1. Common Opportunistic Infections in HIV Patients, Part 2 Chris Farnitano, MD Thursday, October 8, 2009 Noon Conference

2. Objectives Discuss most common opportunistic infections (OIs): Dx and Rx Discuss immune reconstitution disease Review primary OI prophylaxis

3. Forms

4. Case Study SP 27 yo male seen in clinic in June 2009 Meds: unboosted atazanavir + Truvada since 1/09; ranitidine T cells 5; viral load 30,000 Why is his anti-HIV cocktail failing?

5. Case Study SP Ritonavir added to boost atazanavir Patient instructed to take ranitidine in AM only and antivirals in PM Blood Cx for AFB, HIV genotype ordered

6. Case Study SP Admitted to Kaiser August, 2009 with diffuse warm, tender lymphadenopathy Biopsy performed, read as suspicious for lymphoma Transferred to CCRMC after 7 days on clarithromycin, ethambutol, rifabutin T Cells 209, viral load 726 What is patient’s diagnosis?

7. What are the most common OI’s? Cohort Studies in pre-triple therapy era: Candida Pneumocystis Carinii Cytomegalovirus Mycobacterium Avium Complex Pneumocystis - second episode Toxoplasmi gondii Herpes zoster

8. Causes of death, PHC HIV clinic 2007-9 RH: Crypto meningitis TW: street drug overdose SA: sepsis, pneumonia and massive hemoptysis DW: metastatic prostate ca RP: CVA, laryngeal ca VA: PML (progressive multifocal leukencephalopathy) AM: bacterial pneumonia, ETOH cirrhosis, wasting

9. OIs diagnosed, PHC HIV clinic 2005-9 PCP pneumonia Esophageal Candidiasis Herpes Simplex Herpes Zoster M. Kansasii immune reconstitution pneumonia Mycobacterium Avium Complex (MAC) Cryptococcal Fungemia, meningitis Histoplasmosis PML

10. Effect of HAART on Opportunistic Infection Incidence Most OI’s have declined 80-90% OI’s seen now mostly in 3 groups undiagnosed HIV+ not in care or not adhering to therapy long time “battle-scarred warriors” failing after a long history of multiple regimens

11. 50-200 T Cells: Pneumocystis Carinii Pnuemonia Toxoplasmosis Cryptococcus

12. Toxoplasmosis

13. <50 T Cells CMV Retinitis Mycobacterium Avium Complex Cryptosporidiosis Progressive Multifocal Leukencephalopathy

14. PML

15. Ockham's razor does not apply for advanced AIDS -often multiple diagnoses present simultaneously ie PCP, CMV, KS, Cocci 12% of bacterial pneumonias also have PCP 10% of PCP pneumonia complicated by bacterial infection search for second etiology if patient not improving

16. Immune reconstitution diseases (HAART attacks) MAC adenitis CMV TB PCP

17. Case Study SP Diagnosis: Immune Reconsitution MAC AFB blood culture from June grew out MAC on 8/12 (hospital day #13) Also: Perianal herpes Squamous cell carcinoma-in-situ, buttock Vancomycin-resistant enterococcus, groin

18. Primary OI prophylaxis PCP -T cells <200 or thrush Toxo -T cells <100 and +Toxo titer MAC - Tcells <50 TB – INH x 9 months if PPD >5mm or quantiferon-TB positive

19. Toxo prophylaxis Septra SS or DS qd or DS TIW Septra Desensitisation: 1cc qd x 3d, then 2cc qd x 3d, then 5ccqd x 3d, then one SS tab qd Dapsone 100mg qd +pyramethamine 50mg qweek + leukovorin 25mg qweek Atovaquone 1500mg qd

20. MAC prophylaxis Zithromax 600mg x 2 tabs qweek reduces infection rate 59% Also seems to reduce risk of PCP

21. Cytomegalovirus Retinitis - Who Gets It? Rare above 50 T Cells Reactivation disease: most HIV patients CMV IgG+ (90% of gay HIV+ men) 90% of CMV disease is retinitis

22. Cytomegalovirus Retinitis - Symptoms painless, progressive visual loss unilateral blurry vision floaters

23. Cytomegalovirus Retinitis - Signs coalescing white perivascular exudates surrounded by hemorrhage brushfire pattern or tomato and cheese pizza

24. Cytomegalovirus Retinitis

26. Cytomegalovirus Retinitis - Diagnosis if you suspect it, obtain ophthalmologist confirmation within 24-48 hrs.

27. Cytomegalovirus Retinitis - Treatment Valgancyclovir 900mg PO BID x 21 days, then qd Adverse effects: neutropenia ANC<500 in 15% thrombocytopenia anemia 50%: nausea, vomiting, abdominal pain or diarrhea

28. Gangcyclivir intraocular implant Consider in addition to systemic therapy: Surgically implanted depo device Effective for 6 months Replace at 6 months if still not immune reconstituted Consider for sight threatening lesions near the central visual field

29. Mycobacterium avium Complex - Who gets it? T Cells <50 screen with blood culture for AFB x 1 q 3 months to detect subclinical disease

30. Mycobacterium avium Complex - Symptoms fever, night sweats weight loss diarrhea

31. Mycobacterium avium Complex - Signs anemia Neutropenia Fever Diarrhea wasting

32. Mycobacterium avium Complex - Diagnosis Blood culture usually positive if symptomatic but takes weeks to grow If need to know sooner then do bone marrow Bx Positive sputum culture usually colonization, not active disease Positive stool culture may be colonization, not active disease, mucosal bx more indicative of disease

33. MAC-filled macrophages in spleen

34. Mycobacterium avium Complex - Treatment Clarithromycin 500mg BID + Ethambutol 15mg/kg/d +/- Rifabutin 300mg qd Treatment failure rate is high without immune reconstitution drug toxicity development of resistance

35. Case Study SP After 4 months of anti-MAC therapy + potent anti-HIV therapy: T Cells 71 viral load <48 Patient still hospitalized Large effusions persist Dubhoff tube required for feeding Diffuse chest/abdominal adenopathy persists MAC Cx’s show partial/complete resistance to all MAC drugs except clofazamine Prognosis?

36. Forms

37. Summary: Pyramid approach Prophylaxis simple: Septra and Zithromax Rule out TB in pneumonia with T Cells <200 Avoid treating PCP empirically An ounce of prevention pills is worth a pound of Treatment pills