Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Antiviral Res. 2010 Nov;88(2):143-51. doi: 10.1016/j.antiviral.2010.08.006. Epub 2010 Aug 13.
Vaginal gels may act as physical barriers to HIV during sexual transmission. However, the extent and significance of this effect are not well understood. During male-to-female sexual transmission of HIV, semen containing infectious HIV is present within the lower female reproductive tract. In cases where a topical gel has previously been applied to the vaginal epithelium, virions must move through gel layers before reaching vulnerable tissue. This additional barrier could affect the functioning of anti-HIV microbicide gels and placebos. To better understand HIV transport in gels, we: (1) quantified diffusion coefficients of HIV virions within semi-solid delivery vehicles; and (2) tested the barrier functioning of thin gel layers in a Transwell system. Two gels used as placebos in microbicides clinical trials, hydroxyethyl cellulose (HEC) and methylcellulose (MC), were found to hinder HIV transport in vitro. The diffusion coefficients for HIV virions in undiluted HEC and MC were 4±2 x 10⁻¹² and 7±1 x 10⁻¹² cm²/s, respectively. These are almost 10,000 times lower than the diffusion coefficient for HIV in water. Substantial gel dilution (80%:diluent/gel, v/v) was required before diffusion coefficients rose to even two orders of magnitude lower than those in water. In the Transwell system, gel layers of approximately 150-μm thickness reduced HIV transport. There was a log reduction in the amount of HIV that had breached the Transwell membrane after 0-, 4-, and 8-h incubations. The ability of a gel to function as a physical barrier to HIV transport from semen to tissue will also depend on its distribution over the epithelium and effects of dilution by vaginal fluids or semen. Results here can serve as a baseline for future design of products that act as barriers to HIV transmission. The potential barrier function of placebo gels should be considered in the design and interpretation of microbicides clinical trials.
阴道凝胶在性传播过程中可能会起到阻止 HIV 的物理屏障作用。然而，这种作用的程度和意义尚不清楚。在 HIV 从男性传播到女性的过程中，含有传染性 HIV 的精液存在于女性下生殖道中。如果之前在阴道上皮上使用了局部凝胶，那么病毒颗粒必须穿过凝胶层才能到达易受感染的组织。这种额外的屏障可能会影响抗 HIV 杀微生物剂凝胶和安慰剂的作用。为了更好地了解 HIV 在凝胶中的传输，我们：(1) 量化了 HIV 病毒颗粒在半固态递药载体中的扩散系数；(2) 在 Transwell 系统中测试了薄凝胶层的屏障功能。在微生态临床试验中用作安慰剂的两种凝胶，羟乙基纤维素 (HEC) 和甲基纤维素 (MC)，被发现阻碍了 HIV 在体外的传输。未经稀释的 HEC 和 MC 中 HIV 病毒颗粒的扩散系数分别为 4±2 x 10⁻¹²和 7±1 x 10⁻¹² cm²/s，分别为。这几乎是 HIV 在水中扩散系数的 10000 倍。在扩散系数上升到甚至比水低两个数量级之前，需要对凝胶进行大量稀释（80%：稀释剂/凝胶，v/v）。在 Transwell 系统中，约 150-μm 厚的凝胶层减少了 HIV 的传输。在 0、4 和 8 小时孵育后，穿过 Transwell 膜的 HIV 量减少了一个对数级。凝胶作为阻止精液中 HIV 向组织传播的物理屏障的能力还取决于其在上皮中的分布以及阴道液或精液稀释的影响。这里的结果可以作为未来设计阻止 HIV 传播的产品的基线。在微生态临床试验的设计和解释中，应考虑安慰剂凝胶的潜在屏障功能。
