Evidence suggests there is a strong biological association between HIV and the sexually transmitted infection (STI) herpes. In 2017, an evidence review found the risk of acquiring HIV at least tripled for people with herpes. Each virus increases the transmission risk of the other.
To strengthen the evidence base, researchers at Bristol Medical School, University of Bristol, UNAIDS, Imperial College London, and the World Health Organisation (WHO), used an established epidemiological formula to estimate the proportion of HIV infections in 2016 that were attributable to herpes at both global and regional level (using regions defined by the WHO).
Before this study, this type of estimate was only available for some African settings. The study also examined the number of HIV infections attributable to herpes by sex and age group (15–24 years, 25–49 years, and 15–49 years).
Estimates were provided for the general population, female sex workers and men who have sex with men. All general population data, and the majority of data relating to female sex workers, came from Africa. Data on men who have sex with men came from the US, Australia, China, Thailand, and the Caribbean.
Around 420,000 of 1.4m sexually acquired HIV infections among adults (ages 15 to 49) in 2016 – roughly a third – were found to be attributable to herpes. The largest number and highest proportion of HIV infections attributable to herpes was found in Africa, where around 37% of HIV incidence in 2016 was linked to herpes. The contribution of herpes to new HIV infections was also high in the Americas at 21% – roughly one in five new HIV infections in the region.
Elsewhere in the world, the proportion of HIV infections associated with herpes ranged between 11% and 13%. This is linked to the fact that a substantial proportion of HIV transmission is driven by injecting drug use in some of these regions, rather than being sexually transmitted.
The proportion of HIV infections attributable to herpes was higher among women than men (35% compared to 26%). It also differed on age, with 32% of new infections among those aged 25 to 49 linked to herpes compared to 23% among those aged 15 to 24. Similar patterns by age and sex were seen in each region and were attributed to the higher prevalence of herpes within these groups.
Around 20,000 HIV infections among female sex workers (27%) and 40,000 among men who have sex with men (20%) were also linked to herpes in the data analysed. The study is limited by its assumption that there is a causal link between herpes and HIV, whereas the transmission and acquisition of both STIs is the result of a complex range of factors. Nonetheless, these estimates provide a starting point in understanding the potentially substantial contribution of herpes to HIV, both globally and regionally.
The findings suggest new preventive interventions against herpes, such as vaccines or microbicides, could not only improve the quality of life of millions of people by reducing the painful symptoms of herpes, but could also have an additional, indirect impact on HIV transmission.
Abstract
Background: A 2017 systematic review and meta-analysis of 55 prospective studies found the adjusted risk of HIV acquisition to be at least tripled in individuals with herpes simplex virus type 2 (HSV-2) infection. We aimed to assess the potential contribution of HSV-2 infection to HIV incidence, given an effect of HSV-2 on HIV acquisition.
Methods: We used a classic epidemiological formula to estimate the global and regional (WHO regional) population attributable fraction (PAF) and number of incident HIV infections attributable to HSV-2 infection by age (15–24 years, 25–49 years, and 15–49 years), sex, and timing of HSV-2 infection (established vs recently acquired). Estimates were calculated by incorporating HSV-2 and HIV infection data with pooled relative risk (RR) estimates for the effect of HSV-2 infection on HIV acquisition from a systematic review and meta-analysis. Because HSV-2 and HIV have shared sexual and other risk factors, in addition to HSV-related biological factors that increase HIV risk, we only used RR estimates that were adjusted for potential confounders.
Findings: An estimated 420 000 (95% uncertainty interval 317 000–546 000; PAF 29·6% [22·9–37·1]) of 1·4 million sexually acquired incident HIV infections in individuals aged 15–49 years in 2016 were attributable to HSV-2 infection. The contribution of HSV-2 to HIV was largest for the WHO African region (PAF 37·1% [28·7–46·3]), women (34·8% [23·5–45·0]), individuals aged 25–49 years (32·4% [25·4–40·2]), and established HSV-2 infection (26·8% [19·7–34·5]).
Interpretation: A large burden of HIV is likely to be attributable to HSV-2 infection, even if the effect of HSV-2 infection on HIV had been imperfectly measured in studies providing adjusted RR estimates, potentially because of residual confounding. The contribution is likely to be greatest in areas where HSV-2 is highly prevalent, particularly Africa. New preventive interventions against HSV-2 infection could not only improve the quality of life of millions of people by reducing the prevalence of herpetic genital ulcer disease, but could also have an additional, indirect effect on HIV transmission.
Authors
Katharine J Looker, Nicky J Welton, Keith M Sabin, Shona Dalal, Peter Vickerman, Katherine ME Turner, Marie-Claude Boily, Sami L Gottlieb
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[link url="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30470-0/fulltext"]The Lancet Infectious Diseases abstract[/link]