日前，Sci Transl Med上刊登的一项新的研究报告"Penetration of Tenofovir and Emtricitabine in Mucosal Tissues: Implications for Prevention of HIV-1 Transmission"说，一种由2种抗逆转录病毒药物组成的药丸Truvada不会同等地穿透所有可能接触过HIV的生殖器官组织。
这些发现表明，妇女可能尤其需要服用不同剂量的Truvada以确保受到针对病毒的防护。 Kristine Patterson及其同事观察了一个有15位健康个人的小组（8位男性及7位女性），他们看到抗逆转录病毒药物在其子宫颈、阴道和直肠粘膜组织和液体中有着不同的浓度。 这些参与者在服用单个剂量的Truvada之后提供了其组织和液体样本。 该研究小组分析了这些样本中的叫做代谢物的指示性化学物质，这些代谢物表明药物分子已经进入了组织内。 在组成Truvada的2种抗逆转录病毒药物中，有一种倾向于浓集于直肠组织并在其中持续较长的时间。 具体地说，在女性生殖道组织中所见的代谢物浓度提示，这两种药物的标准剂量可能不足以预防HIV的感染。 这些结果表明，HIV药物对某些组织的穿透能力要比对其它组织更为有效，这一因素可能改变未来HIV预防试验的设计方法。（生物谷Bioon.com）
doi:10.1126/scitranslmed.3003174
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Penetration of Tenofovir and Emtricitabine in Mucosal Tissues: Implications for Prevention of HIV-1 Transmission
Kristine B. Patterson1, Heather A. Prince1, Eric Kraft2,*, Amanda J. Jenkins2, Nicholas J. Shaheen1, James F. Rooney3, Myron S. Cohen1 and Angela D. M. Kashuba2
A mainstay of strategies to prevent HIV-1 transmission is to use antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP). Critical to the design and interpretation of PrEP prevention trials is the ability to make accurate pharmacological measurements of ART drugs in human genital and colorectal mucosal tissues, the principal route of HIV transmission. Here, we evaluated two drugs that are preferentially used for PrEP: tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC). A single oral dose of TDF/FTC (Truvada) was administered to 15 healthy individuals. Over the next 14 days, TFV and FTC were measured in blood plasma and genital secretions using a sensitive assay (lower level of quantification, 0.1 ng/ml). The active intracellular phosphorylated metabolites of these drugs [TFV diphospate (TFV-DP) and FTC triphosphate (FTC-TP)] were measured in homogenates prepared from rectal, vaginal, and cervical tissues. TFV and FTC were detected in blood plasma 14 days after administration of a single dose. The area under the concentration-time curve from 24 hours to 14 days (AUC1–14d) for FTC in genital secretions was 27-fold greater than in blood plasma, whereas the AUC1–14d for TFV was only 2.5-fold greater in genital secretions than in blood plasma. In rectal tissue, TFV and TFV-DP concentrations were detectable for 14 days and were 100-fold higher than the concentrations in vaginal and cervical tissues. Vaginal and cervical tissue concentrations of FTC were 10- to 15-fold higher than in rectal tissue. Despite high concentrations of FTC in vaginal and cervical tissue, FTC-TP concentrations in all tissue types were detected for only 2 days after dose. The exposure to TFV, TFV-DP, FTC, and FTC-TP was wide ranging depending on the type of mucosal tissue. These results demonstrate the need for detailed pharmacological studies to improve the application of ART for PrEP to prevent transmission of HIV.
