This patient most likely has central nervous system (CNS) Toxoplasma gondii infection. He has not been adherent to antiretroviral therapy, and his CD4 cell count has decreased to less than 100/µL, putting him at risk for opportunistic infection. Clinical presentation of CNS toxoplasmosis typically involves new headaches and focal neurologic deficits and may also include fever and seizures. The findings on this patient's MRI are classic for toxoplasmosis, with multiple ring-enhancing lesions. Because CNS toxoplasmosis in AIDS results from reactivation of earlier infection, patients usually have a positive result for IgG antibody but not IgM. He should be treated empirically and followed for clinical and radiographic response, which typically occurs within 1 to 2 weeks.

Primary CNS lymphoma generally requires a more severe degree of immunosuppression than most other AIDS-related complications, most commonly occurring when the CD4 cell count drops below 50/µL; the incidence has decreased with effective antiretroviral therapy. Although primary CNS lymphoma may present with more than one lesion on MRI, it most often presents with a single large lesion. Primary CNS lymphoma is strongly associated with Epstein-Barr virus infection, and polymerase chain reaction of cerebrospinal fluid to detect Epstein-Barr virus can facilitate the diagnosis. The prognosis remains poor.

Cryptococcal meningoencephalitis is another common CNS infection in AIDS but rarely results in focal mass lesions on imaging, more often presenting with mental status changes than focal deficits and seizure. The serum cryptococcal antigen and cerebrospinal fluid antigen are positive in 95% and 99% of cases, respectively; therefore, a negative antigen test result argues against this diagnosis.

Progressive multifocal leukoencephalopathy presents in AIDS with focal deficits and mental status changes. Onset usually occurs over several weeks, compared with several days for toxoplasmosis, and fever is uncommon. Furthermore, progressive multifocal leukoencephalopathy lesions on MRI are typically white-matter, noninflammatory lesions (unless accompanied by immune reconstitution inflammatory syndrome) with minimal enhancement and no mass effect.