How are adenovirus infections treated following hematopoietic stem cell transplantation (HSCT)?

Updated: Apr 15, 2021
  • Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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The increasing use of unrelated donors and umbilical cord blood often requires increasing use of T-cell–depleted transplants to prevent acute graft-versus-host disease. Risk of mortality due to reactivated viruses is proportional to the degree of HLA-mismatch between donor and recipient and time to T-cell reconstitution. T-cell–depleted grafts, delayed engraftment, and high levels of viremia are major risk factors for adenoviral disease after HSCT. Engraftment or reconstitution of T-cell–specific immunity is vital to recovery from pulmonary or disseminated infection, regardless of antiviral therapy. [36]  In one study involving children who underwent hematopoietic stem cell transplantation, all patients who died of adenoviral infection lacked specific T cells against adenovirus. [36]  Rapid transfer of donor-derived, virus-specific memory T cells offers substantial promise in controlling severe disease with low adverse effects in those with intolerance or nonresponse to antivirals. Indeed, banking of donor-derived and third-party–derived virus-specific T cells is being explored for use in HSCT and can provide broad defense against multiple endemic viruses. [37, 38, 39, 40]

Some benefit of both ribavirin and cidofovir has been documented in case series, as demonstrated by decreased viremia and concomitant clinical improvement with antiviral therapy. [41, 42, 43, 44]  Intravenous cidofovir treatment resulted in complete clinical resolution in 56 of 57 pediatric HSCT recipients, in whom the virus became undetectable without dose-limited nephrotoxicity. [45]  Intravenous immunoglobulin (IVIG) has also been used in conjunction with antivirals. [46, 47]

A significant advance in antiviral therapy, brincidofovir is a lipid conjugate of cidofovir that may be given orally and demonstrates potent activity against adenovirus. While diarrhea may be significant, it appears to have significantly reduced bone marrow or renal toxicity in clinical studies with limited numbers of patients in an expanded access program. No significant resistance to brincidofovir has been observed. Preventive treatment and therapy initiated early into viremia after HSCT appears to reduce viral burden, severe disease, and overall mortality. [48, 49, 50] The biopharmaceutical company, Chimerix, Inc, ended its clinical trials of brincidofovir for the treatment of adenovirus infections in May 2019. Remaining drug was made available via expanded access for serious adenoviral and orthopoxvirus infections until the supply exhausted in August 2020.  Brincidofovir is not FDA-approved nor available via expanded access at this time.  [51]

A rabbit model has demonstrated in vitro and in vivo effectiveness of topical filocidofivir similar to cidofovir against ocular adenovirus infection. [52]

 


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