The document discusses TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV-infected patients, detailing its pathophysiology, implications, and risk factors. It highlights that TB-IRIS often occurs after initiation of antiretroviral therapy (ART) and is characterized by an exaggerated inflammatory response due to the recovery of the immune system. The document also differentiates between paradoxical and unmasking TB-IRIS, focusing on their clinical features and diagnostic challenges.

1. TB-ASSOCIATED IMMUNE
RECONSTITUTION INFLAMMATORY
SYNDROME (TB-IRIS)
DR KD DELE IJAGBULU
DEPT OF FAMILY MEDICINE (AUGUST 2022)

2. INTRODUCTION: IRIS IN HIV
• This is an inflammatory response in HIV-infected patients triggered by initiation
or re-initiation of antiretroviral therapy (ART)
• Most cases in those with low CD4 and high viral loads
• Usually associated with an immunological improvement when the ill HIV patient
commences ART
• This is seen as an increase in CD4 cell count and/or a rapid decrease in viral load
• IRIS in HIV usually within the first 4-8 weeks after initiation of ART
• Mycobacterium tuberculosis is implicated in approximately half of adults with
IRIS.

3. POTENTIAL
ADVERSE
OUTCOMES FROM
HAART
• A. Side effects of HAART drugs:
Depending on the medications, these may include nausea, lethargy,
cold, loss of taste sensation, anxiety, anorexia, depression, peripheral
neuropathy, CNS and psychiatric manifestations, anaemia,
pancreatitis, hepatotoxicity, lipodystrophy, etcetera. These side
effects often result in medication non-compliance, drug resistance,
progression to AIDS, and increased mortality.
• B. The risk for drug-drug interactions:
Usually seen in HIV/AIDS patients receiving treatment for other co-
infections like tuberculosis, fungal infections. Drugs metabolized by
the cytochrome P450 enzyme system includes NNRTI, PIs, anti-
tubercular, anti-cancer drugs. These drugs interact with each other
either by inducing or inhibiting the efficacy of one another
• C. Immune reconstitution syndrome (IRIS):
IRIS is a potential complication of initiation of HAART. It can occur in
up to a third of cases of HIV patients initiated on HAART. It is a state
of hyper-inflammatory response against latent infections that
happens after the improvement in CD4 cell count and immune
response once therapy for HIV has started. The knowledge of any
latent infections in patients is crucial before starting HAART in
HIV/AIDS patients. The clinical presentation and severity of IRIS
depend on the organism involved, location of the infection, and
severity of inflammatory response

4. IRIS:
PATHOGENESIS -
MULTIFACTORIAL

5. IRIS IN HIV: COMMON AETIOLOGIES:
Inflammatory reactions to pathogens:
• Mycobacteria: TB, MAC
• Fungi: Cryptococcal meningitis, Pneumocystis pneumonia
• Viruses: CMV retinitis, Progressive multifocal leukoencephalopathy (PML)
from JC; HSV, VZV, Hep B/C, HPV
• Bacteria: Bartonella, T. pallidum
• Parasites: Toxoplasma, Strongyloides
Malignancies and autoimmune phenomena
• Kaposi’s sarcoma
• Sarcoidosis, Malignancies, Grave’s disease, inflammation at site of tattoo

6. CLINICAL MANIFESTATIONS: IRIS IN HIV
• The following criteria usually need to be met before the diagnosis of the
IRIS in HIV positive patients:
• The patient should be HIV-positive.
• The patient should be receiving HAART with either a decrease in HIV Viral
Load from baseline or an increase in CD4+ cells from baseline or both.
• Clinical symptoms should be consistent with an inflammatory process.
• Clinical course not consistent with:
• Expected course of previously diagnosed Opportunistic Infection (OI).
• Expected course of newly diagnosed OI.
• Drug toxicity or side effects.

