|Year : 2021 | Volume
| Issue : 2 | Page : 70-78
Clinical and laboratory profile of tuberculosis in HIV-positive patients and occurrence of tuberculosis-associated immune reconstitution inflammatory syndrome
MV S. Subbalaxmi1, Sravanthi Guduru1, Anu Kapoor2, Naval Chandra1
1 Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Radiodiagnosis, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
|Date of Submission||02-Oct-2020|
|Date of Decision||25-Nov-2020|
|Date of Acceptance||02-Feb-2021|
|Date of Web Publication||17-Jul-2021|
M V S. Subbalaxmi
Additional Professor, Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana - 500082
Source of Support: None, Conflict of Interest: None
Background: Tuberculosis (TB) is the most common opportunistic disease in human immunodeficiency virus (HIV)-positive persons.
Methods: We prospectively studied the clinical, radiological, cytological, histopathological and microbiological presentation of TB in HIV-positive patients and occurrence of immune reconstitution inflammatory syndrome (IRIS) in HIV TB co-infected patients.
Results: Out of 70 patients studied, 47 were male. Fever was the most common symptom (n = 61, 87.1%). The most common laboratory finding was anaemia (n = 67, 95.7%). In 32 (45.7%) patients presenting with TB, HIV infection was diagnosed. A CD4+ count <200/mm3 was seen in 57 (81.4%) patients. Extra-pulmonary TB (44.3%) was more common than pulmonary TB. All patients were started on anti-TB treatment; 6 had developed IRIS.
Conclusions: Our observations suggest that screening all HIV-seropositive patients for TB and careful monitoring for the occurrence of IRIS while on anti-TB treatment are helpful in managing HIV HIV-TB co-infected patients.
Keywords: Human immunodeficiency virus, immune reconstitution inflammatory syndrome, tuberculosis, CD4+ count
|How to cite this article:|
S. Subbalaxmi M V, Guduru S, Kapoor A, Chandra N. Clinical and laboratory profile of tuberculosis in HIV-positive patients and occurrence of tuberculosis-associated immune reconstitution inflammatory syndrome. J Clin Sci Res 2021;10:70-8
|How to cite this URL:|
S. Subbalaxmi M V, Guduru S, Kapoor A, Chandra N. Clinical and laboratory profile of tuberculosis in HIV-positive patients and occurrence of tuberculosis-associated immune reconstitution inflammatory syndrome. J Clin Sci Res [serial online] 2021 [cited 2022 Aug 20];10:70-8. Available from: https://www.jcsr.co.in/text.asp?2021/10/2/70/321703
| Introduction|| |
Tuberculosis (TB) is the most common opportunistic disease in human immunodeficiency virus (HIV)-positive persons. HIV pandemic has caused a resurgence of TB, resulting in increased morbidity and mortality worldwide. Most of the time, TB is recognised as the early manifestation of undetected acquired immunodeficiency syndrome (AIDS).
In persons infected with HIV, the lifetime risk of developing TB is 50%–70% as compared to a 10% risk in HIV-negative individuals. Due to this relationship, there has been a dramatic increase in the incidence of clinical TB in countries with high prevalence of HIV and TB. Diagnosis and successful treatment of people with TB avert millions of deaths each year (an estimated 54 million over the period 2000–2017), but there are still large and persistent gaps in detection and treatment.
The only rapid test for diagnosis of TB currently recommended by World Health Organization (WHO) is the Xpert MTB/RIF assay (Cepheid, USA). It can provide results within 2 h, and was initially recommended (in 2010) for the diagnosis of pulmonary TB in adults. Since 2013, it has also been recommended for use in children and to diagnose specific forms of extrapulmonary TB (EPTB). This test has much better accuracy than sputum smear microscopy. The WHO recommends GeneXpert as the initial diagnostic test for people living with HIV in whom TB is suspected. GeneXpert test has a sensitivity of 98% among acid-fast bacilli (AFB)-positive cases and 70% among AFB-negative specimens. Because of the very frequent association of TB and HIV, it has become necessary to look for HIV in TB-infected patients and vice versa.
