A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007).
A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007).
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DOI：
10.1371/journal.pone.0060147
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mayer K
中科院分区：
文献类型：
--
作者：
McGowan I;Hoesley C;Cranston RD;Andrew P;Janocko L;Dai JY;Carballo-Dieguez A;Ayudhya RK;Piper J;Hladik F;Mayer K
直肠杀微生物剂是需要的，以减少与无保护的接受性肛交相关的艾滋病毒感染的风险。MTN-007研究旨在评估1%替诺福韦凝胶的安全性(一般和粘膜)、粘附性和可接受性。受试者以1：1：1：1的比例随机接受1%替诺福韦凝胶、羟乙基纤维素安慰剂凝胶、2%壬醇-9凝胶的甘油减量制剂，或不接受治疗。每种凝胶都是单次给药，然后每天给药7次。黏膜安全性评价包括组织学、粪便钙保护素、上皮细胞塌陷、细胞因子表达(mRNA和蛋白)、微阵列、粘膜T细胞表型的流式细胞术和直肠微生物区系。可接受性和依从性分别通过计算机管理的问卷和交互式电话回复来确定。65名参与者(45名男性和20名女性)被招募到这项研究中。在研究的各个分支中，≥2级不良事件的数量没有显著差异。未来产品使用的可能性(可接受性)为87%(减甘油配方的替诺福韦1%凝胶)、93%(羟乙基纤维素安慰剂凝胶)和63%(壬醇-9凝胶)。在研究期间，粪便钙保护素、直肠微生物区系和上皮细胞塌陷没有因治疗而异。在组织学、粘膜基因表达、蛋白质表达和T细胞表型等方面发现了明显差异的证据。这些变化主要局限于非氧合酚-9凝胶与其他研究臂的比较。替诺福韦1%凝胶剂的还原甘油制剂是安全的，在直肠内耐受性良好，应推进到2期开发。临床试验.gov NCT01232803。
Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel. Participants were randomized 1∶1:1∶1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively. Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms. The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development. ClinicalTrials.gov NCT01232803.
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影响因子：
3.7
作者：
Rohan LC;Moncla BJ;Kunjara Na Ayudhya RP;Cost M;Huang Y;Gai F;Billitto N;Lynam JD;Pryke K;Graebing P;Hopkins N;Rooney JF;Friend D;Dezzutti CS
通讯作者：
Dezzutti CS
DOI：
10.1097/qai.0b013e318156ef16
发表时间：
2007-12-01
影响因子：
3.6
作者：
McGowan, Ian;Elliott, Julie;Anton, Peter A.
通讯作者：
Anton, Peter A.
影响因子：
24.5
作者：
Smithson, JE;Campbell, A;Jewell, DP
通讯作者：
Jewell, DP
影响因子：
3.1
作者：
Tabet, SR;Surawicz, C;Celum, CL
通讯作者：
Celum, CL
南非开普敦社区和临床环境中的异性肛交。
影响因子：
3.6
作者：
Kalichman SC;Simbayi LC;Cain D;Jooste S
通讯作者：
Jooste S