Pre-Exposure Prophylaxis with Tenofovir plus Emtricitabine Prevents HIV Infection in "Humanized" Mice

		SUMMARY: Mice genetically engineered to have a human immune system were protected from infection with both injected and rectally administered HIV if they were first given tenofovir plus emtricitabine, the drugs in the Truvada combination pill, researchers reported in the January 21, 2010 issue of the open access journal PLoS One. While most of the mice given a placebo became HIV infected, this was the case for only 1 of the mice that received tenofovir/emtricitabine pre-exposure prophylaxis (PrEP). This strategy is currently being tested in humans in a series of ongoing clinical trials.

By Liz Highleyman

Paul Denton from the University of Texas Southwestern Medical Center at Dallas and colleagues designed a preclinical study to investigate whether rectal and intravenous HIV transmission can be blocked by antiretroviral drugs administered prior to exposure.

Successful antiretroviral PrEP could reduce new HIV infections among targeted populations including discordant couples, injection drug users, at-risk women, and men who have sex with men," the authors noted as background. PrEP could be particularly effective if a single antiretroviral combination were found to be "broadly protective across multiple routes of transmission."

Several PrEP studies have looked at monkeys, but monkeys are not susceptible to HIV, and it is not clear whether prevention strategies that are effective against SIV, a related monkey virus, would carry over to humans.

The present study therefore used humanized bone marrow/liver/thymus (BLT) mice, which are genetically modified to have their normal immune systems "knocked out" and replaced with human immune system components. BLT mice are susceptible to HIV infection via 3 physiological routes: vaginal, rectal, and intravenous.

The mice were given either systemic tenofovir/emtricitabine or placebo for 7 days. On day 3 they were exposed to HIV, administered wither rectally or intravenously. In effect, the study tested a combination of pre-exposure and post-exposure prophylaxis (PEP).

Results

	BLT mice given antiretroviral PrEP were efficiently protected against HIV infection regardless of the route of exposure.
	With rectal HIV exposure, none of 9 mice given tenofovir/emtricitabine PrEP were infected, compared with 12 of 19 mice given placebo.
	For intravenous HIV exposure, only 1 of 9 mice given PrEP was infected, compared with all mice given placebo.

"Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals," the investigators concluded. "These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS."

Department of Internal Medicine and Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX; AIDS and Cancer Virus Program, SAIC-Frederick, Inc, National Cancer Institute, Frederick, MD.

2/5/10

Reference
PW Denton, JF Krisko, DA Powell, and others. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice. PLoS One 5(1): e8829 (Abstract). January 21, 2010.