The introduction of antiretroviral therapy (ART) drastically reduced the mortality of HIV-infected patients. IHowever, concomitant treatment of TB and HIV can lead to drug interactions and the possibility of paradoxical worsening of TB called immune reconstitution inflammatory syndrome (IRIS).
IRIS develops shortly after the initiation of ART and is associated with an exacerbated immune response to a co-infecting pathogen. Low cluster differentiation (CD4+) T-lymphocyte counts before ART initiation (50-100 cells/mm3) followed by a successful CD4+ T-cell increase is one of the most important risk factors to develop IRIS. We, therefore, studied the clinical, radiological, cytological, histopathological and microbiological presentation of TB in HIV-positive patients and occurrence of IRIS in HIV TB co-infected individuals.
| Material and Methods|| |
This prospective observational study included 70 patients with HIV-TB co-infection admitted to our institute between January 2018 and May 2019. Written informed consent was obtained from all of them. Written informed consent was obtained from all the study participants. Pregnant and lactating women, subjects <18 years, HIV-positive patients diagnosed with opportunistic infections other than TB were excluded from the study. The study was approved by the Institutional Ethics Committee.
The diagnosis of HIV infection was based on the demonstration of antibodies to HIV and/or the direct detection of HIV or one of its components using fourth-generation enzyme linked immunosorbet assay (ELISA). The fourth-generation ELISA tests combine the detection of antibodies to HIV with the detection of P24 antigen of HIV. Testing was done by HIV Vironostika 4th Generation enzyme-linked immunosorbent assay (ELISA) (Biomeriux, France). All reactive specimens were tested by HIV tri dot (J Mitra, India), a rapid assay that allows differentiation between HIV-1 and HIV-2. HIV tests were scored as positive (highly reactive) or negative (non-reactive) or indeterminate (partially reactive). CD4+ counts were determined using Fluorescence-activated cell sorting (FACS) flow cytometry method (Becton, Dickinson). In all the confirmed cases of HIV, diagnosis of TB was made by clinical examination and further confirmed by sputum smear microscopy by Ziehl–Neelsen and/or auramine–rhodamine staining for acid-fast bacilli (AFB), chest radiograph, fine-needle aspiration cytology (FNAC), histopathological examination, TB culture, fluid analysis, clinical response to anti-TB treatment (ATT). International Network for the Study of HIV-associated IRIS (INSHI) case definition was used in determining IRIS.
A detailed clinical history was obtained for each case followed by a complete general physical and systemic examination. Data regarding the duration of HIV, detailed drug history, side effects of medication were recorded. Laboratory investigations such as complete haemogram, complete urine examination, liver function tests, renal function tests, electrocardiography, chest radiograph, HIV ELISA, Dot Blot, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibodies (anti-HCV Ab) were performed for each case.
The following special investigations were performed as per the requirement of each case. These included: cluster differentiation CD4+ T-lymphocyte count, HIV viral load, abdominal ultrasonography, contrast enhancement computed tomography (CECT), magnetic resonance imaging (MRI), sputum testing, cerebrospinal fluid (CSF), pleural, ascitic fluid analysis, fine-needle aspiration cytology (FNAC), histopathological and microbiological testing.
All data were recorded in a case record form and entered into Microsoft Excel sheet (Microsoft Corporation, Richmond, USA). Continuous variables are presented on mean (range) and categorical variables are presented as numbers and percentages.
| Results|| |
Seventy patients with HIV-TB co-infection were included in the study. Of these, 47 (67.1%) were males. Age distribution ranged from 20 to 79 years with a mean age of 49.5 years. The most common age group observed was 30–49 years accounting 58.6% of the study participants. The distribution of symptoms among the study population is presented in [Table 1]. The most common symptom in our patients was fever seen in 61 (87.1%) patients followed by generalised weakness in 37 (52.9%) patients.
