Risk of HSV-2 Acquisition Among Women with Bacterial Vaginosis: Systematic Review and Meta-Analysis

Objective: Bacterial vaginosis is a dysbiosis of the vaginal microbiome, typically characterized by a loss of <i>Lactobacillus</i>. <i>Lactobacillus</i> plays a crucial role in vaginal immunity and protection against sexually transmitted infections. Herpes simplex virus 2, the primary cause of genital herpes, impacts 13% of people worldwide. We undertook this systematic review and meta-analysis to examine the risk of herpes simplex virus 2 acquisition in women with bacterial vaginosis. Secondarily, we examined the impact of bacterial vaginosis on herpes simplex virus 2 shedding, reactivation, and symptoms. Data sources: We searched PubMed, EMBASE, Cochrane, Web of Science, Google Scholar, and ClinicalTrials.gov for articles published before 1 July 2023 for microbiome and herpes simplex virus type 2. Studies were limited to human subjects and the English language. An updated search was performed in January 2026. This study was registered on PROSPERO (CRD42023439139). Methods of study selection: Studies on non-pregnant, reproductive-aged cisgender women that diagnosed bacterial vaginosis by Amsel Criteria, Nugent Scoring or used molecular techniques, and those that detected herpes simplex virus 2 by serological assay or PCR testing were included. Our search identified 863 results with four publications eligible for inclusion. For our secondary outcomes, 40 results were identified regarding herpes simplex virus 2 shedding, with two publications eligible for inclusion, which did not meet our threshold for meta-analysis. There were 21 results identified for herpes simplex virus 2 reaction and 115 results for herpes simplex virus 2 symptoms, with no articles being eligible for inclusion. Tabulation, integration, and results: Quality assessment was performed following data extraction using the quality assessment scales from the Joanna Briggs Institute. Results were extracted, and the pooled hazard ratio was calculated with 95% confidence interval. A total of 1906 women were included in this analysis, and 255 acquired herpes simplex virus 2. The pooled unadjusted hazard ratios produced an effect size of 1.91, (95% confidence interval 1.4649–2.4980), and a <i>p</i>-value of <0.0001, while the pooled adjusted hazard ratios produces an effect size of 1.85, (95% confidence interval of 1.3556–2.5162), and a <i>p</i>-value of 0.0001 indicating that bacterial vaginosis is associated with a increased risk of herpes simplex virus 2 acquisition. Conclusions: This systematic review with meta-analysis indicates that bacterial vaginosis is associated with a significantly increased risk (91% unadjusted, 85% adjusted) of herpes simplex virus 2 acquisition, indicating that bacterial vaginosis treatment may reduce herpes simplex virus 2 acquisition. A notable limitation of these findings is the relatively small number of studies eligible for inclusion in this systematic review and meta-analysis.