Objectives Diagnose and manage common opportunistic infections (OIs) - PDF document

Objectives • Diagnose and manage common opportunistic infections (OIs) in HIV • Know the indications and preferred regimens for primary Opportunistic Infections and prophylaxis for OIs Immune Reconstitution • Understand the features and management of immune Inflammatory Syndrome reconstitution inflammatory syndrome (IRIS) • Understand the data regarding when to start ART in the setting of an acute OI Catherine Koss, MD Assistant Professor OIs and IRIS at MMA 2018: Division of HIV, Infectious Diseases, and Global Medicine Dec 6 Pulmonary disease (PCP, KS, TB) Dr. Laurence Huang December 7, 2018 Dec 7 Zoster and zoster vaccine Dr. Lisa Winston Dec 8 Tuberculosis Dr. Sarah Puryear CD4 count correlates with risk of specific OIs in Disclosures untreated HIV disease TB I have received grant funding from the National Institutes of Health and the VZV/Zoster 600 Gilead Research Scholars Program in HIV. 500 Pneumococcal/bacterial PNA CD4 cell count Lymphoma 400 Kaposi sarcoma 300 Pneumocystis PNA Toxoplasmosis MAC Histoplasmosis 200 Cryptococcosis CMV PML Cryptosporidiosis Primary CNS Candidal esophagitis 100 lymphoma 0 >500 200‐500 100‐200 50‐100 <50 CD4 count strata Adapted from Bartlett JG et al. Medical Management of HIV, 2012 1 | [footer text here]

With potent ART, incidence of OIs continues to decline Resources for OI management N = 63,541 U.S. patients in NA‐ACCORD, 2000‐2010 PCP Candidal esophagitis MAC https://aidsinfo.nih.gov/guidelines Ward 86 Management Recommendations http://hivinsite.ucsf.edu/InSite?page=md‐ward86‐index Buchacz K et al. JID 2016. We still see OIs in the U.S. among: Case 1 1) Patients newly diagnosed with HIV who present with an OI (late HIV dx) 44 y/o M with HIV • CD4 94 cells/mm 3 2) Patients who are aware of their HIV status but face barriers to taking ART • not on ART or prophylaxis 3) Patients for whom ART fails to achieve adequate immunologic/virologic 1 month of progressive dyspnea, • response non‐productive cough, fevers, night sweats, and weight loss CD4 <200 or OI at HIV diagnosis Globally United States, 2016 1 Exam: Afebrile, 90% RA Tuberculosis 40% 36% • • Diffuse crackles bilaterally and 33% #1 cause of AIDS deaths 27% mild wheezing 30% Cryptococcal meningitis 2 17% 20% Labs: WBC 8.3 • 223,000 cases in 2014 9% 10% • 181,000 deaths • LDH 386, Beta‐D‐glucan>500 0% • 15% of AIDS deaths • ABG: 7.44/35/59 on room air 13‐24 25‐34 35‐44 45‐54 55+ Age, years 1. CDC HIV Surveillance Supplemental Report 2018; 23(4). 2. WHO Cryptococcal Guidelines 2018. 2 | [footer text here]

CT Chest Case 1 continued • Started on empiric CTX/doxycycline + TMP‐SMX/prednisone • Could not obtain induced sputum • Bronchoscopy with BAL performed for microbiologic confirmation: - Bacterial culture: oral flora - AFB smear and culture: negative - PCP positive • TMP‐SMX + prednisone continued Which empiric therapy would you start? Pneumocystis pneumonia • PCP = Pneumocystis pneumonia A. Ceftriaxone + doxycycline • Caused by P. jirovecii B. TMP‐SMX + prednisone - ubiquitous fungus - P. carinii now refers to the organism that infects rodents C. Ceftriaxone + doxycycline + TMP‐SMX + prednisone • 90% of cases occur at CD4 <200 cells/mm 3 D. RIPE - Most cases with CD4 <100 E. Ganciclovir • Subacute presentation of nonproductive cough, progressive dyspnea, fever • Hypoxemia; normal lung exam or dry crackles DHHS OI Guidelines 2018. 3 | [footer text here]

See Dec 6 talk by PCP: Treatment PCP: Imaging Dr. Laurence Huang Disease Preference Regimen Potential toxicities • CXR pattern: Adverse effects are common severity (21 days then start secondary ppx) - Classic: bilateral, reticular interstitial infiltrates  Rash, fever, leukopenia, Moderate to Preferred TMP + SMX (weight‐based) thrombocytopenia, azotemia, severe Adjust dose for renal function hepatitis, hyperkalemia - Pleural effusions, cavitation, intrathoracic adenopathy are rare IV  PO after clinical improvement • Try to “treat through” reactions if PaO2 <70 possible - May be normal • Desensitization protocols available A‐a grad  35 Steroids within 72 hours for patients with allergy Prednisone 40 mg BID x 5 days • STOP and do not re‐challenge if pt Prednisone 40 mg daily x 5 days has Stevens‐Johnson syndrome or Prednisone 20 mg daily x 11 days toxic epidermal necrolysis • If normal CXR  high‐resolution CT for ground glass - High negative predictive value Mild Preferred TMP + SMX (weight‐based) PaO2  70 A‐a grad <35 • Cystic disease – increased risk of spontaneous pneumothorax • PTX should prompt high suspicion for PCP DHHS OI Guidelines 2018. DHHS OI Guidelines 2018. NIH‐UC Expert Panel for Corticosteroids as Adjunctive Therapy for PCP. NEJM 1990. PCP: Laboratory diagnostics PCP: Treatment failure • Elevated LDH: Common, non‐specific • If patient not improving after 3 days, is this treatment failure? • Plasma β‐D‐glucan - Generally no; early worsening at 3‐5 days is common - Sensitivity 92%, specificity 65% 1 - (1‐3)‐β‐D‐glucan is a component of the cell wall of most fungi - Wait at least 4‐8 days for a clinical response before switching therapy for clinical failure • Other causes of positive BDG: candidiasis , histoplasmosis, cryptococcus • Dx requires microbiologic confirmation • Evaluate for concurrent infections as a cause for clinical failure • No culture system for P. jirovecii - consider repeat bronch • Sensitivity of stained respiratory specimen depends on method, experience of lab - Induced (not expectorated) sputum : <50‐90% - BAL : 95‐100% - Organisms detectable for days‐weeks after rx • Do not delay empiric therapy PCP cysts in silver‐stained 1. Sax P et al. CID 2011. DHHS OI Guidelines 2018. bronch specimen. CDC PHIL. 4 | [footer text here]

