THE ARTICLE BY Chen et al1 in this issue of Sexually Transmitted Diseases outlines the increasing recognition of herpes simplex virus type 2 (HSV-2) infection in the developing world. This study, which evaluated more than 550 South African men attending sexually transmitted disease (STD) clinics with genital ulcer disease (GUD), revealed the presence of HSV-2 only in 29.2% of men and mixed HSV and bacterial infection in an additional 6.6% of men. Thus, HSV was identified in more than 36% of men with GUD, and was the most frequently identified etiologic agent.1 The fact that 25% of ulcers had no identifiable pathogen indicates that research into other etiologies of GUD should be pursued. This study confirms the burgeoning evidence that HSV-2 is currently the most prevalent cause of genital ulcers in almost all areas of the world.2–6 Whether this observation relates to a true alteration in the spectrum of genital ulcers or better diagnostic technologies is unclear; however, it is more likely to be the latter.7 The enhanced sensitivity of polymerase chain reaction-based laboratory methods as compared with culture, and the stability under transport of viral DNA as compared with infectious viruses in “field” conditions, are probably the major factors in the recent finding implicating HSV as a cause of large chancroidal or syphilitic-like ulcerations.1–3,5 The role of GUD in facilitating the transmission of HIV is well documented8–19 (Sanchez J, Campos P, Courtois B, et al, unpublished data, 1999). In genital HSV-2 lesions, HIV virions are shed in high titer for prolonged periods.20 Prospective studies should define the relative amounts of HIV shed in Treponema pallidum versus Haemophilus ducreyi versus herpes simplex virus ulcerations, because emphasis on syndromic STD control as a means of HIV prevention has largely ignored viral STDs.21,22 In vitro data show significant interactions between HIV and herpes viruses, and coinfection of the same cell is well documented.23,24 Whether the size of the genital lesion or the difference in the inflammatory response between viral and bacterial infections differ enough to significantly alter HIV replication kinetics and subsequent rates of transmission of infection is currently unclear.25–29 The article by Chen et al illustrates that future studies that evaluate the duration of HIV shedding in bacterial versus viral genital ulcers and whether treatment of such ulcers markedly reduce HIV shedding in lesions are needed. This virologist would point out that copy levels of HIV RNA in genital lesion swabs appear to be even greater than levels reported in semen from persons with gonococcal urethritis.20,25 Thus, approaches to STD control that are directed at bacterial STDs only are leaving a significant potential of HIV transmission uncovered. Without a doubt, all STDs play a role in facilitating the transmission of HIV, and like bacterial STDs, the in vitro and in vivo observations that show an interaction between HSV-2 and HIV need to be brought to the clinic.21,30 In addition to generating important data on the etiology of GUD in South Africa, the article by Chen et al provides important information about the seroprevalence of HSV-2 in this region. It is interesting to note that even in the face of universal seropositivity to herpes simplex virus type 1, men with urethritis and GUD syndromes have a high prevalence of herpes simplex virus type 2 (HSV-2) infection; more than 60% of men older than 20 years who attend STD clinics in South Africa are HSV-2 seropositive.1 Human immunodeficiency virus seropositivity was significantly higher is HSV-2 seropositive persons presenting with GUD or urethritis. Whether this is due to an increased risk of HIV acquisition by persons who are HSV-2 seropositive, or to more frequent reactivation of HSV-2 among those with HIV infection is unclear31–34; however, the fact that rates of HSV-2 seropositivity are similar in men with and without genital lesions supports the former. The complexities of HSV-HIV interactions are fascinating intellectually and investigatively, but frustrating therapeutically. How can one define the attributable risk for HSV-related GUD in HIV acquisition and transmission?8,11,19 Intervention studies may require suppressive, postexposure, or at least intermittent therapy with antivirals. At first glance, these therapies may seem expensive and daunting; however, generic acyclovir is inexpensive, and the role this drug plays in the reduction of HIV transmission may be greater than is currently appreciated.34–36 Whereas such trials are difficult to undertake, the continued spread of HSV-2 and HIV suggests that a bit of boldness and consideration of such studies will serve scientific inquiry, preventative interventions, and people of the developing world better than complacency.
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Lawrence Corey (2000) studied this question.