Tuberculosis Immune Reconstitution Inflammatory Syndrome Research Articles

Mortality among persons with tuberculosis in Zambian hospitals: A retrospective cohort study.

Tuberculosis (TB) mortality in Zambia remains high at 86 per 100,000 populations, translating to approximately 15,000 TB-related deaths annually. We conducted a nationwide retrospective cohort study to understand predictors, time to death, and probable causes of mortality among persons on TB treatment in Zambia. We reviewed medical records for persons with TB registered in 54 purposively selected hospitals in Zambia between January and December 2019. We fitted a Cox proportional hazards model to identify predictors of mortality. Of the 13,220 records abstracted, 10,987 were analyzed after excluding records of persons who transferred in from other hospitals, those with inconsistent dates and those whose treatment outcome was not evaluated. The majority of persons with TB were men, (61.5%, n = 6,761) with a median age of 36 years (IQR: 27-46 years). Overall, 1,063 (9.7%) died before completing TB treatment (incidence rate = 16.9 deaths per 1,000 person-months). Median age at death was 40 years (IQR: 31-52). The majority of deaths (75.7%, n = 799) occurred in the first two months of TB treatment, with a median time to death of 21 days (IQR: 6-57). Independent risk factors for TB mortality included age >54 years, being treated in Eastern, Southern, Western, Muchinga and Central provinces, receiving treatment from a third-level or mission hospital, methods of diagnosis other than Xpert MTB/RIF, extrapulmonary TB (EPTB), and positive HIV status. Probable causes of death were septic shock (18.8%), TB Immune Reconstitution Inflammatory Syndrome (TB IRIS) (17.8%), end-organ damage (13.4%), pulmonary TB (11.4%), anemia (9.6%) and TB meningitis (7.8%). These results show high mortality among people undergoing TB treatment in Zambia. Interventions targeted at persons most at risk such as the elderly, those with EPTB, and those living with HIV, can help reduce TB-related mortalities in Zambia.

Where you least expect it: paradoxical tuberculosis-immune reconstitution inflammatory syndrome and wrist joint tuberculosis as the initial manifestation in a patient who is HIV-seronegative.

Where you least expect it: paradoxical tuberculosis-immune reconstitution inflammatory syndrome and wrist joint tuberculosis as the initial manifestation in a patient who is HIV-seronegative.

Paralytic Ileus During Treatment of Pulmonary and Renal Tuberculosis in a Non-Human Immunodeficiency Virus Patient: An Unusual Presentation of Tuberculosis-immune Reconstitution Inflammatory Syndrome.

Paralytic ileus as tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is extremely rare. We herein report a 44-year-old man with pulmonary and renal tuberculosis who developed paralytic ileus 14 days after starting antituberculosis therapy (ATT) despite an initial favorable response to ATT. Paralytic ileus was successfully managed with conservative care. He initially required hemodialysis because of obstructive uropathy due to renal tuberculosis, but he was able to withdraw from dialysis after placement of ureteral stents. TB-IRIS can affect organs other than the original sites of tuberculosis, and the combined use of steroids may be effective for its prevention and treatment.

Tuberculosis-immune reconstitution inflammatory syndrome in an immunocompetent patient

Tuberculosis-immune reconstitution inflammatory syndrome is commonly seen among patients with acquired immunodeficiency syndrome either as a paradoxical worsening of an already diagnosed disease or as an uncovering of a dormant infection. There is evidence of paradoxical worsening of central nervous system tuberculosis (CNS-TB) once the treatment is instituted even among immunocompetent patients leading to significant morbidity. We report a case of a previously well young woman with paradoxical worsening of CNS-TB after commencement of treatment. This case highlights an important possible clinical sequelae of CNS-TB, a practicing physician should be aware of.

