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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 3  |  Page : 167-171

Risk factors for active tuberculosis in human immunodeficiency virus-infected individuals


1 Department of General Medicine, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Infectious Diseases, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India
4 Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, India
5 Department of Microbiology, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission18-Jun-2018
Date of Decision22-Sep-2018
Date of Acceptance25-Oct-2018
Date of Web Publication13-Aug-2019

Correspondence Address:
Vijay Prakash Turaka
Department of General Medicine, Christian Medical College, Vellore, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cjhr.cjhr_91_18

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  Abstract 


Context: Tuberculosis (TB) has become the most common opportunistic infection among individuals with human immunodeficiency virus (HIV) infection worldwide and continues to be a major killer resulting in 0.4 million deaths every year. While some of the risk factors for developing TB in HIV-infected individuals are known, identifying other risk factors will help in screening strategies to pick out those at higher risk for closer follow-up. Aims: The aim of this study was to identify the risk factors related to the development of active TB in HIV-infected individuals. Settings and Design: This case–control study among the HIV-infected individuals was carried out at a HIV clinic in a large tertiary care hospital in South India. Methods: HIV-infected individuals >18 years of age with confirmed TB were chosen as cases. For each case, two age- and sex-matched controls, diagnosed to have HIV infection without active TB or history of TB, were included. The potential risk factors for the development of active TB were evaluated using the odds ratios (ORs) and logistic regression analysis. Results: A total of 150 patients, 50 cases (mean age: 39.3 ± 7.2 years) and 100 controls (mean age: 40.2 ± 7.1 years) were included. On univariate analysis, smoking (OR 8.14, 95% confidence interval [CI]: 3.13–21.21; P < 0.001), low body mass index (OR 6.31, 95% CI: 2.75–14.48; P < 0.001), chronic obstructive pulmonary disease (P = 0.013), ethanol consumption (OR 8.61, 95% CI: 3.57–20.81; P < 0.001), CD4 cell count < 200 cells/μL (OR 13.12, 95% CI: 5.64–30.50; P < 0.001), and not on antiretroviral treatment (ART) (13.34, 95% CI: 5.85–30.41; P < 0.001) were associated with active TB. The risk factors found to be independently associated were CD4 counts < 200 cells/μL (OR 5.75, 95% CI: 1.81–18.20; P = 0003), smoking (OR 7.40, 95% CI: 1.47–37.15; P = 0.015), and not being on ART (OR 13.94, 95% CI: 3.84–50.61; P < 0.001). Conclusion: Initiating ART as soon as possible and patient education on modifiable risk factors including counseling for smoking cessation for HIV-infected individuals are warranted.

Keywords: Human immunodeficiency virus, risk factors, tuberculosis


How to cite this article:
Turaka VP, Nair RG, Sebastian T, Kannangai R, Michael JS, Varghese GM. Risk factors for active tuberculosis in human immunodeficiency virus-infected individuals. CHRISMED J Health Res 2019;6:167-71

How to cite this URL:
Turaka VP, Nair RG, Sebastian T, Kannangai R, Michael JS, Varghese GM. Risk factors for active tuberculosis in human immunodeficiency virus-infected individuals. CHRISMED J Health Res [serial online] 2019 [cited 2019 Oct 17];6:167-71. Available from: http://www.cjhr.org/text.asp?2019/6/3/167/264383




  Introduction Top


Tuberculosis (TB) caused by Mycobacterium tuberculosis along with human immunodeficiency virus (HIV) infection continues to be a major killer resulting in 0.4 million deaths every year, majority of whom live in Sub-Saharan Africa and Asia. The World Health Organization (WHO) reports that in 2015, there were an estimated 10.4 million cases of TB globally, of which 1.2 million (11%) were HIV-infected individuals. Almost 57% of TB cases among people living with HIV were not diagnosed or treated, resulting in 390000 TB-related deaths among people living with HIV in 2015.[1] Among the 34 million HIV-infected individuals worldwide, 14 million are estimated to have latent or active TB.[2] HIV-infected individuals with latent TB have a 20-fold increase in the development of active TB.[3] Individuals with HIV and TB co-infections face a heavy toll as the immune system is compromised to a great extent. The declining CD4 cells which occur in HIV infection as the disease progresses lead to a greater risk of TB reactivation and development of active disease. Thus, TB has become the most common HIV-associated opportunistic infection in the world, and it accelerates the HIV disease progression as well. Nearly 25% of TB-related mortalities are attributed to HIV infection, and TB is attributed to nearly one-third of AIDS-related mortality worldwide. Although antiretroviral treatment (ART) is shown to reduce the incidence of TB by up to 80%, the incidence of active TB remains high within the first few months of ART initiation.[4] This is probably related to the unmasking of subclinical TB associated with immune recovery after initiating ART. While some of the risk factors for the development of TB in HIV-infected individuals such as low CD4 cell count are known, the development of active TB in HIV-infected individuals with reasonable CD4 counts suggests other contributing factors as well.

