Article Text

Download PDFPDF

Short report
HIV and herpes simplex virus type 2 epidemiological synergy: misguided observational evidence? A modelling study
  1. Ryosuke Omori1,2,
  2. Nico Nagelkerke3,4,5,
  3. Laith J Abu-Raddad6,7
  1. 1 Division of Bioinformatics, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan
  2. 2 PRESTO, JST, Kawaguchi, Saitama, Japan
  3. 3 Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
  4. 4 Medical Microbiology, University of Manitoba, Winnipeg, Canada
  5. 5 Institute of Public Health, College of Medicine and Health Science, United Arab Emirates University, Al Ain, United Arab Emirates
  6. 6 Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar
  7. 7 Department of Healthcare Policy and Research, Weill Cornell Medicine, Cornell University, New York, USA
  1. Correspondence to Dr Ryosuke Omori, Division of Bioinformatics, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan; omori{at}


Objectives To investigate whether observational studies of HIV and herpes simplex virus type 2 (HSV-2) infections have the capacity to assess the HIV/HSV-2 epidemiological synergy.

Methods An individual-based Monte Carlo model was used to simulate HIV/HSV-2 epidemics in two scenarios: no HIV/HSV-2 biological interaction and HSV-2 seropositivity enhancing HIV acquisition. Cross-sectional observational studies were simulated by sampling individuals from the population to assess resulting crude and adjusted ORs of the HIV/HSV-2 association. Meta-analyses were conducted to estimate the pooled mean ORs. Impact of under-reporting of sexual behaviour and miscapture of high-risk individuals was assessed through sensitivity analyses.

Results Assuming no HIV/HSV-2 biological interaction, the crude HIV/HSV-2 OR ranged between 1.38 and 9.93, with a pooled mean of 6.45 (95% CI 5.81 to 7.17). Adjustment for the number of sexual partners over last year, over lifetime and for both partner numbers simultaneously reduced the mean OR to 5.45 (95% CI 4.90 to 6.06), 3.70 (95% CI 3.32 to 4.12) and 3.54 (95% CI 3.17 to 3.94), respectively. Assuming HIV/HSV-2 biological interaction, the crude OR ranged between 3.44 and 9.95, with a pooled mean of 8.05 (95% CI 7.14 to 9.07). The adjustments reduced the mean OR to 7.00 (95% CI 6.21 to 7.90), 3.76 (95% CI 3.32 to 4.25) and 3.68 (95% CI 3.25 to 4.17), respectively. Under-reporting of partners reduced the confounder-adjustment effects. Miscapture of high-risk individuals considerably lowered the estimated ORs.

Conclusions It is difficult to control for sexual-behaviour confounding in observational studies. The observed HIV/HSV-2 association appears more consistent with two infections sharing the same mode of transmission, rather than with HSV-2 enhancing HIV acquisition.

  • epidemiologic study
  • sexual behaviour
  • sexual networks
  • mathematical model
  • odds ratio

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

Statistics from


  • Handling editor Katy ME Turner

  • Contributors NN conceived this study. RO designed the study, developed the mathematical model and analysis plan, and performed the analyses. NN and LJA-R contributed to study design and plan of analysis. LJA-R wrote the first draft of the article. All authors contributed to the interpretation of the results and drafting of the article.

  • Funding RO acknowledges the support of Precursory Research for Embryonic Science and Technology (PRESTO) grant number JPMJPR15E1 from Japan Science and Technology Agency (JST), and Japan Society for the Promotion of Science (JSPS), Grant-in-Aid for Young Scientists (B) 15K19217. This publication was made possible by NPRP grant number 5-752-3-177 from the Qatar National Research Fund (a member of Qatar Foundation). The findings achieved herein are solely the responsibility of the authors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.