The Effect of Highly Active Antiretroviral Therapy-Induced Immune Reconstitution on Development and Outcome of Progressive Multifocal Leukoencephalopathy: Study of 43 Cases with Review of the Literature

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Abstract
The authors investigated the effect of highly active antiretroviral therapy (HAART) on the onset and outcome of progressive multifocal leukoencephalopathy (PML) in a group of 43 patients with histological or clinicovirological diagnosis of PML. In eight of these cases (19%), PML symptoms presented 21 to 55 days after the start of HAART, concomitantly with a CD4 cell-count increase and plasma human immunodeficiency virus type 1 (HIV-1) RNA load (VL) decrease. Four of these patients died of PML. Apart from baseline VL, we did not identify any other variable that could distinguish these forms of immune reconstitution PML from those occurring in patients either untreated or failing to respond to therapy. To compare the viroimmunological response to HAART with PML outcome, we evaluated a subgroup of 23 patients untreated at the time of PML onset. No different pattern of response to HAART was observed between patients who died or survived to PML. However, start of HAART was delayed of ≥3 months after onset of PML in half of the latter patients. In conclusion, HAART-associated immune reconstitution seems to play a role on development of a substantial number of PML cases. Although the authors could not demonstrate a directly deleterious effect of HAART on PML progression, prompt initiation of HAART after diagnosis of PML and subsequent successful response were often associated with bad PML outcome.

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