PMID- 31146534
OWN - NLM
STAT- MEDLINE
DCOM- 20200812
LR  - 20200812
IS  - 1931-8405 (Electronic)
IS  - 0889-2229 (Linking)
VI  - 35
IP  - 9
DP  - 2019 Sep
TI  - A Multiple Dose Phase 1 Assessment of Rilpivirine Long Acting in a Model of 
      Preexposure Prophylaxis Against HIV.
PG  - 794-804
LID - 10.1089/AID.2018.0265 [doi]
AB  - The MWRI-01 study characterized the safety, acceptability, pharmacokinetic (PK), 
      and pharmacodynamic (PD) profile of rilpivirine (RPV) long acting (LA) in a model 
      of preexposure prophylaxis (PrEP). Prospective, open-label Phase 1 study. The 
      safety and acceptability of three repeated doses of RPV LA were monitored. Blood, 
      tissue (rectal, cervical, and vaginal), and biological fluids (vaginal and 
      endocervical) were collected at baseline and at 1- to 2-month intervals 
      throughout the study for PK and PD assessment. Eight women and four men received 
      three intramuscular doses of 1,200 mg of RPV LA given 8 weeks apart. There were a 
      total of 195 adverse events (AEs) reported, of which 138 (70.8%) were Grade 1 and 
      55 (28.2%) were Grade 2. The most common AE was injection site pain. Geometric 
      mean (90% confidence interval) plasma RPV concentrations at 56 days after the 
      first and third doses were 39 (33-45) ng/mL (female)/29 (17-40) ng/mL (male) and 
      59 (45-62) ng/mL (female)/40 (30-51) ng/mL (male), respectively. Exposure to RPV 
      LA was associated with significant inhibition of HIV-1(BaL) viral replication in 
      the ex vivo rectal explant model (p < .0001) that persisted for up to 4 months 
      after the third dose of RPV LA. In contrast, no viral suppression was seen in 
      cervicovaginal tissue. Multiple dose administration of RPV LA was safe and well 
      tolerated, and was associated with prolonged suppression of viral replication in 
      rectal explant tissue.
FAU - Cranston, Ross D
AU  - Cranston RD
AD  - University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
FAU - Dezzutti, Charlene S
AU  - Dezzutti CS
AD  - University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
AD  - Magee Women Research Institute, Pittsburgh, Pennsylvania.
FAU - Siegel, Aaron
AU  - Siegel A
AD  - Magee Women Research Institute, Pittsburgh, Pennsylvania.
FAU - Engstrom, Jarret
AU  - Engstrom J
AD  - Magee Women Research Institute, Pittsburgh, Pennsylvania.
FAU - Shetler, Cory
AU  - Shetler C
AD  - Magee Women Research Institute, Pittsburgh, Pennsylvania.
FAU - Richardson-Harman, Nicola
AU  - Richardson-Harman N
AD  - Alpha StatConsult, LLC, Damascus, Maryland.
FAU - Abebe, Kaleab Z
AU  - Abebe KZ
AD  - University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
FAU - Back, David
AU  - Back D
AD  - University of Liverpool, Liverpool, United Kingdom.
FAU - Else, Laura
AU  - Else L
AD  - University of Liverpool, Liverpool, United Kingdom.
FAU - Egan, Deidre
AU  - Egan D
AD  - University of Liverpool, Liverpool, United Kingdom.
FAU - Khoo, Saye
AU  - Khoo S
AD  - University of Liverpool, Liverpool, United Kingdom.
FAU - Egan, James E
AU  - Egan JE
AD  - University of Pittsburgh Graduate School of Public Health, Pittsburgh, 
      Pennsylvania.
FAU - Stall, Ronald
AU  - Stall R
AD  - University of Pittsburgh Graduate School of Public Health, Pittsburgh, 
      Pennsylvania.
FAU - Williams, Peter
AU  - Williams P
AD  - Janssen Research and Development, Beerse, Belgium.
FAU - Brand, Rhonda M
AU  - Brand RM
AD  - University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
FAU - Parikh, Urvi M
AU  - Parikh UM
AD  - University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
FAU - McGowan, Ian
AU  - McGowan I
AD  - Orion Biotechnology, Ottawa, Canada.
AD  - University of Miami, Miller School of Medicine, Miami, Florida.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190716
PL  - United States
TA  - AIDS Res Hum Retroviruses
JT  - AIDS research and human retroviruses
JID - 8709376
RN  - 0 (Anti-HIV Agents)
RN  - FI96A8X663 (Rilpivirine)
SB  - IM
MH  - Adult
MH  - Anti-HIV Agents/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Cervix Uteri/virology
MH  - Drug Administration Schedule
MH  - Female
MH  - HIV Infections/*prevention & control
MH  - HIV Seronegativity
MH  - HIV-1/drug effects/physiology
MH  - Humans
MH  - Injections, Intramuscular
MH  - Male
MH  - *Pre-Exposure Prophylaxis
MH  - Prospective Studies
MH  - Rectum/virology
MH  - Rilpivirine/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Vagina/virology
MH  - Virus Replication/drug effects
MH  - Young Adult
OTO - NOTNLM
OT  - PrEP
OT  - long acting
OT  - prophylaxis
OT  - rectum
OT  - rilpivirine
OT  - vagina
EDAT- 2019/05/31 06:00
MHDA- 2020/08/13 06:00
CRDT- 2019/06/01 06:00
PHST- 2019/05/31 06:00 [pubmed]
PHST- 2020/08/13 06:00 [medline]
PHST- 2019/06/01 06:00 [entrez]
AID - 10.1089/AID.2018.0265 [doi]
PST - ppublish
SO  - AIDS Res Hum Retroviruses. 2019 Sep;35(9):794-804. doi: 10.1089/AID.2018.0265. 
      Epub 2019 Jul 16.