Management of Toxoplasmosis in HIV Patients
Immediate Assessment and Risk Stratification
All HIV-infected patients must be tested for Toxoplasma IgG antibody immediately after HIV diagnosis to detect latent infection and guide prophylaxis decisions. 1, 2, 3
Key Clinical Presentations
HIV patients with toxoplasmosis typically present with:
- Fever (86.6%), headaches (84.5%), and motor deficits (69.1%) as the most common symptoms 4
- Multiple bilateral ring-enhancing lesions on brain imaging, particularly in basal ganglia and corticomedullary junction 1
- Focal neurological deficits indicating toxoplasmic encephalitis (TE), the most common manifestation 5, 6
A presumptive diagnosis is based on clinical symptoms, positive Toxoplasma serology, and characteristic brain imaging findings—do not wait for definitive diagnosis to initiate treatment. 1, 6
Treatment Algorithm Based on CD4 Count and Disease Status
For Asymptomatic Seropositive Patients (Primary Prophylaxis)
Initiate primary prophylaxis immediately when CD4+ count falls below 100 cells/µL in Toxoplasma IgG-positive patients. 1, 2, 7
Preferred regimen: Trimethoprim-sulfamethoxazole (TMP-SMZ) double-strength (160mg/800mg) once daily, which provides dual protection against both toxoplasmic encephalitis and Pneumocystis pneumonia 1, 2, 7
Alternative regimens for sulfa-allergic patients:
- Dapsone 50mg daily plus pyrimethamine 50mg weekly plus leucovorin 25mg weekly 1, 7
- Do NOT use aerosolized pentamidine—it provides zero protection against toxoplasmic encephalitis despite preventing PCP 7
For Active Toxoplasmic Encephalitis (Acute Treatment)
The gold standard treatment is pyrimethamine plus sulfadiazine plus leucovorin (folinic acid), initiated immediately upon presumptive diagnosis. 2, 8, 9
Dosing regimen:
- Pyrimethamine: Loading dose of 2 mg/kg/day orally divided twice daily for 2 days (maximum 50 mg/day), then maintenance dose of 1 mg/kg/day orally once daily (maximum 25 mg/day) 1, 2
- Sulfadiazine: 25-50 mg/kg/dose given four times daily 1
- Leucovorin (folinic acid): 10-25 mg/day to prevent bone marrow suppression 1, 8
For sulfa-allergic patients: Pyrimethamine plus clindamycin is the preferred alternative 1, 2, 9
Alternative option: TMP-SMZ at 5 mg/kg trimethoprim plus 25 mg/kg sulfamethoxazole IV or orally twice daily for 6 weeks 7, 9
Treatment Duration and Monitoring
Continue acute therapy for at least 6 weeks, assuming clinical and radiological improvement. 1, 2, 7 Longer courses may be required for extensive disease or poor response 1
Critical monitoring requirement: Perform complete blood count at least weekly while on daily pyrimethamine to detect bone marrow suppression (neutropenia, anemia, thrombocytopenia) 1, 8
If signs of folate deficiency develop (pallor, purpura, glossitis, sore throat), reduce dosage or discontinue pyrimethamine and administer leucovorin 5-15 mg daily until normal hematopoiesis returns. 8
Lifelong Suppressive Therapy (Secondary Prophylaxis)
Patients who have had toxoplasmic encephalitis require lifelong suppressive therapy to prevent relapse, which occurs rapidly if therapy is discontinued. 1, 2, 7
Preferred maintenance regimen: Pyrimethamine plus sulfadiazine with leucovorin at reduced doses indefinitely 1, 7
Alternative for sulfa-allergic patients: Pyrimethamine plus clindamycin, though only pyrimethamine plus sulfadiazine provides dual protection against PCP 1
When to Consider Discontinuing Prophylaxis
Primary prophylaxis can be safely discontinued when CD4 count rises above 200 cells/µL for at least 3 months on antiretroviral therapy. 1, 7, 3
However, for secondary prophylaxis (after prior TE episode), evidence is insufficient to recommend discontinuation despite immune reconstitution—most clinicians favor continuing lifelong therapy given the high relapse risk 1, 7. The relapse rate with pyrimethamine-based maintenance therapy is approximately 11% in the post-HAART era 10
Restart prophylaxis immediately if CD4 drops below 100-200 cells/µL or if any signs of toxoplasmosis recurrence develop. 7, 3
Special Populations
Pregnant Women
Chemoprophylaxis should be administered to pregnant HIV-infected women using the same criteria as other adults (CD4 <100 cells/µL). 1
However, pyrimethamine-containing regimens can reasonably be deferred during pregnancy due to teratogenicity concerns and low TE incidence during pregnancy. 1, 8 If treatment is necessary, concurrent leucovorin administration is strongly recommended 2, 8
Pediatric Patients
HIV-infected children with congenital toxoplasmosis require 12 months of treatment with pyrimethamine plus sulfadiazine plus leucovorin. 1, 2
For acquired TE in children: Use pyrimethamine 2 mg/kg/day for 3 days, then 1 mg/kg/day, plus sulfadiazine 25-50 mg/kg/dose four times daily, plus leucovorin 10-25 mg/day for at least 6 weeks 1
Prevention of Exposure
Counsel all HIV-infected patients, especially seronegative ones, on toxoplasmosis prevention:
- Cook meat to internal temperature of 150°F (65.5°C)—meat should not be pink inside 1, 2
- Wash hands after handling raw meat, gardening, or soil contact 1, 2
- Wash fruits and vegetables thoroughly before eating raw 1, 2
- Change cat litter boxes daily, preferably by HIV-negative persons; otherwise wash hands thoroughly afterward 1, 2
- Keep cats indoors; feed only canned/dried commercial food or well-cooked table food 1
Patients need not part with their cats or have cats tested for toxoplasmosis. 1
Critical Pitfalls to Avoid
Do not confuse primary prophylaxis (prevention in at-risk patients) with secondary prophylaxis (maintenance after acute TE)—the latter requires more aggressive lifelong suppression. 7
Do not delay empiric treatment while awaiting brain biopsy—initiate therapy immediately in Toxoplasma-seropositive patients with compatible neuroimaging and symptoms 6. Consider biopsy only if no response after 10-14 days of treatment 1
Do not use monotherapy with dapsone, pyrimethamine, azithromycin, clarithromycin, or atovaquone alone for TE prophylaxis—these are inadequate 1
Retest seronegative patients for Toxoplasma IgG when CD4 falls below 100 cells/µL to detect seroconversion and initiate prophylaxis if positive. 1, 3