Toxoplasma gondii Infection and Cerebral Toxoplasmosis in HIV-infected Patients

Vera Lucia Pereira-Chioccola; José Ernesto Vidal; Chunlei Su


Future Microbiol. 2009;4(10):1363-1379. 

In This Article


The antiparasitic drug combination employed is key for effective treatment. However, the recommended drugs act primarily against the tachyzoites, but do not eradicate the bradyzoites.

Cerebral toxoplasmosis therapy in AIDS patients includes acute treatment, secondary prophylaxis (treatment maintenance) and primary prophylaxis.

Acute Treatment

Three randomized double-blinded trials of cerebral toxoplasmosis treatment have been published comparing pyrimethamine plus sulfadiazine with pyrimethamine plus clindamycin,[172,173] and pyrimethamine plus sulfadiazine with trimethoprim/sulfamethoxazole.[174] In a recent review of these studies The Cochrane Collaboration did not identify any superior regimen among these three combinations for cerebral toxoplasmosis treatment.[175]

Usually, we consider the following regimens as first-choice initial therapy. The first option is treatment for 6 weeks with sulfadiazine (1.0–1.5 g oral route [PO] every 6 h) associated with pyrimethamine (100–200 mg PO loading dose, then 50 PO daily) and folinic acid (10–20 mg PO daily), which reduces the likelihood of the hematologic toxicities associated with pyrimethamine therapy.[97] The second association is trimethroprim/sulfamethoxazol (5/25 mg/kg PO or intravenous [IV] every 12 h for 4–6 weeks).[176,177] This last therapeutic scheme is uncommon in most developed and developing countries. However, there are several observational studies that confirm the efficacy and safety shown in the single available randomized clinical trial.[175–181] The potential advantages of trimethroprim/sulfamethoxazol include less adverse events, posology, parenteral formulation, cost and accessibility. These characteristics are particularly important for treating severely ill patients. An alternative regimen for patients without tolerance to sulfa drugs is the combination for 6 weeks of pyrimetamine (100–200 mg PO loading dose, then 50 PO daily), clindamycin (600–900 PO or IV every 6 h) and folinic acid (10–20 mg PO daily).[97] Longer treatment courses might be appropriate if the clinical or radiologic diagnoses show that there has been an incomplete response or the degree of infection is still extensive after 6 weeks.

In the exceptional setting where none of the previous regimens can be administrated, the following options might be considered. Treatment for 6 weeks with pyrimethamine and folinic acid (as in first-choice regimen) associated with azithromycin (1.2–1.5 g PO daily) or atovaquone (750 mg PO every 6 h). However, we are not aware of any comparative studies between the efficacies of this association and the first-choice therapy.

Complications such as expansive brain lesions with a mass effect (e.g., deviation of the middle line structures or imminent risk of cerebral herniation) and cases with diffuse encephalitis should be administered adjunctive corticosteroids (e.g., dexamethasone). Anticonvulsivant agents should be administrated in the occurrence of seizures. However, the use of prophylactics should be discouraged.

No consensus has been reached for the timing of HAART when cerebral toxoplasmosis is present in antiretroviral-naive patients. We and others[103] consider that HAART should be started after at least 2 weeks of antiparasitic therapy.

Primary Prophylaxis

Primary prophylaxis against T. gondii in AIDS patients has been shown to be effective in preventing cerebral toxoplasmosis reactivation. For this reason, current guidelines recommend the use of a double-strength tablet daily dose of trimethroprim/sulfamethoxazol in Toxoplasma-seropositive patients who have a CD4+ T-cell count below 100 cells/mm3.[180] In our setting, considering that around 20% of AIDS-related patients develop cerebral toxoplasmosis when CD4+ T-cell counts are between 100 and 200 cells/mm3,[61] we recommend primary prophylaxis in patients with CD4+ T-cell counts of below 200 cells/mm3. Primary prophylaxis should be discontinued in patients showing a good response to HAART, which can be defined as a CD4 cell count above 200 cells/mm3 after 3 months.[180]

Secondary Prophylaxis

The combination of pyrimethamine (25–50 mg/day) plus sulfadiazine (500 mg every 6 h) plus leucovorin (10–20 mg/day) is highly effective as suppressive therapy for patients with cerebral toxoplasmosis. When patients cannot take the sulfadiazine four times a day regimen, an alternative is the use of the same total daily dose in a twice a day regimen.[181] In patients who cannot tolerate sulfa drugs, an alternative option is pyrimethamine plus clindamycin (600 mg clindamycin every 8 h is recommended).[180] There is little data available regarding the potential use of trimethroprim/sulfamethoxazol in secondary prophylaxis of cerebral toxoplasmosis. A small uncontrolled study in patients who had been receiving HAART for a median of 13 months suggested that trimethroprim/sulfamethoxazol could be used as a suppressive regimen.[182] However, considering its efficacy and safety in the treatment of acute cerebral toxoplasmosis and the reduced pill burden, trimethroprim/sulfamethoxazol seems to be a reasonable alternative when the conventional maintenance therapy is not possible. In this scenario, we suggest trimethroprim/sulfamethoxazol 2.5/12.5 mg/kg PO every 12 h.

Secondary prophylaxis can be safely discontinued when HIV-infected patients receiving effective HAART with successfully completed initial therapy for cerebral toxoplasmosis have a sustained increase of CD4+ T-cell count above 200 cell/mm3 (e.g., after 6 months). On the other hand, the same prophylaxis should be reintroduced if the CD4 cell count decreases below 200 cells/mm3.[180]


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