1 / 36

DHS/HIV/ARV Rx/PP

HIV/AIDS Opportunistic Infection Update David H. Spach, MD Medical Director Northwest AIDS Education and Training Center Associate Professor of Medicine Division of Infectious Diseases University of Washington, Seattle. DHS/HIV/ARV Rx/PP. Opportunistic Infection: Update.

urania
Download Presentation

DHS/HIV/ARV Rx/PP

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. HIV/AIDS Opportunistic Infection UpdateDavid H. Spach, MDMedical DirectorNorthwest AIDS Education and Training CenterAssociate Professor of MedicineDivision of Infectious DiseasesUniversity of Washington, Seattle DHS/HIV/ARV Rx/PP

  2. Opportunistic Infection: Update • Pneumocytis pneumonia • Toxoplasmosis • Mycobacteriumavium complex • Cytomegalovirus • Esophageal candidiasis • Cryptococcal meningitis • Cryptosporidiosis DHS/HIV/ARV RX/PP

  3. Pneumocystis Pneumonia DHS/HIV/PP

  4. Pneumocystis PneumoniaNew Developments • Basic Science- Pneumocystiscarinii changed to Pneumocystisjiroveci*- Characterization of 14- demethylase enzyme • Epidemiology- Reactivation of latent organisms versus acute acquisition • New Diagnostics- PCR-based test on oral washes • Resistance to TMP-SMX- Mutations identified in dihydropterate synthase (DHPS)- Presence of mutation associated with increased mortality • Immune Reconstitution- Marked inflammatory response about 15-30 days after HAART *Pronounced “yee row vet zee” & named after the Czech pathologist Otto Jirovec DHS/HIV/Clin Manifestations/PP

  5. Pneumocystis: Lanosterol 14- Demethylase Ergosterol Biosynthesis Lanosterol 14- Demethylase (Erg 11) Inherent Azole Resistance Ergosterol Cytoplasmic Membrane From: Morales IJ, et al. Am J Respir Mol Bio 2003;Feb 26 (e-Publication).

  6. Pneumocystis in Asymptomatic Individuals • Methods- N = 16 HIV-infected patients- BAL samples (n = 47)- Genotyping of P. jiroveci • Results- 35/47 from patients positive for P. jiroveci- 7 with P. jiroveci 7-10 months after acute PCP; all 7 had different genotype at follow-up than found during acute PJP- TMP-SMX did not always clear infection From: Wakefield AE et al. J Infect Dis 2003;187:901-8. DHS/ HIV/PP

  7. Discontinuation of PCP ProphylaxisRecommendations from USPHS/IDSA Guidelines Criteria Setting Primary Prophylaxis Secondary Prophylaxis CD4 > 200 for > 3 months CD4 > 200 for > 3 months From: MMWR 2001;50 (RR-11):1-52. DHS/HIV/OIs/PP

  8. Pneumocystis & Immune Reconstitution • Timing- Typically 7 to 30 days after starting HAART • Clinical Manifestations- High grade-fever- Patchy infiltrates- BAL: few Pneumocystis organisms, severe inflammatory foci • Treatment- Restart corticosteroids From: Wislez M et al. Am J Respir Crit Care Med 2001;164:847-51. DHS/ HIV/PP

  9. Toxoplasmosis DHS/HIV/PP

  10. Discontinuation of Toxoplasmosis ProphylaxisRecommendations from USPHS/IDSA Guidelines Criteria Setting CD4 > 200 for > 3 months CD4 > 200 for > 6 months and Completed Initial Rx and Asymptomatic for Toxo Primary Prophylaxis Secondary Prophylaxis From: MMWR 2001;50 (RR-11):1-52. DHS/HIV/OIs/PP

  11. Mycobacteriumavium Complex DHS/HIV/PP

  12. MAC: Immune Reconstitution Syndrome • Low CD4 (< 50): more severe illness; fevers, weight loss, leukocytosis, positive blood cultures (Race, Lancet, 1998) • High CD4 (> 100-150): fewer systemic symptoms, more localized suppurative disease (Phillips, JAIDS, 1998) • Treatment: continue HAART and MAC therapy, NSAIDS, steroids (for severe symptoms), local surgery? Slide From Bob Harrington, MD DHS/ID/Cases/PP

