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Pre-exposure drug treatment holds HIV at bay

In experiments at the University of North Carolina at Chapel Hill School of Medicine, mice with "humanized" immune systems were able to fend off infections by the AIDS virus after receiving antiretroviral drugs before the rodents were administered HIV either intravenously or rectally.

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Published: February 9, 2010

It may be possible to develop a preventative program targeting all AIDS risk groups, researchers say after testing pre-exposure drug treatments on mice with humanlike immune systems.

The announcement by researchers at the University of North Carolina at Chapel Hill School of Medicine of a successful trial of pre-exposure use of antiretroviral drugs in mice with "humanized" immunity comes on the heels of a disappointing AIDS vaccine study in Thailand.

Systemic pre-exposure prophylaxis, or PrEP, administration of antiretroviral drugs provides protection against intravenous and rectal transmission of HIV in mice with human immune systems, according to a study the UNC researchers published Jan. 21 in the online journal PLoS ONE.

"These results provide evidence that a universal approach to prevent all forms of HIV transmission in all settings might be possible," said J. Victor Garcia-Martinez, professor in the department of medicine at the UNC-Chapel Hill.

"This could greatly facilitate the implementation of a single program capable of targeting virtually all groups of people at high risk of HIV infection," Garcia, the study's senior author.

The study was conducted using genetically engineered Bone Marrow Liver Thymic, or BLT, mice. Mice normally aren't susceptible to infection by human-specific virus such as HIV. This means that can't be used to test the effectiveness of drugs and vaccines against human virus.

In 2006, while he was at the University of Texas Southwestern Medical Center, in Dallas, Garcia led a team that worked in conjunction with researchers at the University of Minnesota to develop the BLT mice.

They implanted human immune system tissue and stem cells in mice that proceeded to produce T-cells and other human immune system components throughout their bodies. The mice were first rendered immune deficient to keep them from rejecting the human tissue and stem cells.

In the UNC research, half the BLT mice received PrEP administration of the antiretroviral drug Truvada and the other half didn't. They were then administered HIV, either intravenously or rectally, in dose much higher than normal human exposure.

Truvada is the brand name of a combination of the antiretroviral drugs tenofvir and emtricitabine.

All of the mice that did not receive Truvada became infected. Of the mice that did received the PrEP drug treatment, none of those exposed rectally became infected and only one of eight who received the IV virus injections became infected.

"Although results from humanized mice cannot be extrapolated directly to humans, our data indicate that one intervention approach could potentially block multiple routes of HIV transmission in people," said Paul Denton, the paper's lead author. Denton is a research instructor in the department of medicine at the UNC School of Medicine.

Mark Wainberg, professor of microbiology and virology at Montreal's McGill University hailed the UNC research as "outstanding."

"This research provides excellent rationale for the continuation of PrEP clinical trials," said Wainberg, director of the McGill AIDS Centre.

The research was funded by the U.S. National Institutes of Health and the Foundation for AIDS Research.

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