PCP: Treatment Case 2 continued Disease Preference Regimen Potential toxicities severity (21 days then start secondary ppx) Adverse effects are common  Rash, fever, leukopenia, Moderate to Preferred TMP + SMX (weight‐based) thrombocytopenia, azotemia, severe Adjust dose for renal function • CT shows bulky necrotic nodes in mediastinum and retroperitoneum hepatitis, hyperkalemia IV  PO after clinical improvement • Try to “treat through” reactions if PaO2 <70 possible A‐a grad  35 Steroids within 72 hours • Desensitization protocols available Prednisone 40 mg BID x 5 days for patients with allergy Prednisone 40 mg daily x 5 days • STOP and do not re‐challenge if pt Prednisone 20 mg daily x 11 days has Stevens‐Johnson syndrome or toxic epidermal necrolysis  Anemia, rash, fever, diarrhea Alternative #1 Clindamycin + primaquine + steroids (rx failure/ Check G6PD toxicity)  Irreversible renal and pancreatic Alternative #2 Pentamidine IV + steroids Historically preferred. Higher mortality islet cell toxicities, arrhythmias, in retrospective studies. We avoid. hypoglycemia, hypotension Mild Preferred TMP + SMX PaO2  70  Anemia, rash, fever, diarrhea Alternative Clindamycin + primaquine. Check G6PD  Rash, fever A‐a grad <35 Dapsone + TMP. Check G6PD  HA, nausea, diarrhea, rash, LFTs Atovaquone BID with food DHHS OI Guidelines 2018. NIH‐UC Expert Panel for Corticosteroids as Adjunctive Therapy for PCP, NEJM 1990. Ward 86 Management Recommendations, HIV InSite. Case 2 CT chest 40 yo M with HIV (CD4 420 and VL <40 on DTG + FTC/TAF 1.5 years ago), • Numerous pulmonary nodules in UL and RML, largest 1.8 cm lost to follow‐up. Presents with several weeks of progressive symptoms: diffuse abdominal pain, fever, diarrhea (10x per day), and cachexia • PMH : - HIV diagnosed 2 years ago, CD4 380, VL 80K • Social History : - Immigrated to CA from Mexico 20 years ago - Marginally housed • Labs : - Hgb 7, normal LFTs, Cr 1.0 - CD4 48 (6%), VL pending 5 | [footer text here]

What is the most likely diagnosis? Case 2 continued • Stool cultures and O&P ‐ Giardia Ag positive A. Cytomegalovirus (CMV) • Serum Cryptococcal Ag (CrAg) ‐ negative • Urine Histoplasma Ag ‐ negative B. Mycobacterium tuberculosis (TB) • Sputum AFB smear x3 ‐ negative C. Mycobacterium avium complex (MAC) • AFB blood cx drawn; started on empiric treatment for MAC D. Lymphoma • Restarted ART: Dolutegravir + FTC/ TDF - switched from FTC/TAF due to drug interaction with rifabutin When to suspect Mycobacterium avium complex Syndromic differential can help predict pathogens in patients with CD4<50 Clinical: • Fever, weight loss, +/‐ diarrhea, Short DDx in AIDS: Short DDx in AIDS: +/‐ abd pain Fever + wasting + lymphadenopathy AIDS + pulmonary nodules Laboratory: Tuberculosis Disseminated MAC • CD4 <50 Fungal (Crypto, Tuberculosis • Elevated alkaline phosphatase Coccidioidomycosis) Disseminated fungal (Histo, Crypto) • Anemia/pancytopenia due to bone Kaposi sarcoma Lymphoma Lymphoma marrow infiltration Diagnostics: Short DDx in AIDS: • AFB blood cultures* AIDS + prolonged diarrhea • Sensitivity 91% for 1 AFB BCx Parasites (cryptosporidium, microsporidium) • Sensitivity 98% for 2 AFB BCx Bacterial (Salmonella, Shigella), mycobacterial (MAC; TB ileitis) • CT abdomen often reveals HSM Viral : CMV colitis and intrabd. lymphadenopathy Fungal : Histoplasmosis • May need tissue bx Other : HIV enteropathy, Malignancy : lymphoma, Kaposi sarcoma (HHV8) Benson and Ellner. CID 1993. *draw prior to azithromycin 6 | [footer text here]