7. IRIS SHOULD BE STRONGLY CONSIDERED WHEN:
• ART has been recently initiated, usually within the last 2–6 weeks, but IRIS has been
reported many months after initiation.
• There has been a substantial decline in HIV viral load, usually with a significant rise in
CD4 count – however, IRIS may occur in the absence of either or both of these.
• Local or systemic inflammatory changes occur related to a previously diagnosed
(paradoxical IRIS) or unrecognised (unmasking IRIS) infectious condition
• IRIS can also occur in non-infectious conditions, including malignancies and
autoimmune diseases.
• An alternative explanation for these changes is not identified. This can be very
challenging as progression of HIV, new opportunistic infections, drug-resistant
pathogens, and medication side effects may present similarly.

8. TB-ASSOCIATED IRIS

9. HIV-TB CO-INFECTION
• Mycobacterium tuberculosis infection remains the world’s most deadly infectious
disease with 10 million cases and nearly 1.5 million deaths in 2018 alone
• TB burden remains highest in parts of the world with high HIV prevalence (eg South
Africa)
• TB and HIV co-infection negatively affects patient outcomes.
• TB infection leads to increased HIV replication and HIV contributes to TB progression
due to HIV mediated immune suppression.
• People living with HIV have a 19 times increased risk of developing TB and make up
17% of all TB deaths worldwide
• TB accounts for one in three AIDS-related deaths, making it the leading contributor to
mortality in people living with HIV

10. HIV-TB CO-INFECTION & ART ROLL-OUT
• The roll-out of anti-retroviral therapy (ART) in settings with high TB and HIV
prevalence has been instrumental in combatting these twin epidemics, with ART
availability reducing TB risk by 58–80%.
• TB mortality in HIV-positive individuals has also decreased by 60%
• However, an important complication of TB-HIV coinfection in the post-ART era is
TB-associated immune reconstitution inflammatory syndrome (TB-IRIS).

11. RISK FACTORS FOR TB IRIS
• Extrapulmonary tuberculosis was the most significant factor associated with IRIS
• disseminated tuberculosis : tubercular lymphadenitis, miliary TB
• low baseline CD4-cell count, usually lower than 50 cells/mm3
• An excellent virological response
• An increased antigenic burden of an opportunistic infection
• An early initiation of ART after an opportunistic infection
• Younger age at initiation of HAART
• IRIS occurs commonly in HIV-infected children initiating ART and occasionally has
severe morbidity.

12. RISK FACTORS FOR TB IRIS
• Positive urine LAM
• CSF neutrophilic predominance predicted IRIS
• High HIV Viral Load: (Viral load >100,000 copies/mL associated with TB-IRIS
• Low CD4 T cell count: (TB IRIS risk: CD4 < 50: 24%; CD4 50–200:12%; and CD4 >
200: 6%)
• CSF neutrophilic predominance
• TBM patients with positive cultures had higher IRIS rates
• Others: Anaemia with Haemoglobin <10; CRP >25; Weight loss ≥10%

13. HIV-TB CO-INFECTION & IRIS
• Depending on the TB disease site and treatment status at ART initiation, this
immune-mediated worsening of TB pathology can take the 3 forms:
• Paradoxical TB-IRIS,
• Unmasking TB-IRIS, and
• (Some use a third classification: CNS TB-IRIS – a paradoxical TB-IRIS subtype.)
• While corticosteroids is currently the only trial-supported therapy for prevention
and management of TB-IRIS, increasing interest has been given to biologic
therapies (such as TNF-α Inhibitors, IL-6 blocker and VEGF inhibitors) directly
targeting the immune pathology.

