Progressive multifocal leukoencephalopathy in patients with immunovirological control and at least 6 months of combination antiretroviral therapy

Objectives and methods : Progressive multifocal leukoencephalopathy (PML) has rarely been reported in people with HIV (PWH) with long-term HIV immune-virological control. We describe the clinical and biological characteristics of patients with confirmed PML among PWH with a CD4(+) cell count more than 200 cells/mu l and an undetectable HIV RNA viral load after at least 6 months of combined antiretroviral therapy (cART) at the time of PML diagnosis, in the large French multicenter Dat'AIDS cohort. Results : Among 571 diagnoses of PML reported in the Dat'AIDS cohort between 2000 and 2019, 10 cases (1.75%) occurred in PWH with a CD4(+) cell count greater than 200 cells/mu l and an undetectable HIV RNA viral load after at least 6 months of cART. Median CD4(+) cell count at PML diagnosis was 395 cells/mu l (IQR 310-477). The median duration between the last detectable HIV viral load and the PML diagnosis was 41.1 months (IQR 8.2-67.4). Only one patient treated with rituximab-based chemotherapy for a large B-cell lymphoma had an established risk factor for PML. Among the nine other patients with no apparent severe immunodeficiency, multiple factors of impaired immunity could have led to the development of PML: hepatitis C virus (HCV) co-infection (n = 6), cirrhosis (n = 4), HHV-8 co-infection (n = 3) with Kaposi's sarcoma (n = 2) in association with Castleman's disease (n = 1) and indolent IgA multiple myeloma (n = 1). Conclusion : This study highlights that factors other than low CD4(+) cell count and high HIV viral load may be associated with the occurrence of PML. Further studies are warranted to investigate in greater detail the immunologic characteristics of PWH with immune-virological control who develop PML.