 attending a HIV care clinic in Chennai. Patients were followed up longitudinally after HAART initiation and baseline demographic, laboratory parameters and treatment characteristics between patients with IRIS events and those without IRIS events were compared. Chi-square or Fisher's exact test for categorical variables and a Wilcoxon rank-sum test for continuous variables were performed using SPSS, version 12.0 software. Patients with IRIS had a significantly lower median baseline CD4+ T-cell count (P = 0.0039). There were no differences in terms of sex, CD4 T-cell %, plasma viral load, time interval between initiating ATT and HAART between the IRIS and non-IRIS patients. Low CD4+ T-cell count (<100 cells/μL) could be used as a marker to screen and monitor patients initiating HAART.
Keywords: HIV, HIV/tuberculosis, immune reconstitution inflammatory syndrome, opportunistic infection, tuberculosis-immune reconstitution inflammatory syndrome, tuberculosis
|How to cite this article:|
Vignesh R, Swathirajan CR, Solomon SS, Shankar EM, Murugavel KG. Risk factors and frequency of tuberculosis-associated immune reconstitution inflammatory syndrome among HIV/Tuberculosis co-infected patients in Southern India. Indian J Med Microbiol 2017;35:279-81
|How to cite this URL:|
Vignesh R, Swathirajan CR, Solomon SS, Shankar EM, Murugavel KG. Risk factors and frequency of tuberculosis-associated immune reconstitution inflammatory syndrome among HIV/Tuberculosis co-infected patients in Southern India. Indian J Med Microbiol [serial online] 2017 [cited 2017 Sep 26];35:279-81. Available from: http://www.ijmm.org/text.asp?2017/35/2/279/209570
| ~ Introduction|| |
Although the advent of highly active antiretroviral therapy (HAART) has led to a dramatic decline of morbidity and mortality associated with HIV infection, a few patients with underlying opportunistic infections (OIs) before initiating HAART are prone to immune reconstitution inflammatory syndrome (IRIS)., IRIS is characterised by the paradoxical worsening of the pre-existing OI with exacerbated inflammatory reactions. Tuberculosis (TB) being the most common OI in India, TB-associated IRIS is most frequently reported.,,,, The pathogenesis of IRIS is not fully understood and there is no common immunological pathway explaining the events of IRIS.,,, Evaluating the risk factors associated with developing IRIS could be a key in identifying a possible biomarker to predict or diagnose IRIS in patients initiating HAART. Hence, this study was conducted to evaluate the risk factors associated with TB-IRIS among the HIV/TB-coinfected patients.
| ~ Subjects and Methods|| |
A total of 175 HIV/TB co-infected patients from Southern India with recent diagnosis of TB infection and initiating HAART were enrolled during 2010–2013 and prospectively followed through 1 year of antiretroviral therapy. Patients were defined as having paradoxical TB-IRIS if they fulfilled the “study definition” by French et al. All the study patients were evaluated at baseline, 2 weeks, 8 weeks, 6 months and 1 year after initiation of HAART and at the time of IRIS events. The baseline demographic, laboratory and treatment characteristics between patients with IRIS events and those without IRIS events were compared using Chi-square or Fisher's exact test for categorical variables and a Wilcoxon rank-sum test for continuous variables. All statistical analyses were performed using SPSS, version 12.0 software (SPSS Inc., Chicago, USA) and statistical significance was defined at a confidence level of 95% (P < 0.05). The study was approved by the Institutional Review Board and informed consent was obtained from all the study participants.
| ~ Results|| |
Of the 175 HIV-1/TB co-infected patients followed up, 148 (85%) were male and 165 (94%) had heterosexually acquired HIV infection. While initiated on HAART, the median CD4+ T-cell count and HIV-1 plasma viral load (PVL) of the study population were 126 cells/μL (IQR, 65.8–219 cells/μL) and 253,000 copies/mL (IQR, 99,150–729,250 copies/mL), respectively. Thirteen patients (7.4%) experienced IRIS after initiating HAART. The median time to onset of IRIS was 4 weeks (IQR, 2–6 weeks) and about 78% of IRIS events were observed to occur within the 1st month after initiation of HAART.
[Table 1] compares the clinical and laboratory characteristics at baseline and after initiation of HAART in the 13 patients with IRIS and in the 162 control patients, who did not develop IRIS after HAART initiation. Patients with IRIS had a significantly lower median baseline absolute CD4+ T-cell count (68 vs. 140; P = 0.0039). There were no differences between the IRIS and non-IRIS group of patients in terms of their CD4+ T-cell % (P = 0.362), PVL (P = 0.542) and the time interval between initiating ATT and HAART (P = 0.215).
|Table 1: Analysis of factors associated with development of immune reconstitution inflammatory syndrome among human immunodeficiency virus/tuberculosis co-infected patients initiating highly active antiretroviral therapy|
Click here to view
| ~ Discussion|| |
Several risk factors have been associated with TB-associated IRIS such as low (typically <100 cells/μL) pre-ART CD4+ T-cell count or its percentage (<10%), higher baseline HIV PVL and stronger CD4+ T-cell increase with HIV PVL decline after HAART., Studies on the risk factors of TB-IRIS are very essential that they are used in risk assessment for patients initiating HAART.
