HIV & TUBERCULOSIS ( The Double Menace ) ( World AIDS Day ) December 1

1. HIV & TUBERCULOSIS( The Double Menace) ( World AIDS Day )December 1 By Dr.K.Bujjibabu. M.D.

2. OVERVIEW • Emergence of HIV epidemic posed major challenge to TB control efforts. • Co-infection of HIV & TB worldwide- 5-6 Million ( 90% in developing countries ) • TB-50%life time risk of developing active disease in HIV patients. • New TB infection & Risk of disease REACTIVATION- common in HIV infected people.

3. Epidemiology • TB infection-1/3 of world’s population(~ 9 million new cases of TB & ~3 million deaths each year.) • Co-infection- 5 - 6 million(90% reside in developing countries.) • Incidence of TB in HIV infected- >100 times that of general population.

4. Study/AuthorPlace(Period)Percentage of TB patientswho are HIV+ve 1) Purohit SD, et al157 - Ajmer - 0.7% (1993-95) 2) Mohanty KC, et al158 - Mumbai - 6.7% (1989-94) 3) Paranjpe S, et al159 - Pune - 15% (1991-96) 4) Tripathy SP, et al160 - Pune - 12.1% (1995) 5) Solomon S, et al 161 - Chennai - 1.7% (1991-93) 6) Samuel NM, et al162 - Chennai - 17% (1996) 7) WHO/IUATLD Project163Delhi - 1% (1995) 8) Sharma SK, et al164- Delhi - 0.4% (1994-99) 9) Vasudevaiah V, 165 - Pondicherry - 4.1% (1994-96)

5. HIV in WOMEN • Important entity for several reasons • Raising in no., steadily • Female CSW–constant source & Major reservoir of infection. • transmitting to their children- increasing the infant&child mortality rate. • Women as a group less access to medical care&potent ART agents.

6. PathogenesisHIV on TB • TB.Disease-Progression of recent infection/ Reactivation of LATENT infection/ Exogenous reinfection. • CD4+ T lymphocytes producing IFN- - A central role in Immune defenses against MTB. • HIV-causes selective depletion of CD4+ • Defects in Macrophage & Monocyte function

7. PathogenesisTB on HIV • MTB-elicits the production of pro inflammatory cytokines(TNF) which up regulates the Intracellular HIV replication. • HIV viremia increases. • Further reduction of CD4+ counts. • Progression of HIV disease.

8. Clinical Features Pulmonary Kochs • Active TB develops early in the course of HIV infection. • 60-80% PTB & 30-40% Extra Pulmonary. • Clinical features vary with CD4+ count. • High CD4+(>300) - Typical PTB manifestations. • Low CD4+ - Disseminated disease;Atypical presentations;lower lung infiltrations (high incidence of Mycobacteremia->25%) • PTB occurring in late stage of HIV disease- CXR may be normal in 40% cases. • Advanced HIV- PTB may occur with TB elsewhere in the body.

9. Clinical Features Extra Pulmonary Kochs • Constitutes 70% of HIV-related TB cases when the CD4+ count < 300. • TB lymphedinitis (peripheral,mediastinal,abdominal)-most common • Features similar in both HIV infected & Immunocompetent but in TWO exceptions– 1) TB lymphadenitis(severe immuno-suppression)-may be acute resembling Acute pyogenic lymphadenitis. 2)Abdominal TB-Visceral lesions & intra abdominal lymphadenopathy with necrosis.

10. Clinical Features Extra Pulmonary Kochs • Bone marrow is also a common site – Granulomas in 60% advanced HIV cases. • CNS : TUBERCULOMA is one among the various CNS manifestations leading to Seizures in HIV patients- ~ 13.04% • TB meningitis may resemble bacterial meningitis-CSF may be normal. • Pericardial Effusions constitute ~ 11%

11. TBM • Incidence 5-7% of patients infected with HIV • Acute to subacute illness • Duration of symptoms may vary from 5 days –9months • Presenting features • fever, can be absent • Headache ,photophobia in 15-20% • Drowsiness and meningism in 20% of cases • Less common features • Cranial nerve palsies, • Visual symptoms • Focal neurological deficit • B/L papilledema, raised ICT

