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HIV / AIDS & Opportunistic Infections

HIV / AIDS & Opportunistic Infections. www.hivma.org. Learning Objectives. HIV – the basics Epidemiology and screening New diagnosis and prognosis Antiretrovirals Opportunistic infections – clinical cases. Human Retroviruses. HTLV-1 Adult T-cell Leukemia, HAM/TSP

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HIV / AIDS & Opportunistic Infections

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  1. HIV / AIDS&Opportunistic Infections www.hivma.org

  2. Learning Objectives • HIV – the basics • Epidemiology and screening • New diagnosis and prognosis • Antiretrovirals • Opportunistic infections – clinical cases

  3. Human Retroviruses HTLV-1 Adult T-cell Leukemia, HAM/TSP HTLV-2 Possible association with HAM/TSP HIV-1 HIV-2 Extremely slow progression to AIDS HIV-1 Group M HIV-1 Group N HIV-2 HIV-1 Group O SIV (Chimpanzee) SIV (Sooty Mangabey)

  4. HIV Infection White Blood Cells Lymphocytes T - Lymphocytes CD4+ T – Lymphocytes (Helper) CD4+ T – Lymphocytes CCR5+ (Memory)

  5. % CD3 63 % CD4 4 % CD8 55 CD3, Abs 569 CD4, Abs 38 CD8, Abs 494 Normal CD4% >30% Normal CD4 >450 AIDS CD4 < 200 CD4% < 14% OI Malignancy Kaposi NHL Cervical cancer T-Cell Panel

  6. Who Should Be Tested? • Routine HIV screening for all individuals ages 13-64 in all health-care settings. • At least annual screening for high risk patients: • Injection drug use (sex partners) • Persons who exchange sex for money/drugs • MSM and sex partners of HIV infected persons • Heterosexuals (sex partner) with >1 sex partner since last HIV test • Repeat test before new sexual relationship.

  7. HIV Test • Routine HIV ELISA (HIV-1/O/2) - Positive  Western Blot • Rapid HIV ELISA - Negative  Routine HIV ELISA - Positive  Western Blot • Window Period: - Routine HIV ELISA ~3 weeks - HIV Quantitative PCR ~7 days

  8. HIV ELISA / WB CD4 count HIV Viral Load CBC w/ diff Comprehensive Chemistry Lipid profile Genotype resistance test Hepatitis A, B, C serologies RPR Toxoplasma serology Testing for GC/Chlamydia TST or IGRA HLA-B*5701 Urinalysis Thrush Genital & peri-anal lesions Pap smear Anal Pap smear (MSM) Lymphadenopathy Skin: KS lesions folliculitis psoriasis Neurologic: peripheral neuropathy neurosyphilis HAND / neuropsych testing Ophthalmologic (CD4 < 50) Initial Evaluation of New HIV

  9. Prognosis 3-yr probability of AIDS = AIDS defining illness or death, not CD4<200 http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf

  10. Primary Infection Sero-conversion CD4 Cell Count Intermediate Stage AIDS Plasma RNA Copies 1,000 CD4 Cells 200 4-8 Weeks Up to 12 Years 2-3 Years Natural Course of HIV Infection

  11. Opportunistic Infections – CD4 < 200 Oral candidiasis Pneumocystis pneumonia

  12. Opportunistic Infections – CD4 < 100 Candida esophagitis Toxoplasma encephalitis

  13. Opportunistic Infections – CD4 < 50 Disseminated cryptococcosis Kaposi sarcoma

  14. Opportunistic Infections – CD4 < 50 CMV Retinitis Molluscum contagiosum Many other… Disseminated Mycobacterium avium Progressive multifocal leukoencephalopathy Cryptosporidiosis & other protozoa

  15. AIDS Defining Illnesses Candidiasis Esophageal Tracheal, bronchial Cervical Cancer, invasive Coccidioides – disseminated Chronic diarrhea (>1 month) Cryptosporidia or Isospora Cryptococcus – extrapulmonary CMV Retinitis Other (not liver, spleen, LN) HSV Chronic ulcer (>1 month) Pulmonary, esophageal Histoplasma – disseminated HIV encephalopathy Kaposi’s sarcoma Lymphoma (NHL) Burkitt’s Immunoblastic Primary CNS Mycobacterium TB – any Other – disseminated/extrapulmonary Pneumonia Pneumocystis Recurrent bacterial (within 1 yr) PML NT Salmonella septicemia, recurrent Toxoplasmic encephalitis Wasting syndrome - HIV MMWR 1992; 41 (RR17)

