Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women.
Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women.
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DOI：
10.1038/nm.4506
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发表时间：
2018-05
期刊：
影响因子：
82.9
通讯作者：
Passmore JS
中科院分区：
文献类型：
--
作者：
McKinnon LR;Liebenberg LJ;Yende-Zuma N;Archary D;Ngcapu S;Sivro A;Nagelkerke N;Garcia Lerma JG;Kashuba AD;Masson L;Mansoor LE;Karim QA;Karim SSA;Passmore JS
一些临床试验表明，抗逆转录病毒（ARV）药物，作为暴露前预防（PrEP），可以预防艾滋病毒感染，保护程度从-49%至86%不等。虽然这些不同的结果被认为主要是由于产品依从性，但生物学因素可能也有影响。尽管有选择地招募高风险参与者进行预防试验，但艾滋病毒风险是异质的，即使在高风险群体中也是如此。为了确定这种异质性是否会影响PrEP结果，我们对CAPRISA 004替诺福韦1%凝胶试验（n=774）进行了事后前瞻性分析，这是首批证明预防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的保护率为57%（95% CI：7 - 80%），而如果存在生殖器炎症，则为3%（95% CI：-104至54%）。在高凝胶粘附者中，替诺福韦的保护作用在无炎症的女性中为75%（95%CI：25 - 92%），而在有炎症的女性中为-10%（95%CI：-184至57%）。HIV风险的宿主免疫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HIV预防工作。
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%. While these divergent outcomes are thought to be due primarily to 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 PrEP outcomes, we undertook a post-hoc prospective analysis of the CAPRISA 004 tenofovir 1% gel trial (n=774), one of the first trials to demonstrate protection against HIV infection. Concentrations of nine pro-inflammatory 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% CI: 7 to 80%), compared to 3% (95% CI: −104 to 54%) if genital inflammation was present. Among high gel adherers, tenofovir protection was 75% (95% CI: 25 to 92%) in women without inflammation compared to −10% (95% CI: −184 to 57%) in women with inflammation. Host immune predictors of HIV risk may modify the effectiveness of HIV prevention tools; reducing genital inflammation in women may augment HIV prevention efforts.
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DOI：
10.1097/qai.0000000000000607
发表时间：
2015-07-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Kashuba AD;Gengiah TN;Werner L;Yang KH;White NR;Karim QA;Abdool Karim SS
通讯作者：
Abdool Karim SS
影响因子：
4.3
作者：
Nagelkerke NJ;Arora P;Jha P;Williams B;McKinnon L;de Vlas SJ
通讯作者：
de Vlas SJ
影响因子：
56.3
作者：
Boily, Marie-Claude;Baggaley, Rebecca F.;Wang, Lei;Masse, Benoit;White, Richard G.;Hayes, Richard J.;Alary, Michel
通讯作者：
Alary, Michel
影响因子：
16.1
作者：
Heffron, Renee;McClelland, R. Scott;Baeten, Jared M.
通讯作者：
Baeten, Jared M.
影响因子：
2.5
作者：
Karim QA;Kharsany AB;Frohlich JA;Baxter C;Yende N;Mansoor LE;Mlisana KP;Maarschalk S;Arulappan N;Grobler A;Sibeko S;Omar Z;Gengiah TN;Mlotshwa M;Samsunder N;Karim SS
通讯作者：
Karim SS