Sofosbuvir as post-exposure prophylaxis for yellow fever-associated viscerotropic disease (YEL-AVD)

J Antimicrob Chemother. 2025 Jan 17:dkae484. doi: 10.1093/jac/dkae484. Online ahead of print.

Abstract

Objectives: Yellow fever-associated viscerotropic disease (YEL-AVD) is a rare but serious complication arising from administration of live-attenuated yellow fever vaccine to individuals with risk factors such as thymectomy. At present there is no evidence-based treatment, and case fatality rates are high. Sofosbuvir, an NS5B nucleotide inhibitor, has activity against yellow fever virus in vitro and in vivo.

Patient and methods: Here we describe clinical and virological response to use of off-licence sofosbuvir as post-exposure prophylaxis for a patient inadvertently given yellow fever vaccine despite previous thymectomy.

Results: A 14-day course of oral sofosbuvir was administered in an outpatient setting with regular clinical and biochemical monitoring. The patient remained well without developing clinical features of YEL-AVD and did not experience adverse effects from the treatment.

Conclusions: This supports the use of sofosbuvir as post-exposure prophylaxis in patients at high risk of developing YEL-AVD. Ongoing trials of efficacy of sofosbuvir in yellow fever infection may result in stronger support for this approach in the future.