Case-crossover analysis of condom use and herpes simplex virus type 2 acquisition

Abstract

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.

Figure 1

Exposure duration-matched model. When acquisition was detected by serology, the case period was fixed as the window between 14 and 90 days before diagnosis (Dx); the control period was fixed as the window between the first day in the study and the 76th day in the study. In this example, all of the sexual behavior reported at visit (a) and a portion of visit (b) contribute to the control period, while all of visit (d) and portions of visits (c) and (e) contribute to the case period.

Figure 2

Forest plot summarizing odds ratios and 95% confidence intervals for change in odds of herpes simplex virus type 2 (HSV-2) acquisition associated with each type of act. The height of each box is proportional to the number of participants included in that analysis.