14. DIAGNOSTIC
CATEGORIES
OF
TB-IRIS
ATT: Anti-TB Therapy
ART: Anti Retroviral
Therapy

15. PARADOXICAL IRIS VS UNMASKING TB-IRIS
• Unmasking IRIS occurs in patients who have an unrecognised opportunistic
infection when ART is initiated, and who then present with exaggerated
inflammatory features of that infection during early ART due to it being
‘unmasked’ by recovering immunity.
• Paradoxical IRIS occurs in patients who are being treated for an OI when they
start ART, but who develop an immune-mediated worsening or recurrence of
features of that infection after starting ART.
• Approximately 10–20% of patients who start ART with advanced
immunosuppression experience clinical deterioration during the first few months
due to IRIS. Most presentations of IRIS occur within the first 3 months of ART.

16. TB-IRIS: PATHOPHYSIOLOGY

17. TB-IRIS: PATHOPHYSIOLOGY
• TB-IRIS results from a disproportionate and dysregulated inflammatory response to TB
produced as a consequence of rapid recovery of the immune system. EG
• TB-IRIS is characterized by exuberant release of interferon- γ (IFN-γ) and related
cytokines by mycobacteria-specific Th1 type CD4 T cells which expand in number and
responsiveness with ART
• ART also causes an increase in cytokines related to Th1 type CD4 T cells such as
Interleukin, IFN, Tumour necrosis factor alpha (TNF-α), and soluble IL-2 receptor
(sCD25)
• There is increasing evidence that the innate immune component of IRIS centres on
aberrant activation and signalling of macrophages and monocytes.

18. MODEL OF TB-IRIS PATHOGENESIS.

19. MODEL OF TB-IRIS PATHOGENESIS.

20. TB-IRIS: PATHOPHYSIOLOGY
• The
immunopathogenesis of
IRIS is characterised by
a dysbalanced
restoration of the
immune system
resulting in pathological
inflammation

21. PARADOXICAL IRIS VS UNMASKING TB-IRIS

23. UNMASKING TB IRIS
CLINICAL FEATURES AND DIAGNOSIS

24. UNMASKING TB IRIS
• Unmasking TB-IRIS is an increasingly recognized complication of initiating ART in
a patient with subclinical or occult TB infection
• Unmasking TB-IRIS is seen in 1–4% of patients initiating ART
• TB is most commonly diagnosed in the first three months after ART-initiation
• Subclinical and occult TB is common in HIV infected patients not on ART
• Up to 40% of those diagnosed with ART-associated TB are actually an unmasking
IRIS
• Pathophysiology: The immunologic response is thought to involve similar
mechanisms to the uncontrolled immune response that occurs after rapid
immune restoration in paradoxical IRIS.

25. UNMASKING TB IRIS
• The presentation of unmasking TB-IRIS is similar to the paradoxical form, though
disseminated TB is more common
• Presentations characterized by weight loss, lymphadenopathy, meningism, severe
pneumonia, and tuberculous abscesses
• TB meningitis is a common presentation of ART-associated TB and is typically
labelled as IRIS
• Onset has been reported from as soon as 4 days after ART initiation (median of
12 days)
• Multiple opportunistic infections can also be unmasked in a single patient
• Diagnosis of unmasking TB-IRIS can be more challenging than paradoxical TB-
IRIS as the symptom trajectory is often not as clear.

26. UNMASKING TB IRIS
• Careful history taking, physical examination, and review of chest radiography at
the time of ART initiation is important to prevent unmasking IRIS
• Risk factors for unmasking TB-IRIS include low baseline CD4 count and high viral
load
• Signs of subclinical TB such as anaemia, significant weight loss, and high CRP are
predictive of developing unmasking IRIS
• Lymphadenopathy on chest x-ray imparts a nine-fold increased risk of developing
unmasking IRIS

27. PREVENTION OF UNMASKING IRIS
Point-of-care screening assays have been developed to identify those patients with
extrapulmonary TB that might be otherwise missed
Tests of both urine and sputum with GeneXpert MTB/RIF Ultra can also improve
detection of TB in HIV+ patients, and return results quickly enough to allow for TB
treatment at the time of ART-initiation
The urine lateral flow assay for LAM has become a vital option to diagnose disseminated
TB in HIV+ patients [WHO guidelines (2019) recommend outpatient LAM testing for
anyone with a CD4 count of less than 100 cells/µL irrespective of symptoms]
Combined prophylaxis with trimethoprim-sulfamethoxazole and ?isoniazid/pyridoxine –
to treat latent TB infection, prevent reactivation in those with advanced have potentials
to prevent unmasking TB-IRIS (esp. TB sand cryptococcus).

28. PARADOXICAL TB IRIS
CLINICAL FEATURES AND DIAGNOSIS

29. EPIDEMIOLOGY: PARADOXICAL TB IRIS
• Incidence 8 – 54% in different studies HIV+ patients with TB starting ART
• Onset of symptoms: Median onset of14 days from ART start
• Many patients require Hospitalisation in 25-50%
• Median duration: 2-3 months in literature, 69 days (IQR = 38-106) in a cohort
studies
• Mortality: infrequent cause of mortality (2-3%) unless CNS involvement; CNS TB-
IRIS = 25-75%)
• The focus is often on Paradoxical IRIS, while CNS Paradoxical IRIS requires special
consideration

30. DIAGNOSTIC DILEMMA: PARADOXICAL TB IRIS
• There is no single diagnostic test for TB IRIS; diagnosis relies primarily on
recognition of the sequential relationship between initiation of antitubercular
therapy (ATT), ART initiation, and deterioration
• Evidence of immune reconstitution, quantified by significant increase in CD4
count between ART-initiation and IRIS onset, further supports the diagnosis of
IRIS.
• TB-IRIS often presents non-specifically with systemic illness and
lymphadenopathy and therefore INSHI definitions require investigations to rule-
out potential IRIS mimics including drug reactions, treatment failure,
superimposed infections, or malignancies

31. APPROACH TO DIAGNOSIS: PARADOXICAL TB IRIS
• There is no confirmatory diagnostic test for TB-IRIS. Helpful tips include:
• 1. Diagnosis of TB confirmed or very likely?
• 2. Improvement on TB treatment prior to ART?
• 3. Symptom onset typically 1-4 weeks on ART
• 4. Deterioration with inflammatory features of TB
• 5. Consider and exclude differential diagnoses
• 6. Exclude drug-resistant TB

32. DIAGNOSIS CONT.:
INSHI CONSENSUS
CASE DEFINITION
•Diagnosis of TB fulfilling WHO criteria
•Initial response to TB treatment
Antecedent requirements
•Onset within 3 months of ART initiation, re-initiation, or regimen change of at least 1
major criterion or 2 minor criteria:
Clinical criteria
•New or enlarging lymph nodes, cold abscesses, or other focal tissue involvement
•New or worsening radiological features of TB
•New or worsening CNS TB
•New or worsening serositis
• Major criteria
•New or worsening constitutional symptoms such as fever, night sweats, or weight loss
•New or worsening respiratory symptoms such as cough, dyspnoea, or stridor
•New or worsening abdominal pain accompanied by peritonitis, hepatomegaly,
splenomegaly, or abdominal adenopathy
• Minor criteria
•Examples: TB drug resistance , poor adherence, another OI or neoplasm
Alternative explanations for clinical deterioration excluded if possible
INSHI = International Network
for the Study of HIV-associated
IRIS

33. FEATURES OF SYSTEMIC INFLAMMATION
• Common clinical findings of systematic inflammations seen in patients with IRIS
• Fever (Temp > 37.7) in 34% patients
• Tachycardia (Pulse rate > 120) in 69%
• History of Night sweats in 61%
• Weight loss of > 2.5% in 2 weeks or > 5% in 4 weeks in 52% patients
• Pulmonary involvement in 39% patients
• Protracted lymphadenopathy – usually cervical (neck) lymph nodes
• Neurological/CNS involvement
• Abdominal (particularly hepatic) features

