Pneumocystis carinii Pneumonia

Prevention of Exposure
(1) Although some authorities recommend that HIV-infected persons at risk for P. carinii pneumonia (PCP) not share a hospital room with a patient who has PCP, data are insufficient to support this recommendation as standard practice (CIII).

Prevention of Disease

Initiation of Primary Prophylaxis
(2) Adults and adolescents who have HIV infection (including pregnant women and those on HAART) should receive chemoprophylaxis against PCP if they have a CD4+T- lymphocyte count of <200/uL (AI), or a history of oropharyngeal candidiasis (AII) (13). Persons who have a CD4+ T-lymphocyte percentage <14% or history of an AIDS-defining illness but do not otherwise qualify should be considered for prophylaxis (BII) (14, 15). When CD4+ T-lymphocyte count monitoring at least every 3 months is not possible, initiation of chemoprophylaxis at a CD4+ T-lymphocyte count of >200 but <250 cells/uL should also be considered (BII) (14).

(3) Trimethoprim-sulfamethoxazole (TMP-SMZ) is the preferred prophylactic agent (AI) (15-17). One double-strength tablet/day is the preferred regimen (AI) (16). However, one single-strength tablet/day (19) is also effective and may be better tolerated (AI). One double strength tablet three times per week is also effective (BI) (18). TMP-SMZ at a dose of 1 double-strength tablet/day confers cross-protection against toxoplasmosis (20) and some common respiratory bacterial infections (16, 21). Lower doses of TMP-SMZ may also confer such protection. For patients who have an adverse reaction that is not life-threatening, treatment with TMP-SMZ should be continued if clinically feasible; for those who have discontinued such therapy due to an adverse reaction, its reinstitution should be strongly considered after the adverse event has resolved (AII). Patients who have experienced adverse events, primarily fever and rash, may tolerate reintroduction of the drug using a gradual increase in dose (desensitization) as per published regimens (BI) (22, 23) or reintroduction of TMP-SMZ at a reduced dose or frequency (CIII): up to 70% of patients can tolerate such reinstitution of therapy.

(4) If TMP-SMZ cannot be tolerated, prophylactic regimens that can be recommended as alternatives include dapsone (BI) (16), dapsone plus pyrimethamine plus leucovorin (BI) (24, 25), aerosolized pentamidine administered by the Respirgard II^TM nebulizer (Marquest, Englewood, CO) (BI) (17) and atovaquone (BI) (26, 27). Atovaquone appears to be as effective as aerosolized pentamidine (27) or dapsone (AI) (26) but is substantially more expensive than the other regimens. For patients seropositive for Toxoplasma gondii who cannot tolerate TMP-SMZ, the following regimens can be recommended as alternatives include dapsone plus pyrimethamine (AI) (24, 25) or atovaquone with or without pyrimethamine (CIII) should be used if an alternative to TMP-SMZ for prophylaxis against both PCP and TE is needed. Because data regarding their efficacy for PCP prophylaxis are insufficient for a firm recommendation, the following regimens generally cannot be recommended for this purpose: aerosolized pentamidine administered by other nebulization devices,intermittently administered parenteral pentamidine, oral pyrimethamine plus sulfadoxine, oral clindamycin plus primaquine, and intravenous trimetrexate. However, the use of these agents may be considered in unusual situations in which the recommended agents cannot be administered (CIII).

Discontinuation of Primary Prophylaxis
(5) Initial reports from three prospective observational studies (28-30), one retrospective review (31), and one randomized trial (32) all have suggested that PCP prophylaxis can be safely discontinued in patients responding to HAART with a sustained increase in CD4+ T-lymphocyte counts from <200 cells/uL to >200 cells/uL. Such reports have mostly included patients receiving primary prophylaxis (no prior episode of PCP) and protease inhibitor containing regimens. In these studies, median follow-up ranged from 6 to 12 months and the median CD4+ T-lymphocyte count at the time of discontinuation of prophylaxis was over 300 cell/uL. At the time PCP prophylaxis was discontinued, many patients had sustained suppression of HIV plasma RNA levels below detection limits of the available assays. While the optimal criteria for discontinuation remain to be defined, providers may wish to discontinue prophylaxis when patients have sustained a CD4+ T-lymphocyte count of >200 cells/uL for at least 3-6 months (CII). Additional criteria might include sustained reduction in viral load sustained for a comparable period (CIII).

Restarting Primary Prophylaxis
(6) There are no data to guide recommendations for reinstitution of primary prophylaxis. Pending the availability of such data, a reasonable approach would be to utilize the criteria for initiation of prophylaxis described above (CIII).

Prevention of Recurrence
(7) Adults and adolescents who have a history of PCP should be administered chemoprophylaxis (i.e., secondary prophylaxis or chronic maintenance therapy) with the regimens indicated above to prevent recurrence (AI) (15).

Discontinuation of Secondary Prophylaxis (chronic maintenance therapy)
(8) Although patients receiving secondary prophylaxis (prior episode of PCP) may also be at low risk for PCP when their CD4+ T-lymphocyte counts increase to > 200 cells/uL, inadequate numbers of patients have been evaluated at this time to warrant a recommendation to discontinue of prophylaxis in such patients.

Notes

Pediatric Notes
(9) Children born to HIV-infected mothers should be administered prophylaxis with TMP-SMZ beginning at 4-6 weeks of age (33) (AII). Prophylaxis should be discontinued for children who are subsequently found not to be infected with HIV. HIV-infected children and children whose infection status remains unknown should continue to receive prophylaxis for the first year of life. The need for subsequent prophylaxis should be determined on the basis of age-specific CD4+ T-lymphocyte count thresholds (Table 7a) (AII). The safety of discontinuing prophylaxis in HIV-infected children receiving HAART has not been studied.

(10) Children who have a history of PCP should be administered lifelong chemoprophylaxis to prevent recurrence (AI) (33).

Note Regarding Pregnancy
(11) Chemoprophylaxis for PCP should be administered to pregnant women as well as to other adults and adolescents (AIII). TMP-SMZ is the recommended prophylactic agent; dapsone is an alternative. Because of theoretical concerns regarding possible teratogenicity associated with drug exposures during the first trimester, providers may choose to withhold prophylaxis during the first trimester. In such cases, aerosolized pentamidine may be considered because of its lack of systemic absorption and the resultant lack of exposure of the developing embryo to the drug (CIII).

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