Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

Toxoplasma gondii Encephalitis

Last Updated: July 25, 2017; Last Reviewed: July 25, 2017

Recommendations for Preventing and Treating Toxoplasma gondii Encephalitis
Preventing 1st Episode of Toxoplasma gondii Encephalitis (Primary Prophylaxis)

Indications for Initiating Primary Prophylaxis:
  • Toxoplasma IgG positive patients with CD4 count <100 cells/mm3 (AII)
Note: All the recommended regimens for preventing 1st episode of toxoplasmosis are also effective in preventing PCP.

Preferred Regimen:
  • TMP-SMX 1 DS PO daily (AII)
Alternative Regimens:
  • TMP-SMX 1 DS PO three times weekly (BIII), or
  • TMP-SMX SS PO daily (BIII), or
  • Dapsonea 50 mg PO daily + (pyrimethamine 50 mg + leucovorin 25 mg) PO weekly (BI), or
  • (Dapsonea 200 mg + pyrimethamine 75 mg + leucovorin 25 mg) PO weekly (BI), or
  • Atovaquoneb 1500 mg PO daily (CIII), or
  • (Atovaquoneb 1500 mg + pyrimethamine 25 mg + leucovorin 10 mg) PO daily (CIII)
Indication for Discontinuing Primary Prophylaxis:
  • CD4 count >200 cells/mm3 for >3 months in response to ART (AI); or
  • Can consider if CD4 count is 100-200 cells/mm3 and HIV RNA levels remain below limits of detection for at least 3-6 months (BII).
Indication for Restarting Primary Prophylaxis:
  • CD4 count <100 to 200 cells/mm3 (AIII)
Treating Toxoplasma gondii Encephalitis

Preferred Regimen (AI):
  • Pyrimethamine 200 mg PO once, followed by dose based on body weight:
    • Body weight ≤60 kg: pyrimethamine 50 mg PO daily + sulfadiazine 1000 mg PO q6h + leucovorin 10–25 mg PO daily (can increase to 50 mg daily or BID)
    • Body weight >60 kg: pyrimethamine 75 mg PO daily + sulfadiazine 1500 mg PO q6h + leucovorin 10–25 mg PO daily (can increase to 50 mg daily or BID)
Note: if pyrimethamine is unavailable or there is a delay in obtaining it, TMP-SMX should be used in place of pyrimethamine-sulfadiazine (BI). For patients with a history of sulfa allergy, sulfa desensitization should be attempted using one of several published strategies (BI). Atovaquone should be administered until therapeutic doses of TMP-SMX are achieved (CIII).

Alternative Regimens:
  • Pyrimethamine (leucovorin)c plus clindamycin 600 mg IV or PO q6h (AI); preferred alternative for patients intolerant of sulfadiazine or who do not respond to pyrimethamineb-sulfadiazine; must add additional agent for PCP prophylaxis, or
  • TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg) (IV or PO) BID (BI), or
  • Atovaquoneb 1500 mg PO BID + pyrimethamine (leucovorin)c (BII), or
  • Atovaquoneb 1500 mg PO BID + sulfadiazined (BII), or
  • Atovaquoneb 1500 mg PO BID (BII)
Total Duration for Treating Acute Infection:
  • At least 6 weeks (BII); longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks
  • After completion of the acute therapy, all patients should be continued on chronic maintenance therapy as outlined below
Chronic Maintenance Therapy for Toxoplasma gondii Encephalitis

Preferred Regimen:
  • Pyrimethamine 25–50 mg PO daily + sulfadiazine 2000–4000 mg PO daily (in 2 to 4 divided doses) + leucovorin 10–25 mg PO daily (AI)
Alternative Regimen:
  • Clindamycin 600 mg PO q8h + (pyrimethamine 25–50 mg + leucovorin 10–25 mg) PO daily (BI); must add additional agent to prevent PCP (AII), or
  • TMP-SMX DS 1 tablet BID (BII), or
  • TMP-SMX DS 1 tablet daily (BII), or
  • Atovaquoneb 750–1500 mg PO BID + (pyrimethamine 25 mg + leucovorin 10 mg) PO daily, or
  • Atovaquoneb 750–1500 mg PO BID + sulfadiazine 2000–4000 mg PO daily (in 2 to 4 divided doses) (BII), or
  • Atovaquoneb 750–1500 mg PO BID (BII)
Discontinuing Chronic Maintenance Therapy:
  • Successfully completed initial therapy, remain asymptomatic of signs and symptoms of TE, and CD4 count >200 cells/mm3 for >6 months in response to ART (BI)
Criteria for Restarting Secondary Prophylaxis/Chronic Maintenance
  • CD4 count <200 cells/mm3 (AIII)
Other Considerations:
  • Adjunctive corticosteroids (e.g., dexamethasone) should only be administered when clinically indicated to treat a mass effect associated with focal lesions or associated edema (BIII); discontinue as soon as clinically feasible.
  • Anticonvulsants should be administered to patients with a history of seizures (AIII) and continued through at least through the period of acute treatment; anticonvulsants should not be used as seizure prophylaxis (BIII).
a Whenever possible, patients should be tested for G6PD deficiency before administrating dapsone. Alternative agent should be used if the patient is found to have G6PD deficiency.
b Atovaquone should be taken with meals or nutritional supplement to ensure adequate oral absorption.
c Pyrimethamine and leucovorin doses: Same as doses listed in Preferred Regimen for Acute Infection
d Sulfadiazine dose: Same as weight-based dose listed in Preferred Regimen for Acute Infection


Key to Acronyms: ART = antiretroviral therapy; BID = twice daily; CD4 = CD4 T lymphocyte cell; DS = double strength; G6PD = glucose-6-phosphate dehydrogenase; IgG = immunoglobulin G; IV = intravenous; PCP = Pneumocystis Pneumonia; PO = orally; q(n)h = every “n” hours; SS = single strength; TE = toxoplasmic encephalitis; TMP-SMX = trimethoprim-sulfamethoxazole

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