Protective viral interference in HEV-ZIKV coinfection: Serological evidence and foetomaternal outcomes in HIV-infected and immunocompetent pregnant women in Nigeria

BACKGROUND: Viral interference - where one viral infection affects susceptibility to another - remains poorly characterized in pregnancy. We investigated whether hepatitis E virus (HEV) and Zika virus (ZIKV) coinfection demonstrates interference patterns and affects foetomaternal outcomes. METHODS: We conducted a cross-sectional seroepidemiological study across three tertiary hospitals in Nigeria from December 2020 to November 2021. We recruited 619 pregnant women aged 15-49 years attending antenatal care or HIV treatment centres. We tested sera for HEV (IgG/IgM) and ZIKV (IgG) antibodies using validated immunoblot assays and calculated viral interference coefficients. FINDINGS: Among 619 pregnant women (238 HIV-infected, 381 immunocompetent), HEV seropositivity was 16.3% (101/619) and ZIKV seropositivity was 19.9% (123/619). Coinfection occurred in 8.1% (50/619), significantly below the expected rate of 13.2% (interference coefficient -39%, P = 0.002), indicating negative viral interference across HIV status and geographical regions. No maternal deaths occurred among coinfected women (0/50) compared with 6.0% (6/100) among HEV mono-infected women. Composite severe maternal outcomes showed an inverse association gradient: 34.0% in HEV mono-infection, 20.3% in ZIKV mono-infection and 16.0% in coinfection (P = 0.04). INTERPRETATION: HEV-ZIKV coinfection demonstrates significant negative viral interference with inverse associations with severe maternal outcomes, challenging assumptions about viral co-infections and warranting mechanistic investigation.