1 / 54

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

abril
Download Presentation

HIV / AIDS & Opportunistic Infections

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 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?

More Related