Case-Crossover Analysis of Condom Use and Herpes Simplex Virus Type 2 Acquisition

Background: Although growing evidence suggests that condoms offer moderate protection against herpes simplex virus type 2 (HSV-2), inability to control for unknown or unmeasured confounders associated with sexual activity may reduce the accuracy of the estimates. The case-crossover design offers increased control of individual-level confounders, and was thus used with the aim of producing a more accurate estimate of the effect of condom use on HSV-2 acquisition. Methods: Data were pooled from 6 prospective studies that measured HSV-2 status at enrollment and over follow-up, and included periodic self-reported condom use and sexual activity. Sexual activity contemporaneous with acquisition was assigned to a case period; earlier sexual activity was assigned to a control period. Conditional logistic regression was used to assess differences in behavior during the case and control periods. Results: One hundred ninety-one eligible participants acquired HSV-2 during follow-up. This approach detected a 3.6% increase in the odds of HSV-2 acquisition with each unprotected act (odds ratio = 1.036; 95% confidence interval: 1.021-1.052), but no increase in the odds of acquisition associated with protected acts (odds ratio = 1.008; 95% confidence interval: 0.987-1.030). Conclusions: This analysis suggests that condoms offer significant protection against HSV-2 transmission.