Adenovirus infection in allogeneic hematopoietic cell transplantation

Abstract

Adenovirus (AdV) infection occurs in 0–20% of patients in the first 3–4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end‐organ damage, and 6‐month overall mortality. The main risk factors for AdV infection are T‐cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III–IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 109/L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre‐emptive start of cidofovir as viral load exceeds the threshold of ≥102–3 copies/mL in blood and/or 106 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus‐specific T‐cell immunity in the first few months post‐HCT by the administration of donor‐derived or third‐party‐donor‐derived virus‐specific T‐cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited.

Cutaneous Applications of the Antiviral Drug Cidofovir: A Review

“…Furthermore, while the current systemic administration of cidofovir is available in IV formulation only, its novel lipid conjugate, brincidofovir, has good oral bioavailability and lower rates of nephrotoxicity and myelotoxicity, making it a favorable alternative to cidofovir. Brincidofovir has been developed as a countermeasure to smallpox and is being investigated for the treatment of many other double-stranded DNA viruses, such as cytomegalovirus, adenovirus, human herpes virus-6, BK virus, vaccinia virus, molluscum contagiosum virus, and even cidofovir-resistant varicella zoster virus [66][67][68]. Recently, brincidofovir was used to treat laryngeal HPV16+ squamous cell carcinoma in situ and recurrent respiratory papillomatosis.…”

Respiratory adenovirus infections in children: a focus on Africa

“…Although HAdV is considered an all-year virus, its prevalence differs between the northern and southern hemispheres [ 13 , 14 ]. Most studies on HAdV epidemiology have been conducted during outbreaks and/or in specific populations, such as hospitalized children or immunocompromised individuals who are more susceptible to HAdV infection [ 14 , 15 ]. Although the contribution of HAdV pediatric respiratory infections is well documented in high- income countries, limited data are available from African countries.…”

“…HAdV can cause severe and fatal disease in both immunocompetent and immunocompromised hosts, particularly in the pediatric under-5 population [ 6 , 39 ]. Among immunocompromised patients, infection is most frequently described in hematopoietic stem cell transplant recipients and solid organ transplant recipients [ 15 , 39 ]. A South African study comparing LRTI cause in hospitalized under-5 children living and not living with HIV showed a significantly higher proportion of adenovirus infections in children living with HIV (32 vs. 27%, P = 0.013) [ 40 ].…”

“…Cidofovir has emerged as the currently preferred antiviral agent for treatment of adenoviral disease, although it is only available intravenously. Cidofovir-related nephrotoxicity and myelotoxicity is a concern, and has been described in high-risk hematopoietic stem cell transplant patients [ 15 , 39 ], However, only a minority of immunocompetent children treated with cidofovir seem to develop nephrotoxicity. Recently, brincidofovir, an oral formulation lipid conjugate of cidofovir, has been reported to have good oral bioavailability, and reduced nephrotoxicity and bone marrow toxicity compared with cidofovir [ 48 ].…”