Unit 10 Treating the Dually Infected Patient: B Family Case

1. Unit 10 Treating the Dually Infected Patient: B Family Case Botswana National Tuberculosis Programme Manual Training for Medical Officers

2. B Family Case: Question 1 • Mr. B is on TB retreatment and ART • Mr. B returns with nausea, vomiting, and jaundice What do you do for Mr. B? Unit 10: Case Studies

3. B Family Case: Answer 1 • Take a detailed history • Do a physical examination • Make sure to assess Mr. B’s liver • Take blood for liver function, electrolytes, full blood count • Bilirubin (100), AST (400 range), ALT (500 range) • Admit Mr. B to the hospital for observation • Stop all TB and HIV medications, but maintain cotrimoxazole Unit 10: Case Studies

4. B Family Case: Question 2 1 week later, Mr. B’s LFTs have decreased to less than 2 x ULN What do you do for Mr. B now? Unit 10: Case Studies

5. B Family Case: Answer 2 • Reintroduce TB drugs • Monitor liver function tests Unit 10: Case Studies

6. B Family Case: Question 3 After a 16 day re-introduction, the patient’s LFTs remain < 2x ULN and Mr. B is without jaundice • When do you consider starting ART again? • Which drugs should Mr. B take? Unit 10: Case Studies

7. B Family Case: Answer 3 • 2-4 weeks after re-starting full doses of anti-tuberculosis drugs • Medications • Alluvia, 2 tabs BD • Ritonavir, 3 capsules BD • Combivir, 1 tab BD *Alluvia is now available in Botswana – it is a tablet form of Kaletra and does not need to be refrigerated Unit 10: Case Studies

8. B Family Case: Question 5 Why should Mr. B take Alluvia + Ritonvir instead of restarting EFV? Unit 10: Case Studies

9. B Family Case: Answer 5 • EFV can cause heptatotoxicity • Since Mr. B is tolerating the ATT, you assume it was the efavirenz that caused the deviation in liver function and jaundice Unit 10: Case Studies

10. Unit 10 Treating the Dually Infected Patient: Case Botswana National Tuberculosis Programme Manual Training for Medical Officers

11. Additional Case • A 45 year old female named TT with fever for 4 weeks, cough with bloody sputum, sweats and weight loss of 7 kg • Sputum is AFB+ • Her HIV test is positive and CD4 is 20 cell/cu mm Chest X-ray shows right paratracheal adenopathy Unit 10: Case Studies

12. Additional Case: Question 1 • What questions do you ask her? • What medications do you start her on? Unit 10: Case Studies

13. Additional Case: Answer 1 • Ask her if she is still menstruating • TT reports that her menses stopped at 43 years of age • Start patient on rifampicin, isoniazid, pyrazinamide and ethambutol plus cotrimoxazole Unit 10: Case Studies

14. TT is started on a four drug TB therapy and is discharged She returns after 1 month Her fevers, night sweats and cough have stopped and she has gained 5kg She is tolerating the TB drugs TB therapy is continued She is started on ARVs including zidovudine, lamivudine andefavirenz Why is she taking efavirenz instead of nevirapine? Additional Case: Question 2 X-ray shows improvement Unit 10: Case Studies

15. Additional Case: Answer 2 TT is taking efavirenz instead of nevirapine because she is beyond child bearing age and because efavirenz is the preferred NNRTI for use in patients taking rifampin Unit 10: Case Studies

16. Additional Case: Question 3 • She comes back to your facility 2 weeks after starting ARVs • She says that her fever, cough and night sweats have come back • She has taken her ARTs as prescribed, but thinks they are making her more sick and she would like to stop them • What other information do you want from her history? • How would you assess her? Unit 10: Case Studies

17. Additional Case: Answer 3 • You want to know whether or not she was adherent to all her medications • Assessing TT • Check for other signs/symptoms: nausea, vomiting and diarrhoea, which may indicate other infections or malabsorption • Check blood pressure, heart rate, temperature, respiratory rate and oxygen saturation • Perform labs: sputum smear for AFB, sputum culture, FBC, liver tests, CD4 count, viral load • Perform a chest x-ray Unit 10: Case Studies

18. Additional Case: Question 4 • What is your differential diagnosis? • What do you look for on physical exam? Unit 10: Case Studies

19. Additional Case: Answer 4 (1) • Differential diagnosis • TB IRIS • Drug-resistant TB • Failure of TB therapy due to poor adherence or malabsorption of medications • Bacterial pneumonia • PCP • Drug toxicity Unit 10: Case Studies

20. Additional Case: Answer 4 (2) 2. Physical examination • Close evaluation of the chest • Listen for adventitious sounds, symmetrical excursion • Check for enlarged lymph nodes • Assess for body swelling (oedema) • Assess for abdominal distention • Asses for jaundice • Complete neurologic exam Unit 10: Case Studies

21. Additional Case: Question 5 (1) • TT reports excellent adherence and denies nausea, vomiting or diarrhoea • Oxygen saturation is 96% on room air • Heart rate, respiratory rate and other vital signs are normal • Remainder of physical exam is normal • Sputum smear negative Diffuse bilateral infiltrates Unit 10: Case Studies

22. Additional Case: Question 5 (2) • What condition(s) do you suspect now? • What is your management plan now? Unit 10: Case Studies

23. Additional Case: Answer 5 • Narrowed differential diagnosis • TB IRIS • PCP • Bacterial pneumonia • Management • Advise her to continue ART and the TB continuation regimen • Educate her, using a caring, respectful attitude • Ask questions and listen • Ensure she understands the benefit of remaining on both treatments • Encouragement • Schedule her to come back in 1-2 weeks, or sooner if she gets worse Unit 10: Case Studies

24. 2 weeks later her symptoms are worse Sputum culture from last visit shows no growth to date Sputum smear is AFB negative Respiratory rate is 28 Oxygen saturation is 90% on room air Crackles heard bilaterally What is your diagnosis? Additional Case: Question 6 X-ray shows no improvement Unit 10: Case Studies

25. Additional Case: Answer 6 • TB IRIS: Occurs in 10-40% of patients • The immune system is likely reacting to dead mycobacteria in the system • The inflammation is worsening as her immune system reconstitutes itself on ART • Risk factors • Starting ARVs within 6 weeks of TB treatment • Disseminated, extra-pulmonary disease • Low baseline CD4 count • Rise in CD4 % • Fall in viral load • High bacillary burden Source: www.who.int/entity/tb/events/tbiris.ppt Unit 10: Case Studies

26. Additional Case: Question 7 How do you manage TT now? Unit 10: Case Studies

27. Additional Case: Answer 7 • Admit her to hospital • Give oxygen • FBC, chemistry panel • Administer corticosteroids to reduce inflammation • If she continues to worsen despite steroid treatment: • Stop ART until she has clinically improved (resolution of chest x-ray, respiratory distress) • Restart ART once clinically stable • Continue TB treatment regimen throughout • If a culture turns positive: • Suspect drug resistance • Do sensitivity testing Unit 10: Case Studies

28. Additional Case: Question 8 • 1 week later, TT remains on ART and TB treatment + steroids • T.T. reports feeling much better • Lungs sound normal • Sputum culture is still negative Chest x-ray shows improvement How long should steroids be continued? Unit 10: Case Studies

29. Additional Case: Answer 8 • Consider a 4 week taper • May need to restart if IRIS recurs Unit 10: Case Studies