Treatment options for progressive multifocal leukoencephalopathy in HIV-infected persons: current status and future directions

ABSTRACT

Progressive multifocal encephalopathy (PML) caused by JC virus was frequently encountered in AIDS patients before combination antiretroviral therapy (cART). Incidence decreased and the outcome improved with cART. The immune reconstitution with cART is beneficial for HIV-infected patients and is an effective treatment for PML. However, when it is excessive an inflammatory response immune syndrome might occur with deterioration of PML. So far, no specific therapy has proven efficacious in small clinical trials in spite of some optimistic case reports. Combination of drugs targeted at different stages of JC virus life cycle seems to have a better effect. Passive and active immune therapies, immune competence “boosters” appear promising. New future approaches such as gene editing are not far away.

Key issues

• JCV causes PML and other neurologic illnesses in immunocompromised persons.

• HIV-associated PML has drastically decreased and the outcome improved with cART.

• Immune reconstitution might clear the JCV, but when it is excessive, it could led to PML-IRIS.

• Current treatments are rarely effective when used alone.

• A combination therapy targeting several steps of JCV life cycle and host factors might be more efficacious.

• Immune competence ‘boosters’, passive and active immune therapies is a promising future area of research.

• Blocking the CTL exhaustion might increase the vaccines efficacy.

• Gene editing targeting both JCV and HIV life cycles and host factors is a reality.

• Designing and conducting clinical trials is still a tremendous challenge due to logistical and feasibility factors and cost.

• An international collaboration is necessary.