Tuberculoma development in tuberculosis immune reconstitution inflammatory syndrome in an infant

Tuberculoma development in tuberculosis immune reconstitution inflammatory syndrome in an infant

Incidence and pattern of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in patients on anti-retroviral therapy: An observational study

BackgroundTuberculosis-immune reconstitution inflammatory syndrome is an atypical, immoderate immune response mounted by the refurbishing immune system against the mycobacterium tuberculosis, commonly seen in HIV-infected individuals. ART significantly enhances one's immunity. However, this enhancement in immunity also sets off a number of inflammatory processes termed as Immune Reconstitution Inflammatory Syndrome (IRIS). MethodsThis observational study was conducted with the aim of assessing the incidence and pattern of TB-IRIS in people living with HIV/AIDS on ART registered at the ART Centre of S.C.B. Medical College and Hospital, Cuttack. They were evaluated for their plasma viral load and CD4 count at baseline. Thereafter, the plasma viral load was assessed every week and the CD4 count was assessed fortnightly. Each study participant was followed-up for a period of three months to look for any onset of TB-IRIS. ResultsA total of 286 patients were included the study. The overall incidence of TB-IRIS was 7.7%. The occurrence of paradoxical TB-IRIS was nearly double than ART-associated TB-IRIS. There was a significant rise in the CD4 cell count in the patients of both paradoxical (p = 0.001) and ART-associated (p = 0.017) TB-IRIS. The plasma viral load at baseline also showed significant differences from the levels documented at the appearance of the TB-IRIS both in both the types i.e. paradoxical (p = 0.001) and ART-associated (p = 0.012) TB-IRIS. ConclusionPeople with HIV/TB coinfection experience high morbidity and death from all kinds of TB-IRIS, necessitating specific attention. As HIV-positive cases and implementation of ART continue to rise, it's vital to quickly rule out TB coinfection.

Role of Corticosteroids in the Treatment of Tuberculosis: An Evidence-based Update

Corticosteroids are often used as an adjunct in the treatment of various forms of tuberculosis (TB) and for the prevention of complications, such as constrictive pericarditis, hydrocephalus, focal neurological deficits, pleural adhesions, and intestinal strictures. Notwithstanding, they have been proven in clinical trials to improve the following outcomes only--death or disability in human immunodeficiency virus (HIV)-seronegative patients with tubercular meningitis and tubercular pericarditis. Despite a lack of specific evidence for efficacy in HIV co-infected patients with tubercular meningitis or pericarditis, corticosteroids are generally recommended in them as well. Corticosteroids significantly decrease the risk of pleural thickening in patients with tubercular pleural effusion; the clinical significance of this finding, however, is unclear. Recently, it has been demonstrated that use of corticosteroids improve the morbidity in HIV co-infected patients with paradoxical TB immune reconstitution inflammatory syndrome (IRIS). However, evidence favouring the use of corticosteroids in other clinical situations is sparse or lacking. Likewise, the biological mechanisms underlying their beneficial effect in TB meningitis and pericarditis remain poorly understood.

Treatment of Tuberculosis and the Drug Interactions Associated With HIV-TB Co-Infection Treatment

Tuberculosis (TB) is a communicable disease that is a major source of illness, one of the ten causes of mortality worldwide, and the largest cause of death from a single infectious agent Mycobacterium tuberculosis. HIV infection and TB are a fatal combination, with each speeding up the progression of the other. Barriers to integrated treatment as well as safety concerns on the co-management of HIV- TB co-infection do exist. Many HIV TB co-infected people require concomitant anti-retroviral therapy (ART) and anti-TB medication, which increases survival but also introduces certain management issues, such as drug interactions, combined drug toxicities, and TB immune reconstitution inflammatory syndrome which has been reviewed here. In spite of considerable pharmacokinetic interactions between antiretrovirals and antitubercular drugs, when the pharmacological characteristics of drugs are known and appropriate combination regimens, dosing, and timing of initiation are used, adequate clinical response of both infections can be achieved with an acceptable safety profile. To avoid undesirable drug interactions and side effects in patients, anti TB treatment and ART must be closely monitored. To reduce TB-related mortality among HIV-TB co-infected patients, ART and ATT (Anti Tuberculosis Treatment) outcomes must improve. Clinical practise should prioritise strategies to promote adherence, such as reducing treatment duration, monitoring and treating adverse events, and improving treatment success rates, to reduce the mortality risk of HIV-TB co-infection.

