aVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA bNational HIV and Retrovirology Laboratories, JC Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada cPartners in Health Research and Development, Kenya Medical Research Institute, Thika, Kenya dInfectious Disease Institute eDepartment of Medicine, Makerere University, Kampala, Uganda fDepartment of Global Health, University of Washington, Seattle, Washington, USA gCentre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya hDepartment of Medical Microbiology and Infectious Disease, University of Manitoba, Winnipeg, Manitoba, Canada iDepartment of Epidemiology jDepartment of Medicine kDepartment of Pediatrics, University of Washington, Seattle, Washington, USA.
AIDS. 2019 Nov 15;33(14):2125-2136. doi: 10.1097/QAD.0000000000002323.
Oral tenofovir-based pre-exposure prophylaxis (PrEP) is an important tool for prevention of new HIV infections, which also reduces subclinical herpes simplex virus type 2 (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.
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.
We compared local and systemic innate and T-cell characteristics in samples collected during PrEP usage and 2 months after PrEP discontinuation.
We found that frequencies of cervical CCR5CD4 cells, regulatory T cells, and tissue macrophages were significantly reduced during PrEP use compared with after PrEP discontinuation. In contrast, peripheral blood CD4 and CD8 T cells expressing markers of activation and trafficking were increased during PrEP usage.
Together, our data are consistent with PrEP altering immunity differentially in the female genital tract compared with circulation in HSV-2+ women. Further study including comparison with 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.
口服替诺福韦为基础的暴露前预防（PrEP）是预防新的 HIV 感染的重要工具，它也可以减少 HIV 阴性、HSV-2 血清阳性个体中无症状单纯疱疹病毒 2 型（HSV-2）脱落和症状性病变。然而，PrEP 对黏膜免疫的影响尚未详细研究。
在这里，我们评估了配对的生殖器组织和全身免疫谱，以描述 PrEP 在性接触 HIV 的 HIV 阴性、HSV-2 血清阳性非洲女性中的黏膜免疫作用。
我们比较了 PrEP 使用期间和 PrEP 停药后 2 个月收集的样本中的局部和全身先天和 T 细胞特征。
我们发现，与 PrEP 停药后相比，宫颈 CCR5CD4 细胞、调节性 T 细胞和组织巨噬细胞的频率在 PrEP 使用期间显著降低。相比之下，在 PrEP 使用期间，外周血 CD4 和 CD8 T 细胞表达激活和归巢标志物的频率增加。
综上所述，我们的数据与 PrEP 在 HSV-2+女性中改变生殖道与循环免疫的差异一致。需要进一步的研究，包括与 HSV-2 阴性女性的比较，以确定这些影响的总体影响和机制。这些结果表明，迫切需要研究人类黏膜隔室，以描述对黏膜感染的免疫反应。