A past history of TB was evident in 17 (24.9%) patients. Other comorbidities noted were diabetes mellitus (DM) in 8 (11.2%) patients. Alcohol consumption and smoking were seen in 29 (41.4%) and 22 (31.4%) patients respectively. The most common sign observed was pallor (n = 60; 85.7%), followed by oral thrush (n = 18; 25.7%) and lymphadenopathy (n = 12; 18.6%). The most common laboratory finding was anaemia (defined as haemoglobin < 11 g/dL) which was seen in 67 (95.7%) of the 70 patients. While 68 (97.1%) patients had HIV-1 infection, two patients had HIV-2 infection. The HIV status in the study population is presented in [Table 2]. Thirty two (45.7%) patients were diagnosed to be HIV-seropositive during workup for TB.
CD4+ counts below 200 cells/mm3 was seen in 57 (81.4%) patients. CD4+ count below 50 cells/mm3 was seen in 17 (24.3%) patients. CD4+ count ≥200 cells/mm3 was seen in 13 (18.6%) patients.
The distribution of type of TB is presented in [Table 3]. We observed disseminated TB and extrapulmonary TB were more common. The involvement of the organ system in EPTB is presented in [Table 4]. The distribution of TB confirmation in the study population is presented in [Table 5]. The imaging findings of TB in HIV-positive patients are presented in [Table 6].
Paradoxical tuberculosis immune reconstitution inflammatory syndrome
Six (8.6%) out of 70 patients experienced IRIS events. Five developed paradoxical IRIS. One developed unmasking IRIS. Individuals who experienced paradoxical IRIS during follow up had lower CD4+ T-cell counts than those who did not develop IRIS. The range of CD4+ counts in patients with IRIS was 49–185 cells with mean CD4+ of 128.6 cells. IRIS was seen in patients in CD4+ <200 cells/mm3 (100%). Five patients of IRIS (83.3%) had hypoalbuminemia with a mean of 2.9 g/dL. IRIS was seen more often in extrapulmonary TB (50.0%).
The median time to ART initiation after ATT was 12 days. The IRIS events occurred at a median time of 14 days after ART initiation. Among five patients of paradoxical IRIS, two patients had central nervous system (CNS) IRIS and two patients had lymph node IRIS, one had both lymph node IRIS and empyema necessitans. One patient who had developed CNS IRIS died.
| Discussion|| |
Patients with HIV-TB co-infection frequently have advanced HIV disease and are at an increased risk of death and new opportunistic infections. HIV/AIDS pandemic has caused a resurgence of TB, resulting in increased morbidity and mortality worldwide. The WHO currently recommends that all HIV-infected persons be screened for TB, and HIV-infected persons without active TB disease be evaluated for the treatment of latent TB infection.
In the present study, of the 70 patients presenting with TB, 47 (67.1%) were male. According to the Global TB Report 2018, the male to female ratio among adults is approximately 2:1. The age of the patients ranged from 20 years to 79 years. Most of the patients were in the the sexually active age group of 30–50 years i.e., about 41 (58.5%). Another study had reported incidence of TB in sexually active age group (31–45 years) was 61.3%.
History of TB was seen in 17 (24.9%) patients. Among the other comorbidities noted, DM was seen in 8 (11.2%) patients. Individuals with DM have three times the risk of developing TB and there are now more individuals with TB-DM co-morbidity than TB-HIV co-infection. Alcohol consumption and smoking were seen in 29 (41.4%) and 22 (31.4%) patients respectively in our study population. There is three-fold increase in the risk of developing active TB in heavy alcohol users. Smoking is a strong risk factor of TB.
The most common sign observed in our patient population was pallor which was seen in 60 (85.7%) patients, followed by oral thrush which was seen in 18 (25.7%) patients, lymphadenopathy in 12 (18.5%) patients. TB is one of the most common causes of lymphadenopathy in HIV-positive patients. In our study, the most common laboratory finding was anaemia (Hb <11 g/dL) which was seen in 67 (95.7%) of the 70 patients. Like most chronic infections, both HIV and TB can cause anaemia. In both infections, decreased production of red blood cells seems to play an important role as a cause of anaemia. Malabsorption syndrome and nutritional deficiencies may aggravate anaemia.
