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Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women.
Nature Medicine ( IF 58.7 ) Pub Date : 2018-May-01 , DOI: 10.1038/nm.4506
Lyle R McKinnon , Lenine J Liebenberg , Nonhlanhla Yende-Zuma , Derseree Archary , Sinaye Ngcapu , Aida Sivro , Nico Nagelkerke , Jose Gerardo Garcia Lerma , Angela D Kashuba , Lindi Masson , Leila E Mansoor , Quarraisha Abdool Karim , Salim S Abdool Karim , Jo-Ann S Passmore

Several clinical trials have demonstrated that antiretroviral (ARV) drugs taken as pre-exposure prophylaxis (PrEP) can prevent HIV infection, with the magnitude of protection ranging from -49 to 86% (refs. ). Although these divergent outcomes are thought to be due primarily to differences in product adherence, biological factors likely contribute. Despite selective recruitment of higher-risk participants for prevention trials, HIV risk is heterogeneous even within higher-risk groups. To determine whether this heterogeneity could influence patient outcomes following PrEP, we undertook a post hoc prospective analysis of results from the CAPRISA 004 trial for 1% tenofovir gel (n = 774 patients), one of the first trials to demonstrate protection against HIV infection. Concentrations of nine proinflammatory cytokines were measured in cervicovaginal lavages at >2,000 visits, and a graduated cytokine score was used to define genital inflammation. In women without genital inflammation, tenofovir was 57% protective against HIV (95% confidence interval (CI): 7-80%) but was 3% protective (95% CI: -104-54%) if genital inflammation was present. Among women who highly adhered to the gel, tenofovir protection was 75% (95% CI: 25-92%) in women without inflammation compared to -10% (95% CI: -184-57%) in women with inflammation. Immunological predictors of HIV risk may modify the effectiveness of tools for HIV prevention; reducing genital inflammation in women may augment HIV prevention efforts.

中文翻译:

生殖器炎症削弱了替诺福韦凝胶在预防女性感染艾滋病毒中的功效。

多项临床试验表明,作为暴露前预防(PrEP)的抗逆转录病毒(ARV)药物可以预防HIV感染,其保护程度为-49%至86%(参考)。尽管这些不同的结果被认为主要是由于产品依从性的差异所致,但生物学因素可能会有所贡献。尽管有选择地招募了较高风险的参与者进行预防试验,但即使在较高风险的人群中,艾滋病毒的风险也各不相同。为了确定这种异质性是否会影响PrEP后的患者预后,我们对CAPRISA 004试验中1%替诺福韦凝胶(n = 774名患者)的结果进行了事后前瞻性分析,这是第一批证明可预防HIV感染的试验之一。在> 2,000次就诊时,在宫颈阴道灌洗液中测量了9种促炎细胞因子的浓度,并使用分级的细胞因子评分来定义生殖器炎症。在没有生殖器炎症的女性中,替诺福韦对HIV的防护率为57%(95%可信区间(CI):7-80%),但如果存在生殖器炎症,则为3%(95%CI:-104-54%)。在高度粘附于凝胶的女性中,无炎症女性的替诺福韦保护率为75%(95%CI:25-92%),而炎症女性则为-10%(95%CI:-184-57%)。HIV风险的免疫学预测因子可能会改变HIV预防工具的有效性;减少女性生殖器炎症可能会增加艾滋病毒的预防工作。在没有生殖器炎症的女性中,替诺福韦对HIV的防护率为57%(95%可信区间(CI):7-80%),但如果存在生殖器炎症,则为3%(95%CI:-104-54%)。在高度粘附于凝胶的女性中,无炎症女性的替诺福韦保护率为75%(95%CI:25-92%),而炎症女性则为-10%(95%CI:-184-57%)。HIV风险的免疫学预测因子可能会改变HIV预防工具的有效性;减少女性生殖器炎症可能会增加艾滋病毒的预防工作。在没有生殖器炎症的女性中,替诺福韦对HIV的防护率为57%(95%可信区间(CI):7-80%),但如果存在生殖器炎症,则为3%(95%CI:-104-54%)。在高度粘附于凝胶的女性中,无炎症女性的替诺福韦保护率为75%(95%CI:25-92%),而炎症女性则为-10%(95%CI:-184-57%)。HIV风险的免疫学预测因子可能会改变HIV预防工具的有效性;减少女性生殖器炎症可能会增加艾滋病毒的预防工作。-184-57%)患有炎症的女性。HIV风险的免疫学预测因子可能会改变HIV预防工具的有效性;减少女性生殖器炎症可能会增加艾滋病毒的预防工作。-184-57%)患有炎症的女性。HIV风险的免疫学预测因子可能会改变HIV预防工具的有效性;减少女性生殖器炎症可能会增加艾滋病毒的预防工作。
更新日期:2018-02-27
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