  16. When to Start HAART? DHHS Guidelines 2011 (http://aidsinfo.nih.gov)

  17. Nucleoside RTI: Abacavir (Ziagen) Didanosine / ddI (Videx) Emtricitabine / FTC (Emtriva) Lamivudine / 3TC (Epivir) Stavudine / d4T (Zerit) Tenofovir (Viread) Zidovudine / AZT (Retrovir) Non-Nucleoside RTI: Efavirenz (Sustiva) Nevirapine (Viramune) Etravirine (Intelence) Rilpivirine (Edurant) Entry/Fusion Inhibitor: Enfuvirtide / T20 (Fuzeon) Maraviroc (Selzentry) Protease Inhibitors: Atazanavir (Reyataz) Darunavir (Prezista) Fosamprenavir (Lexiva) Inidinavir (Crixivan) Lopinavir/Ritonavir (Kaletra) Nelfinavir (Viracept) Ritonavir (Norvir) Tipranavir (Aptivus) Integrase Inhibitor: Raltegravir (Isentress) Combinations: Atripla (Tenofovir + FTC + Sustiva) Combivir (AZT + 3TC) Epzicom (Abacavir + 3TC) Trizivir (AZT + Abacavir + 3TC) Truvada (Tenofovir + FTC) Antiretrovirals

  18. HIV Replicative Cycle

  19. ART Basics • General concepts: • Need 3 active agents: (2 NRTI) + (NNRTI or PI or Integrase inhibitor) • Treatment is life-long. Discontinuing ART results in viral rebound. • Goal of therapy • HIV VL < 50 = “undetectable viral load” • ART Resistance • Baseline resistance • Suboptimal medication adherence (90-95% compliance) • Suboptimal pharmacokinetics • Suboptimal potency of the regimen • Resistant strains are “archived” = permanent • Common initial regimens: Atripla (Tenofovir + FTC + Sustiva) - QD Truvada + Reyataz + Norvir - QD Truvada + Isentress - BID Combivir + Kaletra - BID

  20. Can We Eradicate Infection? Nature Medicine 2003; 9:853-860

  21. Rash Any antiretroviral Mild to severe (SJS) First 2 months Nausea/Vomiting Any antiretroviral R/O hepatitis Symptomatic management Diarrhea Any, but usually PIs Symptomatic management Renal failure Tenofovir (Truvada/Atripla) First several months CNS/Psychiatric Efavirenz (Sustiva/Atripla) First several weeks Drug-Drug Interaction New prescriptions Fluticasone, Statins PPIs OTC St. John’s Wort Common adverse reactions

  22. When Should You Stop HAART? • Patient clearly non-compliant (active drug abuse) – not “stopping” and actually “starting” • Severe drug reaction: Abacavir hypersensitivity reaction – fever, rash, GI, and/or pulmonary symptoms within 6 weeks of initiation, association with HLA-B*5701. Lactic acidosis (ddI/d4T>AZT) – malaise, myalgias, non-specific symptoms or critically ill, pancreatitis/hepatitis, elevated serum lactate and acidemia. NNRTI hypersensitivity – occurs within 6 weeks of initiation, hepatitis (fulminant hepatic failure) and/or rash (Stevens-Johnson). Nevirapine hepatotoxicity risk factors: pregnancy, HBV/HCV, CD4 > 250 [F] or CD4 > 400 [M].

  23. HIV-Associated Dyslipidemia Fat Accumulation HIV Lipohypertrophy Increase abdominal fat Dorsocervical fat pad Metabolic Changes Increased Triglycerides Increased LDL Decreased HDL Insulin resistance

  24. Case #1 • 31 M with history of HIV presents with fevers and progressive DOE x 3 weeks. • He reports he was diagnosed with HIV about 10 years ago when he developed shingles. He never followed-up and has never been on HAART. • He does not know his last CD4 count or viral load.

  25. ROS: 20 lbs weight loss x1 year Night sweats for past month Diarrhea SH: Acquired by MSM Born & raised in Ohio Moved to AZ 2 yrs ago Visits homeless shelters Physical Exam: 101.80F 94 110/60 16 Pulse Ox 92% GEN – appears comfortable OP – thrush LUNGS – diffuse crackles ABD – soft, non-tender SKIN – no lesions MS – alert & oriented Case #1

  26. CXR

  27. Laboratory Results • CD3 87 • CD4 9 • CD8 75 • CD3, Abs 610 • CD4, Abs 64 • CD8, Abs 530 • HIV VL 500K

  28. Differential Diagnosis?

  29. Differential DiagnosisPneumonia in HIV • CAP – Pneumococcus, Influenza • Pneumocystis • TB • Coccidioides • Histoplasma • Cryptococcus

  30. Diagnostic Tests • Nasal Influenza swab - negative • Blood cultures - negative • Urine S.pneumonia antigen - negative • Sputum culture - normal flora • Sputum AFB smear - negative x3 • Sputum fungal smear - negative • Induced sputum PCP DFA - negative • Serum Cryptococcal antigen - negative • Coccidioides ELISA - negative

