The odd couple of viruses — HIV-1 and HSV-2

"HSV-2 increases the risk of HIV-1 acquisition by twofold," says Lawrence Corey, M.D., professor of medicine and laboratory medicine at the University of Washington and head of the Program in Infectious Diseases at the Fred Hutchinson Cancer Research Center. "Both microscopic and macroscopic genital ulcerations, due to HSV, break the epithelial barrier and are associated with an influx of activated T-cells, making it easier for HIV to infect an individual."

Studies have shown the significant risk factor for HIV-1 acquisition to be seropositivity for HSV-2, rather than clinical disease. Moreover, HSV-2 seropositivity significantly increases the risk of HIV-1 transmission.

Geographic regions included the Northeast, represented by Boston, the Mid-Atlantic, represented by Baltimore, the Southeast, represented by Atlanta, the Midwest, represented by Chicago, the Southwest, represented by Dallas and the West, represented by Denver. Six clinics in each city were selected as clinical sites, with each clinic asked to enroll 150 individuals between the ages of 18 and 59 who were attending the clinic as a routine office visit. Study enrollment was constrained to include equal numbers of men and women and equal numbers of subjects in each of four age groups, from 18-29, 30-39, 40-49, and 50-59 years of age. Study participants were asked whether they had ever been told by a healthcare provider that they had genital herpes, and they were also tested for the presence of anti-HSV-2 antibodies.

Caught unaware Of more than 5,400 subjects, only 4.3 percent acknowledged that they had genital herpes. By contrast, 25.5 percent of subjects were seropositive for anti-HSV-2 antibodies, suggesting that only one in six persons with genital herpes is aware of harboring the virus.

Initial active infection is followed by latent infection, in which HSV-2 lies dormant in dorsal root ganglia. Clinical disease recurs when the virus is reactivated and travels through the nerves to the skin, where it produces a symptomatic outbreak, with virus particles being shed from the active lesions.

However, asymptomatic outbreaks can also occur.

"HSV-2 can also be reactivated and travel along the nerves, back to the skin and not form active lesions, yet viral shedding can occur," Dr. Corey says. "Whenever viral shedding occurs, the HSV-2-infected patient may be able to infect another person during skin-to-skin sexual contact."

Clinical presentation Ninety percent of subjects with HSV-2 infection are unaware that they are infected.

"People aren't being tested," Dr. Corey says, "and even the most experienced providers misdiagnose HSV outbreaks." Outbreaks can occur in areas difficult to see or in areas not considered 'genital.' Most infections are subtle, and patients often attibute HSV outbreaks to other causes.

"Most HSV-2 infections are unrecognized, but are symptomatic," Dr. Corey continues. "The 'typical' presentation consists of painful vesiculopustular lesions in the genital, anal or perianal region. However, the 'typical' genital herpes outbreak is atypical. Lesions can be vulvar, scrotal or perianal fissures, rather than the ulcers considered characteristic of genital herpes outbreaks. Other symptoms might include cervicitis or proctitis, dysuria or a vaginal or urethral discharge. Instead of painful lesions, the patient might feel only a slight vulvar, penile or scrotal or perianal irritation. All genital excoriations should be evaluated for HSV," Dr. Corey advises.