TB Flashcards
What ARV to start in HIV/TB coinfection?
Tdf/ftc plus EFV - most studied
ABC/3TC also ok but Iris and drug hypersensitivity both common may be hard to tell between the 2
RAL or DTG suitable 3rd agents but less data
Rifabutin instead of rifampicin if needing booster - only ritonavir not to use cobi with rifabutin or rifampicin
Dose of RAL if using with rifampicin?
800mg BD - REFLATE TB2 study ral 400mg bd ‘not non inferior’ to EFV
Dose of DTG if used with rifampicin
50mg BD - switch to OD 2 weeks after stopping rifampicin
Can doravirine be used in context of tb coinfection?
Possible with rifabutin only and at 100mg BD - to
Continue this for 2 weeks after dropping rifabutin
What tb treatment
To give if patient already suppressed on ARVs?
If on EFV, dtg or RAL plus 2 nucs then rifampicin and double dose dtg and ral
If on a boosted PI to use rifabutin instead
If on cobi rifabutin would need to be 150mg 3x week
Steroid DDI
Accelerated by rifamycins - increase steroid dose
Also with PI - risk of adrenal suppression
Methadone DDI tb tx
Reduced plasma levels and increased elimination with rifampicin - may need close monitoring and side effects on cessation rifampicin
What if patient has hep C and TB at same time?
Majority of patients - treat TB first then Hep C as DAA contraindicated with rifampicin
Definition of DILI
AST or ALT >3x ULN in presence of symptoms or
AST or ALT >5x ULN in absence of symptoms
Management of DILI
Consider stopping all potentially hepatotoxic drugs immediately - isoniazid, rifampicin, pyrazinamide, septrin - continue ART unless likely to cause hepatotoxicity
Check hep A, B, C serology
Ask about exposure to other hepatotoxic eg alcohol
Until cause identified treat with two or more anti tv drugs without risk of hepatotoxicity eg ethambutol, streptomycin, levo
Once ALT/AST drops below 2x ULN reintroduce as per table
Which drugs have highest risk of hepatotoxicity in pre existing liver disease
Pyrazinamide followed by isoniazid then rifampicin
What to do if hepatotoxicity occurs in individual with pre existing liver disease? (Rise of 2-3x abnormal baseline lfts)
Avoid pyrazinamide and treat with isoniazid and rifampicin for 9/12 adding ethambutol for first 8 weeks
Or avoid isoniazid and tx with rifampicin ethambutol pyrazinamide and levo for 6/12
Monitor bloods at least 2 weekly and patient to report any anorexia, nausea, vomiting, jaundice
GI side effects of TB treatment
Epigastric pain, nausea, vomiting are common especially in first 2 weeks
Try anti emetics
Can take with food (except rifampicin doses under 600mg), change timings, could switch to a regime without food restrictions if needed
Peripheral neuropathy
Occurs with isoniazid so pyridoxine co administered. can increase pyridoxine to 50mg od if peripheral neuropathy occurs.
Second line drugs need higher dose pyridoxine
Rash (as tx SE)
Most often caused by ethambutol
Occurs in first 2/12 tx
Widespread or worsening rash with systemic symptoms - stop all drugs and careful reintroduction as per table
Reintroduction of tb drugs after Dili or rash
Reintroduce all at once
If reaction occurs to all at once sequentially introduce as per table
If reaction severe or occurs again after reintroduction start with 1/10th first day dose of each drug
Definition of paradoxical TB IRIS
One major or two minor clinical criteria - no alternative explanation for deterioration
Major - new/enlarging LNs, cold abscesses, focal tissue involvement. New or worsening radiological features. New or worsening CNS TB. New or worsening serositis.
Minor - new or worsening constitutional symptoms, new or worsening resp symptoms, new or worsening abdo pain, in retrospect resolution of clinical or radiological findings without having made a change in tb tx
Definition unmasking IRIS
Major and one of two minor criteria must be met
Major - not receiving treatment when ART is started and presents with tb within 3 months of starting att
Minor - heightened intensity of clinical manifestations, once established on tb tx a clinical course that is complicated by a paradoxical reaction
When does TB IRIS occur?
Within 60 days
Median 15 days
Most individuals had advanced HIV
When to start ARVs in tb/hiv co infection
SAPIT trial
If CD4 <50 start within 2 weeks
Otherwise as soon as practically possible but within 4 weeks
Delay until 8 weeks for CNS TB
Symptoms of TB IRIS
Fever and increased or new lymphadenopathy
Dusky red skin overkykng
Need to exclude - tx failure, drug hypersensitivity, OI, malignancy
Management TB IRIS
Corticosteroids - prednisolone or methylpred 1-1.5mg/kg with gradual reduction after 1-2 weeks
Rifampicin will reduce steroid effect
Management of TB in pregnancy
Usual drugs at usual doses - no data to suggest teratogenic effect. Isoniazid not teratogenic even if used in first 4/12.
Increased risk peripheral neuropathy with isoniazid so increase pyridoxine
Tx latent tb in pregnancy
Isoniazid recommended for pregnant women who are likely to have acquired tb recently and therefore at a higher risk of disease progression. If less risk then can be deferred until after delivery.
