Antiviral Treatment of Human Influenza A(H5N1) Infection: Treatment Timing, Clinical Outcomes, Virological Outcomes, and Antiviral Resistance: A Systematic Review
Haaly Al Muaafy Ruslan Musanip1, Juniastuti1,2*, Kaiser Gerald Handoyo1, Rizal Rachbini Mahlevi¹
Abstract
Human influenza A(H5N1) infection remains a clinically important zoonotic disease, but evidence on antiviral effectiveness is limited by observational designs, heterogeneous treatment timing, and potentially overlapping patient populations. This systematic review synthesized evidence on antiviral regimens, treatment timing, clinical and virological outcomes, and antiviral resistance in laboratory-confirmed human A(H5N1) infection. A systematic search of PubMed, Scopus, and ScienceDirect was conducted from database inception to 1 July 2026. Methodological quality was assessed using the Newcastle–Ottawa Scale and the JBI Case Series Checklist. The clinical and methodological characteristics varied across studies; consequently, the findings were synthesized narratively. Potential population overlap was considered when synthesizing findings across publications to avoid duplicate aggregation of patient data. Of 2,329 records identified, 22 publications were included. Oseltamivir treatment was associated with a lower hazard of death than no documented anti-influenza antiviral treatment (adjusted hazard ratio 0.51, 95% confidence interval 0.34–0.77). Treatment within 2 days showed lower odds of death, although the overall estimate was not statistically significant (adjusted odds ratio 0.17, 95% confidence interval 0.03–1.04). Among patients without respiratory failure at treatment initiation, earlier treatment was associated with lower mortality (adjusted odds ratio 0.17, 95% confidence interval 0.03–0.89). Evidence for other antivirals was limited, and one confirmed treatment-emergent H274Y neuraminidase resistance event was identified. Overall, oseltamivir, particularly when initiated early and before advanced respiratory failure, was associated with improved clinical outcomes, although causal inference remains limited by confounding, heterogeneity, and potentially overlapping study populations.
Keywords
influenza A(H5N1); oseltamivir; antiviral therapy; treatment timing; antiviral resistance
Cite This Article
Musanip, H. A. M. R., Juniastuti., Handoyo, K. G., Mahlevi, R. R. (2026). Antiviral Treatment of Human Influenza A(H5N1) Infection: Treatment Timing, Clinical Outcomes, Virological Outcomes, and Antiviral Resistance: A Systematic Review. International Journal of Scientific Advances (IJSCIA), Volume 7| Issue 5: Sep – Oct 2026, Pages 644-654 URL: https://www.ijscia.com/wp-content/uploads/2026/10/Volume7-Issue5-Sep-Oct-No.1085-644-654.pdf
Volume 7 | Issue 5: Sep – Oct 2026
