Browsing by Author "Lund, Jennifer M."

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    HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV- 1-Exposed Seronegative Women on Oral Preexposure Prophylaxis
    (Journal of virology, 2016) Lund, Jennifer M.; Broliden, Kristina; Pyra, Maria N.; Thomas, Katherine K.; Donnell, Deborah; Irungu, Elizabeth; Muwonge, Timothy R.; Mugo, Nelly; Manohar, Madhuri; Jansson, Marianne; Mackelprang, Romel; Marzinke, Mark A.; Baeten, Jared M.; Lingappa, Jairam R.
    Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P 0.008). Using a cutoff of>90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (P 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals.
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    Pre-exposure prophylaxis differentially alters circulating and mucosal immune cell activation in HSV-2 seropositive women
    (AIDS (London, England), 2019) Richert-Spuhler, Laura E.; Pattacini, Laura; Plews, Margot; Irungu, Elizabeth; Muwonge, Timothy R.; Katabira, Elly; Mugo, Nelly; Meyers, Adrienne F.A.; Celum, Connie; Baeten, Jared M.; Lingappa, Jairam R.; Lund, Jennifer M.
    Oral tenofovir-based pre-exposure prophylaxis (PrEP) is an important tool for prevention of new HIV infections, which also reduces subclinical HSV-2 shedding and symptomatic lesions in HIV-negative, HSV-2-seropositive individuals. However, the impact of PrEP on mucosal immunity has not been examined in detail. Design: Here we evaluate paired genital tissue and systemic immune profiles to characterize the immunological effects of PrEP in HIV-negative, HSV-2-seropositive African women sexually exposed to HIV. Methods: We compared local and systemic innate and T-cell characteristics in samples collected during PrEP usage and two months after PrEP discontinuation. Results: We found that frequencies of cervical CCR5+CD4+ cells, regulatory T-cells, and tissue macrophages were significantly reduced during PrEP use compared to after PrEP discontinuation. In contrast, peripheral blood CD4+ and CD8+ T-cells expressing markers of activation and trafficking were increased during PrEP usage. Conclusions: Together, our data are consistent with PrEP altering immunity differentially in the female genital tract compared to circulation in HSV-2+ women. Further study including comparison to HSV-2 negative women is needed to define the overall impact and mechanisms underlying these effects. These results point to the critical need to study the human mucosal compartment to characterize immune responses to mucosal infections