Pneumocystis Prophylaxis
Rationale and Background
Despite advances in the management of HIV disease, Pneumocystis carinii pneumonia (PCP) remains an important complication and cause of significant morbidity. PCP prophylaxis is very effective and has been demonstrated to prolong life. The risk of developing PCP becomes significant when the patient's CD4 cell count falls to about 200/mm3 and increases progressively as it declines.
Guidelines
An algorithmic approach to PCP prophylaxis is presented in the Figure1. Effective agents for PCP prevention include trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, aerosol pentamidine (AP), and atovaquone.
- All HIV-infected patients who have a prior history of PCP or whose CD4
cell count is less than 200/mm3 should receive prophylaxis.
-
Consideration should be given to starting prophylaxis in patients with higher CD4 cell counts who have a history of thrush.
-
Primary prophylaxis can be safely discontinued in patients whose CD4 cell count rises above 200/mm3 for 3 months on combination antiretroviral therapy. Secondary prophylaxis (maintenance therapy) in patients with a history of PCP can also be stopped in this context.
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TMP-SMX is the drug of choice for PCP prophylaxis. The recommended dose is one double-strength (DS) or single-strength (SS) tablet per day.
- TMP-SMX is preferred to dapsone because of increased efficacy and protection
against conventional bacterial infections. It is preferred to AP because
of increased efficacy, lower cost, protection against toxoplasmosis and
conventional bacterial infections, and lower risk of extrapulmonary pneumocystosis.
It is preferred to atovaquone because of much lower cost (Table
1).
- Twenty-five to fifty percent of patients with HIV infection have toxicity
to TMP-SMX. The most common side effects include fever, rash, and leukopenia.
Strategies for managing mild reactions include discontinuation of the drug
and resuming it at same or lower dose or use of a desensitization protocol
(gradually increasing doses administered over several days). Many patients
can be treated through mild drug reactions using acetaminophen and/or antihistamine
for symptom management.
- Dapsone 100 mg po qd is recommended as the alternative agent in patients
who cannot tolerate TMP-SMX. Side effects of dapsone include fever, rash,
and hemolytic anemia. G6PD qualitative assay should be performed before
starting dapsone therapy. For dapsone to be effective as prophylaxis against
toxoplasmosis, it should be given in conjunction with pyrimethamine 50 mg
po weekly. Folinic acid is recommended to prevent bone marrow suppression.
- For patients who cannot tolerate dapsone, AP or atovaquone is recommended.
- AP 300 mg per month is given by Respirgard II jet nebulizer using 6 ml
sterile water delivered at 6 L/min from a 50 psi compressed air source until
the reservoir is dry, usually over 45 minutes. Active tuberculosis (TB)
should be ruled out with PPD, chest x-ray, and other studies if necessary
before initiating AP. Appropriate measures should be in place to prevent
TB transmission in persons receiving AP. These include use of individual
rooms or booths with negative pressure ventilation, air exhaust to the outside,
scheduling to permit air exchange prior to use by another patient, use of
particulate respirators by workers administering the drug, and restriction
of patients from returning to waiting areas until their coughing subsides.
- Atovaquone is dosed as 1500 mg of suspension po qd with food. Side effects
include gastrointestinal intolerance, rash, headache, and fever.
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Comments about these guidelines are welcome and can be sent to the author at hlibman@caregroup.harvard.edu