Introduction An HSV-2 vaccine could reduce the health and economic burden of HSV-2, including neonatal herpes. However, such a vaccine might increase susceptibility to HIV infection through immune cell recruitment to genital tissues. If so, HSV-2 vaccination may decrease HSV-2 incidence but also increase HIV incidence.

Methods We explored these tradeoffs in a mathematical model of HSV-2 transmission dynamics and vaccination that includes static HIV incidence using ordinary differential equations. We modelled scenarios resembling the United States in terms of HSV-2 and HIV transmission. We examined scenarios where HSV-2 vaccination either did or did not increase HIV susceptibility. We assumed that HSV-2 infection led to increased HIV susceptibility, but no other interactions between HSV-2 and HIV.

Results Assuming vaccine efficacy against infectiousness of 0.5, vaccination may decrease HSV-2 incidence by 22%. However, when vaccination increases HIV susceptibility, this benefit comes at the cost of increased HIV incidence: 1.6, 2.0, or 2.5% in populations with low, moderate, and high HIV exposure rates, respectively. When vaccination does not increase HIV susceptibility, HIV incidence decreased by 7.0, 6.1, and 4.9%, respectively. The magnitude of these effects depend on additional factors such as the degree to which HSV-2 vaccination increases HIV susceptibility, HSV-2 vaccine coverage, and baseline HSV-2 prevalence.

Conclusion Our analysis shows how models can describe tradeoffs of public health interventions offering substantial benefits and possible harms. Models can be used to weigh the relative benefits and costs of a specific intervention, or to examine whether an intervention results in a net gain or net loss in quality adjusted life years. Our analysis illustrates the need for updated estimates of the quality-of-life impact of HSV-2 in different individuals in order to weigh the public health benefits of HSV-2 vaccination against potentially adverse outcomes. More research is needed to better describe the interaction between HSV-2 and HIV infection and transmission.