Clinical Epidemiology and Survival of Progressive Multifocal Leukoencephalopathy in the Era of Highly Active Antiretroviral Therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Abstract

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.

Cidofovir in combination with HAART and survival in AIDS-associated progressive multifocal leukoencephalopathy

“…Several case series have evaluated cidofovir as a treatment against PML with good results [2,9,10], and some reports showed an improvement under a therapy with cidofovir after progression of PML under HAART [8,20,22,24,31]. In contrast, in a prospective non-randomized pilot study [19], a retrospective multicenter cohort study [30], and in a retrospective observational study [3], cidofovir did not prolong survival in patients with PML.…”

“…However, in previous studies, highly active anti-retroviral therapy (HAART) led to an improved outcome in AIDS-associated PML [3,5,13]. Contradictive results have been published on a possible additional efficacy of cidofovir [2,3,9,10,12,19,23,30]. Cidofovir is an acyclic nucleoside phosphonate with highly selective activity against mouse polyomaviruses in vitro [1,6,7,27], but on the other hand, cidofovir showed only minimal effect in toxic concentrations for the target cell against JC virus replication or multiplication in an immortalized human neuroglial cell line [17].…”

JC virus DNA in cerebrospinal fluid samples from Brazilian AIDS patients with focal brain lesions without mass effect

“…5,[36][37][38] In recent years, many studies have documented improved survival rates among PML patients who receive HAART. 31,[37][38][39][40][41][42][43] This association may be strongest when therapy includes a protease inhibitor. 44 There are some factors associated with prolonged survival in patients with PML: use of HAART, high CD4 cell count at time of diagnosis, increase of CD4 cell count by O100 cell/ml, low HIV viral load, PML as initial AIDS diagnosis, low JC virus levels in CSF, clearance of JC virus from CSF and lack of neurological progression 2 months after diagnosis.…”

New features of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy and natalizumab

“…Indeed, HAART has been recognized as the only intervention to have a significant impact in PML outcome. Survival beyond 1 year increased from just below 10% (Berger et al, 1998b) to 50% (Antinori et al, 2003). Interestingly, unlike other opportunist infections, the incidence of PML was not affected by HAART, and a recent study showed PML as the third cause of neurological disease in HIV-infected patients after CNS toxoplasmosis and HIV encephalopathy (Antinori et al, 2003).…”