Abstract
Background: Progressive multifocal leukoencephalopathy (PML) caused by JC virus (JCV) remains a severe opportunistic infection in people with advanced HIV infection. Combined antiretroviral therapy (cART) is the cornerstone of management, but prognosis remains poor in many cases and effective adjunctive therapies are lacking. Programmed death-1 (PD-1) blockade with pembrolizumab has emerged as a potential strategy to restore antiviral immune responses.
Methods: We conducted a retrospective case series of four adults with HIV-associated PML treated with pem brolizumab under compassionate use between January 2023 and May 2025 at a tertiary hospital in Spain. Diagnosis was established by compatible neurological and radiological findings together with detection of JCV-DNA in cerebrospinal fluid (CSF) by polymerase chain reaction. All patients received pembrolizumab (2 mg/kg every 3 weeks for at least one cycle) combined with bictegravir/emtricitabine/tenofovir alafenamide. Clinical, virological, immunological and safety data were collected.
Results: Four patients were included, three men and one woman, with a median age of 43 years (interquartile range [IQR] 25-56). Median baseline CD4+ T-cell count was 142 cells/µL (IQR 9-390), median plasma HIV viral load was 5.5 * 10^5 copies/mL, and median baseline NIHSS score was 3 (IQR 2-7). After pembroli zumab initiation, all patients showed neurological improvement, virological response, or both. Two patients experienced early neurological improvement, with NIHSS decreasing from 4 to 2 and from 3 to 1. In the other two patients, CSF JCV-PCR decreased from 5 * 10^5 copies/mL to undetectable and from 1 * 10^6 to 150 copies/mL, respectively, accompanied by parallel neurological improvement. Median CD4+ T-cell increase during early follow-up was +35 cells/µL (IQR 20-60). Treatment was well tolerated. No immune-related ad verse events, infusion reactions, or vascular complications were observed. One patient developed a transient low-grade fever that resolved spontaneously without treatment interruption.
Conclusions: In this small case series, pembrolizumab combined with cART was feasible and well tolerated in patients with HIV-associated PML and was associated with virological and neurological improvement. These f indings support further evaluation of PD-1 blockade as adjunctive therapy in selected cases of HIV-associ ated PML.
DOI: doi.org/10.63721/26JCTC0137
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