title: Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients.
abstract: No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥ 1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.
authors.affiliation: Transplant Infectious Diseases Program, Department of Internal Medicine, University of Nebraska Medical Center, Lincoln, Nebraska 68198-5400, USA. dflorescu@unmc.edu
authors.forename: Diana F
authors.initials: DF
authors.lastname: Florescu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Pergam
authors.forename: Michael N
authors.initials: MN
authors.lastname: Neely
authors.forename: Fang
authors.initials: F
authors.lastname: Qiu
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
authors.forename: SingSing
authors.initials: S
authors.lastname: Way
authors.forename: Jane
authors.initials: J
authors.lastname: Sande
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lewinsohn
authors.forename: Judith A
authors.initials: JA
authors.lastname: Guzman-Cottrill
authors.forename: Michael L
authors.initials: ML
authors.lastname: Graham
authors.forename: Genovefa
authors.initials: G
authors.lastname: Papanicolaou
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: Joseph
authors.initials: J
authors.lastname: Rigdon
authors.forename: Wendy
authors.initials: W
authors.lastname: Painter
authors.forename: Herve
authors.initials: H
authors.lastname: Mommeja-Marin
authors.forename: Randall
authors.initials: R
authors.lastname: Lanier
authors.forename: Maggie
authors.initials: M
authors.lastname: Anderson
authors.forename: Charles
authors.initials: C
authors.lastname: van der Horst
mesh_terms: D000256:Adenoviridae / Q000187:drug effects* / Q000276:immunology; D000257:Adenoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects* / Q000276:immunology; D007223:Infant; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; C525733:brincidofovir; D003596:Cytosine