Prepared by the AETC National Coordinating Resource Center based on recommendations from the CDC, National Institutes of Health, and HIV Medicine Association/Infectious Diseases Society of America Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Pneumocystis Pneumonia Slide Set

These slides were developed using recommendations published in May The intended audience is clinicians involved in the care of patients with HIV. Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. -AETC National Coordinating Resource Center About This Presentation May 2013www.aidsetc.org 2

 Epidemiology  Clinical Manifestations  Diagnosis  Prevention  Treatment  Considerations in Pregnancy Pneumocystis jiroveci Pneumonia (PCP) May 2013www.aidsetc.org 3

 Caused by P jiroveci (formerly P carinii)  Ubiquitous in the environment  Initial infection usually occurs in early childhood  PCP may result from reactivation or new exposure  In immunosuppressed patients, possible airborne spread PCP: Epidemiology May 2013www.aidsetc.org 4

 Before widespread use of PCP prophylaxis & effective ART, PCP seen in 70-80% of AIDS patients in the U.S.  In advanced immunosuppression, treated PCP associated with 20-40% mortality  Substantial decline in incidence in U.S. & W. Europe, owing to prophylaxis and ART  Most cases occur in patients unaware of their HIV infection, in those who are not in care, and in those with advanced AIDS (CD4 count <100 cells/µL) PCP: Epidemiology (2) May 2013www.aidsetc.org 5

Risk factors:  CD4 count <200 cells/µL  CD4 percentage <14%  Prior PCP  Oral thrush  Recurrent bacterial pneumonia  Unintentional weight loss  High HIV RNA PCP: Epidemiology (3) May 2013www.aidsetc.org 6

 Progressive exertional dyspnea, fever, nonproductive cough, chest discomfort  Subacute onset, worsens over days-weeks (fulminant pneumonia is uncommon)  Chest exam may be normal, or diffuse dry rales, tachypnea, tachycardia (especially with exertion)  Extrapulmonary disease seen rarely; occurs in any organ, associated with aerosolized pentamidine prophylaxis PCP: Clinical Manifestations May 2013www.aidsetc.org 7

 Clinical presentation, blood tests, radiographs suggestive but not diagnostic  Organism cannot be cultured  Definitive diagnosis should be sought  Hypoxemia: characteristic, may be mild or severe (PO2 35 mmHg)  LDH >500 mg/dL is common but nonspecific  1,3β-D-glycan may be elevated; uncertain sensitivity and specificity PCP: Diagnosis May 2013www.aidsetc.org 8

 CXR: various presentations  May be normal in early disease  Typical: diffuse bilateral, symmetrical interstitial infiltrates  May see atypical presentations, including nodules, asymmetric disease, blebs, cysts, pneumothorax  Cavitation, intrathoracic adenopathy, and pleural effusion are uncommon (unless caused by a second concurrent process) PCP: Diagnosis (2) May 2013www.aidsetc.org 9

 Chest CT, thin-section  Patchy ground-glass attenuation  May be normal  Gallium scan  Pulmonary uptake PCP: Diagnosis (3) May 2013www.aidsetc.org 10

May 2013www.aidsetc.org 11 Chest X ray: PCP with bilateral perihilar opacities, interstitial prominence, hyperlucent cystic lesions. (Credit: HIV Web Study, hivwebstudy.org, © University of Washington) Chest X ray: PCP with bilateral, diffuse granular opacities. (Credit: L. Huang, MD; HIVInSite) PCP: Diagnosis (Imaging)

High-resolution computed tomograph (HRCT) scan of the chest showing PCP. Bilateral patchy areas of ground-glass opacity are suggestive of PCP. Credit: L. Huang, MD; HIV InSite PCP: Diagnosis (Imaging) (2) May 2013www.aidsetc.org 12

 Definitive diagnosis requires demonstrating organism:  Induced sputum (sensitivity 90%)  Spontaneously expectorated sputum: low sensitivity  Bronchoscopy with bronchoalveolar lavage (sensitivity 90-99%)  Transbronchial biopsy (sensitivity %)  Open-lung biopsy (sensitivity %)  PCR: high sensitivity for BAL sample; may not distinguish disease from colonization PCP: Diagnosis (4) May 2013www.aidsetc.org 13

