Australian Herpes Management Forum

Research Update: High Risk of Human Immunodeficiency Virus in Men Who Have Sex with Men with Herpes Simplex Virus Type 2

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August 2006

What's known?

HSV-1 typically causes oropharyngeal infection, and transmission occurs primarily through personal contact during childhood, although it can also be transmitted sexually.

HSV-2 is mainly associated with genital disease, and transmission is usually sexual.

Both viruses can cause either anogenital or oropharyngeal infection.

Genital HSV-2 infection increases the risk of human immunodeficiency virus (HIV) type 1 acquisition, likely via mucosal or epithelial disruption, which provides a portal of entry for HIV and via recruitment of CD4-positive T lymphocytes during HSV-2 reactivation.

What’s New?

The relation between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) acquisition was evaluated among 4,295 high-risk, HIV-negative men who have sex with men in an intensive behavioural intervention (colloquially referred to as "EXPLORE") study in the United States from 1999 to 2003.

Sexual behaviour data were obtained by computer-assisted self-interview, and sera were collected semi-annually for HIV and HSV-2 serology.

HSV-2 infection was classified as ‘‘recent incident’’ (at the first HSV-2 seropositive visit), ‘‘remote incident’’ (within 24 months of the first positive visit), and ‘‘prevalent’’ (for visits >24 months after the first HSV-2 positive visit).

Baseline HSV-2 prevalence was 20.3%.

HSV-2 incidence was 1.9 per 100 person-years; significant risk factors were African-American race, unprotected receptive anal intercourse, an HIV-positive male sex partner, and six or more male partners in the prior 6 months.

Overall HIV incidence was 1.9 (95% CI: 1.7, 2.2) per 100 person-years.

HIV risk was elevated among men who have sex with men with recent incident HSV-2 (adjusted HR = 3.6, 95% CI: 1.7, 7.8), remote incident HSV-2 (adjusted HR = 1.7, 95% CI: 0.8, 3.3), and prevalent HSV-2 (adjusted HR = 1.5, 95% CI: 1.1, 2.1) infection compared with HSV-2 seronegative participants.

The intensive, 10-session risk-reduction behavioural intervention tested in the EXPLORE study did not reduce HIV incidence to a statistically significant degree and had no effect on HSV-2 incidence, despite the statistically significant reduction in reported unprotected receptive anal intercourse

No herpes simplex virus type 1 (HSV-1) testing was done in this study and the finding that 17 percent of HSV-2 seronegative participants did report genital ulcer disease symptoms indicates that genital HSV-1 infections may have been relatively common in this cohort.

It is evident from these data that HSV-2 infection is an important risk factor for HIV acquisition among men who have sex with men, although it remains uncertain whether incident HSV-2 confers additional risk compared with prevalent HSV-2.

Reference

E. L. Brown, A. Wald, J. P. Hughes, R. A. Morrow, E. Krantz, K. Mayer, S. Buchbinder, B. Koblin, and C. Celum. High Risk of Human Immunodeficiency Virus in Men Who Have Sex with Men with Herpes Simplex Virus Type 2 in the EXPLORE Study American Journal of Epidemiology. Advance Access published August 8, 2006, DOI: 10.1093/aje/kwj270

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