HIV and herpes simplex virus type 2 epidemiological synergy: misguided observational evidence? A modelling study

Sex Transm Infect. 2018 Aug;94(5):372-376. doi: 10.1136/sextrans-2017-053336. Epub 2017 Dec 4.

Abstract

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.

Keywords: epidemiologic study; mathematical model; odds ratio; sexual behaviour; sexual networks.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cross-Sectional Studies
  • Female
  • HIV / isolation & purification
  • HIV Infections / epidemiology*
  • HIV Infections / transmission
  • HIV Infections / virology
  • Herpes Genitalis / epidemiology*
  • Herpes Genitalis / transmission
  • Herpes Genitalis / virology
  • Herpes Simplex / epidemiology
  • Herpesvirus 2, Human / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Models, Statistical*
  • Monte Carlo Method
  • Observational Studies as Topic / standards*
  • Prevalence
  • Regression Analysis
  • Reproducibility of Results
  • Risk Factors
  • Sexual Behavior
  • Sexual Partners
  • Young Adult