Herpes Treatment Could Help Keep HIV at Bay

Valtrex lowered both viruses in female genital tract, study found

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HealthDay Reporter

WEDNESDAY, Feb. 21, 2007 (HealthDay News) -- Although it doesn't target HIV directly, a herpes drug may go a long way toward reducing HIV load in women who carry both viruses, a new study shows.

Treatment with valacyclovir (Valtrex) or a cheaper herpes antiviral, acyclovir, could also reduce HIV transmission during sexual intercourse, say international researchers who conducted the trial in Africa.

"Our results open a new avenue and raise hopes for HIV control (both prevention and care) in a period where new tools are desperately needed," said lead researcher Dr. Nicolas Nagot, an epidemiologist at the London School of Hygiene and Tropical Medicine.

The findings are published in the Feb. 22 issue of the New England Journal of Medicine.

AIDS experts have long recognized the deadly partnership between the herpes simplex virus (HSV) and HIV.

"You can imagine that if you have genital herpes, the ulcers that are associated with that could act as a direct gateway through which the HIV could travel," explained Dr. Rowena Johnston, vice president of research at the Foundation for AIDS Research (amfAR), based in New York City.

Furthermore, active genital herpes infection, whether symptomatic or asymptomatic, causes the body's immune system to send a rush of activated T-cells to the area of herpes activity. "Once these cells are activated and busy trying to find the herpes, their activation means that they are in the exact state they need to be in for HIV to infect them," explained Johnston.

On the flip side, HIV can debilitate the immune system and thereby encourage herpes flare-ups, said another infectious disease expert, Dr. Philip Keiser, of the University of Texas Southwestern Medical Center in Dallas.

"The number of outbreaks of HSV in someone who is HIV are much higher," he said. "So, the two viruses are clearly co-factors; they both stimulate each other."

In some African countries, the problem is compounded by the fact that more than 60 percent of adults are thought to be infected with the herpes virus, Johnston said. By contrast, the U.S. rate of genital herpes infection is about one in five, according to the U.S. Centers for Disease Control and Prevention.

All of this suggests that interventions that control HSV might also help control HIV.

Nagot's team conducted a randomized, double-blinded, placebo-controlled trial involving 140 women from the West African nation of Burkina Faso, all of whom tested positive for both HIV, the virus that causes AIDS, and HSV-2, the herpes strain most often linked to genital infection.

The patients -- who were for various reasons ineligible for antiretroviral HIV-suppressing drugs at the time of the study -- received either 500 milligrams of HSV-suppressing Valtrex twice daily or a placebo for 12 weeks. The researchers then tracked the women for three months of follow-up.

They found that use of Valtrex cut down the amount of time HIV was highly present and active in the genital tract -- "shedding" -- by 59 percent, on average, and significantly reduced HIV viral load -- both within the female genital tract and in the bloodstream.

For the first time, the study proves in a clinical setting, "that HIV replication is causally related (at least in part) to HSV replication; and we have demonstrated that this replication can be reduced (in the genital fluids and plasma) with an antiviral therapy that is only directed at HSV-2," said study senior researcher Dr. Philippe Mayaud, also of the London School of Hygiene and Tropical Medicine.

Herpes treatment could never offer full protection against HIV, the researchers stressed. However, by lowering levels of HIV within the genital tract, it may reduce sexual transmission of the virus.

Furthermore, by lowering blood levels of HIV, herpes treatment should bolster patients' immune systems and thus "prolong the time until [they] need to start antiretroviral therapy," Mayaud said.

Valtrex, which remains under patent to maker GlaxoSmithKline, might still be too expensive for widespread use in developing countries. But the study's authors said another generic drug, acyclovir, is showing similar promise and is much cheaper.

The Burkina Faso trial was too short to show any Valtrex-linked reductions in HIV-related symptoms or illness in the women, Mayaud said. "The logical next step is to study the effect of acyclovir or valcyclovir over a longer duration, to study the impact on HIV-related outcomes linked to disease progression, like the decline in CD4 [T-cell] counts," he said.

The study also raises the intriguing possibility that a herpes vaccine might help control HIV transmission, too.

So far, efforts to develop a 100-percent effective HSV vaccine have failed, Nagot said. But immunization, "even if imperfect at preventing acquisition of HSV, might have a great public health impact at decreasing HSV shedding and indirectly at preventing acquisition or transmission of HIV," he said. "We hope our research (and that of others that will follow) will reinvigorate this field."

For now, getting inexpensive HSV-suppressing medications to people infected with both herpes and HIV seems reasonable, the experts said.

"Certainly for women, if they have evidence of HIV, this argues that you should give them something to suppress their HSV along with the HIV, and keep them on it routinely," said Keiser. He noted that Valtrex has a very good side-effect profile, even over the long term.

And Johnston said the study reinforces an important lesson.

"You come to the realization that dealing with HIV is not necessarily about dealing with HIV alone," she said. "Treating herpes is really a very important step towards trying to reduce the overall global burden of HIV, because we know that HSV is such a significant risk factor for getting HIV and transmitting it."

More information

Find out more about the fight against HIV/AIDS at amfAR.

SOURCES: Nicolas Nagot, M.D., epidemiologist, and Philippe Mayaud, M.D., reader, infectious disease and reproductive health, both of the London School of Hygiene and Tropical Medicine, U.K.; Rowena Johnston, M.D., vice president, research, Foundation for AIDS Research, New York City; Philip Keiser, M.D., professor, medicine, University of Texas Southwestern Medical Center, Dallas; Feb. 22, 2007, New England Journal of Medicine

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