34. PARADOXICAL TB-IRIS
SYNDROMES & SUB-
TYPES
CLINICAL FEATURES AND DIAGNOSIS

35. MAJOR PARADOXICAL TB-IRIS SYNDROMES
• 1. Lymphadenitis
• 2. Pulmonary
• 3. Neurological
• 4. Abdominal
• 5. Serositis (effusions)
• 6. Features of systemic inflammation
• - High fevers, marked tachycardia, weight loss

36. IMPORTANT DIFFERENTIAL DIAGNOSES
Manifestation Differential diagnoses
Lymph node enlargement Kaposi’s sarcoma
Lymphoma
Pulmonary infiltrate Bacterial pneumonia
PCP
Kaposi’s sarcoma
Pleural effusion Bacterial empyema
Kaposi’s sarcoma
Meningitis Bacterial
Tuberculous
Cryptococcal
Space-occupying lesion Toxoplasmosis
Cryptococcoma
Primary CNS lymphoma
Fever with general
deterioration
Bacterial sepsis
NTM
Kaposi’s or lymphoma

37. CNS TB-IRIS
CLINICAL FEATURES AND DIAGNOSIS

38. NEUROLOGICAL TB-IRIS
• Given the physical and immunologic peculiarities of the central nervous system,
paradoxical IRIS in the setting of CNS TB requires specific considerations in
diagnosis and management.
• 12% with paradoxical TB-IRIS have CNS involvement
• CNS TB-IRIS is common – up to 50% of TB Meningitis patients starting ART develop
IRIS
• Occurs in patients with or without CNS TB prior to ART
• Despite making up about 12% of all TB-IRIS, neurological manifestations contribute
to the vast majority of TB-IRIS mortality
• The prognosis of CNS-TB-IRIS is poor with studies showing mortality in 13–30% of
cases and disability in an additional 30%

39. PREDICTORS OF CNS/NEUROLOGICAL TB-IRIS
• CNS-TB-IRIS is diagnosed when symptoms of CNS-TB recur after ART-initiation
after initially improving on Anti-TB treatment
• Symptoms reappear a median of 14 days after ART initiation
PREDICTORS OF CNS IRIS INCLUDE:
• High viral load and low CD4 T cell count at initial presentation remain risk factors.
• At TBM diagnosis, increased CSF neutrophil and CSF culture-positivity predict
future development of paradoxical TBM-IRIS .
• Also, high CSF TNF-α and low IFN-γ at TBM diagnosis may be predictive

40. CLINICAL FEATURES OF CNS TB-IRIS
• CNS TB-IRIS can include all forms of CNS TB, most prominently:
• – Meningitis
• – Intracranial Tuberculoma/S
• – Brain Abscess
• – Spinal Epidural Abscess
• – Radiculomyelopathy and Radiculomyelitis
• The most common symptoms are headache, neck stiffness, confusion and new-
onset seizures
• Other symptoms: paraparesis, disconjugate eye movements, aphasia, and
decreased vision

41. DIFFERENTIAL CNS IRIS
• While neurologic worsening after ART-initiation in a patient being treated for
TBM is strongly indicative of CNS-TB-IRIS, several other conditions should be
considered.
• When CSF culture or molecular diagnostics are positive, it is important to rule out
drug-resistant TB, which can occur in more than 10% of TBM cases and is
associated with poor outcome
• Cryptococcal meningitis, toxoplasmosis, CMV encephalitis, HIV encephalopathy or
progressive multi-focal leukoencephalopathy may be present as co-infections
with TBM and may be unmasked due to ART

42. PREVENTION OF CNS IRIS
• DELAY INITIATION OF ART!!
• RISK vs BENEFITS: The high morbidity and mortality of CNS-TB-IRIS makes the risk of
IRIS related to early ART initiation higher than the risk of developing additional
infections related to delaying ART.
• Delay ART initiation until 8 weeks after TB treatment initiation, irrespective of CD4 count
• 8 weeks of adjunctive corticosteroids with TB treatment demonstrates reduced mortality
• The rationale for adjunctive steroids is the dampening of pathologic immune responses,
of which IRIS is one.