Some of the risk factors for TB in HIV-infected individuals are well known. The incidence of TB in HIV-infected individuals with CD4 cell count <200 cells/cumm, a body mass index (BMI) <18.5 kg/m 2, and anemia was found to be higher.[5] The absence of antiretroviral therapy is also a significant risk factor for the development of TB.[6] However, in the current era of widely available ART, the development of TB more than 6 months after starting ART also poses a significant burden.[7] Hence, identifying the risk factors will help in screening strategies to pick out the individuals at highest risk for closer follow-up and interventions. Furthermore, better understanding of these risk factors will allow modifying the risk factors and planning and implementation of effective preventive strategies such as isoniazid preventive therapy (IPT). Hence, the aim of this study was to identify the risk factors related to the development of active TB in HIV-infected individuals in the region.


  Methods Top


This case–control study among the HIV-infected individuals was carried out at a HIV clinic in a large tertiary care hospital in South India during August 2011–July 2012. The HIV-infected individuals >18 years of age with confirmed TB were chosen as cases for the study. Patients with HIV were screened for possible active TB using a symptom screen consisting of cough of any duration, fever of any duration, or night sweats lasting 3 weeks or more during the previous 4 weeks and those found to be negative on this symptom screen were chosen as controls. For each case, two age- and sex-matched controls who were diagnosed to have HIV infection without active TB or history of TB were included based on the simple random sampling from the HIV patients attending the same clinic. HIV infection was confirmed by the WHO/NACO Strategy 3 by three assays consisting of chemiluminescent microparticle immunoassay, ELISA, and immunochromatography. The diagnosis of TB was based on the clinical features consistent with TB and positive mycobacterial culture or GeneXpert (MTB/RIF assay) or histopathology showing necrotizing granulomatous inflammation.

An informed consent was obtained from all participants of the study. The patients were interviewed, and all information was collected on a predesigned pro forma which included questions about smoking, alcohol consumption, concomitant diseases, medication, and past infections. Clinical information from the patients including history of fever, cough, weight loss, vomiting, seizures, altered sensorium, abdominal pain, and diarrhea were collected. Physical examination was performed and documented. CD4 counts within the last 6 months were also documented. This study was approved by the Institutional Review Board and Ethics Committee.

The potential risk factors for the development of active TB were evaluated using the odds ratios (ORs) and logistic regression analysis using SPSS version 17.0 (SPSS South Asia (P) Ltd, Bangalore, India). Initially, all factors were evaluated using a Chi-square test. Based on these results, multivariate logistic regression analysis was performed consisting of all factors significant at P < 0.05.


  Results Top


A total of 150 patients were recruited into the study which included 50 cases and 100 controls. The mean age (±standard deviation) of the HIV-infected individuals with active TB was 39.3 ± 7.2 years and 40.2 ± 7.1 years among those without TB. Both cases and controls were predominantly men (80%). Of the HIV-infected individuals, 40 (26.6%) were unemployed, 30 (20%) manual laborers, 14 (9.3%) drivers, 12 (8%) agriculture workers, and 11 (7.3%) housewives. The mean BMI among the cases was 18.53 ± 2.84 kg/m2 while the controls had a mean of 22.87 ± 4.43 kg/m2. The median interquartile range (IQR) CD4 counts of cases and controls was 100 cells/μL (53–196) and 370 cells/μL (210–512), respectively. The median (IQR) duration of diagnosis of HIV infection among the cases was 2.5 months (0–13.5) and that of controls 24 months (9–57). Only 22% of cases were on ART while 79% controls were on ART at enrollment. The median (IQR) duration of ART among cases was 4 months (2–48 months) and among controls was 24 months (6–36 months). In 42% of cases, diagnosis of active TB led to the detection of HIV infection. Out of the 50 patients with TB, 29 (58%) had extrapulmonary and 16 (32%) had pulmonary TB. Five patients were started on empirically on antituberculosis treatment. The extrapulmonary organs involved were lymph node (n = 15), bone marrow (n = 7), pleura (n = 2), cerebrospinal fluid (n = 2), ascitic fluid (n = 1), epidural abscess (n = 1), and chest wall abscess (n = 1). The baseline characteristics are summarized in [Table 1].
Table 1: Baseline characteristics among cases and controls

