Effect of Suppressive Therapy on Behavioral Determinants of HSV-2 Transmission

描述(申请人提供)：22%的美国成年人对单纯疱疹病毒2型(HSV-2)有抗体，这表明慢性感染了最常见的导致生殖器疱疹的病毒。在性活跃人群中预防单纯疱疹病毒2型传播的战略仍然有限，似乎只有部分保护作用。这些策略包括生物医学(源伴侣的抗病毒治疗)和行为，如使用避孕套，披露HSV-2血清状态，以及限制性接触或伴侣数量。在一项安慰剂对照试验中，在HSV-2不和谐夫妇中，每天用万乃洛韦治疗源伴侣的传播率降低了50%。然而，每天接受抗病毒抑制治疗以降低传播风险的人可能不太可能向伴侣透露他们的HSV状况或使用避孕套，和/或有更频繁的性行为或更多的性伴侣。因此，在人群的基础上，源伴侣抑制疗法在减少传播方面的有益影响可能会被对性行为的不利影响所抵消。如果没有发现这种有害的影响，如果对预防传播的每日抑制疗法的可接受性和坚持性很高，那么这种预防方式可以更有信心地推广。我们计划进行一项每日抑制性阿昔洛韦与间歇性阿昔洛韦的开放标签随机临床试验，用于治疗HSV-2血清阳性异性恋男性和女性生殖器疱疹复发。我们假设，被随机接受抗病毒抑制治疗的HSV-2阳性单身异性恋者与随机接受间歇性治疗的人相比，不会更有可能从事危险的性行为，而且对抑制治疗的依从性将会很高。参与者将被跟踪一年，以评估向性伴侣披露HSV-2状态、性伴数量、性行为频率、避孕套使用和坚持治疗的情况。这些结果将通过保密的、基于计算机的评估中的自我报告来衡量，并辅之以依从性的药片计数。然后，我们将模拟抑制治疗和性行为改变对人群水平HSV-2流行率的潜在冲突影响。这一项目与相关的职业发展活动相结合，将使首席调查员获得宝贵的临床试验经验，并作为性传播疾病领域的临床研究人员实现独立。

DESCRIPTION (provided by applicant): Twenty-two percent of the U.S. adult population has antibodies to herpes simplex virus type 2 (HSV-2), indicating chronic infection with the most common virus causing genital herpes. Strategies for the prevention of HSV-2 transmission among sexually active persons remain limited and appear only partially protective. Such strategies include both biomedical (antiviral therapy of the source partner) and behavioral, such as condom use, disclosure of HSV-2 serostatus, and limiting the frequency of sexual encounters or the number of partners. Daily treatment of source partners with valacyclovir in a placebo-controlled trial in HSV-2 discordant couples decreased transmission by 50%. However, a person taking daily antiviral suppressive therapy to reduce the risk of transmission might be less likely to disclose their HSV status to a partner or use condoms, and/or have more frequent sexual encounters or more sexual partners. Thus, on a population basis the beneficial effect of source partner suppressive therapy in reducing transmission could potentially be outweighed by a detrimental effect on sexual behavior. If no such detrimental effect were found, and if acceptability and adherence to daily suppressive therapy for transmission prevention were high, then this prevention modality could be promoted with increased confidence. We plan to conduct an open-label randomized clinical trial of daily suppressive acyclovir versus episodic acyclovir for treatment of genital herpes recurrences among HSV-2 seropositive heterosexual men and women. We hypothesize that HSV-2 seropositive single heterosexuals randomized to antiviral suppressive therapy will be no more likely to engage in risky sexual behavior than those randomized to episodic treatment, and that adherence to suppressive therapy will be high. Participants will be followed for 1 year to assess disclosure of HSV-2 status to sex partners, number of sex partners, frequency of sexual activity, condom use, and adherence to therapy. These outcomes will be measured by self-report in a confidential, computer-based assessment, supplemented by pill counts for adherence. We will then model the potentially conflicting effects of suppressive therapy and sexual behavior change on population-level prevalence of HSV-2. This project, combined with related career development activities, will enable the Principal Investigator to gain valuable clinical trial experience and achieve independence as a clinical researcher in the field of sexually transmitted diseases.