43. TREATMENT OF CNS IRIS
• Corticosteroids: Prednisone (1.5mg/kg/day)
• Many immunomodulating therapies have been tried with some success in
treating CNS-TB-IRIS once it has developed
• The differential poor corticosteroid response to TB IRIS suggests that more
potent or focused immunomodulating therapy might be necessary for TBM-IRIS
• Some successes with treating severe cases of CNS-TB-IRIS with TNF-α inhibitors
such as infliximab and adalimumab, generally after failure of corticosteroids
• Thalidomide (caution: teratogenic) has been used with some effect for treatment
of otherwise intractable intracranial tuberculomas

44. ABDOMINAL FEATURES
FOR TB-IRIS
CLINICAL FEATURES AND DIAGNOSIS

45. ABDOMINAL
FEATURES OF TB
IRIS
Lymph node enlargement
• Abscess formation
• Peritonitis and ascites
• Liver/Hepatic involvement
• Splenic involvement and rupture
• Intestinal involvement
• Renal involvement

46. HEPATIC TB-IRIS VS DRUG-INDUCED LIVER INJURY
Hepatic TB-IRIS
• RUQ pain, nausea
and vomiting
• Tender
hepatomegaly
• Cholestatic LFT
derangement
• +/- mild jaundice
• Usually other TB-
IRIS manifestations
Drug-induced liver
injury
• Similar symptoms
• Typically, not
hepatomegaly
• Transaminitis +/-
jaundice
• Absence of other
TB-IRIS features
Ps., Note:
• Patients may
present with
clinical picture
between these two
• Biopsy or treat as
DILI
• Two conditions
may co-exist

47. PARADOXICAL TB-IRIS
TREATMENT, PROGNOSIS, & PREVENTION

48. TB-IRIS TREATMENT REGIMENS.
• Corticosteroids: There is more rapid improvement in symptoms, radiography,
inflammatory markers, performance and quality of life with four-week course of
prednisone
• Immunomodulators have been used (anecdotal reports)
• TNF-α Inhibitors
• Infliximab clinical improvement in patients with TB-IRIS refractory to
corticosteroids.
• Adalimumab for refractory CNS TB-IRIS
• Thalidomide: For cases of steroid dependent IRIS (cryptococcal meningitis and
disseminated TB). It leads to clinical improvement and allowed steroid tapering.
Assoc clinical and radiographic improvement of intracranial tuberculomas
• IL-6 blocker (Tocilizumab) in severe and steroid-refractory cases

49. TB-IRIS TREATMENT REGIMENS.
• Others include:
• NSAIDs: Based on symptomatic improvement in mild cases
• Montelukast (Leukotriene antagonist): Cases of severe IRIS saw clinical
improvement with montelukast
• Pentoxifylline: Provides clinical improvement for TB-IRIS
• VEGF Inhibitors: Bevacizumab used for CNS-TB-IRIS (retinal)

50. TB-IRIS: TREATMENT CONT. – CORTICOSTEROIDS
• Corticosteroids have been shown to reduce morbidity and improve symptoms in
paradoxical TB-IRIS,
• And can be used in mycobacterial and fungal forms of IRIS when other causes for
deterioration have been excluded, and particularly when IRIS features are severe.
• It is important to ensure that the underlying OI is treated appropriately.
• ART should be continued, unless the IRIS is life-threatening (e.g., neurological
involvement in TB-IRIS with depressed level of consciousness).
• For paradoxical TB-IRIS, prednisone can be commenced at a dose of 1.5 mg/kg/day
and weaned over 4 weeks, but a longer course may be required if symptoms recur
on weaning.
• Steroids should not be used in patients with Kaposi’s sarcoma.

