Comparative Effectiveness of Treatment Options for Genital Herpes Infection in Pregnant Women to Reduce Adverse Pregnancy Outcomes

Preterm delivery (PTD), along with low birthweight (LBW), is the leading cause of perinatal mortality and morbidity. In the U.S., 12% of livebirths are PTDs, resulting in more than $26 billion in medical costs annually. The impact on infant health and staggering costs makes PTD one of the top research priorities of PCORI, AHRQ, the Institute of Medicine (IOM) and the World Health Organization (WHO), due to a lack of effective interventions to reduce PTD.

Genital herpes infection is prevalent, with a recent WHO estimation of 500 million people worldwide infected. Treating pregnant women with genital herpes infection, especially before the 3rd trimester, has been shown to reduce the risk of PTD and LBW, thus it can be an effective intervention to reduce PTD/LBW. However, the effectiveness and benefit of treating genital herpes to reduce PTD and LBW needs to be further demonstrated in order to be incorporated into the treatment decision making process. Currently, many pregnant women choose not to treat genital herpes due to a general aversion to taking medications during pregnancy for the safety of their fetuses, and a lack of demonstrated evidence of benefits. Paradoxically, the choice of no treatment for genital herpes may adversely impact fetal health, leading to PTD and LBW. Given that pregnant women frequently prefer no treatment, studies are urgently needed to establish the risk-benefit profile between treatment and no treatment for genital herpes infection in the context of improving fetal health, including the timing of treatment (before the 3rd trimester). This study is designed to provide clear evidence of treatment effectiveness in real-world clinical practice, and risk-benefit profiles to inform both treatment decisions by pregnant women and clinicians.

Study Aims:

This proposed comparative effectiveness study will address the following questions:

1. Does treating genital herpes infection in pregnant women reduce the risk of adverse pregnancy outcomes including PTD or LBW? (treated vs. untreated)
2. Does the timing of the treatment during pregnancy influence the treatment effectiveness on reducing adverse pregnancy outcomes (PTD and LBW)? (head-to-head comparison of treatment timing: before the 3rd trimester vs. during the 3rd trimester).
3. Do other treatment metrics, including treatment duration, dosage, and compliance, impact treatment effectiveness in reducing the risk of PTD and LBW?
4. Does treatment effectiveness vary depending on the type (or severity) of underlying genital herpes infection? (e.g., treating symptomatic genital herpes infection vs. treating latent/asymptomatic genital herpes)
5. Does genital herpes infection in pregnancy, if untreated, increase the risk of PTD and LBW, compared to no genital herpes infection? (untreated vs. controls without genital herpes) In addition, this study is especially relevant in addressing racial disparities, given that minority pregnant women have higher rates of both genital herpes infection and PTD: 3 times the infection rate and 150% higher PTD rate among African-Americans compared to Whites. Thus, demonstrating the effectiveness of treating genital herpes in reducing PTD could lead to a reduction in the existing racial disparity in PTD rates.