12. Matted cervical TB lymphedinitis

13. Tuberculous Lymphedinitis

14. Beaded AFB- FNAC CLN

15. MOTT in HIV • Infections with atleast 12 different types have been reported.(CD 4 + < 50). • Most common is with MAI complex. • Prior infection with MTB decreases the risk of MAC infection. • Can cause Endo bronchial lesions, abdominal pain, diarrhoea & lymphadenopathy. •  by blood cultures/ tissue culture. • Rx Clarithromycin + Ethambutol

16. Investigations & Diagnosis • Sputum microscopy ( ZN Staining). • Sputum for AFB+ ve in 40-67% of PTB. • Cultures+ ve in 74-95% . • Sputum+ decreases with low CD4 counts. • 5% of HIV+ve PTB patients have sputum+ve despite normal CXR. • Cultures are essential to increase the yield. • Blood cultures for MTB+ve in 15% of HIV-TB cases.

17. Acid-Fast bacilli in Sputum

18. Chest Radiograph • CXR features varies with CD4 levels. • CD4> 300 /cu mm:- The pattern is similar as reactivation TB involving upper lobes with cavitation/infiltrates • CD4<300/cu mm:- The patern is difuse or lower lobe Bilateral reticulo nodular infiltrates or milliary pattern. • Pleural effusions • Bilateral hilar/mediastinal adenopathy. • Pericardial effusions

19. LEFT UPPER LOBE TB

20. Before treatment

22. AFTER TREATMENT

23. CLINICAL /CXR/SPUTUM DIFFERENCES IN PTB IN EARLY & ADVANCED HIV

24. MANTOUX • More than 5 mm considered as positive • 7-10% of Mx +ve HIV patients develop active TB each year • 1% of Mx positive HIV - ve patients develop active disease • Mx is considered as routine test for screening all HIV+ve patients to start chemo prophylaxis. • Used as an adjunt to diagnose Childhood TB. • Limited value for diagnosing adult TB infection.

25. Other Investigations • Bronchoscopy : • BAL / Trans Bronchial Biopsy : Yield - 30 - 40 % • Rapid Diagnostic tests : • NAA: Nucleic acid amplification tests: 2 tests have • been approved by FDA- • 1) Amplified MTB Direct( MTD) • 2) Amplicor MTB test AFB POSITIVE + POSITIVE NAA = ACTIVE MTB AFB POSITIVE + NEGATIVE NAA = MOTT

26. Investigations- Extra Pulm. TB Lymph node biopsyCT/US guided aspirationsCT/US guided Biopsy of LIVER, Spleen, Abdominal LNBone marrow aspiration/biopsySynovial fluid analysisSkin biopsy

27. (Treatment Regimens for Tuberculosis-WHO) Recommended Regimen Tx Category Intensive Phase Continuation Phase 2 EHRZ 1 4 HR 11 2 SHRZE + 1 EHRZ 5 HRE 111 2 HRZ 5 HRE

28. Recommendations • ATT plus one of the following: • AZT / LAM / EFZ • AZT / LAM / ABC • AZT / LAM / SQV/ r • HAART after TWO months of ATT: • AZT / LAM / EFZ • AZT / LAM / ABC • AZT / LAM / SQV/r • ATT plus CD4 Monitoring; start • HAART if indicated. ART for individuals with TB Situation PTB& CD4<50/mm or extra pulm TB PTB & CD4 50-200 or total lymp.count<1200 PTB & CD4 >200 or total lymph count >1200 NVP can be used only if no option, as RIF reduces its efficacy

29. Screening and Prevention • All HIVs should be screened yearly for TB with tuberculin skin test. • Induration of 5 mm or more is considered as positive. • All patients with positive tuberculin test should undergo clinical and radiological evaluation to exclude active TB. • Indications for prophylaxis for TB in HIV. 1.Induration of 5 mm or more at 48 hours on tuberculin skin test. 2. History of close contact with persons who have active TB. 3. Finding of anergy in patients with prolonged exposure M.tuberculosis (eg.in homeless shelter,Jail)

30. Ccontd Recommendations(as by CDC`s advisory committee for the Elimination of TB) • 1. INH 300mg OD for 6-9 months. • 2.INH twice weekly for 9 months(minimum 76 doses). • 3. RIF+PZA daily for 2 months (Minimum 60 doses) in patients receiving NNRTI`s or Pis • 4 RIF 600 mg OD for 6-12 months • 5. Completion of therapy is based on the total number of doses received, not on duration of therapy alone. • Prophylaxis in patients with MDR TB PZA+fluroquinolone daily for 12 months PZA+ETB daily for 12 months.

31. thank you