One of the markers of malnutrition is hypoalbuminemia. In our study population, hypoalbuminemia was seen in 57 (81.4%) patients. Severe hypoalbuminemia was present in 4 (7.0%) patients. Causes of decreased serum albumin levels are multifactorial and include poor nutrition (decreased synthesis), liver disease (decreased production), renal disease (wasting of serum albumin in the urine) and chronic inflammation (decreased production or increased destruction). Albumin remained a strong predictor of mortality after adjusting for multiple factors.
In HIV-positive patients, there is an increase in serum globulin levels. In our study population, 50 (71.4%) patients were found to have elevated globulins. Forty-six (65.7%) patients were found to have A/G reversal.
Out of 70 HIV-TB co-infected patients, a significant number of patients i.e., 32 (45.7%) patients were diagnosed to be HIV during workup for TB [Table 2]. Individuals with a new diagnosis of TB are nearly 19 times more likely to be co-infected with HIV than those without TB. As per the CDC classification, either pulmonary or extrapulmonary TB is an AIDS-defining illness. All patients diagnosed with TB should be screened for HIV and vice versa.
In our study 38 patients were already diagnosed to be HIV positive. Out of 38, 26 (37.1%) patients were on ART treatment, 12 (17.1%) patients were treatment defaulters. Among 26 patients who are on ART, 18 patients were male. Among 26 patients who were on ART, we noted low CD4+ counts in 23 patients (CD4+ count had <200 cells/mm3). The median CD4+ count of these 26 patients was 110.5 cells/mm3. Among patients who were on ART, nine patients had a history of TB. A high prevalence of TB was reported from a recent study in South Africa. The study involved 1544 patients on ART, where 424 (30.1%) developed active TB in 5 years.
Among 70 patients, 68 (97.1%) patients had HIV-1, while 2 (2.8%) had HIV-2. Worldwide, the predominant virus is HIV-1 (95% of all HIV infections worldwide) HIV-2 is estimated to be more than 55% genetically distinct from HIV-1. It is less infectious and progresses more slowly than HIV-1, resulting in fewer deaths. In our study, HIV-2 was seen in patient of haemophilia, and HIV2 was most probably due to his earlier transfusion. Associated HBsAg positivity was seen in 4 (5.71%) patients, while none had HCV positivity in our series.
CD4+ count below 200 cells/mm3 was seen in 57 (81.4%) patients. CD4+ count below 50 cells/mm3 was seen in 17 (24.2%) patients. CD4+ count equal and above 200 cells/mm3 was seen in 13 (18.5%) patients. CD4+ counts reflect the level of immunity and also risk for opportunistic infections. A prospective study found an increased risk of mortality in HIV patients with severe immune deficiency (i.e. CD4+ <200 cells/mm3) when they were co-infected with TB.
We observed disseminated TB and EPTB, more common. In our study, among EPTB without any pulmonary involvement, most common organ involved was CNS which was seen in about 14 patients constituting about 46.6%, followed by lymph node TB which was seen in 10 (32.2%) patients, followed by skeletal TB in 3 (10%), pleural TB in 2 (6.6%), abdominal TB in 2 (6.6%) patients.
Among disseminated or miliary TB, out of 31 (44.3%) patients, pulmonary TB was seen in 24 (77.4%) patients. Miliary TB was seen in about 5 (7.1%) patients. Lymph nodal TB was seen in about 23 (74.1%) patients. Most of lymph node TB had associated pulmonary TB. Lymph nodes are the most common site of EPTB infection among HIV-infected individuals.
Among HIV-TB patients with pulmonary involvement, AFB positivity in sputum was seen in only 5 (15.6%) patients. In HIV TB coinfected patients, sputum positivity is seen in fewer patients due to a lower prevalence of cavitary disease. Hence, the diagnosis of TB based on sputum AFB positivity may be difficult in HIV patients.
