Postcoital Bioavailability and Antiviral Activity of 0.5% PRO 2000 Gel: Implications for Future Microbicide Clinical Trials
Postcoital Bioavailability and Antiviral Activity of 0.5% PRO 2000 Gel: Implications for Future Microbicide Clinical Trials
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DOI：
10.1371/journal.pone.0008781
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发表时间：
2010-01-22
期刊：
影响因子：
3.7
通讯作者：
Herold, Betsy C.
中科院分区：
文献类型：
--
作者：
Keller, Marla J.;Mesquita, Pedro M. M.;Herold, Betsy C.
背景：阴道杀微生物剂的药代动力学和药效学通常在禁欲女性中进行评估。然而，性的物理行为可能会调节凝胶分布，临床前研究表明，精浆干扰几种杀微生物剂的抗病毒活性。本研究比较了生物活性和浓度的PRO 2000在宫颈阴道灌洗（CVL）收集在没有或以下coitus.Methods：CVL样品收集从10个异性恋夫妇在基线，性行为后，单剂量的0.5%PRO 2000凝胶和性别，凝胶应用后，没有性别。分别通过荧光素酶和空斑测定监测CVL对TZM-bl细胞的HIV-1感染和CaSki细胞的HSV-2感染的影响。结果：PRO 2000应用后收集的CVL显著抑制HIV-1和HSV-2（p = 0.01）。然而，性行为后抗病毒活性降低，并且与不存在PRO 2000相比，在HIV（p = 0.45）或HSV-2（p = 0.56）的情况下获得的性交后CVL中未观察到显著的保护作用。少PRO 2000恢复在性交后CVL，这与干扰精浆，可能有助于降低抗病毒activity.Conclusions：性交后的反应PRO 2000不同于性交前的措施和获得的结果可能提供深入了解的临床试验结果中，有没有显着的保护对HIV-1或HSV-2。在进行大规模疗效试验之前，应将性交后研究纳入临床研究。
Background: The pharmacokinetics and pharmacodynamics of vaginal microbicides are typically assessed among sexually abstinent women. However, the physical act of sex may modulate gel distribution, and preclinical studies demonstrate seminal plasma interferes with the antiviral activity of several microbicides. This study compared the biological activity and concentration of PRO 2000 in cervicovaginal lavage (CVL) collected in the absence or following coitus.Methods: CVL samples were collected from ten heterosexual couples at baseline, after sex, after a single dose of 0.5% PRO 2000 gel and sex, and after gel application without sex. The impact of CVL on HIV-1 infection of TZM-bl cells and HSV-2 infection of CaSki cells was monitored by luciferase and plaque assay, respectively. PRO 2000 concentrations were measured by fluorescence.Results: CVL collected after PRO 2000 application significantly inhibited HIV-1 and HSV-2 (p = 0.01). However, the antiviral activity was reduced following sex and no significant protective effect was observed in postcoital CVL obtained in the presence compared to the absence of PRO 2000 for HIV (p = 0.45) or HSV-2 (p = 0.56). Less PRO 2000 was recovered in postcoital CVL, which, in conjunction with interference by seminal plasma, may have contributed to lower antiviral activity.Conclusions: Postcoital responses to PRO 2000 differ from precoital measures and the results obtained may provide insights into the clinical trial findings in which there was no significant protection against HIV-1 or HSV-2. Postcoital studies should be incorporated into clinical studies before embarking on large-scale efficacy trials.