Back to our patient from several days ago – 65M with HIV/AIDS, CD4 count 24, and prior CNS toxoplasmosis *compliant with his secondary prophylaxis treatment*, now BIBEMS for new AMS.  The head CT (WITH contrast) showed no new lesions, but the old lesions were larger with edema.  Is this definitely reactivation of Toxoplasmosis? 
NO.  Failure of secondary prophylaxis for CNS Toxo (when compliant) has been reported only a few times in the literature, so we should be worried about other etiologies as well.  In HIV patients with CD4 counts < 200, we are especially concerned about opportunistic infections and AIDS-associated tumors.  In general, lesions with mass effect are most likely primary CNS lymphoma, Toxoplasmosis, or CNS TB.  Toxoplasmosis lesions are more likely to be multiple and small, while lesions that are solitary or >4cm are more consistent with CNS lymphoma, but these are not pathognomonic features.  
Less likely, but still possible, are brain abscesses secondary to Staphylococcus, Streptococcus, Salmonella, Aspergillus, Nocardia, Rhodococcus, Listeria, cryptococcus granulomas, syphilitic gummas, and PML.
Any of these etiologies could account for the increased size of the lesions and require extensive workup including possible stereotaxic biopsy.