Among 70 patients, 23 (32.8%) patients had microbiological confirmation in the form of AFB or GeneXpert. AFB positivity was seen in about 11 (47.8%) patients. Of which, AFB isolated in sputum was seen in five patients, followed by AFB in lymph node (n=4), pus (n=1), ascitic fluid (n=1). Fourteen (60.8%) patients had GeneXpert positive in various fluids. CSF GeneXpert was positive in six patients, followed by sputum, pleural and lymph node. Among those 14, 12 patients had GeneXpert positivity without AFB positivity. In HIV TB co-infected patients, studies found that those who were negative to the AFB test were found positive to MTB/RIF GeneXpert. This could be due to the ability of MTB/RIF GeneXpert to detect very low numbers of bacilli [130–150 bacilli colony forming units (CFU)/mL] compared to acid alcohol fast bacilli which may require a higher number of bacilli (5000–10,000 bacilli CFU/mL).
Chest radiograph is a primary tool to evaluate TB in HIV. Chest radiograph was obtained in all 70 patients. Out of 70 patients, 41 (58.5%) had normal chest radiographs, making the diagnosis challenging. The most common chest radiographic finding in this study was pleural effusions which were seen in 11 (15.7%), followed by pulmonary infiltrates in 8 (11.4%) patients, consolidation in 5 (7.1%) and miliary pattern in 4 (5.71%) patients. HIV-infected patients with TB are less likely to have cavitary pulmonary disease than are HIV-uninfected patients with TB, and up to 22% of HIV-infected persons with pulmonary TB have normal chest radiograph findings.
CT and/or MRI was done in 56 (80.0%) patients. Thirty four (60.7%) patients underwent CECT chest. In cases with pulmonary TB, the most common radiological finding on CECT chest was nodules, seen in 15 patients. The other common findings were consolidation seen in 8, tree in bud appearance in 5, cavity in 5 and miliary pattern in 5 patients [Figure 1]. The radiologic features of primary TB are lower lobe consolidation, miliary pattern, lymphadenopathy, pleural effusions. The radiologic features of post-primary TB are upper lobe consolidation, cavitation, centrilobular nodules and tree in bud appearance. In our study population, all patients with miliary and lower lobe consolidation had CD4+ count <200 cells/mm3. In patients with advanced disease, with CD4+ count below 200 cells/mm3, the most common presentation is a primary TB pattern with a tendency to haematogenous (miliary) spread and consolidation.
|Figure 1: Spectrum of lesions of pulmonary tuberculosis in HIV-positive people. HRCT chest showing miliary pattern (a). HRCT chest showing diffuse ground glass opacities (b). HRCT chest showing cavities in both the lungs (c). HRCT chest showing multiple pulmonary nodules (d). HRCT chest showing focal consolidation in right lung (e). HRCT chest showing Tree in bud appearance (f) HIV = human immunodeficiency virus; HRCT = High resolution computed tomography|
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In our study, 34 (60.7%) patients underwent CECT chest. Twenty-two (64.7%) patients had thoracic lymphadenopathy. Among these 22 patients, 15 patients had necrotic lymph nodes (peripherally enhancing with central non-enhanced areas), 11 (32.3%) had pleural effusion, 6 (17.6%) patients had pericardial effusion [Figure 2].
