PMID- 20098623
OWN - NLM
STAT- MEDLINE
DCOM- 20100520
LR  - 20220316
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 1
DP  - 2010 Jan 21
TI  - Systemic administration of antiretrovirals prior to exposure prevents rectal and 
      intravenous HIV-1 transmission in humanized BLT mice.
PG  - e8829
LID - 10.1371/journal.pone.0008829 [doi]
LID - e8829
AB  - 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.
FAU - Denton, Paul W
AU  - Denton PW
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center 
      at Dallas, Dallas, Texas, United States of America.
FAU - Krisko, John F
AU  - Krisko JF
FAU - Powell, Daniel A
AU  - Powell DA
FAU - Mathias, Melissa
AU  - Mathias M
FAU - Kwak, Youn Tae
AU  - Kwak YT
FAU - Martinez-Torres, Francisco
AU  - Martinez-Torres F
FAU - Zou, Wei
AU  - Zou W
FAU - Payne, Deborah A
AU  - Payne DA
FAU - Estes, Jacob D
AU  - Estes JD
FAU - Garcia, J Victor
AU  - Garcia JV
LA  - eng
GR  - HHSN266200400088C/PHS HHS/United States
GR  - R01 AI073146/AI/NIAID NIH HHS/United States
GR  - 5T32AI005284/AI/NIAID NIH HHS/United States
GR  - R33 AI071940/AI/NIAID NIH HHS/United States
GR  - AI073146/AI/NIAID NIH HHS/United States
GR  - T32 AI005284/AI/NIAID NIH HHS/United States
GR  - R21 AI071940/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100121
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Organophosphonates)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 99YXE507IL (Tenofovir)
RN  - G70B4ETF4S (Emtricitabine)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/administration & dosage/*analogs & derivatives
MH  - Animals
MH  - Anti-HIV Agents/*administration & dosage
MH  - Deoxycytidine/administration & dosage/*analogs & derivatives
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Emtricitabine
MH  - Flow Cytometry
MH  - HIV Infections/prevention & control/*transmission
MH  - HIV-1
MH  - Mice
MH  - Organophosphonates/*administration & dosage
MH  - Rectum
MH  - Tenofovir
PMC - PMC2809117
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/01/26 06:00
MHDA- 2010/05/21 06:00
PMCR- 2010/01/21
CRDT- 2010/01/26 06:00
PHST- 2009/10/16 00:00 [received]
PHST- 2009/12/23 00:00 [accepted]
PHST- 2010/01/26 06:00 [entrez]
PHST- 2010/01/26 06:00 [pubmed]
PHST- 2010/05/21 06:00 [medline]
PHST- 2010/01/21 00:00 [pmc-release]
AID - 09-PONE-RA-13610R1 [pii]
AID - 10.1371/journal.pone.0008829 [doi]
PST - epublish
SO  - PLoS One. 2010 Jan 21;5(1):e8829. doi: 10.1371/journal.pone.0008829.