1. 1 Tuberculosis and HIV HAIVN Harvard Medical School AIDS Initiative in Vietnam

2. 2 By the end of this session, participants will be able to: Explain the significance of TB/HIV co- infection Describe the clinical presentation of TB in PLHIV Outline TB treatment regimens Explain drug-resistant TB Describe common interactions between ARV and TB drugs Learning Objectives

3. 3 Vietnam is ranked 12th in the world for incident TB The incidence in the general population is 180/100,000 TB Epidemiology (1)

4. 4 TB Epidemiology (2) Global TB Control. WHO 2010 Ước tính các ca Lao mới (tất cả các dạng) trên 100 000 dân Vietnam Không ước tính Ước tính tỉ lệ mới mắc lao, theo quốc gia, 2009

5. 5 TB / HIV Epidemiology Global TB Control. WHO 2010 Vietnam Tỉ lệ hiện mắc HIV trong các ca Lao mới, tất cả lứa tuổi (%) Không ước tính

6. 6 TB is the most common OI in developing countries and the most common cause of death among HIV patients TB infection: speeds the progression of HIV by increasing viral replication worsens immunological suppression in HIV patients HIV increases mortality among patients with TB TB/HIV Interaction (1)

7. 7 Most TB cases are caused by reactivation of latent TB infection In Vietnam, an estimated 50-60% of the population has latent TB infection HIV greatly increases the chance for latent TB infection to become active TB/HIV Interaction (2) StatusRisk of active TB infection HIV negative10% lifetime risk HIV negative IDU 1% risk per year HIV infected10% risk per year

8. 8 Clinical Presentation of PLHIV with TB

9. 9 HIV worsens the signs and symptoms of TB, as shown in the chart The Effects of HIV on TB Symptom /SignHIV PositiveHIV Negative Dyspnea97%81% Fever79%62% Sweats83%64% Weight loss89%83% Diarrhea23%4% Hepatomegaly41%21% Splenomegaly40%15% Lymphadenopathy35%13% Ref: Chest 1994;106:1471-6

10. 10 Clinical Presentation and CD4 (1)

11. 11 Clinical Presentation and CD4 (2) CD4 > 500 “Typical” presentation: Fever Cough Weight loss Bloody sputum CD4 < 200 “Atypical” presentation: fever of unknown etiology weight loss minimal cough Extra-pulmonary disease more likely Sputum sample more likely to be negative Signs and Symptoms of Pulmonary TB

12. 12 Typical Chest X Ray Early stages of HIV (CD4 > 500):  Infiltrates predominantly in upper lobes  Pulmonary cavities present  Pleural effusions

13. 13 Atypical Chest X Ray Advanced stages of HIV (CD4 < 200): Pulmonary cavities absent Infiltrates in middle and lower lobes Nodular infiltrates Effusions can be pleural and pericardial Mediastinal lymphadenopathy with no pulmonary infiltrates Normal CXR in 10 %

14. 14 Extra-pulmonary TB (1) Extra-pulmonary Tuberculosis (EPTB) occurs when bacteria spread outside of the lung and cause disease Occurs more commonly in people with weak immune systems e.g. PLHIV May occur with or without concomitant pulmonary TB

15. 15 Extra-pulmonary TB (2) Occurs most often when a person’s CD4 < 100 Most commonly manifests as: Abdominal and lymph node TB (very often) TB meningitis (5-10%), Tuberculoma Pericarditis Pleural effusion Cutaneous Renal

16. 16 Extra-pulmonary TB (3)

17. 17 Extra-pulmonary TB (4)

18. 18 TB HIV Co-infection Key Clinical Practice Points “Typical” pulmonary TB less common “Atypical”, smear negative and extra-pulmonary TB more common WHO and Vietnam MOH guidelines allow TB treatment on clinical suspicion without positive smear test

19. 19 MOH and WHO Recommend: “THE ANTIBIOTIC TRIAL” When indicated, use one course of broad spectrum antibiotics including coverage for typical and atypical causes of community acquired pneumonia Under such circumstances, avoid Fluoroquinolones to prevent undue delay in diagnosis of TB

20. 20 Treatment Regimens for PLHIV with TB

21. 21 TB National Treatment Protocol (1) DrugDosage Isoniazid (H)5 mg/kg/day Rifampin (R)10 mg/kg/day Pyrazinamide (Z)20-30 mg/kg/day Streptomycin (S)15 mg/kg/day Ethambutol (E)15-25 mg/kg/day Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.

