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Anti-Herpes Drug May Help Control HIV

Scientists look at valacyclovir in new study

Valacyclovir, a drug commonly used to control the virus that causes genital herpes, appears to reduce the levels of human immunodeficiency virus (HIV) in patients who do not have genital herpes, according to a study by researchers at the National Institutes of Health (NIH), Case Western Reserve University, and Emory University, and in Lima, Peru.

The study of 18 patients is the first to show that the drug does not require the presence of herpes simplex virus- 2 (HSV-2) to suppress HIV in patients. The researchers hope to confirm their results in a larger study.

“These findings are very encouraging,” said senior author Leonid Margolis, PhD, of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “If valacyclovir’s effectiveness against HIV can be confirmed in a larger cohort, it could be added to the mix of drugs used to suppress the virus, and might prove especially helpful in cases in which HIV has developed resistance to other drugs.”

The study was published online March 13 in Clinical Infectious Diseases.

The new results follow a 2008 study by the same research team, which showed that acyclovir suppresses HIV in laboratory cultures of human tissues that were infected with various kinds of herpes viruses. Valacyclovir is referred to as a prodrug for acyclovir because it’s structurally similar to acyclovir and is converted to acyclovir in the body. For the current study, the researchers used valacyclovir because it remains in the blood longer than acyclovir and therefore would not need to be taken as often.

Earlier studies have shown that acyclovir reduces HIV levels in patients co-infected with HIV and HSV-2, the virus that causes genital herpes. However, this effect was attributed to the drug’s anti-HSV-2 activity. The decrease in immune activity results in fewer active immune cells for HIV to infect.

In contrast, the laboratory results reported in the new study indicated that valacyclovir likely reduced HIV levels by interfering directly with HIV’s reproductive machinery and did not require the presence of HSV-2. HSV-2 chemically alters acyclovir by attaching phosphates to it. It is this altered form of the drug that suppresses HSV-2. The researchers believe this form also interferes with HIV’s ability to reproduce. In their earlier study, the investigators found that many other kinds of herpes viruses can also attach phosphate groups to acyclovir. Margolis noted that these other herpes viruses are widespread and that most people harbor at least one of them.

“We wanted to find out whether such a mechanism could operate in the cells of patients with HIV,” Margolis said.

The researchers enrolled 18 HIV-infected patients in their study, none of whom were infected with HSV-2, and treated them with valacyclovir. For 12 weeks, half of the enrolled patients took valacyclovir twice a day while the other half received placebo. After 2 weeks, the placebo group received valacyclovir while the group originally treated with the drug switched to placebo.

The researchers found that when the patients took valacyclovir, their blood HIV levels declined significantly. Typically, HIV patients take a “cocktail” of several anti-HIV drugs because a single drug is not enough to suppress the virus. Multiple HIV medications also hinder the virus’ ability to develop resistance to the drugs.

The researchers conducted a genetic analysis and found that the HIV in the study volunteers did not develop resistance to valacyclovir.

Because HIV has a history of becoming resistant to the drugs used to treat it, the researchers do not discount the possibility that the virus could develop resistance to valacyclovir with longer treatment. Given the ability of valacyclovir to lower HIV levels, however, the researchers believe that the drug could one day be added to the cocktail of medications given to HIV-infected people.

Source: NIH; March 13, 2015.

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