In vitro comparison of topical microbicides for prevention of human immunodeficiency virus type 1 transmission
In vitro comparison of topical microbicides for prevention of human immunodeficiency virus type 1 transmission
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DOI：
10.1128/aac.48.10.3834-3844.2004
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发表时间：
2004-10-01
影响因子：
4.9
通讯作者：
Hart, CE
中科院分区：
文献类型：
--
作者：
Dezzutti, CS;James, VN;Hart, CE
采用标准化方案比较配制供人类使用的候选杀微生物剂的细胞毒性和抗人类免疫缺陷病毒1型（HIV-1）活性。所评估的杀菌剂有邻苯二甲酸纤维素（CAP）、Carraguard、K-Y加壬氧醇-9 （K-Y- n9）、PRO 2000（0.5和4%）、SPL7013（5%）、UC781（0.1和1%）和Vena Gel及其附带的安慰剂。通过ATP释放试验评估产品对宫颈和结肠上皮细胞系、外周血单核细胞（PBMCs）和巨噬细胞（MPhi）的毒性，并测试其对极化上皮单层经上皮耐药（TER）的影响。通过检测传染性HIV-1从上皮细胞转移到活化的PBMC，以及PBMC和MPhi感染来评估抗HIV-1活性。CAP、Carraguard、PRO 2000、SPL7013和UC781及其安慰剂的毒性比K-Y-N9和Vena Gel低20- 50倍。无毒产物浓度均未破坏TER。除Carraguard、K-Y-N9和Vena Gel外，所有产品均能抑制实验室适应的HIV-1（Ba-L）和HIV-1（LAI）分离株从上皮细胞向PBMC和PBMC转移HIV-1（Ba-L）。K-Y-N9、Vena Gel和Carraguard对原发HIV-1(A)、HIV-1(C)和HIV-1（CRF01-AE）分离株的PBMC感染无效。这些毒性结果与先前报道的结果的一致性表明，我们的方案可能有助于预测体内毒性。此外，我们系统的抗hiv -1测试为做出更明智的决定提供了理性的基础，可以考虑哪些产品用于临床试验。
A standardized protocol was used to compare cellular toxicities and anti-human immunodeficiency virus type 1 (HIV-1) activities of candidate microbicides formulated for human use. The microbicides evaluated were cellulose acetate phthalate (CAP), Carraguard, K-Y plus nonoxynol-9 (K-Y-N9), PRO 2000 (0.5 and 4%), SPL7013 (5%), UC781 (0.1 and 1%), and Vena Gel, along with their accompanying placebos. Products were evaluated for toxicity on cervical and colorectal epithelial cell lines, peripheral blood mononuclear cells (PBMCs), and macrophages (MPhi) by using an ATP release assay, and they were tested for their effect on transepithelial resistance (TER) of polarized epithelial monolayers. Anti-HIV-1 activity was evaluated in assays for transfer of infectious HIV-1 from epithelial cells to activated PBMCs and for PBMC and MPhi infection. CAP, Carraguard, PRO 2000, SPL7013, and UC781 along with their placebos were 20- to 50-fold less toxic than K-Y-N9 and Vena Gel. None of the nontoxic product concentrations disrupted the TER. Transfer of HIV-1(Ba-L) from epithelial cells to PBMCs and PBMC and MPhi infection with laboratory-adapted HIV-1(Ba-L) and HIV-1(LAI) isolates were inhibited by all products except Carraguard, K-Y-N9, and Vena Gel. K-Y-N9, Vena Gel, and Carraguard were not effective in blocking PBMC infection with primary HIV-1(A), HIV-1(C), and HIV-1(CRF01-AE) isolates. The concordance of these toxicity results with those previously reported indicates that our protocol may be useful for predicting toxicity in vivo. Moreover, our systematic anti-HIV-1 testing provides a rational basis for making better informed decisions about which products to consider for clinical trials.