Salmona Maud, Feghoul Linda, LeGoff Jérôme
Université de Paris, Inserm U976, Insight team, F-75010, Paris France Unité Virologie et greffes, Département des agents infectieux, Hôpital Saint-Louis, APHP, F-75010 Paris, France.
Virologie (Montrouge). 2021 Feb 1;25(1):43-56. doi: 10.1684/vir.2021.0883.
Human adenoviruses (HAdV) infections are generally mild and resolve spontaneously in immunocompetent individuals. However, HAdV infections can have a major clinical impact in immunocompromised patients. HAdV infections are associated with high morbidity and mortality in recipients of allogeneic stem cell transplants, particularly children. There are currently no drug approved for the treatment of HAdV infections. Nevertheless, some nucleotide analogues are used under temporary authorization for use, such as cidofovir or brincidofovir. Cidofovir inhibits the replication of HAdV but its nephrotoxicity and its low tissue concentrations severely limit its use. Brincidofovir, a cidofovir prodrug, with a better bioavailability and no nephrotoxicity was evaluated in the treatment of HAdV infections, but its development was recently stopped and it is currently no longer available in ATU. Other molecules with anti-HAdV activity are still in early stages of development. Adoptive immunotherapy by adenovirus-specific T-cell transfer is an interesting option but should be anticipated in patients with high risks of disseminated infections. Given the small therapeutic panel available, it is critical to continue the search for new anti-HAdV molecules, which remains mainly conducted by academic laboratories.
人腺病毒(HAdV)感染在免疫功能正常的个体中通常症状较轻且可自发缓解。然而,HAdV感染在免疫功能低下的患者中可产生重大临床影响。HAdV感染在异基因干细胞移植受者中,尤其是儿童中,与高发病率和死亡率相关。目前尚无获批用于治疗HAdV感染的药物。尽管如此,一些核苷酸类似物在临时授权下使用,如西多福韦或布林西多福韦。西多福韦可抑制HAdV的复制,但其肾毒性和低组织浓度严重限制了其应用。布林西多福韦是西多福韦的前药,具有更好的生物利用度且无肾毒性,曾被评估用于治疗HAdV感染,但其研发最近已停止,目前在ATU不再可用。其他具有抗HAdV活性的分子仍处于研发早期阶段。通过腺病毒特异性T细胞转移进行的过继性免疫疗法是一个有吸引力的选择,但对于有播散性感染高风险的患者应提前考虑。鉴于可用的治疗药物有限,继续寻找新的抗HAdV分子至关重要,这一工作主要仍由学术实验室开展。