1401. Infliximab for Immune Reconstitution Inflammatory Syndrome (IRIS) in Tuberculous Meningitis; A Treatment Paradox

BackgroundTumor necrosis factor (TNF)-α inhibitors are known for the reactivation of latent tuberculosis (TB). As a paradox, it has been reported to have a role in the treatment of immune reconstitution inflammatory syndrome (IRIS) from anti-TB therapy.MethodsWe report a case of paradoxical worsening of central nervous system TB after initiation of anti-TB medications, which was treated successfully with infliximab (TNF-α inhibitor).ResultsA 34-year-old man from Nepal with a history of untreated latent TB presented with complaints of occipital headache, slurred speech, and witnessed seizure. His physical exam was consistent with hyperreflexia. MRI of the brain revealed multiple small contrast-enhancing lesions in cerebral hemispheres. CT Chest showed bilateral centrilobular nodules suggestive of miliary TB. Cerebrospinal fluid (CSF) analysis showed pleocytosis, high protein, and low glucose. He was started on isoniazid, rifampin, ethambutol, and pyrazinamide along with high-dose dexamethasone for TB meningitis. Later, MTB DNA probe from bronchioalveolar lavage and CSF detected Mycobacterium Tuberculosis which was pan-susceptible. Repeat MRI of the brain 6 months into therapy revealed worsening of brain lesions. Moxifloxacin and linezolid were added to the regimen given clinical progression on first-line therapy. 6-months into this enhanced regimen he started experiencing blurring of vision. Visual field mapping showed left homonymous hemianopia. Repeat MRI of the brain confirmed extensive changes of basilar meningitis completely enveloping the optic chiasm. IRIS from TB was suspected. His prednisone dose was increased, and 3-doses of infliximab infusion were, 2-weeks apart were administered which showed clinical and radiological improvement.MRI Brain MRI Brain (axial T2/flair sequence) shows hyperintensities in multiple locations including the involvement of the left optic nerve and the left occipital region.ConclusionExacerbation of pre-existing clinical symptoms, formation of new lesions, or cavitation of prior pulmonary infiltrates is known as tuberculosis IRIS or paradoxical reaction. Despite the clinical and radiological exacerbation, mycobacterial cultures usually stay negative. Continuation of anti-TB medications and high-dose corticosteroids are the backbone of treatment but in refractory cases, immune modulation is needed with anti-TNF-α agents.Disclosures All Authors: No reported disclosures

Classical complement and inflammasome activation converge in CD14highCD16- monocytes in HIV associated TB-immune reconstitution inflammatory syndrome.

Inflammasome-derived cytokines, IL-1β and IL-18, and complement cascade have been independently implicated in the pathogenesis of tuberculosis (TB)-immune reconstitution inflammatory syndrome (TB-IRIS), a complication affecting HIV+ individuals starting antiretroviral therapy (ART). Although sublytic deposition of the membrane attack complex (MAC) has been shown to promote NLRP3 inflammasome activation, it is unknown whether these pathways may cooperatively contribute to TB-IRIS. To evaluate the activation of inflammasome, peripheral blood mononuclear cells (PBMCs) from HIV-TB co-infected patients prior to ART and at the IRIS or equivalent timepoint were incubated with a probe used to assess active caspase-1/4/5 followed by screening of ASC (apoptosis-associated speck-like protein containing a CARD domain) specks as a readout of inflammasome activation by imaging flow cytometry. We found higher numbers of monocytes showing spontaneous caspase-1/4/5+ASC-speck formation in TB-IRIS compared to TB non-IRIS patients. Moreover, numbers of caspase-1/4/5+ASC-speck+ monocytes positively correlated with IL-1β/IL-18 plasma levels. Besides increased systemic levels of C1q and C5a, TB-IRIS patients also showed elevated C1q and C3 deposition on monocyte cell surface, suggesting aberrant classical complement activation. A clustering tSNE analysis revealed TB-IRIS patients are enriched in a CD14highCD16- monocyte population that undergoes MAC deposition and caspase-1/4/5 activation compared to TB non-IRIS patients, suggesting complement-associated inflammasome activation during IRIS events. Accordingly, PBMCs from patients were more sensitive to ex-vivo complement-mediated IL-1β secretion than healthy control cells in a NLRP3-dependent manner. Therefore, our data suggest complement-associated inflammasome activation may fuel the dysregulated TB-IRIS systemic inflammatory cascade and targeting this pathway may represent a novel therapeutic approach for IRIS or related inflammatory syndromes.

