日前,，Sci Transl Med上刊登的一項新的研究報告"Penetration of Tenofovir and Emtricitabine in Mucosal Tissues: Implications for Prevention of HIV-1 Transmission"說,，一種由2種抗逆轉(zhuǎn)錄病毒藥物組成的藥丸Truvada不會同等地穿透所有可能接觸過HIV的生殖器官組織。
這些發(fā)現(xiàn)表明,，婦女可能尤其需要服用不同劑量的Truvada以確保受到針對病毒的防護(hù),。 Kristine Patterson及其同事觀察了一個有15位健康個人的小組（8位男性及7位女性），他們看到抗逆轉(zhuǎn)錄病毒藥物在其子宮頸,、陰道和直腸粘膜組織和液體中有著不同的濃度,。 這些參與者在服用單個劑量的Truvada之后提供了其組織和液體樣本。 該研究小組分析了這些樣本中的叫做代謝物的指示性化學(xué)物質(zhì)，這些代謝物表明藥物分子已經(jīng)進(jìn)入了組織內(nèi),。 在組成Truvada的2種抗逆轉(zhuǎn)錄病毒藥物中,，有一種傾向于濃集于直腸組織并在其中持續(xù)較長的時間。 具體地說,，在女性生殖道組織中所見的代謝物濃度提示,，這兩種藥物的標(biāo)準(zhǔn)劑量可能不足以預(yù)防HIV的感染,。 這些結(jié)果表明,，HIV藥物對某些組織的穿透能力要比對其它組織更為有效，這一因素可能改變未來HIV預(yù)防試驗的設(shè)計方法,。（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.
