Abstract
Successful antiretroviral pre-exposure prophylaxis (PrEP) for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT). BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003) and intravenous (Chi square = 13, df = 1, p = 0.0003) HIV-1 transmission. 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. 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.
Highlights
Preventing the spread of HIV to new individuals is critical to stopping the HIV/AIDS pandemic
Systemic pre-exposure prophylaxis (PrEP) dosing in the Bone marrow/Liver/Thymus mice (BLT) mice continued for 4 days following exposure to simulate how systemic PrEP is expected to continue beyond the last high risk action for a given period before a person would stop the regimen (Figure 1A)
We provide in vivo preclinical evidence supporting the hypothesis that systemic antiretroviral PrEP can provide broad protection from HIV transmission
Summary
Preventing the spread of HIV to new individuals is critical to stopping the HIV/AIDS pandemic. Novel approaches to prevent HIV transmission, including effective vaccines, are being considered and developed [6]. Antiretroviral pre-exposure prophylaxis (PrEP) has been postulated to be a potentially highly effective prevention modality [7,8,9,10,11,12,13,14,15]. There are many reasons to consider implementing targeted antiretroviral PrEP until less toxic, easier to deliver and more potent prevention methods become available. In 2007, 500,000 (,33%) HIV positive pregnant women worldwide received antiretrovirals to prevent HIV transmission between them and their children [5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
