Chapel Hill, NC—When it comes to antivirals for HIV prevention, what’s good for the goose isn’t the same as what’s good for the gander.

A new study in the Journal of Infectious Diseases points out that women need daily doses of the antiviral medication Truvada to prevent HIV infection while men only need two doses per week. University of North Carolina at Chapel Hill pharmacy researchers explain that how the drug accumulates in different body tissues makes the difference.

“Our data highlight the fact that one dose does not fit all,” noted senior author Angela Kashuba, PharmD, of the UNC Eshelman School of Pharmacy. “In determining how best to use drugs to protect people from HIV, we need to understand where in their body they are at risk for being infected, along with the concentration of drug that is needed to protect that site from infection.”

Previous clinical studies have shown that Truvada, the only prophylactic drug approved by the FDA to help prevent the spread of HIV, is more effective at reducing infection rates in men than in women, even with similar rates of drug adherence.

The recent study is the first to explain the varied clinical trial results by showing that vaginal, cervical and rectal tissue all respond differently to Truvada.

For example, according to the study, twice as much of the drug is needed to prevent HIV infection in vaginal and cervical tissue than rectal tissue because fewer components of Truvada make it into those two tissue types. In addition, more DNA material that the virus uses to reproduce is present in vaginal and cervical tissues.

“The more DNA material there is available for HIV to work with, the more medicine is needed to block the process,” said lead author Mackenzie Cottrell, PharmD, MS. “In essence, we calculated the most effective drug-to-DNA ratio for each tissue type.”

For the study, the researchers used human cells in a test tube to measure DNA and how much Truvada was needed to prevent HIV infection in them. Next, they dosed healthy female volunteers with Truvada to determine how much of the drug got into vaginal, cervical and rectal tissue as well as how much DNA material was present.

Combining the test tube and human data, the team was able to create a mathematical model that predicts the drug-to-DNA ratios in vaginal, cervical and rectal tissues and calculates the amount of drug needed to prevent HIV from infecting human tissues.

“This model is predictive of recent PrEP trial results where 2-3 doses/week was 75-90% effective in men but ineffective in women,” study authors conclude. “These data provide a novel approach for future PrEP investigations that can optimize clinical trial dosing strategies.”

Kashuba added that the researchers “would like to remind people who are taking pre-exposure prophylaxis that Truvada should be taken every day to reduce the risk of acquiring HIV infection. Patients should not change their medication regimen without first consulting their physicians.”

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