  13. Discontinuation of MAC ProphylaxisRecommendations from USPHS/IDSA Guidelines Criteria Setting Primary Prophylaxis Secondary Prophylaxis CD4 > 100 for > 3 months CD4 > 100 for > 6 months and Completed 12 months MAC RX and Asymptomatic for MAC From: MMWR 2001;50 (RR-11):1-52. DHS/HIV/OIs/PP

  14. Cytomegalovirus DHS/HIV/PP

  15. Valganciclovir (Valcyte)Induction Therapy for CMV Retinitis Study Design Week 4: Non-progression • Methods - N = 160 - Newly diagnosed CMV retinitis • Regimens - Valganciclovir: 900 mg PO bid x 21d, 900 mg PO qd x 7d - Ganciclovir: 5 mg/kg IV bid x 21d, 5 mg/kg IV qd x 7d From: Martin DF et al. N Engl J Med 2002;346:1119-26. DHS/OIs/HIV

  16. Discontinuation of CMV ProphylaxisRecommendations from USPHS/IDSA Guidelines Criteria Setting Primary Prophylaxis Secondary Prophylaxis Not Applicable CD4 > 100-150 for > 6 months and No evidence of active disease and Regular ophtho examinations From: MMWR 2001;50 (RR-11):1-52. DHS/HIV/OIs/PP

  17. Esophageal Candidiasis DHS/HIV/PP

  18. Fluconazole: Mechanism of Action Ergosterol Biosynthesis Lanosterol 14- Demethylase Fluconazole Ergosterol Cytoplasmic Membrane

  19. Fluconazole: Mechanism of Resistance Ergosterol Biosynthesis Altered Binding Site Lanosterol 14- Demethylase Fluconazole Ergosterol Efflux Pump Fluconazole

  20. Caspofungin: Mechanism of Action Beta-Glucan Synthase Beta-Glucan Synthase Echinocandins Glucan Fibrils Cytoplasmic Membrane Cell Wall

  21. Fluconazole-Resistant Esophageal CandidiasisTreatment Options • Fluconazole (Diflucan) 400-800 mg PO qd • Itraconazole Solution (Sporonox) 100 mg PO bid • Caspofungin (Cancidas) 50-70 mg IV qd • Amphotericin B 0.3-0.7 mg/kg IV qd • Liposomal Ampho B ? Optimal Dose Dose Drug DHS/HIV/OIs/PP

  22. Candida Species: In Vitro Testing • C. albicans- Fluconazole (S)- Fluconazole (R) • C. glabrata- Fluconazole (S)- Fluconazole (R) Organism Caspofungin (MIC 50) Fluconazole (MIC 50) 0.1640 1.2540 0.200.20 0.200.40 From: Vazquez JA et al. Antimicrob Agents Chemo 1997;41:1612-4. DHS/HIV/OIs/PP

  23. Caspofungin (Cancidas) vs. AmphotericinTreatment of Esophageal Candidiasis Study Design Clinical & Endoscopic Response (ITT) • Methods - N = 128 (123 HIV-infected*) -*Mean CD4 = 84 cells/mm3 - Documented Candida esophagitis - Randomized, double-blind study • Regimens (14 days) - Caspofungin: 50 mg IV qd - Caspofungin: 70 mg IV qd - Amphotericin B: 0. 5 mg/kg IV qd From: Villanueva A et al. Clin Infect Dis 2001;33:1529-35. DHS/OIs/HIV

  24. Fluconazole-Resistant Esophageal CandidiasisTreatment with Caspofungin Study Design Clinical Response • Methods - N = 14 - Esophageal candidiasis - Failed Fluconazole 200 mg/d or - Isolate with Fluconazole MIC > 16 • Regimens - Caspofugin • Response - Defined as resolution of all symptoms and substantial improvement on endoscopy From: Kartsonis NK et al. J Acquir Immune Defic Syndr 2002;31:183-7. DHS/OIs/HIV