Анализ однонуклеотидных полиморфизмов, ассоциированных с риском развития синдрома восстановления иммунной системы, у пациентов с ко-инфекцией ВИЧ и туберкулеза

Tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) is the development or progression of tuberculosis associated with restoration of active immune response to mycobacteria following the initiation of antiretroviral therapy in HIVinfected patients. The incidence of TB-IRIS is 18% with mortality reaching 2%. Investigation of TB-IRIS in Russia is very important, since the prevalence of TB coinfection is common among HIV-infected patients; in addition to that, HIV is often detected at late stages characterized by severe immunosuppression, which increases the risk of TB-IRIS. This review focuses on single-nucleotide polymorphisms and some other genetic factors associated with an increased risk of TB-IRIS. Key words: antiretroviral therapy, HIV infection, genetic predisposition, single-nucleotide polymorphisms, TB-IRIS, tuberculosis, gene expression

RAPID ONSET MILIARY TB: A MANIFESTATION OF IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Tuberculosis (TB) is now an uncommon entity in the United States, with an estimated incidence of 2.7 per 100,000 persons. (1) Infection with human immunodeficiency virus (HIV) is a significant risk factor for TB infection. The initiation of antiretroviral therapy (ART) may be associated with immune reconstitution inflammatory syndrome (IRIS), with the subsequent unmasking of previously subclinical infections, including TB. We present an uncommon case that dramatically presented with miliary TB shortly following the initiation of ART. CASE PRESENTATION: A 68-year-old female immigrant with a history depression, parkinson's disease, and known acquired immunodeficiency syndrome (AIDS)/HIV infection not treated for 6 years, presented with weakness, night sweats, and progressive dry cough for two weeks. She had been started on ART (bictegravir/emtricitabine/tenofovir) one month prior, with a pre-treatment viral load of 84,000 copy/mL, and CD4 count of 69 /µL. Physical examination at presentation revealed normal vital signs and bilateral rhonchi. Laboratory testing was notable for leukopenia (3.99 x10^6 /µL). Chest radiograph showed multiple bilateral nodules. Chest computed tomography (CT) revealed innumerable bilateral nodules, with mediastinal and axillary lymphadenopathy. (Fig 1) Three consecutive sputum samples were positive for acid fast bacilli. The diagnosis of miliary tuberculosis was made, and she was started on rifampin, isoniazid, ethambutol, and pyrazinamide (RIPE therapy), along with pyridoxine. Given the potential for drug interaction between rifampin and bictegravir, the latter was switched to dolutegravir for the duration of six planned months of antibiotic treatment. DISCUSSION: Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) is an early complication of antiretroviral therapy in patients with TB, that results from the rapid restoration of immune function, with a consequent exaggerated immune response, causing an exacerbation of pre-existing infections, or the unmasking of subclinical infections. TB-IRIS is characterized by severe localized or systemic inflammatory reactions against Mycobacterium tuberculosis antigens. One retrospective study showed an incidence of 8% in HIV and TB co-infected patients who were started on ART. (2) Our case notably had a dramatic presentation, with severe miliary TB on chest imaging, with no known history of TB. Additionally, chest radiography obtained merely one month prior to her presentation had been normal, demonstrating the rapidity with which miliary TB may develop following the initiation of ART. CONCLUSIONS: Patients with risk factors, such as immigration, should be monitored closed following the initiation of ART, for the manifestation of previously subclinical infections, such as TB. Reference #1: Schwartz, MD, Price SF, Pratt RH, et al. Tuberculosis - United States, 2019. MMWR Morb Mortal Wkly Rep. 2020;69:286-289 Reference #2: 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. 2004 Dec 15;37(5):1574-6. DISCLOSURES: No relevant relationships by Rohan Kataria, source=Web Response No relevant relationships by Pius Ochieng, source=Web Response No relevant relationships by NISHANT SHARMA, source=Web Response No relevant relationships by Pandi Todhe, source=Web Response

