1. HIV/TB – Case Studies David Schlossberg, MD, FACP Medical Director, TB Control Program Philadelphia Department of Health

2. A 23 year-old African-American man presents with a 3-week history of fever, cough and 15 pound weight loss. He admits to IVDA. Physical exam is unremarkable except for fever. Routine cultures are negative, but AFB smear of sputum is positive. HIV serology is positive, with CD4 = 120. Case # 1

3. TB in AIDS – Be suspicious! Often initial manifestation of AIDS ANY respiratory symptoms –Suspect even with clear CXR Subclinical: NO resp symptoms and clear CXR – Ten Tanzanian patients (2%) with CD4 >200 Cultures positive in 10/10 Smears negative in 7/10 Mtei et al, Clin Infect Dis 2005;40:1500-7

4. TB in Advanced AIDS Frequently atypical: –CXR: clear, mid and lower lung zones, effusion, adenopathy –Extrapulmonary involvement common – up to 70%: lymphadenopathic, meningeal, hepatic, renal, pleural, cutaneous, spinal, miliary –PPD negative > 60% –Exogenous reinfection possible May > reactivation in some sub-groups

5. Anti-TB Rx in HIV Same as in HIV- negative patients, except: –Avoid once-weekly continuation phase –Avoid twice-weekly Rx if CD4 <100 –Nine months if culture positive after 2 mos –Six-month minimum, even for culture-negative Good response to therapy; early mortality may be high, but relapse rate < 5% Drug interactions (rifamycins) (www.cdc.gov/nchstp/tb/pubs/mmwrhtml/maj_guide.htm

6. A 29 year-old Hispanic woman with AIDS is on HAART. Her viral load is undetectable, and her CD4 count is 550. She was recently exposed to a cousin with TB, and her PPD is 17x20mm. She is asymptomatic, and her CXR is normal. She just found out she is pregnant. Case # 2

7. LTBI in HIV HIV and TB feed on each other –Immunosuppression is a risk for progression to TB –MTB induces replication of HIV Progression of LTBI to TB disease: –Nosocomial outbreak: 35% within 60 days –10% per year (vs. 10% lifetime risk if HIV-negative)

8. Therefore, treat LTBI aggressively –Pregnancy - any stage –Even with history of prior treatment –Even for contacts with negative PPD –9 months preferable to 6 months

9. Case # 3 A nineteen-year-old white male IVDA presented with cavitary pulmonary TB and was found to be HIV-positive (CD4 = 275). Both HAART and anti-TB Rx were initiated, with good clinical response. However, after 3 weeks, he developed fever, new pulmonary infiltrates and intrathoracic lymphadenopathy.

10. www.milartgl.com/HTML/

11. Lung infiltrate Lymphadenitis Intracranial tuberculoma Subcutaneous abscess Etc., etc., etc. Immune Reconstitution Syndrome (Paradox, “HAART Attacks”) HAART + anti-TB Rx: up to 35%

12. Vidal J, et. al. Rev. Inst. Med. Trop. S. Paulo vol.45 no.3 São Paulo May/June 2003

13. http:// www.itg.be/itg/DistanceLearning/LectureNotesVandenEndenE/imagehtml/ppages/CD_1082_013c.htm Subcutaneous abscess – Immune Reconstitution in patient with AIDS And Miliary TB, on HAART

14. Management of IRIS Rule out other causes Continue ART and anti-TB Rx Treat symptomatically –NSAIDS –Corticosteroids

15. Try to Prevent IRIS: Already on ART – just add anti-TB Rx Simultaneous Dx of HIV plus TB: –CD4 > 350 - Start Anti-TB Rx + ART –CD4 < 350 - Rx TB; Delay ART 4-8 weeks CD4 < 50 - some would start both ART + Anti-TB Rx

16. Take-Home Points: HIV + TB TB is common Immunosuppression causes unusual presentations LTBI progression to TB is significant risk Drug interactions are frequent IRIS may mimic treatment failure or new infection

17. Thank You!