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On univariate analysis, smoking (OR 8.14, 95% confidence interval [CI]: 3.13–21.21; P < 0.001), low BMI (OR 6.31, 95% CI: 2.75–14.48; P < 0.001), chronic obstructive pulmonary disease (P = 0.013), ethanol consumption (OR 8.61, 95% CI: 3.57–20.81; P < 0.001), CD4 cell count < 200 cells/μL (OR 13.12, 95% CI: 5.64–30.50; P < 0.001), and not on ART (13.34, 95% CI: 5.85–30.41; P < 0.001) had significant association with active TB [Table 2]. Individuals with diabetes mellitus, chronic kidney disease, and chronic liver disease were not found to be at increased risk of developing TB.
Table 2: Summary of the risk factors among the cases and controls and their significance on univariate analysis

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On multivariate analysis, smoking (OR 7.40, 95% CI: 1.47–37.15; P = 0.015), CD4 cell count <200 cells/μL (OR 5.75, 95% CI: 1.82–18.21; P = 0.003), and not on ART (OR 13.94, 95% CI: 3.84–50.61; P < 0.001) were independently associated with active TB in HIV-infected individuals [Table 3].
Table 3: Odds ratio and confidence intervals of significant risk factors on multivariate analysis

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  Discussion Top


In this study where we evaluated the risk factors for the development of active TB in HIV-infected individuals, the following important risk factors were found to be independently associated. CD4 counts <200 cells/μL (OR 5.75, 95% CI: 1.82–18.21; P = 0.003), smoking (OR 7.40, 95% CI: 1.47–37.15; P = 0.015), and not being on ART (OR 13.94, 95% CI: 3.84–50.61; P < 0.001) showed several fold increase in risk of developing active TB. Data from India on risk factors for TB in HIV infection are limited and our data demonstrate modifiable risk factors and potential prevention options.

Majority of TB cases in our study occurred in patients who have not been on ART or within few months after ART initiation. Furthermore, 42% of cases in our study, the diagnosis of TB led to the detection of HIV infection. Risk factors such as low CD4 cell counts and low BMI were found to be significant, similar to the previous studies.[8] The risk of active TB among individuals with CD4 cell counts <200 was nearly 6 times higher than those with higher CD4 cells counts (OR = 5.75). This finding is in line with a previous study from South India which evaluated TB incidence in patients on ART which reported that majority of patients with TB (87.7%) had a baseline CD4 cell count <200/cumm.[9] Reducing immunity with declining CD4 cell count results in reactivation of latent TB and increases the risk of acquiring new infection. Our study also demonstrates that not being on ART greatly increases the risk of the development of TB (OR = 13.94). This indicates that one of the most effective ways to prevent active TB in people with HIV infections is initiating ART as soon as possible. Previous studies also have shown that TB incidence decreased by about 80% in those who are on ART.[4],[10] Unfortunately, only a smaller proportion (38%) of TB cases in our study was on ART, indicating that there is still an unreached population who is not diagnosed early and initiated on ART.

Another important finding in this study is smoking as independent risk factor for TB (OR = 7.4) which is modifiable. The association of smoking and active TB in non-HIV-infected individuals has been well documented.[11],[12],[13] However, a similar association in HIV-infected individuals are sparse. The strong association of smoking and TB in HIV-infected individuals as observed in this study warrants counseling and health education in these patients. Even though alcohol consumption, another modifiable risk factor, was found to be significant on univariate analysis, it did not span out to be an independent risk. Patients should be informed about the harmful effects of smoking and alcohol, and adequate efforts must be taken for encouraging them to quit. Sufficient effort should be taken to inform the patients of the dreadful consequences of smoking and alcohol and encourage them to quit. In addition to smoking and alcohol, low BMI (OR 6.31) also was found to be a risk factor for TB. This could be because of the weight loss in active TB or increased risk of the development of TB as documented in other studies.[14],[15] Although diabetes mellitus is another known risk factor for active TB, the low number of individuals in this study did not show any significant association with active TB.

Our study highlights the importance of continued effort in getting patients with HIV infection into care and intensifies diagnostic and preventive strategies for TB. The HIV-infected individuals with identified risk factors such as low CD4 count, absence of ART, smoking, and low BMI require closer follow-up and intense screening for prevention and case-finding strategy. This high-risk target group may also benefit from IPT once active TB is ruled out. However, the efficacy of IPT for patients on ART across the spectrum of patient characteristics and CD4 cell counts is still limited.