Lung biopsy using silver stain to demonstrate P jiroveci organisms in tissue Credit: A. Ammann, MD; UCSF Center for HIV Information Image Library PCP: Diagnosis (Histopathology) May 2013www.aidsetc.org 14

 Treatment may be initiated before definitive diagnosis is established  Organism persists for days/weeks after start of treatment PCP: Diagnosis (5) May 2013www.aidsetc.org 15

 Insufficient data to support isolation as a standard practice, but data suggest high-risk patients may benefit from isolation from persons with known PCP PCP: Preventing Exposure May 2013www.aidsetc.org 16

 Initiate:  CD4 <200 cells/µL or history of oropharyngeal candidiasis  Consider for:  CD4% <14% or history of AIDS-defining illness  CD cells/µL if Q 3-month CD4 monitoring is not possible  Discontinue:  On ART with CD4 >200 cells/µL for >3 months  Reinitiate:  CD4 decreases to <200 cells/µL PCP: Primary Prophylaxis May 2013www.aidsetc.org 17

 Preferred:  Trimethoprim-sulfamethoxazole (TMP-SMX) DS 1 tablet PO QD*  TMP-SMX SS 1 tablet PO QD  For patients who experience non life-threatening adverse events, consider desensitization or dosage reduction * Effective as toxoplasmosis prophylaxis (for CD4 count <100 cells/µL + positive serology) PCP: Primary Prophylaxis (2) May 2013www.aidsetc.org 18

 Alternative:  TMP-SMX DS 1 tablet PO 3 times Q week  Dapsone 100 mg PO QD or 50 mg BID  Dapsone 50 mg QD + pyrimethamine 50 mg Q week + leucovorin 25 mg Q week*  Dapsone 200 mg + pyrimethamine 75 mg + leucovorin 25 mg, all Q week*  Aerosolized pentamidine 300 mg Q month via Respirgard II nebulizer (other devices not recommended)  Atovaquone 1,500 mg PO QD* * Effective as toxoplasmosis prophylaxis (for CD4 count <100 cells/µL + positive serology) PCP: Primary Prophylaxis (3) May 2013www.aidsetc.org 19

 Duration: 21 days for all treatment regimens  Preferred: TMP-SMX is treatment of choice  Moderate-severe PCP  TMP-SMX: mg/kg/day TMP and mg/kg/day SMX IV or PO in divided doses Q6-8H  Mild-moderate PCP  As above, or TMP-SMX DS 2 tablets TID  Adjust dosage for renal insufficiency PCP: Treatment May 2013www.aidsetc.org 20

 Alternatives  Moderate-severe PCP  Pentamidine 4 mg/kg IV QD  Recommended for patients who cannot tolerate TMP-SMX or experience clinical failure with TMP-SMX; do not combine use  Primaquine 30 mg (base) PO QD + clindamycin 600 mg IV Q6H or 900 mg IV Q8H or 300 mg PO Q6H or 450 mg PO Q8H  More effective than pentamidine, less toxicity PCP: Treatment (2) May 2013www.aidsetc.org 21

 Alternatives  Mild-moderate PCP  Dapsone 100 mg PO QD + TMP 15 mg/kg/day PO in divided doses TID  Similar efficacy, fewer side effects than TMP-SMX, but more pills  Primaquine 30 mg (base) PO QD + clindamycin 300 mg PO Q6H or 450 mg PO Q8H  Atovaquone 750 mg PO BID  Less effective than TMP-SMX, but fewer side effects PCP: Treatment (3) May 2013www.aidsetc.org 22

 Adjunctive:  Corticosteroids  For moderate-to-severe disease (room air PO2 35 mmHg)  Give as early as possible (within 72 hours)  Prednisone 40 mg BID days 1-5, 40 mg QD days 6-10, 20 mg QD days 11-21, or methylprednisolone at 75% of respective prednisone dosage PCP: Treatment (4) May 2013www.aidsetc.org 23

 For patients not on ART, start ART within 2 weeks of PCP diagnosis, if possible  In one study, lower rates of AIDS progression or death with early ART initiation (no data on patients with respiratory failure requiring intubation)  IRIS has been reported; follow for recurrence of symptoms PCP: ART Initiation May 2013www.aidsetc.org 24

May 2013  25  Monitor closely for response to treatment, and for adverse effects of treatment PCP: Monitoring and Adverse Events

