title: Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.
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.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Denton
authors.forename: John F
authors.initials: JF
authors.lastname: Krisko
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Powell
authors.forename: Melissa
authors.initials: M
authors.lastname: Mathias
authors.forename: Youn Tae
authors.initials: YT
authors.lastname: Kwak
authors.forename: Francisco
authors.initials: F
authors.lastname: Martinez-Torres
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Payne
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: J Victor
authors.initials: JV
authors.lastname: Garcia
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005434:Flow Cytometry; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D015497:HIV-1; D051379:Mice; D063065:Organophosphonates / Q000008:administration & dosage*; D012007:Rectum; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine