Exploring the effects of Schistosoma mansoni infection treatment on female HIV susceptibility

Background: The prevalence of infection with the trematode Schistosoma mansoni (Sm) exceeds 50% in many regions of sub-Saharan Africa, and there are ecologic and epidemiologic links with HIV acquisition. The biological underpinning of this association is not clear, especially since Sm, unlike the related species S. haematobium, classically does not directly involve the genital mucosa. Methods: HIV-negative, schistosomiasis-infected adult women from Entebbe, Uganda were provided with weight-based oral praziquantel according to Ugandan clinical guidelines. Mucosal and blood samples were collected before treatment, and 4 and 8 weeks later. The effect on cervical HIV susceptibility and genital inflammation was quantified using an ex vivo HIV entry assay. Results: Schistosomiasis treatment induced a profound (>2 fold) reduction of HIV entry into CD4+ T cells that was sustained up to two months, and was apparent in both cervix and blood. Transient mucosal immune activation was seen after Sm treatment, with elevated genital levels of interferon-α and interleukin-1α. Transcriptomic analysis of blood mononuclear cells confirmed post-treatment up-regulation of Type I Interferon (IFN-I) pathways and partial reversal of Sm-dysregulated interferon signalling. IFN-α-mediated blockade of virus entry into PBMC-derived CD4+ T cells was confirmed ex vivo. Expression of α4β7+ on blood CD4 T cells was elevated in participants with high worm burden, but was not reduced after Sm treatment. Conclusions: Schistosomiasis treatment and/or prevention may reduce HIV susceptibility, potentially through de-repression of IFN-I pathways. Given the high prevalence of this neglected tropical infection, further work to confirm and expand these observations is merited.

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