A marked decrease in incidence has been observed for most central nervous system (CNS)
opportunistic infections (OIs) after the use of
highly active antiretroviral therapy (
HAART) in developed countries. However, the spectrum of these OIs in
acquired immunodeficiency syndrome (
AIDS) patients has remained almost unchanged. CNS
toxoplasmosis,
cryptococcosis,
tuberculosis, and
progressive multifocal leukoencephalopathy (PML) remain the most frequent ones. Primary CNS
lymphoma should be included in the differential diagnosis of all cases with focal lesions. Final diagnosis is currently made by combining neuroimaging techniques (single-photon emission computed tomography [SPECT], positron emission tomography [PET], magnetic resonance imaging [MRI] and/or computed tomography [CT] scan) and molecular studies of cerebrospinal fluid (CSF) and therapeutical response. Stereotactic biopsy should only be performed in the case of atypical lesions or nonresponse to recommended treatments.
After treatment of the acute phase, lifelong maintenance
therapy is necessary to prevent OI recurrences. Once
HAART is initiated, some patients can develop a clinical worsening of some CNS OIs with or without atypical neuroimaging manifestations. This paradoxical worsening is known as the
immune reconstitution inflammatory syndrome (IRIS) and it results from reconstitution of the immune system's ability to recognize pathogens/
antigens in patients with prior OIs and low CD4+ T-cell counts. In this context, IRIS can be seen in patients with CNS
cryptococcosis,
tuberculosis, or PML. On the other hand,
HAART-induced immune reconstitution can improve the prognosis of some untreatable diseases such as PML, and can allow maintenance
therapy of some CNS OI to be safely discontinued in patients with high and sustained CD4+ T-cell response.