|Figure 2: Extrapulmonary thoracic manifestations of tuberculosis in HIV-seropositive individuals. Chest radiograph (postero-anterior view) showing left pleural effusion (a). CT chest (obtained from different patients) showing moderate pleuropericardial effusion (b); multiple mediastinal necrotic lymph nodes (c) HIV = Human immunodeficiency virus; CT = Computed tomography|
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The abdomen TB includes the involvement of peritoneum and its reflections, the gastrointestinal tract, the lymphatic system and solid organs such as the liver. Abdominal lymph node involvement is best evaluated on CT. Contrast-enhanced CT may show peripheral enhancement (the central liquefactive portion is non-enhancing) or heterogeneous enhancement and rarely homogeneous enhancement. In our study, 27 (48.2%) patients underwent CECT abdomen. Twenty-one (77.7%) patients had abdominal lymphadenopathy. Out of 21, 15 showed necrotic lymph nodes, 8 (29.6%) had splenic granulomas. 4 (14.8%) had hepatic granulomas, 1 (3.7%) patient had ileocecal thickening [Figure 3].
|Figure 3: Abdominal manifestations of tuberculosis in HIV-seropositive individuals. CT abdomen (obtained from different patients) showing multiple granulomas in liver and spleen (a); splenic granulomas (b); splenic abscess (c); multiple necrotic retroperitoneal lymph nodes (d); ascites (e); and psoas abscess (f) HIV = human immunodeficiency virus; CT = Computed tomography|
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Characteristics of TB are the involvement of basal meninges with thick basal exudate. The basal enhancement, hydrocephalus, tuberculomas and infarcts are more common in tubercular meningitis than in pyogenic meningitis. In our study population, 17 (30.3%) patients underwent MRI brain. The most common MRI brain finding was ring-enhancing lesions seen in about 12 (70.5%) patients followed by leptomeningeal enhancement in 7 (4.1%) patients. Brain parenchymal involvement is most frequently seen in the form of a TB granuloma.
In spinal TB, vertebral body destruction, marrow oedema, soft-tissue abscesses, hyperintensity and enhancement of disc and loss of disc height commonly ensue. In our study population, three (5.3%) patients underwent MRI spine and one patient underwent bone scintigraphy to know the extent of TB spread. One had paradiscal involvement, one had hyperintensities with ring-enhancing in multiple vertebra, one had vertebral body destruction. In our study, one patient who presented with chronic left hip pain and difficulty in walking, MRI pelvis showed osteomyelitis involving the left iliac crest and right ala of sacrum [Figure 4]. To know the extent of spread bone scintigraphy was done which was suggestive of multifocal osteomyelitis possibly TB. The patient was started on ATT and responded well to treatment.
|Figure 4: Spectrum of skeletal presenations of tuberculosis in HIV-seropositive individuals. MRI spine showing TB spondylodiscitis with paradiscal involvement (a). magnetic resonance imaging spine showing spinal TB involving multiple vertebrae (b). CT Computed tomography abdomen showing bilateral psoas abscesses (c). magnetic resonance imaging pelvis with hips showing multifocal lesions in the left iliac bone and right femur (d)|
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CECT chest and abdomen in two patients showed vascular thrombosis. One patient had pulmonary artery thrombosis. One patient had a large thrombus extending from left femoral to common iliac vein and IVC [Figure 5]. Mycobacterium tuberculosis is able to activate macrophages directly and induces them to produce cytokines, especially tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and IL-6. TNF-α and IL-1 blocks the protein C anticoagulant pathway and can elicit tissue factor production on endothelium and monocytes.
|Figure 5: Vascular complications of HIV infection. CT chest showing acute pulmonary thromboembolism (a). CT abdomen showing large thrombus extending from common iliac vein into inferior vena cava (b) HIV = Human immunodeficiency virus; CT = Computed tomography|
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Bone marrow biopsy remains an important examination in patients of fever of unknown origin, especially in immunocompromised patients. Bone marrow aspiration and biopsy were done in three patients. All three patients showed granulomas, two patients showed necrosis along with granulomas.
Lymph node biopsy was done in four patients. All four patients showed necrotizing granulomas. Three out of four patients showed AFB positivity (Figure 6). Morphologically, criteria for the diagnosis of TB in tissue are caseous necrosis and granulomas, of which the former is the most specific and sensitive. The demonstration of AFB by Ziehl–Neelsen stain in TB is the gold standard for the diagnosis of TB.
