Assessment and management of dengue

Dear Editor

I read “Assessment and Management of Dengue” with interest. It could be strengthened by including information on a recent NIH-funded Phase 2 clinical trial for a novel dengue therapeutic. The article provides a comprehensive overview of current diagnostic approaches but could benefit from discussing emerging antiviral treatments. Specifically, I would like to bring to your attention an ongoing NIAID-supported Phase 2 clinical trial evaluating AV-1, one of the first monoclonal antibody therapies being investigated for dengue. This human monoclonal antibody, developed by AbViro, aims to neutralize the dengue virus, potentially reducing morbidity and mortality associated with the disease. This approach significantly differs from current management strategies, which rely solely on supportive care.

The trial (ClinicalTrials.gov identifier: NCT06799741), conducted at the Johns Hopkins Bloomberg School of Public Health and the University of Vermont Vaccine Testing Center, enrolls at least 84 healthy volunteers. The study is designed to assess the safety and efficacy of AV-1 at various doses following exposure to an attenuated dengue virus strain (a weakened form of the virus unlikely to cause severe illness). The trial investigates AV-1’s ability to mitigate symptoms when administered either before or after dengue virus infection.

Following an initial screening and physical examination, volunteers are randomly assigned to one of two groups: one receiving AV-1 one day before being challenged with the attenuated dengue virus and the other receiving AV-1 four days after exposure. Each dosage group includes 12 participants receiving AV-1 and 2 receiving placebo at one of three dosage levels—100 mg, 300 mg, or 900 mg—administered via a 60-minute intravenous infusion.

To assess AV-1’s potential as a dengue treatment, each volunteer is also inoculated with the attenuated dengue virus. Previous studies using this challenge virus indicated that most volunteers develop a rash and mild symptoms such as joint and muscle pain or headache. Still, none experienced severe dengue or dengue fever. Volunteers are monitored through regular follow-up visits over at least 155 days. Researchers collect physical exam data, diary cards, and blood samples to evaluate immune responses, viral clearance, and, most importantly, symptom progression and severity. The study's primary outcomes are the reduction in symptom severity and duration of illness.

Given the substantial global burden of dengue and the current lack of specific antiviral treatments, this study represents a significant advancement. More details can be found in the NIH press release dated February 11, 2025. Highlighting this study would give readers a more complete picture of the evolving dengue treatment landscape and the potential for future targeted therapies.

National Institute of Allergy and Infectious Diseases (NIAID). A Phase 2 study to evaluate the safety and efficacy of AV-1, a human monoclonal antibody, against dengue virus (DENV). ClinicalTrials.gov identifier: NCT06799741. Updated February 11, 2025. Accessed March 19, 2025. https://clinicaltrials.gov/study/NCT06799741