Herpes treatment can help co-infected HIV patients

Research suggests herpes infection increases risk of HIV infection

For about two decades research data have suggested that genital herpes is a risk factor in HIV acquisition. But now there is a growing consensus among investigators that genital herpes may account for a significant proportion of new HIV infection, an expert says.

"If you're HIV negative and have genital herpes -- even if you don't know you're infected with herpes — your risk of becoming HIV infected is increased by two-to-three fold," says Connie L. Celum, MD, MPH, a professor of medicine in the Department of Medicine, Division of Allergy and Infectious Diseases, at the University of Washington in Seattle, WA.

People who are co-infected with genital herpes and HIV can have an increase in their HIV levels during herpes reactivation, even when they don't recognize that their herpes is reactivated, Celum says.

"It increases one's viral load, and it increases the infectiousness of HIV in these individuals who have herpes," she explains.

These findings are significant because worldwide an estimated 80 to 85 percent of people who are HIV infected also are infected with herpes simplex virus type 2 (HSV-2), Celum notes.

In a study of 4,295 high-risk, HIV-negative men who have sex with men (MSM), Celum and co-investigators found that the overall HIV acquisition rate was 1.9 per 100 person-years. But among participants who had been recently infected with HSV-2, the HIV acquisition rate was 6.9 per 100 person-years.1

This data came from the EXPLORE behavioral intervention study conducted in six United States cities, including San Francisco, CA; Denver, CO; New York, NY; Chicago, IL; Boston, MA, and Seattle.

"We went back at the end of the study and determined HSV-2 data at entry to study and exit and found out who was already infected with herpes when they entered the study and who became infected during the study," Celum says.

"Close to 2 percent acquired herpes during the follow-up period," Celum says. "The risk factors for acquiring herpes were being African American, having unprotected anal sex, having an HIV-positive male sex partner, and having multiple partners, meaning six or more male partners in the prior month."

One out of five men had herpes at baseline, and the men who were infected with HSV had about a 50 percent higher risk of becoming HIV infected than those who were not HSV infected, Celum says.

"The highest risk was among the men who acquired herpes during the follow-up," she adds. "Their risk was more than double."

Researchers now are studying whether herpes treatment can reduce HIV transmission.

"Among HIV-infected persons with herpes, randomized to placebo or a herpes drug, you can lower HIV blood levels by little over a half log during herpes suppression, and there's a little less infection in the genital tract," Celum says.

"So people now are beginning to believe this is not a spurious observation in epidemiological studies," she adds. "You can demonstrate that by doing nothing else, you can get a viral load reduction by suppressing herpes."

In one recent study, investigators found that women infected with HIV who received HSV suppressive therapy with valacyclovir and who were ineligible for highly active antiretroviral therapy (HAART) had a significant decrease in the frequency of genital HIV-1 RNA and in the mean quantity of HIV. HSV treatment also resulted in a reduction in the mean plasma HIV-1 RNA.2

The study concludes that its results may be relevant to HIV-1 prevention and management.2

"Now we're waiting for a couple of big studies that are asking questions on a larger scale: Can you reduce risk of HIV acquisition among gay men in the Americas and among women in Africa [with HSV treatment]?" Celum says.

Also, researchers would like to answer a question that's very important in the AIDS field about whether viral load reductions in people treated with HSV therapy were durable and significant enough to have an impact on disease progression, Celum notes.

"What one would like to see is a delay to HAART," Celum says.

These are the questions that still need to be more definitively answered, she says:

* Can you suppress herpes and not have someone become HIV infected?

* Can you reduce the risk of transmitting HIV through HSV suppression?

* Can you benefit someone in terms of disease progression through HSV therapy?

Until recently, the HIV medical community has paid less attention to herpes/HIV co-infections than to other co-infections.

"People in general have been [apathetic] about dealing with chronic viral infections," Celum says. "Until you can tell there's an intervention that works, they're not that keen to find another virus, and then when you do you open counseling questions such as when did they get herpes and what does it mean?"

It takes time and resources for HIV clinicians to test and counsel for herpes, and until the recent studies were published, there hasn't seemed to be much reason for doing so, she notes.

"Unless you know it will have an impact on behavior or another transmission risk, they're not interested in doing it," Celum says.

Early in the AIDS epidemic, many providers identified people with HIV because they had persistent HSV-2 infection, but now co-infection largely is overlooked.3

"In the post-HAART era, most providers don't see patients come in with painful chronic herpes ulcers that last for weeks, so herpes is not staring them in the face as much as it did 15 years ago, and providers view it as a minor problem," she says. "It's not an opportunistic infection that kills people, and it's largely asymptomatic, so why bother?"

With the recent herpes/HIV studies already published and more on the way, this attitude could change, Celum says.

"We think these data we're waiting for so eagerly may impact public health issues," she says. "Can we use herpes suppression for HIV prevention, or can we use herpes suppression to delay the time until a patient begins HAART? People are watching with interest, but are waiting for those data before they can take this issue more seriously."

References:

  1. Brown EL; Wald A; Hughes JP, et al. High risk of human immunodeficiency virus in men who have sex with men with herpes simplex virus type 2 in the EXPLORE study. Am J Epidem. 2006;164(8):733-741.
  2. Nagot N; Ouédraogo A; Foulongne V, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007;356:790-799.
  3. Corey L. Synergistic copathogens -- HIV-1 and HSV-2. N Engl J Med. 2007;356:854-856.