  25. Cryptococcal Meningitis DHS/HIV/PP

  26. Cryptococcal Meningitis: 14-Day Induction Therapy Suspected or Confirmed Cryptococcal Meningitis*Serial LPs ifOpening Pressure > 200 mm H2O 1 3 2 Ampho B0.7-1.0 mg/kg/d+5-Flucytosine100 mg/kg/d Ampho B0.7-1.0 mg/kg/d Fluconazole400-800 mg/d Initial LP: Reduce opening pressure by 50%Daily LPs: Maintain opening < 200 mm H2OCessation of LPs: once opening pressure normal for several consecutive days DHS/OI/PP

  27. Cryptococcal Meningitis: 10 Week Consolidation Therapy Cryptococcal Meningitis2 Week Lumbar Puncture with Negative Culture 1 3 2 Fluconazole400 mg/d Ampho B0.7-1.0 mg/kg/d Itraconazole400 mg/d DHS/OI/PP

  28. Cryptococcal MeningitisCSF Pressure Post-Treatment & Outcome Study Design Week 2 Outcome: Clinical Failure • Methods - N = 161 - HIV-infected - Cryptococcal meningitis - Retrospective analysis - Week 2 outcome - Compared pre/post CSF OP • Baseline - 60% > 250 mm H2O - 30% > 350 mm H2O From: Graybill JR et al. Clin Infect Dis 2000;30:47-54. DHS/OIs/HIV

  29. Cryptococcal MeningitisFeatures of High (> 350 mm H2O) CSF Pressure • Clinical Features - More frequent headache & meningismus - More frequent papilledema & abnormal reflexes • Lab Features - Higher CSF Cryptococcal antigen - More frequent positive India ink • Outcome Features - Reduced short-term survival if CSF pressure > 250 From: Graybill JR et al. Clin Infect Dis 2000;30:47-54. DHS/OIs/HIV

  30. Cryptococcal MeningitisStrategies for Reducing High CSF Pressure • Lumbar Puncture - 18 gauge needle - Drained until CSF pressure < 200 mm H2O - Repeat as often as needed • Medical Therapy - Corticosteroids? - Acetazolamide? - Mannitol? From: Graybill JR et al. Clin Infect Dis 2000;30:47-54. DHS/OIs/HIV

  31. Cryptococcal MeningitisAcetazolamide for Reducing High CSF Pressure • Background - N = 22 Thai HIV-infected - Confirmed cryptococcal meningitis - CSF pressure > 200 mm H2O - Randomized, placebo-controlled • Regimens - Acetazolamide versusPlacebo • Results - No benefit, trial stopped secondary adverse effects From: Newton PN et al. Clin Infect Dis 2002;35:769-72. DHS/OIs/HIV

  32. Cryptosporidiosis DHS/HIV/PP

  33. Cryptosporidiosis in HIV/AIDSCombination Therapy • Study Design- N = 13- CD4 count < 100 cells/mm3 (median 30 cells/mm3) - Chronic cryptosporidiosis (median duration 12 weeks) • Regimen- Paromomycin 1g bid + Azithromycin 600 mg qd x 28d followed by Paromomycin 1g bid x 12 weeks From:Smith NH et al. J Infect Dis 1998;178:900-3. DHS/HIV/Clin Manifestations/PP

  34. Cryptosporidiosis: Combination Therapy Stool Frequency Oocyst Excretion From: Smith NH et al. J Infect Dis 1998;178:900-3. DHS/HIV/OIs/PP

  35. Cryptosporidiosis:Nitazoxanide Therapy Study Design Response • Methods - N = 100 (50 adults, 50 children) - Cryptosporidiosis diarrhea - HIV testing not performed • Regimens* - Nitazoxanide: 500 mg bid x 3d - Placebo: bid x 3d Children- Age 4-11 yrs: 200 mg bid x 3d- Age 1-3 yrs: 100 mg bid x 3d From: Rossignol J-F et al. J Infect Dis 2001;184:103-6. DHS/OIs/HIV

  36. Cryptosporidiosis: Treatment • HAART • Antimicrobial Agents- Paromomycin- Azithromycin- Nitazoxanide • Antimotility Agents From: Chen X-M, et al. N Engl J Med 2002;346;1723-31. DHS/HIV/ARV RX/PP

More Related