Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are used for HIV treatment and prevention. Previously, we found that topical rectal tenofovir gel caused immunological changes in the mucosa. Here we assessed the effect of oral TDF/FTC in three HIV pre-exposure prophylaxis trials, two with gastrointestinal and one with cervicovaginal biopsies. TDF/FTC induced type I/III interferon-related (IFN I/III) genes in the gastrointestinal tract, but not blood, with strong correlations between the two independent rectal biopsy groups (Spearman r=0.91) and between the rectum and duodenum (r=0.81). Gene set testing also indicated stimulation of type I/III pathways in the ectocervix, as well as of cellular proliferation in the duodenum. mRNA sequencing, digital droplet PCR, proteomics, and immunofluorescence staining confirmed IFN I/III pathway stimulation in the gastrointestinal tract. Thus, oral TDF/FTC stimulates an IFN-I/III signature throughout the gut, which could increase antiviral efficacy but also cause chronic immune activation in HIV prevention and treatment settings.

中文翻译：

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在没有HIV感染的情况下，常用的抗逆转录病毒药物治疗会在肠道中诱导I / III型干扰素签名

替诺福韦富马酸替索罗非酯（TDF）和恩曲他滨（FTC）用于治疗和预防HIV。以前，我们发现局部直肠替诺福韦凝胶引起粘膜的免疫学改变。在这里，我们在三项HIV暴露前预防试验中评估了口服TDF / FTC的效果，其中两项进行了胃肠道检查，一项进行了宫颈阴道活检。TDF / FTC在胃肠道而非血液中诱导了I / III型干扰素相关（IFN I / III）基因，在两个独立的直肠活检组之间（Spearman r = 0.91）以及在直肠和十二指肠之间存在强相关性（ r = 0.81）。基因组测试还表明刺激了子宫颈中的I / III型通路以及十二指肠中的细胞增殖。mRNA测序，数字液滴PCR，蛋白质组学，免疫荧光染色证实了胃肠道中的IFN I / III途径刺激。因此，口服TDF / FTC会刺激整个肠道的IFN-I / III信号，这可能会提高抗病毒功效，但也会在HIV预防和治疗环境中引起慢性免疫激活。