FNAC was done in three patients, out of which two from lymph node and one from spleen. All three patients showed necrosis out of which 2 had necrotizing granulomas and 2 had stain positive for AFB. Caseation alone was the most common specific and sensitive finding. In cases with non-caseating granulomas, AFB stain is very useful to identify tubercle bacilli and thereby ascertain the aetiology of the granulomatous process.
Hence, lymph node biopsy along with AFB staining is a valuable tool in the evaluation of HIV-positive patients to identify the cause of lymphadenopathy and to confirm the diagnosis of TB.
All patients were started on ATT after radiological, microbiological or pathological confirmation. In our study population, 64 (91.4%) patients were alive; 6 patients had died. Among six patients who died, one patient died of CNS IRIS, two patients died of renal failure, one patient died of meningitis, two patients died of respiratory failure. In our study, the side effects of ATT were seen in five patients. Four patients had ATT induced hepatitis. One patient had rifampicin induced rash.
In our study, six patients experienced IRIS events. Five developed paradoxical IRIS. One developed unmasking IRIS. Individuals who experienced paradoxical IRIS during follow-up had lower CD4+ T-cell counts than those who did not develop IRIS. The range of CD4+ counts in patients with IRIS was 49–185 cells/mm3 with mean CD4+ of 128.6 cells/mm3. The median time to ART initiation after ATT was 12 days. The IRIS events occurred at a median time of 14 days after ART initiation. The onset of TB-IRIS manifestation was within 3 months of combination ART (CART) initiation. Within 1–3 months of initiation of treatment, paradoxical reactions generally occur.
It is likely to be due to a complex interplay of the host immune responses, tubercle bacilli virulence, antigen load, the site of infection and the effects of chemotherapy. The massive delivery of membrane antigens after the initiation of ATT has been advocated as the cause of 'paradoxical' responses in immune incompetent patients. Another possible mechanism is immunologic restoration after ART and recovery of specific responses to certain antigens.
Starting CART close to the treatment of opportunistic infection, a low CD4+ cell count, and a high viral load are the common risk factors for the development of IRIS in the majority of studies.
Among five patients of paradoxical IRIS, two patients had CNS IRIS and two patients had lymph node IRIS, one had both lymph node IRIS and empyema necessitans. TB empyemas are typically loculated and associated with pleural thickening and enhancement, findings that represent involvement of the pleura. If not treated early, tuberculous empyemas may be complicated with bronchopleural fistula or extension into the chest wall (empyema necessitans). After treatment and healing, residual pleural thickening with calcification can develop, potentially leading to fibrothorax.
Most reported cases have complicated the treatment of lymph node or cerebral disease, with enlargement of nodes seen in approximately 30% in one large series. One patient with CNS TB with IRIS died during the study period. The incidence of IRIS in HIV-TB co-infection is 8%–43%. EPTB has also been reported to be associated with a higher risk of TB-IRIS. Low CD4+ T-lymphocyte counts before ART initiation followed by a successful CD4+ T-cell increase is one of the most important risk factors to develop IRIS.
The aim of this present study was to describe the clinical, laboratory profile of TB in HIV-positive patients. Our study is unique because in addition to clinical and laboratory profile we have studied the occurrence of paradoxical TB IRIS. This study had shown a myriad of manifestations of TB in HIV-positive patients and challenges in diagnosis. Both pulmonary and extrapulmonary manifestations can present in atypical way in HIV-positive patients. To prevent IRIS, in all HIV-infected patients, TB should be ruled out before starting ART.
This is a prospective hospital-based study with a small sample size and may not reflect the exact situation of the condition in the community. Viral load testing could not be done due to logistic reasons.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
WHO. Global Tuberculosis Report 2018. September 18, 2018. Available from: https://www.who.int/tb/publications/global_report/en/. [Last accessed on 2019 Mar 11].
Sharma SK, Mohan A, Kadhiravan T. HIV-TB co-infection: Epidemiology, diagnosis & management. Indian J Med Res 2005;121:550-67.
