HIV-1 is the predominant strain of human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS). When people refer to HIV without saying which type of virus, they usually mean HIV-1.

Previously it was thought that the herpes simplex virus 2 (HSV-2) had to be present for valacyclovir to be effective against HIV.

Co-senior author Benigno Rodriguez, associate professor of medicine and infectious diseases at CWRU School of Medicine, says:

"These results demonstrated that the mechanism by which valacyclovir acts against HIV is not only through the presence of HSV-2."

The results of the trial suggest not only that valacyclovir is effective for more HIV patients than previously thought, but they also point to new avenues for developing HIV drugs.

Such news will be most welcome given that some forms of HIV-1 are now resistant to current drugs.

Prof. Rodriguez says their work also reveals important clues about how the drug decreases HIV-1 levels.

Valacyclovir reduces viral load by blocking HIV-1 replication

The findings suggest that valacyclovir reduces viral load because once it activates inside HIV-infected cells, it stops the virus from replicating.

There is a known link between HIV-1 and HSV-2 in that herpes causes periodic outbreaks of genital lesions that make herpes-infected people more likely to contract HIV through intimate contact.

Outbreaks of herpes are treated either with acyclovir or its newer sibling valacyclovir, which can be given in less frequent doses.

Earlier work with acyclovir had already suggested that the drug blocked HIV-1 reproduction, even in the absence of HSV-2. This prompted the new trials of valacyclovir in HIV-infected patients.

The study reports the results of two trials that ran between 2009 and 2012. One trial was in the US and the other in Peru. Altogether, 18 HIV-1 infected patients who tested negative for HSV-2 were enrolled. They had low CD4 cell counts and they were not taking antiretrovirals.

The patients were randomly assigned to one of two groups. In one group, the treatment began with the active drug, in the other group, it began with a placebo. The study was double-blind, meaning that throughout, neither the patients nor the clinicians who gave them the treatment knew whether they were receiving the active drug or the placebo.

The patients took the drug (active or placebo) twice daily for 12 weeks. The trial was also a crossover trial, so after a 2-week break with no medication, the groups switched - the placebo was replaced by active drug and the active drug was replaced by placebo. Another 12 weeks of taking the drug twice a day followed.

HIV viral loads were down with valacyclovir, and up with placebo

The results showed that when the patients were on valacyclovir, their HIV viral loads went down, and when they were on placebo, their HIV viral loads went up.

Co-senior author Michael M. Lederman, a professor of medicine at CWRU, says:

"Our most recent clinical study demonstrates that acyclovir blocks HIV replication directly. The anti-HIV activity of valacyclovir does not depend on blocking the inflammation caused by herpes simplex virus 2."

The CWRU team believes the study offers valuable clues to new anti-HIV drug development, using agents based on the molecular structure of valacyclovir, as Prof. Lederman explains:

"The drug might be an agent that can be used safely in some people with HIV infection who have a form of HIV that is highly resistant to other antiretroviral drugs. Valacyclovir might well augment the cocktail of medications they take for reducing HIV replication. Valacyclovir is a well-tolerated drug, and it doesn't have a lot of side effects."

Funds for the study came from various institutes and programs with the National Institutes of Health (NIH).

Meanwhile, Medical News Today recently learned about a study presented at a conference that showed the antiretroviral Truvada reduced HIV infection risk by 86%. The researchers found that taking the drug daily was highly effective at preventing HIV infection in men who have sex with men.

Written by Catharine Paddock PhD