51. TB-IRIS: TREATMENT CONT. – OTHER ASPECTS
• Symptomatic management: Analgesia, anti-emetics
• Procedures including lymph node aspiration, pericardiocentesis, paracentesis, and
thoracentesis are sometimes required to alleviate symptoms or manage
complications
• TB-IRIS is not an indication to extend Anti-TB Treatment, except in patients with
abscesses or tuberculomas that have persisted despite six months of TB treatment
in which ongoing active infection is suspected
• Importantly ART should be continued, except when there is life-threatening
neurologic disease (see section on CNS-TB-IRIS)

53. PREVENTION
It is important to consider opportunistic infection prior to ART initiation as initiating
treatment for them first may reduce the risk of IRIS developing.
This is particularly true for CNS TB and cryptococcal meningitis where ART initiation
should be delayed during the initial weeks of treatment in order to reduce the risk
of IRIS.
Tuberculous mass lesions (tuberculomas) have been associated with life-threatening
CNS-IRIS.
In most patients with TB, ART can be safely initiated about 2 weeks after TB
treatment has commenced.
However, extrapolating from experience in adults with HIV-associated cryptococcal
meningitis, ART initiation should be delayed by at least 6–8 weeks.
Routine prophylactic use of NSAIDs or corticosteroids to reduce the risk of IRIS is
not recommended,
Rather patients at high risk for IRIS should be closely monitored for new or
worsening symptoms so that IRIS can be timeously identified and treated.

54. WHO RECOMMENDATION
• TB treatment should be initiated first
• Followed by ART within the first 8 weeks of TB treatment
• If CD4 count < 50 initiate ART within 2 weeks
• Caution in patients with TB meningitis
• NOTE: Patients with low CD4 count
• Are at higher risk for paradoxical TB-IRIS when start ART while on TB
treatment
• ART initiation around 2 weeks on TB treatment reduces mortality
• But increases TB-IRIS incidence by > 2- fold

55. DEFER ART AS PER THE ART CLINICAL GUIDELINES

56. DEFER ART AS PER GUIDELINES

57. PROGNOSIS
• Prognosis varies based on site of disease and treatment protocols
• The course of TB-IRIS is most frequently self-limited
• TB-IRIS found a 2% all-cause mortality attributable to IRIS.
• However, inconsistent criteria for defining TB-IRIS associated death and variant
follow-up time have led to individual studies reporting anything from no deaths,
to mortality as high as 38%
• Without standard glucocorticoid treatment, TB-IRIS is independently associated
with 48-week mortality

58. SUMMARY
• TB-IRIS in all forms causes significant morbidity and mortality in persons with
HIV/TB coinfection
• It requires special focus given its partially iatrogenic nature.
• Preventing Unmasking TB-IRIS will require improved TB detection at ART
initiation.
• As availability of ART and implementation of HIV test and treat continues to
increase, ability to rapidly rule out TB coinfection is important.
• Delaying the commencement of ARVs for at least the first two weeks of TB
treatment remains vital for the prevention of Paradoxical TB-Iris

59. THANK YOU!
FOR YOUR TIME

60. SOME REFERENCES
• Quinn CM, Poplin V, Kasibante J, Yuquimpo K, Gakuru J, Cresswell FV, Bahr NC.
Tuberculosis IRIS: Pathogenesis, Presentation, and Management across the
Spectrum of Disease. Life (Basel). 2020 Oct 29;10(11):262. doi:
10.3390/life10110262. PMID: 33138069; PMCID: PMC7693460.
• Meintjes G, Stek C, Blumenthal L, et al. Prednisone for the Prevention of
Paradoxical Tuberculosis-Associated IRIS N Engl J Med 2018; 379:1915-1925. DOI:
10.1056/NEJMoa1800762
• 2019 ART Clinical Guidelines for the Management of HIV in Adults, Pregnancy,
Adolescents, Children, Infants and Neonates. Republic of South Africa National
Department of Health