Genital Herpes and HIV/AIDS: Related Epidemics

Genital herpes infection is widely recognized as a driver of the HIV/AIDS epidemic.

Yet little has been done to integrate HSV treatment into the global fight to end HIV/AIDS.

According to World Health Organization: HSV-2 has been shown to increase the risk of HIV acquisition and transmission, which is especially important in populations with a high prevalence of HIV.

World Health Organization Preferred Product Characteristics for HSV

Epidemiological studies have identified a strong and consistent synergistic relationship between HIV and HSV-2 infections (1, 2).

The risk of HIV acquisition is approximately tripled in the presence of prevalent HSV-2 infection, and five times higher for those with incident HSV-2 infection (3). The increased risk could be mediated by at least two possible mechanisms (4): first, HSV-2 infection and reactivation stimulate infiltration into the genital mucosa of immune cells expressing receptors for HIV (CD4+ T cells and DC-SIGN+ dendritic cells) (5, 6). Second, HSV-associated breaks in the skin and genital mucosa, including microscopic ulcerations, provide a more effective portal of entry for HIV. (7)

It is challenging to estimate precisely how HSV-2- associated increased HIV acquisition risk translates into the number of HIV infections that could be averted if HSV-2 infections were prevented; however, according to existing modelling studies, HSV-2 infection might account
for 30–50%
of new HIV infections in some populations that have high HIV prevalence (8,9).


1. Barnabas RV, Celum C. Infectious co-factors in HIV-1 transmission. Herpes simplex virus type-2 and HIV-1: new insights and interventions. Curr HIV Res. 2012;10:228–37. 

2. Bradley J, Floyd S, Piwowar-Manning E, Laeyendecker O, Young A, Bell-Mandla N et al. Sexually transmitted bedfellows: exquisite association between HIV and herpes simplex virus type 2 in 21 communities in southern Africa in the HIV Prevention Trials Network 071 (PopART) study. J Infect Dis. 2018;218:443–52. doi:10.1093/infdis/jiy178. 

3. Looker KJ, Elmes JAR, Gottlieb SL, Schiffer JT, Vickerman P, Turner KME et al. Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis. Lancet Infect Dis. 2017. doi:10.1016/S1473-3099(17)30405-X. 

4. Rebbapragada A, Wachihi C, Pettengell C, Sunderji S, Huibner S, Jaoko W et al. Negative mucosal synergy between herpes simplex type 2 and HIV in the female genital tract. AIDS. 2007;21:589–98. doi:10.1097/QAD.0b013e328012b896. 

5. Zhu J, Hladik F, Woodward A, Klock A, Peng T, Johnston C et al. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nat Med. 2009;15:886–92. doi:10.1038/nm.2006. 

6. Johnson KE, Redd AD, Quinn TC, Collinson-Streng AN, Cornish T, Kong X et al. Effects of HIV-1 and herpes simplex virus type 2 infection on lymphocyte and dendritic cell density in adult foreskins from Rakai, Uganda. J Infect Dis. 2011;203:602–9.doi:10.1093/infdis/jiq091. 

7. Celum C, Levine R, Weaver M, Wald A. Genital herpes and human immunodeficiency virus: double trouble. Bull World Health Organ. 2004;82:447–53. 

8. Freeman EE, Orroth KK, White RG, Glynn JR, Bakker R, Boily M-C et al. Proportion of new HIV infections attributable to herpessimplex 2 increases over time: simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics. Sex Transm Infect. 2007;83 Suppl 1:i17-24. doi:10.1136/sti.2006.023549. 

9. Masese L, Baeten JM, Richardson BA, Bukusi E, John-Stewart G, Graham SM et al. Changes in the contribution of genitaltract infections to HIV acquisition among Kenyan high-risk women from 1993 to 2012. AIDS. 2015;29:1077–85. doi:10.1097/ QAD.0000000000000646.  

Relevant Studies

The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics

Global and regional estimates of the contribution of herpes simplex virus type 2 infection to HIV incidence: a population attributable fraction analysis using published epidemiological data

Persistence of HIV-1 receptor–positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition

Proportion of new HIV infections attributable to herpes simplex 2 increases over time: simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics

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