Anti-herpes drug to treat HIV?

Research is continuing to discover new drugs to help in the fight against HIV/AIDS. The research isn’t just for drugs; it’s also for vaccines and some other techniques to try to prevent the transmission of and, finally, cure AIDS.

Valacyclovir is a drug primarily used to treat people infected with Herpes Simplex virus (HSV). It has also been used to treat patients with chickenpox, patients infected with Epstein-Barr virus and to prevent cytomegalovirus infections. It’s been available to use for quite some time and often works well to treat people with HSV infections like genital herpes, herpes labialis (cold sores) or shingles (caused by another herpesvirus, Herpes zoster) and some other viral diseases.

When this medication is given, it gets taken up by herpes-infected cells and metabolized; it gets changed a bit and becomes a powerful drug. Once metabolized, it blocks the infecting Herpes virus from replicating its DNA, keeping it from producing more of the virus. In the past, it’s been noted that some HIV and HSV co-infected patients, when placed on valacyclovir (along with being maintained on their regular doses of antiretroviral medications for HIV) experience a further drop in their HIV viral loads (as well as in their HSV viral loads) beyond what their antiviral cocktail had previously produced.

It was thought that this was a side effect of treatment for HSV. That perhaps the immune system cells that HIV infects were less likely to become infected. Or, perhaps, there were fewer of them around to become infected. All thought to be a kind of side effect of the valacyclovir.

Researchers from an arm of the National Institutes of Health (NIH) decided to look more closely at this phenomenon. They wanted to see if valacyclovir could decrease HIV in patients who weren’t infected with HSV. The NIH researchers recruited other sites to help carry out the study, including Emory, Case Western and the Civic Association for Health and Education in Peru.

The research started off as an ex vivo experiment. They added valacyclovir to cultured cells that were infected with HIV but not infected with HSV. They saw that valacyclovir suppressed HIV production in the cells. Their next step was to see if they could get similar results in humans.

Researchers enrolled eighteen volunteers who were infected with HIV but not HSV. In the first part of the experiment, half of the volunteers were given valacyclovir, one pill twice a day. The other group got a placebo twice a day. At the midpoint of the experiment, the groups were switched so that the placebo group started getting valacyclovir and the (former) valacyclovir group got placebo for the remainder of the trial. HIV viral loads were measured in all participants at baseline (before starting the study), while on placebo and while on valacyclovir. The data showed that when patients were on valacyclovir, their HIV viral loads dropped. When they were on placebo, their HIV viral loads increased. So valacyclovir seemed to be responsible for a drop in viral load in the patients.

Vaccine, via Pixabay

Vaccine, via Pixabay

This study had a very small number of patients, and it will need to be repeated with more volunteers, but it would be exciting if similar results were obtained in the larger group for a few reasons:

First off, valacyclovir has been around for a while. It’s been well-studied, most of its side effects are known and doctors are familiar with using it. Sometimes when a brand new drug is approved by the Food and Drug Administration, unexpected side effects appear sometime after the drug is licensed. As valacyclovir is is battle-tested, that’s unlikely to happen here.

Second, compared to other HIV medications, valacyclovir is cheap. In the US, the price normally runs around $45 for a one month supply. Most anti-HIV drugs are much more expensive: Kaletra, a protease inhibitor, costs about $850 for a one month supply. Raltegravir, and integrate strand inhibitor, is about $1300/month. Viread, an NRTI, is about $1,000/month. If its success can be replicated, this means that valacyclovir would be a real bargain.

Third, some strains of HIV have become resistant to certain antiretroviral medications. Valacyclovir could be placed into the armamentarium of antiretroviral drugs and could be added if a specific patient develops a resistance to a different drug.

Using an antiviral drug that wasn’t designed to treat HIV may encourage researchers to continue to think outside the box when looking for additional HIV meds. And the thinking outside the box might spread to other researchers like those working on vaccines and other treatments.

So valacyclovir looks like it might be a promising candidate to treat HIV in the near future, depending on how well the larger study turns out. With good results, this might be available in a few years.

Mark Thoma, MD, is a physician who did his residency in internal medicine. Mark has a long history of social activism, and was an early technogeek, and science junkie, after evolving through his nerd phase. Favorite quote: “The most exciting phrase to hear in science... is not 'Eureka!' (I found it!) but 'That's funny.'” - Isaac Asimov

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