World Health Organization. A Clinical Manual for Southeast Asia. WHO/TB/96.200 (SEA).
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.
World Health Organization. Essential Prevention and Care Interventions for adults and Adolescents Living with HIV in Resource Limited Settings. Geneva: World Health Organization; 2008.
Kamath R, Sharma V, Pattanshetty S, Hegde MB, Chandrasekaran V. HIV-TB coinfection: Clinico-epidemiological determinants at an antiretroviral therapy center in Southern India. Lung India 2013;30:302-6.
] [Full text]
Ronacher K, Joosten SA, van Crevel R, Dockrell HM, Walzl G, Ottenhoff TH. Acquired immunodeficiencies and tuberculosis: Focus on HIV/AIDS and diabetes mellitus. Immunol Rev 2015;264:121-37.
Rehm J, Samokhvalov AV, Neuman MG, Room R, Parry C, Lönnroth K, et al
. The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review. BMC Public Health 2009;9:450.
Bates MN, Khalakdina A, Pai M, Chang L, Lessa F, Smith KR. Risk of tuberculosis from exposure to tobacco smoke: A systematic review and meta-analysis. Arch Intern Med 2007;167:335-42.
Lee SW, Kang YA, Yoon YS, Um SW, Lee SM, Yoo CG, et al
. The prevalence and evolution of anemia associated with tuberculosis. J Korean Med Sci 2006;21:1028-32.
Feldman JG, Gange SJ, Bacchetti P, Cohen M, Young M, Squires KE, et al
. Serum albumin is a powerful predictor of survival among HIV-1-infected women. J Acquir Immune Defic Syndr 2003;33:66-73.
UNAIDS 2008. UNAIDS Report on the Global AIDS Epidemic 2008. UNAIDS, Geneva, Switzerland: Available from: http://data.unaids.org/pub/GlobalReport/2008/JC1511_GR08_ExecutiveSummary_en.pdf.
Gupta A, Wood R, Kaplan R, Bekker LG, Lawn SD. Prevalent and incident tuberculosis are independent risk factors for mortality among patients accessing antiretroviral therapy in South Africa. PLoS One 2013;8:e55824.
Ackah AN, Digbeu H, Daillo K, Greenberg AE, Coulibaly D, Coulibaly IM, et al
. Response to treatment, mortality, and CD4+ lymphocyte counts in HIV-infected persons with tuberculosis in Abidjan, Cote d'Ivoire. Lancet 1995;345:607-10.
Curvo-Semedo L, Teixeira L, Caseiro-Alves F. Tuberculosis of the chest. Eur J Radiol 2005;55:158-72.
Patkar D, Narang J, Yanamandala R, Lawande M, Shah GV. Central nervous system tuberculosis: Pathophysiology and imaging findings. Neuroimaging Clin N Am 2012;22:677-705.
White NW. Venous thrombosis and rifampicin. Lancet 1989;2:434-5.
Arora VK, Gupta R. Trends of extra-pulmonary tuberculosis under revised national Tuberculosis control programme: A study from South Delhi. Indian J Tuberc 2006;53:77-83.
Bukharie H. Paradoxical response to anti-tuberculous drugs: Resolution with corticosteroid therapy. Scand J Infect Dis 2000;32:96-7.
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.
Karmakar S, Sharma SK, Vashishtha R, Sharma A, Ranjan S, Gupta D, 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;2011:239021.
Whalen C, Okwera A, Johnson J, Vjecha M, Hom D, Wallis R, et al
. Predictors of survival in human immunodeficiency virus-infected patients with pulmonary tuberculosis. The Makerere University-Case Western Reserve University Research Collaboration. Am J Respir Crit Care Med 1996;153:1977-81.
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.
Olalla J, Pulido F, Rubio R, Costa MA, Monsalvo R, Palenque E, et al
. Paradoxical responses in a cohort of HIV-1-infected patients with mycobacterial disease. Int J Tuberc Lung Dis 2002;6:71-5.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]