  31. Pneumocystis jiroveci • Subtle – symptoms for weeks to months • 90% with CD4 < 200 or CD4% < 15% • CXR findings variable – possibly negative • Negative CXR – role of HRCT • Diagnosis: • Induced Sputum DFA 50-90% • BAL DFA 90-99% • Transbronchial Bx 95+%

  32. PaO2 < 70 mmHg A-a > 35 mmHg Corticosteroids IV TMP/SMX IV Pentamidine PO TMP/SMX Clinda + Primaquine TMP/Dapsone Atovaquone Therapy • Clinical deterioration common within 3-5d of initiation of therapy, particularly in those not receiving corticosteroids. • Treatment failure if no improvement or worsening after at least 4-8d of therapy.

  33. Prophylaxis TMP/SMX, Dapsone, Atovaquone, Aero Pentamidine Stop prophylaxis when CD4 > 200 x 3 months 20 Prophylaxis: • Requires QD TMP/SMX, not QMWF 10 Prophylaxis: - CD4 < 200, or CD4% < 14% - History of thrush - AIDS defining illness

  34. Pneumonia in HIV • S.pneumoniae remains most common cause. Other organisms = H.influenza, S.aureus, P.aeruginosa. • Give Pneumovax and revaccinate when CD4 > 200. • Pulmonary TB in HIV patients with CD4 > 350 similar to that in non-HIV infected individuals. • Pulmonary TB in AIDS patients – typically no cavitation, appears more like consolidation or diffuse infiltrates. • TB in HIV patients – at higher risk of extrapulmonary disease at all CD4 counts. • AIDS patients and HIV patients with unknown CD4 count presenting with pneumonia  Respiratory Isolation.

  35. Coccidioides • Common cause of pneumonia in Arizona • CD4 < 250, past history NOT a risk factor • Radiographs – diffuse or focal infiltrates • Serologic tests ~60% sensitivity • Diagnosis – fungal culture, smear ~40% • Disseminated disease frequent: lymph nodes, meningitis, skin

  36. Case #2 • 42 M with history of IVDA presents with complaints of intermittent fever, HA, and increasing lethargy over the past 4 weeks. • He is subsequently found to be HIV + with a CD4 count of 23. • He reports having been in and out of jail on several occasions. • Poor historian, appears confused.

  37. MRI Brain

  38. Differential Diagnosis?

  39. Differential DiagnosisCNS Lesions in HIV • Toxoplasma Encephalitis • Primary CNS Lymphoma • Bacterial brain abscess • Progressive Multifocal Leukoencephalopathy • TB • Cryptococcus • CMV Encephalitis • Chagas disease

  40. Diagnostic Tests • Blood cultures - negative • Serum Cryptococcal antigen - negative • Toxoplasma IgG positive, IgM negative • LP: 8 WBC (90%L), 64 G, 60 P • Toxoplasma DNA PCR negative • CMV and JC virus PCRs negative • TB PCR negative • Cryptococcal antigen negative

  41. 80% have CD4 < 100 95+% Toxoplasma IgG+ ~30% single lesion CSF PCR sensitivity 50% Definitive dx = brain bx Therapy – 6 wks Pyrimethamine/Sulfadiazine Pyrimethamine/Clindamycin 10 Prophylaxis (CD4 < 100) DS TMP/SMX QD Pyrimethamine/Dapsone Toxoplasma Encephalitis Adapted from http://www.cdc.gov

  42. Cryptococcal Meningitis • Majority of cases occur in patients with CD4 < 50. • Classic meningeal symptoms/signs (neck stiffness & photophobia) infrequent. • Disseminated disease common: pulmonary, blood, skin. • Elevated opening pressure > 75% (> 20cm H2O). • Cryptococcal antigen 90+% sensitive (serum & CSF). • Treatment: Ampho B +/- Flucytosine x 2wks  Fluconazole Repeated LP for symptomatic elevated ICP

  43. Case #3 • 29M diagnosed with AIDS ~2 months ago (Thrush), started on HAART 6 weeks ago. • Presents with acute onset of fever, cough, pleuritic chest pain, and dyspnea. • He looks well despite Temp 102.60F. Exam only notable for L sided bronchial breath sounds. • CD4 count 29  146.

  44. CXR

  45. CT Chest

  46. Blood cultures Fungal BC Mycobacterial BC Serum Cryptococcal Ag Urine Histoplasma Ag RPR LDH 188 WBC 12.9 (88%N) BAL Bacterial Cx - BAL Fungal Cx - BAL Mycobacterial Cx - BAL PCP DFA - BAL Viral Cx - BAL Cytology: WBC/RBC, benign bronchial cells Transbronchial Bx: Bronchial mucosa - crush artifact Laboratory Studies

  47. Diagnosis?

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