Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected
Adults and Adolescents
Pneumocystis jiroveci Pneumonia Slide Set
Prepared by the AETC National Resource Center
based on recommendations from the CDC,
National Institutes of Health, and HIV Medicine
Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in May 2013. 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become out of date quickly.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 Resource Center
http://www.aidsetc.org
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Pneumocystis jiroveci Pneumonia:
Epidemiology
 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
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PCP: Epidemiology (2)
 Before widespread use of PCP prophylaxis and
effective ART, PCP seen in 70-80% of AIDS
patients in the United States
 In advanced immunosuppression, treated PCP
associated with 20-40% mortality
 Substantial decline in incidence in United
States and Western 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)
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PCP: Epidemiology (3)
Risk factors:
 CD4 count <200
cells/µL
 Recurrent bacterial
pneumonia
 CD4 percentage
<14%
 Unintentional
weight loss
 Prior PCP
 High HIV RNA
 Oral thrush
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PCP: Clinical Manifestations
 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
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PCP: Diagnosis
 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 <70 mmHg or A-a gradient >35
mmHg)
 LDH >500 mg/dL is common but nonspecific
 1,3β-D-glycan may be elevated; uncertain
sensitivity and specificity
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PCP: Diagnosis (2)
 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)
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PCP: Diagnosis (3)
 Chest CT, thin-section
 Patchy ground-glass attenuation
 May be normal
 Gallium scan
 Pulmonary uptake
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PCP: Diagnosis (Imaging)
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Chest X ray: PCP with bilateral, diffuse
granular opacities
Chest X ray: PCP with bilateral perihilar
opacities, interstitial prominence, hyperlucent
cystic lesions
Credit: L. Huang, MD; HIV InSite
Credit: HIV Web Study, www.hivwebstudy.
org, © 2006 University of Washington
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PCP: Diagnosis (Imaging) (2)
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
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PCP: Diagnosis
 Definitive diagnosis requires demonstrating
organism:
 Induced sputum (sensitivity <50% to >90%)
 Spontaneously expectorated sputum: low sensitivity
 Bronchoscopy with bronchoalveolar lavage
(sensitivity 90-99%)
 Transbronchial biopsy (sensitivity 95-100%)
 Open-lung biopsy (sensitivity 95-100%)
 PCR: high sensitivity for BAL sample; may not
distinguish disease from colonization
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PCP: Diagnosis (Histopathology)
Lung biopsy using silver stain to
demonstrate P jiroveci organisms in
tissue
Credit: A. Ammann, MD; UCSF Center for HIV Information
Image Library
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PCP: Diagnosis
 Treatment may be initiated before
definitive diagnosis is established
 Organism persists for days/weeks after
start of treatment
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PCP: Preventing Exposure
 Insufficient data to support isolation as a
standard practice, but data suggest highrisk patients may benefit from isolation
from persons with known PCP
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PCP: Primary Prophylaxis
 Initiate:
 CD4 <200 cells/µL or history of oropharyngeal
candidiasis
 Consider for:
 CD4% <14% or history of AIDS-defining illness
 CD4 200-250 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
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PCP: Primary Prophylaxis (2)
 Preferred:
 Trimethoprim-sulfamethoxazole (TMP-SMX)
DS 1 tablet PO QD*
 TMP-SMX SS 1 tablet PO QD
 For patients who experience non lifethreatening adverse events, consider
desensitization or dosage reduction
* Effective as toxoplasmosis prophylaxis (for CD4 count <100 cells/µL +
positive serology)
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PCP: Primary Prophylaxis (3)
 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)
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PCP: Treatment
 Duration: 21 days for all treatment
regimens
 Preferred: TMP-SMX is treatment of
choice
 Moderate-severe PCP
 TMP-SMX: 15-20 mg/kg/day TMP and 75-100 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
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PCP: Treatment (2)
 Alternatives
 Moderate-severe PCP
 Pentamidine 4 mg/kg IV QD
 Recommended for patients who cannot tolerate TMPSMX 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
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PCP: Treatment (3)
 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
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PCP: Treatment (4)
 Adjunctive:
 Corticosteroids
 For moderate-to-severe disease (room air PO2
<70 mmHg or A-a gradient >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
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PCP: ART Initiation
 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
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PCP: Monitoring and Adverse Events
 Monitor closely for response to
treatment, and for adverse effects of
treatment
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PCP: Monitoring and Adverse Events (2)
 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
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PCP: Treatment Failure
 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
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PCP: Treatment Failure (2)
 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
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PCP: Preventing Recurrence
 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
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PCP: Preventing Recurrence (2)
 Discontinue secondary prophylaxis for patients
on ART with sustained increase in CD4 count
from <200 cells/µL to >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 or if PCP recurs at
CD4 count >200 cells/µL
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PCP: Considerations in Pregnancy
 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
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PCP: Considerations in Pregnancy (2)
 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
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PCP: Considerations in Pregnancy (3)
 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
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Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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About This Slide Set
 This presentation was prepared by Susa
Coffey, MD, for the AETC National
Resource Center in May 2013
 See the AETC NRC website for the most
current version of this presentation:
http://www.aidsetc.org
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