 TMP-SMX: rash, Stevens-Johnson syndrome, fever, leukopenia, thrombocytopenia, azotemia, hepatitis, hyperkalemia  Atovaquone: headache, nausea, diarrhea, rash, fever, transaminase elevations  Dapsone: methemoglobinemia and hemolysis, rash, fever  Pentamidine: pancreatitis, hypo- or hyperglycemia, leukopenia, fever, electrolyte abnormalities, cardiac dysrhythmia  Primaquine and clindamycin: methemoglobinemia and hemolysis, anemia, rash, fever, diarrhea PCP: Monitoring & Adverse Events (2) May 2013www.aidsetc.org 26

 Lack of clinical improvement or worsening of respiratory function after at least 4-8 days of treatment  If patient not on corticosteroid therapy, early deterioration (day 3-5) may be caused by inflammatory response to lysis of P jiroveci organisms  Rule out concomitant infection PCP: Treatment Failure May 2013www.aidsetc.org 27

 Treatment failure resulting from drug toxicities in up to 1/3 of patients  Treat adverse reactions or switch regimen  Treatment failure caused by lack of drug efficacy in 10% of patients  No data to guide treatment decisions  For TMP-SMX failure in moderate-to-severe PCP, consider IV pentamidine or primaquine + IV clindamycin  For mild disease, may consider atovaquone PCP: Treatment Failure (2) May 2013www.aidsetc.org 28

 Secondary prophylaxis (chronic maintenance therapy) for life unless immune reconstitution on ART  Preferred: TMP-SMX 1 DS PO QD, or 1 SS PO QD  Alternatives:  TMP-SMX DS 1 tablet PO 3 times Q week  Dapsone 100 mg PO QD or 50 mg BID  Dapsone 50 mg QD + pyrimethamine 50 mg Q week + leucovorin 25 mg Q week  Dapsone 200 mg + pyrimethamine 75 mg + leucovorin 25 mg, all Q week*  Aerosolized pentamidine 300 mg Q month via Respirgard II nebulizer (other devices not recommended)  Atovaquone 1,500 mg PO QD  Atovaquone 1,500 mg PO QD + pyrimethamine 25 mg QD + leucovorin 10 mg PO QD PCP: Preventing Recurrence May 2013www.aidsetc.org 29

 Discontinue secondary prophylaxis for patients on ART with sustained increase in CD4 count from 200 cells/µL for ≥3 months  If PCP occurred at CD4 count >200 cells/µL, prudent to continue prophylaxis for life (regardless of CD4 count)  Restart maintenance therapy if CD4 count decreases to 200 cells/µL PCP: Preventing Recurrence (2) May 2013www.aidsetc.org 30

 Diagnosis and indications for treatment: as in nonpregnant women  Preferred treatment: TMP-SMX  Limited data suggest small increased risk of birth defects after 1st trimester TMP exposure, but pregnant women with PCP should be treated with TMP-SMX  Consider increased doses of folic acid (>0.4 mg/day) in 1st trimester: may decrease risk of congenital anomaly but may increase risk of therapeutic failure  Pentamidine embryotoxic in animals PCP: Considerations in Pregnancy May 2013www.aidsetc.org 31

 Dapsone: risk of mild maternal hemolysis with long-term therapy; risk of hemolytic anemia in fetuses with G6PD deficiency  Pentamidine embryotoxic in animals  Primaquine: not generally used in pregnancy, risk of hemolysis; risk of hemolytic anemia in fetuses with G6PD deficiency  Clindamycin, atovaquone: appear safe in pregnancy PCP: Considerations in Pregnancy (2) May 2013www.aidsetc.org 32

 Corticosteroid indications as in nonpregnant women; monitor for hyperglycemia  Increased risk of preterm labor and delivery; monitor if pneumonia occurs after 20 weeks of gestation  Prophylaxis as in nonpregnant adults  Consider aerosolized pentamidine or atovaquone during 1st trimester, if risk of teratogenicity caused by systemic agents is a concern PCP: Considerations in Pregnancy (3) May 2013www.aidsetc.org 33

 AIDS Info: Access the Guidelines Online May 2013www.aidsetc.org 34

May 2013www.aidsetc.org 35  This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in May 2013  See the AETC NCRC website for the most current version of this presentation: About This Slide Set