22. RegimePrescription regimen 1: 2 S(E)HRZ / 6 HE 2 S(E)RHZ / 4 RH* newly diagnosed TB cases Regimen 2: 2 SHRZE/1 HRZE/5 H3R3E3 recurrent TB and failure to Regimen 1 TB National Treatment Protocol (2)

23. 23 TB Treatment: Special Situations Some special situations require a more aggressive course of treatment, including: Miliary TB Pericarditis Meningitis Spondilitis with neurological complications For pregnant women: avoid streptomycin - can cause permanent deafness in baby Use ethambutol instead

24. 24 Drug Resistant TB (1) TypeMeaning Mono-resistanceResistant to only 1 anti-TB drug Poly-resistance (PDR) Resistant to more than 1 anti-TB drug, but not INH and RIF combination Multi-drug resistance (MDR) Resistant to at least INH and RIF, the 2 most effective anti-TB drugs Extensively drug-resistant (XDR) MDR and further resistance to any fluoroquinolone and at least one of three injectable second-line drugs: amikacin, kanamycin, or capreomycin Drug resistant TB is TB for which anti-TB drugs have little or no effect against the TB causing agent

25. 25 Drug Resistant TB (2) Causes of drug resistant TB include: Inadequate treatment regimens Interrupted availability to drug treatment Poor quality of drug treatment Incomplete treatment adherence Results from spontaneous mutations of MTB exposed to drugs Quy HT, Buu TN et al Int J Tuberc Lung Dis 2006;10(2):160-166.

26. 26 Multi Drug-Resistant (MDR) TB in Vietnam Among reported cases in 2008, it is estimated that: 2.7% of new TB cases had MDR-TB 19% of re-treatment cases had MDR-TB 3500 MDR-TB cases among reported pulmonary TB cases in 2009 Global TB Control. WHO 2010

27. 27 TB and ARV Drug Interactions (1) ARVEffectTreatment/Solution NVP  37% Switch to EFV, if available (NVP OK, if necessary*) EFV  25%EFV still effective PI (LPV/r, IDV)  80-90% Do not use PI with RIF: refer to specialty center for treatment Rifampicin decreases drug levels of some ARVs:

28. 28 TB and ARV Drug Interactions (2) TBARVToxicity INHd4T Peripheral neuropathy: prevent with pyridoxine (B6) 25-50 mg/day INH, RIF, PZA NVP, EFVHepatotoxicity Note overlapping toxicities of TB and ARV drugs

29. 29 TB Prevention WHO Guidelines

30. 30 TB is the most common OI in Vietnam In the HIV OPC, a significant percentage of patients will have TB or on TB treatment at any one time The waiting area and exam rooms at the OPC are an environment at high risk for TB transmission TB Prevention

31. 31 Step 1: Screen and test Early recognition of patients with suspected or confirmed TB disease. Symptoms that may indicate TB include: Cough > 2 weeks, fever, weight loss, night sweats, lymphadenopathy Screen all patients who have any symptoms: CXR, sputum BK lymph node aspirate (if indicated) Prevent Transmission of TB in HIV Care Settings (1)

32. 32 Step 2 : Education Instruct patients to wear face masks if they have active TB or if they are coughing/sneezing Standard Face Masks Prevent TB transmission if worn by the TB patient DO not prevent the wearer from acquiring TB Special Face Masks: N95 or FFP2 Protect the wearer Only needed in high risk areas: spirometry or bronchoscopy rooms, or MDRTB treatment centers Prevent Transmission of TB in HIV Care Settings (2)

33. 33 Step 3: Separate All patients who have active TB or are TB suspects should: wear a mask be separated from other patients At OPC, there should be a separate waiting area: This waiting area should be well- ventilated Prevent Transmission of TB in HIV Care Settings (3)

34. 34 Step 4: Provide services quickly If possible, triage active TB patients to the front of the line and quickly provide care to reduce the amount of time that others are exposed to them. Prevent Transmission of TB in HIV Care Settings (4)

35. 35 Step 5: Environmental Control Ventilation Natural ventilation relies on open doors and windows to bring in air from the outside Fans may also assist to blow the air out of the room. Prevent Transmission of TB in HIV Care Settings (5)

36. 36 TB/HIV co-infection is common among PLHIV in Vietnam HIV infection increases risk for active TB infection by over 100 fold TB treatment regimens are the same for both HIV+/- patients Clinical presentation of TB varies by CD4 count Measures to prevention TB at OPCs are needed Key Points

37. 37 Key Points TB/HIV co-infection is common among PLHIV in Vietnam HIV infection increases risk for active TB infection by over 100 fold Clinical presentation of TB varies by CD4 count TB treatment regimens are the same for both HIV+/- patients

38. 38 Thank you! Questions?