There are some limitations to this study. First, as an age- and sex-matched case–control study, there were limitations in the selected controls. Majority of the cases and consequently the controls turned out to be men. Second, the lower number of cases in this study had only small number of risk factors such as diabetes mellitus which did not turn out to be significant. Third, there may have been some risk factors which we failed to include in this study such as contact with other cases, treatment adherence, and biological factors.


  Conclusion Top


This study reports important modifiable risk factors for the development of TB in HIV-infected individuals in South India. Most important independent risk factors for active TB among HIV-infected individuals included smoking, lower CD 4 cell count, and the lack of ART. Initiating ART as soon as possible and enhanced TB screening before and after ART initiation are warranted. Health education for HIV-infected individuals including counseling for smoking cessation is important for preventing active TB. IPT in high-risk individuals after ruling out active TB may be an appropriate strategy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
WHO. Global Tuberculosis Report; 2016.  Back to cited text no. 1
    
2.
WHOTB/HIV facts; 2012-2013.  Back to cited text no. 2
    
3.
Page KR, Godfrey-Fausset P, Chaisson RE. Tuberculosis-HIV Co-infection: Epidemiology, Clinical Aspects and Interventions in Reichman and Hershfield's Tuberculosis: A comprehensive International Approach. New York: Informa Healthcare; 2006. p. 371.  Back to cited text no. 3
    
4.
Lawn SD, Wood R, De Cock KM, Kranzer K, Lewis JJ, Churchyard GJ, et al. Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources. Lancet Infect Dis 2010;10:489-98.  Back to cited text no. 4
    
5.
Karo B, Haas W, Kollan C, Gunsenheimer-Bartmeyer B, Hamouda O, Fiebig L, et al. Tuberculosis among people living with HIV/AIDS in the German clinSurv HIV cohort: Long-term incidence and risk factors. BMC Infect Dis 2014;14:148.  Back to cited text no. 5
    
6.
Cui Z, Lin M, Nie S, Lan R. Risk factors associated with tuberculosis (TB) among people living with HIV/AIDS: A pair-matched case-control study in Guangxi, China. PLoS One 2017;12:e0173976.  Back to cited text no. 6
    
7.
Lawn SD, Bekker LG, Wood R. How effectively does HAART restore immune responses to Mycobacterium tuberculosis? Implications for tuberculosis control. AIDS 2005;19:1113-24.  Back to cited text no. 7
    
8.
Van Rie A, Westreich D, Sanne I. Tuberculosis in patients receiving antiretroviral treatment: Incidence, risk factors, and prevention strategies. J Acquir Immune Defic Syndr 2011;56:349-55.  Back to cited text no. 8
    
9.
Rajasekaran S, Raja K, Jeyaseelan L, Vijilat S, Priya K, Mohan K, et al. Post-HAART tuberculosis in adults and adolescents with HIV in india: Incidence, clinical and immunological profile. Indian J Tuberc 2009;56:69-76.  Back to cited text no. 9
    
10.
Girardi E, Sabin CA, d'Arminio Monforte A, Hogg B, Phillips AN, Gill MJ, et al. Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America. Clin Infect Dis 2005;41:1772-82.  Back to cited text no. 10
    
11.
Lienhardt C, Fielding K, Sillah JS, Bah B, Gustafson P, Warndorff D, et al. Investigation of the risk factors for tuberculosis: A case-control study in three countries in West Africa. Int J Epidemiol 2005;34:914-23.  Back to cited text no. 11
    
12.
Gajalakshmi V, Peto R. Smoking, drinking and incident tuberculosis in rural India: Population-based case-control study. Int J Epidemiol 2009;38:1018-25.  Back to cited text no. 12
    
13.
Bates MN, Khalakdina A, Pai M, Chang L, Lessa F, Smith KR, et al. Risk of tuberculosis from exposure to tobacco smoke: A systematic review and meta-analysis. Arch Intern Med 2007;167:335-42.  Back to cited text no. 13
    
14.
Lönnroth K, Williams BG, Cegielski P, Dye C. A consistent log-linear relationship between tuberculosis incidence and body mass index. Int J Epidemiol 2010;39:149-55.  Back to cited text no. 14
    
15.
Nicholas S, Sabapathy K, Ferreyra C, Varaine F, Pujades-Rodríguez M, Frontières, et al. Incidence of tuberculosis in HIV-infected patients before and after starting combined antiretroviral therapy in 8 sub-Saharan African HIV programs. J Acquir Immune Defic Syndr 2011;57:311-8.  Back to cited text no. 15
    



 
 
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  [Table 1], [Table 2], [Table 3]



 

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