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME: THE RISK OF ADALIMUMAB CESSATION IN TB TREATMENT

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pharmacologic inhibition of tumor necrosis factor-alpha (TNF-a) is a mainstay in the treatment of autoimmune disease. Guidelines recommend starting TNF-a antagonists after a negative screening test result for tuberculosis (TB) infection is confirmed, due to the increased risk of reactivation TB in an immunosuppressed host. We present the case of a patient on adalimumab who developed extrapulmonary TB and immune reconstitution inflammatory syndrome (IRIS) after starting TB treatment. CASE PRESENTATION: A 67-year-old woman with a history of psoriasis, on adalimumab therapy for one year, presented to our hospital with chills, fevers, and a non-productive cough for one month. She denied hemoptysis and night sweats but acknowledged a 30-pound weight loss over the prior two months. On presentation, she was afebrile, normotensive, saturating 95% on room air. Chest X-ray was notable for bilateral miliary nodules and CT scan showed extensive miliary lesions in her lungs and spleen. She was admitted to the medicine service and put on airborne isolation. Interferon-gamma release assay (IGRA) and testing for HIV were negative. Induced sputum was collected, acid-fast bacilli (AFBs) were noted on smear microscopy, and PCR-based assay confirmed presence of Mycobacterium tuberculosis (MTb). Mycobacterial blood cultures were sent. Anti-TB therapy was started, and she was discharged to home isolation. One month later, she re-presented with dyspnea on exertion. Repeat CT scan showed a large left pleural effusion and a small pericardial effusion. AFB stain and culture of pleural fluid was negative. Repeat sputum AFB stain and culture was also negative, and MTb was not detected by PCR. Prior blood cultures resulted as positive for MTb. She was discharged home after clinical improvement with resolution of her dyspnea. DISCUSSION: TB is one of the top 10 causes of death worldwide. 20% of patients with active TB can have false negative IGRAs, especially if immunosuppressed. IRIS, most often seen in HIV+ patients, can develop with TB treatment initiation. Paradoxical worsening of clinical status occurs as the depressed immune system begins to recover. Patients on TNF-a antagonists are also at risk for IRIS, more commonly in lung and extrapulmonary TB. Thus, the combination of TNF-a antagonist discontinuation and TB treatment placed our patient at heightened risk for IRIS. CONCLUSIONS: This case demonstrates TB dissemination in an immunocompromised patient on a TNF-a antagonist who developed IRIS with adalimumab cessation and TB treatment initiation. Among commonly used biologic agents, adalimumab has been associated with a greater risk for both TB infection and IRIS development after starting TB treatment. Clinicians should be aware of this risk and monitor patients accordingly once treatment is initiated. Reference #1: World Health Organization. Global tuberculosis report 2019. Geneva, Switzerland: World Health Organization; 2019. Reference #2: Dobler, C. C. (2016). Biologic agents and tuberculosis. Microbiology Spectrum, Dec; 4(6). Reference #3: Cheng, V. C. et al. Clinical spectrum of paradoxical deterioration during antituberculosis therapy in non-HIV-infected patients. Eur. J. Clin. Microbiol. Infect. Dis. 21, 803–809 (2002). DISCLOSURES: No relevant relationships by Mark Adelman, source=Web Response No relevant relationships by Vickie Kassapidis, source=Web Response

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Case Report: Central Nervous System Tuberculosis Immune Reconstitution Inflammatory Syndrome in a Non-HIV Patient

Tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) is an abnormal, excessive immune response against live or dead Mycobacteria tuberculosis that may occur during or even after completion of anti-TB therapy, commonly in HIV-infected patients. However, this has also been reported amongst HIV negative patients. We report a case of CNS TB-IRIS in a 57-year-old HIV negative man with miliary TB and tuberculoma. He first presented with 4 months of chronic constitutional symptoms. His symptoms improved on standard anti-TB (isoniazid, rifampicin, ethambutol, pyrazinamide) initially, but he developed worsening left hemiparesis after 1 month of treatment. He was restarted on tapering dose of dexamethasone, and anti-TB was intensified with intramuscular streptomycin for 2 months. His gained full muscle power 4 months later. Serial brain imaging subsequently showed slow treatment response with partial resolution of brain lesions. However, he developed another episode of left hemiparesis with facial asymmetry and slurred speech after 16 months of anti-TB treatment. Repeated MRI brain showed 2 large frontal ring enhancing lesions and lesions in cerebellar hemispheres and vermis regions. Due to diagnostic uncertainties and compressive nature of the brain lesions, craniotomy and excision biopsy of the right frontal lesion were performed. There were no evidence of drug resistant TB and no other brain pathologies were found. Moxifloxacin was added post operatively to achieve better CNS penetration. Patient eventually recovered and achieved full muscle strength of left upper and lower limbs.

