Approach to adenovirus infections in the setting of hematopoietic cell transplantation

To review risk-based pre-emptive treatment for adenovirus (ADV) based on quantitative PCR (qPCR) and to provide an update on clinical trials of brincidofovir (BCV) and ADV-specific cytotoxic T lymphocytes (ADV-CTLs).

ADV qPCR in various body compartments enables distinction of clinically significant infection and assessment of treatment responses. Plasma ADV qPCR monitoring and aggressive pre-emptive treatment is recommended for high-risk patients. Pre-emptive therapy at low viral load is associated with faster virologic response and improved outcomes. BCV has demonstrated virologic responses against all clinically significant ADV serotypes. Prolonged administration of oral BCV may be limited by gastrointestinal toxicity; an intravenous BCV formulation does not show gastrointestinal toxicity in early studies. ADV-CTLs can be generated from ADV-seropositive individuals using a variety of systems. Banked ADV-CTLs can achieve durable responses in patients for whom no donor-derived cell therapy product is available.

Disseminated ADV disease is associated with substantial mortality in hematopoietic cell transplant recipients. Routine monitoring by plasma ADV qPCR and pre-emptive therapy at low viral load are associated with improved outcomes in high-risk patients. BCV and ADV-CTLs are promising modalities currently undergoing clinical trials.