CDC studies link between herpes and HIV prevention

Guidelines may take a while to emerge

Should HIV-positive patients and pregnant women be screened for genital herpes (HSV-2)? Should patients infected with both viruses be put on HSV-2 prophylaxis? Are sexual behaviors different for HIV-infected people with and without HSV-2? Can the prevention of HSV-2 dovetail with HIV management?

Those are some of the complex issues a group of consultants wrestled with recently during a genital herpes prevention meeting sponsored by the Centers for Disease Control and Prevention in Atlanta. The consultants were asked to address the gamut of issues related to the genital herpes epidemic - from its relationship to HIV prevention, to its health burden on adolescents and pregnant women; from the potential benefits of serological screening of the general population, to the effectiveness of antiviral therapy in preventing transmission.

Several developments in the sexually transmitted disease have fueled consideration of a nationwide prevention effort: the high prevalence of genital herpes in the United States, estimated to be as high as one in five people;1 the recent availability of accurate, type-specific assays that can determine whether asymptomatic people carry the virus; and increased awareness that HSV-2 infection can enhance HIV transmission and possibly increase viral load in those already infected with HIV.

The link between genital herpes and HIV has led CDC officials to consider whether HIV prevention is a specific outcome of herpes prevention, and if so, how big a role it could play in reducing the spread of HIV.

"The hypothesis is that it could be a very big fraction, given its role in HIV transmission in general, given the fact that herpes is an ulcerative STD, and given that it appears to infect a quarter of the population in this country," says Hunter Handsfield, MD, the meeting's coordinator and visiting scientist in the CDC's division of STD prevention.

The role HSV-2 in the HIV epidemic in the United States is thought to be greatest among heterosexuals, where the epidemic is growing the fastest. Several studies have shown that heterosexuals with genital herpes are twice as much at risk for HIV acquisition as those who are not infected, and that HIV-positive people are more likely to have HSV-2 than the general population.2

While the dynamic of transmission enhancement between the two viruses is fairly clear, there is less research on how HSV-2 affects the course of HIV infection and vice versa. Laboratory studies indicate that HSV-2 may increase HIV expression, particularly because herpes lesions activate CD4 lymphocytes. Anecdotally, HSV-2 infections tend to be more frequent and prolonged in immunocompromised patients, the consultants noted.

Many research questions remain

Those consultants who focused on the prevention relationship between HSV-2 and HIV noted the lack of a model that could predict what the benefits would be of an intervention program - i.e., the efficacy and cost-effectiveness of HSV-2 prophylaxis for co-infected patients or regular HSV screening for HIV-positive patients. While the group agreed that the CDC should make a high priority of developing guidelines for HSV-2 prevention, there are many research questions that need to be answered, such as the effect of HSV-2 shedding on HIV viral load and disease progression, the level of HSV-2 strains that are resistant to acyclovir, and the impact of adding HSV-2 prophylaxis to an already heavy drug burden for HIV-positive patients.

Independent of its relationship to HIV, genital herpes poses dilemmas for clinicians and counselors, both in treatment and prevention issues. Although neonatal genital herpes causes high morbidity, genital herpes infection in adults is often considered more for its stigma than its impact on health. Indeed, one of the central issues of a prevention program would be weighing the benefit of having patients know they are infected vs. the psychological and social burden that knowledge could impose. Complicating the issue of screening is the lack of definitive information on preventive interventions, the group noted.

"The impact of being told is a big concern because it could cause people to worry more than necessary," said John Douglas, MD, associate director of the disease control service at the Denver Public Health Department.

Indeed, the most common question Douglas and other STD experts receive from physicians related to genital herpes is how to manage or counsel the partners of HSV-positive patients, he noted.

There are other issues that must be considered before prevention guidelines can be promulgated, questions that some consultants believed required more research before they could be adequately answered, such as how much genital herpes would need to be prevented to make a prevention program cost-effective. Another pressing question is what behavior changes couples are willing to accept in order to prevent HSV-2 transmission. Also, there is uncertainty regarding what the message around condoms should be. Unlike many STDs, consultants noted that condoms are not 100% effective against genital herpes, as the virus can be transmitted through contact with unprotected parts of the genitals.

After two days of meeting, the consultants made no hard conclusions about the specifics of a genital herpes prevention program, but agreed that the CDC should move ahead in its efforts to formulate one and to set a research agenda that can shed light on many of the unanswered questions about HSV-2.

References

1. Fleming D, McQuillan G, Johnson R, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997; 337:1,105-1,110.

2. Hook E. Herpes simplex virus infection as a risk factor for HIV infection in heterosexuals. J Infect Dis 1992; 251-255.