Complement-driven inflammasome activation on circulating blood monocytes in immune reconstitution inflammatory syndrome in TB-HIV coinfected patients

Abstract Inflammasome and complement pathways have been independently implicated in the pathogenesis of Tuberculosis (TB) immune reconstitution inflammatory syndrome (IRIS), a clinical complication affecting individuals initiating antiretroviral therapy (ART). Here we sought to investigate whether dysregulated complement contributes to inflammasome activation during TB-IRIS. Caspase-1+ specks are cytosolic inflammasome aggregates responsible for IL-1β and IL-18 release. We detected higher numbers of monocytes with spontaneous caspase-1+ specks in IRIS patients (n=9, baseline median CD4 count= 46 cells/mL and VL= 606,754 copies/mL) in comparison with TB infected, non-IRIS controls (n=7, baseline median CD4 count= 47 cells/mL and VL= 85,831 copies/mL) at IRIS time-point (p<0.05). Patients experiencing IRIS also showed elevated C1q and C3 deposition on monocytes, followed by increased levels of the membrane attack complex (MAC) molecule, C9 (p<0.01). Levels of membrane-bound C9 (r= 0.69, p<0.05), and the cell-associated MAC inhibitor, CD59 (r = 0.6 p <0.05), correlated with IL-18 plasma levels and were associated with caspase-1 activation on patients-derived monocytes (r= 0.85, p<0.001 and r= 0.97, p<0.001, respectively to C9 and CD59), supporting a role for sublytic MAC-driven membrane pore formation in inflammasome activation on patient cells. Because the expression level of CD59 strongly correlated with caspase-1 activation within the CD14high monocyte subsets, our data suggest that those cells were able to prevent full MAC deposition, therefore undergoing sublytic MAC-driven inflammasome activation. This data may help identify new targets for prevention or treatment of TB-IRIS inflammatory syndrome.

P24 The successful use of anakinra to control protracted immune reconstitution inflammatory syndrome in HIV associated tuberculosis: a report of two cases

Abstract Background Paradoxical inflammatory reactions are well known to complicate tuberculosis (TB) and are observed with greater frequency in patients who are co-infected with HIV. Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical inflammatory reaction following early immune system recovery after initiation of antiretroviral therapy. IRIS complicates one in five cases of HIV-associated TB. Most cases of IRIS respond to short courses of corticosteroids; however, morbidity and mortality is increased in central nervous system TB or with protracted reactions. There are no evidence-based treatment guidelines but montelukast, thalidomide and anti-tumour necrosis factor agents have been used to treat protracted paradoxical TB IRIS. Interleukin-1 mediated inflammation has been implicated in TB IRIS. We describe two cases using anakinra (recombinant human interleukin-1 receptor inhibitor) to control protracted, life-threatening inflammation in HIV associated TB. Methods The cases are presented in the results section. Results Case 1: A 33-year-old female from Ethiopia presented with sub-acute onset of fever, malaise with massive abdominal and thoracic lymphadenopathy. She was diagnosed with HIV (CD4=60 cells/mm3) and fully sensitive TB from lymph node aspirate. Despite two courses of TB treatment she developed a 3-year protracted IRIS with fevers, malaise and multiple cold abscesses and was unable to wean below 20mg prednisolone. AA amyloidosis developed with nephrotic range proteinuria and renal amyloid deposition on biopsy. Inflammation failed to respond to montelukast or colchicine, prompting anakinra initiation (100mg daily) with rapid clinical response, resolution of proteinuria, normalisation of inflammatory markers and successful weaning of corticosteroids. She is maintained on 100mg alternate-daily anakinra having failed an attempt to withdraw the treatment at seven years. Case 2: A 41-year-old Zimbabwean teacher with HIV (stable on antiretroviral therapy, complete viral suppression, CD4=245 cells/mm3) presented with one month of fever, weight-loss and headache with no neurological deficit. He was diagnosed with isoniazid mono-resistant miliary TB with tuberculomata in his medulla, pons and both cerebral hemispheres on magnetic resonance imaging (MRI). Following initiation of TB treatment, he developed worsening headaches, left sided weakness and dysphasia with increasing size and surrounding oedema of his tuberculomata on brain MRI. Brain biopsy demonstrated necrotic granulomatous inflammation with visible acid-fast bacilli but no mycobacterial growth, compatible with paradoxical inflammation. He required protracted and high dose dexamethasone. After 18 months without successfully weaning steroids, with cognitive and functional impairment and unstable tuberculomata on serial brain MRI, anakinra was initiated with significant clinical, functional and radiological improvement. He is maintained steroid-free on 100mg alternate-daily anakinra at four years. Conclusion This is the first published report using anakinra to control severe and life-threatening protracted paradoxical inflammation and reduce steroid exposure in HIV-associated tuberculosis. Disclosures A.J. Keeley None. V. Parkash None. A. Tunbridge None. J. Greig None. P. Collini None. R.S. Tattersall None.

Tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome in HIV: immunological review of manifestation and immunopathogenesis

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Verma C, Swami B, Upadhyay V, et al. Tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome in HIV: immunological review of manifestation and immunopathogenesis. HIV & AIDS Review. International Journal of HIV-Related Problems. 2020;19(2):67-73. doi:10.5114/hivar.2020.96486. APA Verma, C., Swami, B., Upadhyay, V., Singh, A., Anang, V., & Saraswati, S. S. et al. (2020). Tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome in HIV: immunological review of manifestation and immunopathogenesis. HIV & AIDS Review. International Journal of HIV-Related Problems, 19(2), 67-73. https://doi.org/10.5114/hivar.2020.96486 Chicago Verma, Chaitenya, Bharati Swami, Vishwanath Upadhyay, Aayushi Singh, Vandana Anang, Shakuntala S Saraswati, and Ankush K Rana. 2020. "Tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome in HIV: immunological review of manifestation and immunopathogenesis". HIV & AIDS Review. International Journal of HIV-Related Problems 19 (2): 67-73. doi:10.5114/hivar.2020.96486. Harvard Verma, C., Swami, B., Upadhyay, V., Singh, A., Anang, V., Saraswati, S., and Rana, A. (2020). Tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome in HIV: immunological review of manifestation and immunopathogenesis. HIV & AIDS Review. International Journal of HIV-Related Problems, 19(2), pp.67-73. https://doi.org/10.5114/hivar.2020.96486 MLA Verma, Chaitenya et al. "Tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome in HIV: immunological review of manifestation and immunopathogenesis." HIV & AIDS Review. International Journal of HIV-Related Problems, vol. 19, no. 2, 2020, pp. 67-73. doi:10.5114/hivar.2020.96486. Vancouver Verma C, Swami B, Upadhyay V, Singh A, Anang V, Saraswati S et al. Tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome in HIV: immunological review of manifestation and immunopathogenesis. HIV & AIDS Review. International Journal of HIV-Related Problems. 2020;19(2):67-73. doi:10.5114/hivar.2020.96486.

Declines in Lung Function After Antiretroviral Therapy Initiation in Adults With Human Immunodeficiency Virus and Tuberculosis: A Potential Manifestation of Respiratory Immune Reconstitution Inflammatory Syndrome.

End-organ impairment has received relatively little research attention as a possible manifestation of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS). In this prospective cohort study, one-half of adults with human immunodeficiency virus and pulmonary tuberculosis experienced meaningful declines in lung function on antiretroviral therapy, suggesting a role for lung function in TB-IRIS definitions.

A pilot metabolomics study of tuberculosis immune reconstitution inflammatory syndrome

BackgroundDiagnosis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is challenging and new tools are needed for early diagnosis as well as to understand the biochemical events that underlie the pathology in TB-IRIS. MethodsPlasma samples were obtained from participants from a randomized HIV/TB treatment strategy study (AIDS Clinical Trials Group [ACTG] A5221) with (n = 26) and without TB-IRIS (n = 22) for an untargeted metabolomics pilot study by liquid-chromatography mass spectrometry. The metabolic profile of these participants was compared at the study entry and as close to the diagnosis of TB-IRIS as possible (TB-IRIS window). Molecular features with p < 0.05 and log2 fold change ≥0.58 were submitted for pathway analysis through MetaboAnalyst. We also elucidated potential metabolic signatures for TB-IRIS using a LASSO regression model. ResultsAt the study entry, we showed that the arachidonic acid and glycerophospholipid metabolism were altered in the TB-IRIS group. Sphingolipid and linoleic acid metabolism were the most affected pathways during the TB-IRIS window. LASSO modeling selected a set of 8 and 7 molecular features with the potential to predict TB-IRIS at study entry and during the TB-IRIS window, respectively. ConclusionThis study suggests that the use of plasma metabolites may distinguish HIV-TB patients with and without TB-IRIS.