PMID- 22943559
OWN - NLM
STAT- MEDLINE
DCOM- 20130425
LR  - 20211021
IS  - 1931-8405 (Electronic)
IS  - 0889-2229 (Print)
IS  - 0889-2229 (Linking)
VI  - 28
IP  - 11
DP  - 2012 Nov
TI  - RMP-02/MTN-006: A phase 1 rectal safety, acceptability, pharmacokinetic, and 
      pharmacodynamic study of tenofovir 1% gel compared with oral tenofovir disoproxil 
      fumarate.
PG  - 1412-21
AB  - This study was designed to assess the safety, acceptability, pharmacokinetic 
      (PK), and pharmacodynamic (PD) responses to rectal administration of tenofovir 
      (TFV) 1% vaginally formulated gel and oral tenofovir disoproxil fumarate (TDF). 
      This study was designed as a phase 1, randomized, two-site (United States), 
      double-blind, placebo-controlled study of sexually abstinent men and women. 
      Eighteen participants received a single 300-mg exposure of oral TDF and were then 
      randomized 2:1 to receive a single and then seven daily exposures of rectal TFV 
      or hydroxyethyl cellulose (HEC) placebo gel. Safety endpoints included clinical 
      adverse events (AEs) and mucosal safety parameters. Blood and colonic biopsies 
      were collected for PK analyses and ex vivo HIV-1 challenge. No serious AEs were 
      reported. However, AEs were significantly increased with 7-day TFV gel use, most 
      prominently with gastrointestinal AEs (p=0.002). Only 25% of participants liked 
      the TFV gel. Likelihood of use "if somewhat protective" was  approximately 75% in both groups. 
      Indices of mucosal damage showed minimal changes. Tissue TFV diphosphate (TFV-DP) 
      C(max) 30 min after single rectal exposure was 6-10 times greater than single 
      oral exposure; tissue TFV-DP was 5.7 times greater following 7-day versus single 
      rectal exposure. In vivo exposure correlated with significant ex vivo tissue 
      infectibility suppression [single-rectal: p=0.12, analysis of covariance (ANCOVA) 
      p=0.006; 7-day rectal: p=0.02, ANCOVA p=0.005]. Tissue PK-PD was significantly 
      correlated (p=0.002). We conclude that rectal dosing with TFV 1% gel resulted in 
      greater TFV-DP tissue detection than oral dosing with reduced ex vivo biopsy 
      infectibility, enabling PK-PD correlations. On the basis of increased 
      gastrointestinal AEs, rectally applied, vaginally formulated TFV was not entirely 
      safe or acceptable, suggesting the need for alternative rectal-specific 
      formulations.
FAU - Anton, Peter A
AU  - Anton PA
AD  - Center for HIV Prevention Research , UCLA AIDS Institute, Department of Medicine, 
      David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. 
      panton@mednet.ucla.edu
FAU - Cranston, Ross D
AU  - Cranston RD
FAU - Kashuba, Angela
AU  - Kashuba A
FAU - Hendrix, Craig W
AU  - Hendrix CW
FAU - Bumpus, Namandje N
AU  - Bumpus NN
FAU - Richardson-Harman, Nicola
AU  - Richardson-Harman N
FAU - Elliott, Julie
AU  - Elliott J
FAU - Janocko, Laura
AU  - Janocko L
FAU - Khanukhova, Elena
AU  - Khanukhova E
FAU - Dennis, Robert
AU  - Dennis R
FAU - Cumberland, William G
AU  - Cumberland WG
FAU - Ju, Chuan
AU  - Ju C
FAU - Carballo-Dieguez, Alex
AU  - Carballo-Dieguez A
FAU - Mauck, Christine
AU  - Mauck C
FAU - McGowan, Ian
AU  - McGowan I
LA  - eng
SI  - ClinicalTrials.gov/NCT00984971
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - UL1 RR024153/RR/NCRR NIH HHS/United States
GR  - P30 MH043520/MH/NIMH NIH HHS/United States
GR  - P30AI50410/AI/NIAID NIH HHS/United States
GR  - 5UM1AI068633/AI/NIAID NIH HHS/United States
GR  - AI060614/AI/NIAID NIH HHS/United States
GR  - P30 AI028697/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121009
PL  - United States
TA  - AIDS Res Hum Retroviruses
JT  - AIDS research and human retroviruses
JID - 8709376
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Organophosphonates)
RN  - 0 (Vaginal Creams, Foams, and Jellies)
RN  - 99YXE507IL (Tenofovir)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics/pharmacology
MH  - Administration, Oral
MH  - Administration, Rectal
MH  - Adult
MH  - Aged
MH  - Anti-HIV Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Double-Blind Method
MH  - Female
MH  - HIV Infections/*drug therapy/epidemiology/pathology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Organophosphonates/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Patient Satisfaction
MH  - Rectum/*drug effects/pathology
MH  - Tenofovir
MH  - Treatment Outcome
MH  - United States/epidemiology
MH  - Vaginal Creams, Foams, and Jellies
PMC - PMC3484811
EDAT- 2012/09/05 06:00
MHDA- 2013/04/26 06:00
PMCR- 2013/11/01
CRDT- 2012/09/05 06:00
PHST- 2012/09/05 06:00 [entrez]
PHST- 2012/09/05 06:00 [pubmed]
PHST- 2013/04/26 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - 10.1089/aid.2012.0262 [pii]
AID - 10.1089/aid.2012.0262 [doi]
PST - ppublish
SO  - AIDS Res Hum Retroviruses. 2012 Nov;28(11):1412-21. doi: 10.1089/aid.2012.0262. 
      Epub 2012 Oct 9.