Earlier studies from Chennai had reported the incidence of TB-associated IRIS among HIV/TB co-infected patients as 7.3%, and in the present study, the incidence was observed to be about 7.4%, which demonstrates the continuing trend in the occurrence of TB-associated IRIS events. A study from the UK had reported the young age of HAART initiation and baseline CD4+ T-cell percentages as risk factors for developing based on univariate analyses. However, in line with few other studies, the present study also did not find the relationship between the age of initiating HAART and developing IRIS.,, The proportion of males in the study population is higher which could be as per the earlier observation from the same institution that females had significantly higher CD4+ T-cell counts than their male counterparts at the time of initiation of HAART. Moreover, when compared to HIV-infected females, males were observed to present with higher rates of TB infection and TB-associated IRIS.
In the present study, the finding that, lower median CD4+ T-cells counts as a significant risk factor (P = 0.0396), corroborates those of several other published studies with low nadir CD4+ T-cell count as a consistent finding in many of the larger case–control studies.,
With about 7.4% of patients initiating HAART observed to develop IRIS, it becomes essential to predict IRIS. Low CD4+ T-cell count being a significant risk factor for IRIS could be used as a marker to screen and monitor patients, who are initiating HAART. Hence, larger prospective cohort studies and clinical trials involving patients initiating HAART are needed to further study the risk factors and the immune pathogenesis of IRIS so as to establish optimal preventative and management strategies for IRIS.
We would like to acknowledge Indian Council of Medical Research, New Delhi, for the funding of this study (ICMR grant no: HIV/50/109/2009/ECD-II).
Financial support and sponsorship
The study was supported by Indian Council of Medical Research, New Delhi.
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Palella FJ Jr., Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al.
Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998;338:853-60.
Kumarasamy N, Solomon S, Chaguturu SK, Cecelia AJ, Vallabhaneni S, Flanigan TP, et al.
The changing natural history of HIV disease: Before and after the introduction of generic antiretroviral therapy in southern India. Clin Infect Dis 2005;41:1525-8.
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.
Kumarasamy N, Chaguturu S, Mayer KH, Solomon S, Yepthomi HT, Balakrishnan P, 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.
Shankar EM, Vignesh R, Ellegård R, Barathan M, Chong YK, Bador MK, et al.
co-infection: A 'danger-couple model' of disease pathogenesis. Pathog Dis 2014;70:110-8.
Solomon S, Balakrishnan P, Vignesh R, Waldrop G, Solomon SS, Murugavel KG, et al.
A rapid and low-cost microscopic observation drug susceptibility assay for detecting TB and MDR-TB among individuals infected by HIV in South India. Indian J Med Microbiol 2013;31:130-7. [Full text]
Narendran G, Swaminathan S. Tuberculosis immune reconstitution inflammatory syndrome: Profile of an enigmatic condition. Curr Sci 2013;105:657-65.
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 preexistent Th1 responses against Mycobacterium tuberculosis
antigens. J Acquir Immune Defic Syndr 2013;64:241-8.
Lai RP, Nakiwala JK, Meintjes G, Wilkinson RJ. The immunopathogenesis of the HIV tuberculosis immune reconstitution inflammatory syndrome. Eur J Immunol 2013;43:1995-2002.
Lanzafame M, Vento S. Tuberculosis-immune reconstitution inflammatory syndrome. J Clin Tuberc Other Mycobact Dis 2016;3:6-9.
French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS 2004;18:1615-27.
Sharma SK, Soneja M. HIV and immune reconstitution inflammatory syndrome (IRIS). Indian J Med Res 2011;134:866.
Grant PM, Komarow L, Andersen J, Sereti I, Pahwa S, Lederman MM, et al.
Risk factor analyses for immune reconstitution inflammatory syndrome in a randomized study of early vs. deferred ART during an opportunistic infection. PLoS One 2010;5:e11416.
Letang E, Miró JM, Nhampossa T, Ayala E, Gascon J, Menéndez C, et al.
Incidence and predictors of immune reconstitution inflammatory syndrome in a rural area of Mozambique. PLoS One 2011;6:e16946.
Naidoo K, Yende-Zuma N, Padayatchi N, Naidoo K, Jithoo N, Nair G, et al.
The immune reconstitution inflammatory syndrome after antiretroviral therapy initiation in patients with tuberculosis: Findings from the SAPiT trial. Ann Intern Med 2012;157:313-24.
Walker NF, Scriven J, Meintjes G, Wilkinson RJ. Immune reconstitution inflammatory syndrome in HIV-infected patients. HIV AIDS (Auckl) 2015;7:49-64.
Kumarasamy N, Venkatesh KK, Cecelia AJ, Devaleenol B, Saghayam S, Yepthomi T, et al.
Gender-based differences in treatment and outcome among HIV patients in South India. J Womens Health (Larchmt) 2008;17:1471-5.