Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice

Paul W. Denton, John F. Krisko, Daniel A. Powell, Melissa Mathias, Youn Tae Kwak, Francisco Martinez-Torres, Wei Zou, Deborah A. Payne, Jacob Estes, J. Victor Garcia

Research output: Contribution to journalArticle

104 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere8829
JournalPLoS One
Volume5
Issue number1
DOIs
StatePublished - Jan 21 2010
Externally publishedYes

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Human immunodeficiency virus 1
HIV-1
mice
disease control
Tenofovir
HIV Infections
Thymus
HIV
infection
drug injection
exposure pathways
Liver
in vivo studies
Drug Users
bone marrow
Bone
Thymus Gland
Acquired Immunodeficiency Syndrome
Bone Marrow
Pre-Exposure Prophylaxis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Denton, P. W., Krisko, J. F., Powell, D. A., Mathias, M., Kwak, Y. T., Martinez-Torres, F., ... Garcia, J. V. (2010). Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice. PLoS One, 5(1), [e8829]. https://doi.org/10.1371/journal.pone.0008829

Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice. / Denton, Paul W.; Krisko, John F.; Powell, Daniel A.; Mathias, Melissa; Kwak, Youn Tae; Martinez-Torres, Francisco; Zou, Wei; Payne, Deborah A.; Estes, Jacob; Garcia, J. Victor.

In: PLoS One, Vol. 5, No. 1, e8829, 21.01.2010.

Research output: Contribution to journalArticle

Denton, PW, Krisko, JF, Powell, DA, Mathias, M, Kwak, YT, Martinez-Torres, F, Zou, W, Payne, DA, Estes, J & Garcia, JV 2010, 'Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice', PLoS One, vol. 5, no. 1, e8829. https://doi.org/10.1371/journal.pone.0008829
Denton, Paul W. ; Krisko, John F. ; Powell, Daniel A. ; Mathias, Melissa ; Kwak, Youn Tae ; Martinez-Torres, Francisco ; Zou, Wei ; Payne, Deborah A. ; Estes, Jacob ; Garcia, J. Victor. / Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice. In: PLoS One. 2010 ; Vol. 5, No. 1.
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