Clinical trial NCT02401230
Conditions: HIV
Keywords: Human Immunodeficiency Virus Acquired Immune Deficiency Syndrome Virus Pre-exposure Prophylaxis
Sponsor: Emory University
Start date: 2015-03-01; Completion date: 2017-01-25
Enrollment: 86 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether the use of rectal lubricants can affect how well the medication, Truvada, will work to prevent infection with HIV when someone is exposed to HIV in the rectum.

Detailed description:
Men who have sex with men (MSM) continue to be disproportionately affected by HIV. The majority of HIV infections among MSM occur through exposure to the rectal mucosa during receptive anal intercourse (RAI). During RAI, many MSM will use lubricants, which can potentially cause mucosal inflammation and damage. A new HIV prevention intervention, called pre-exposure prophylaxis (PrEP), recommends that MSM at risk of HIV infection take a daily anti-HIV medication called Truvada (tenofovir/emtricitabine) which is highly effective. However, it is not known if the use of lubricant during RAI will interfere with the efficacy of PrEP for HIV prevention.

Arms: arm 1: Subjects will insert 5 mL of lubricant in rectum for seven consecutive days arm 2: Subjects will take one Truvada tablet orally for seven consecutive days arm 3: Subjects will insert 5 mL of lubricant in rectum and take one Truvada tablet orally for seven consecutive days
Interventions: intervention 1: Truvada intervention 2: Gel lubricant
Intervention descriptions: intervention 1: Truvada is a combination of 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate taken orally. intervention 2: Five ml of an over the counter sexual lubricant will be dispensed using an applicator.

Protocol documents:
Prot_000.pdf: 
 
 
Rectal Lubricant Use and Pre-Exposure Prophylaxis in Men Who Have Sex with Men 
 
Version Date: September 26, 2016 
 
NCT02401230 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
2 
 
 
 
 
TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
 
 
Investigators: 
 
Colleen F. Kelley MD, MPH 
Assistant Professor of Medicine 
Division of Infectious Diseases 
Department of Medicine 
Emory School of Medicine 
Assistant Professor of Epidemiology 
Rollins School of Public Health 
 
Patrick S. Sullivan DVM, PhD 
Associate Professor 
Dept of Epidemiology 
Rollins School of Public Health 
 
Sheila Heeke, FNP 
Co-Investigator 
The Hope Clinic 
Division of Infectious Diseases 
Department of Medicine 
Emory School of Medicine 
 
 
Marcus Bolton, Ed.M. 
Senior Program Coordinator 
The Hope Clinic 
Division of Infectious Diseases 
Department of Medicine 
Emory School of Medicine 
 
Theron Stuart 
Project Coordinator 
The Hope Clinic 
Division of Infectious Diseases 
Department of Medicine 
Emory School of Medicine 
 
 
 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
3 
 
 
 
 
ABSTRACT 
 
Rationale:  Men who have sex with men (MSM) continue to be disproportionately affected by 
HIV. The majority of HIV infections among MSM occur through exposure to the rectal mucosa 
during receptive anal intercourse (RAI).  During RAI, many MSM will use lubricants, which can 
potentially cause mucosal inflammation and damage.  A new HIV prevention intervention, 
called pre-exposure prophylaxis (PrEP), recommends that MSM at risk of HIV infection take a 
daily anti-HIV medication called Truvada (tenofovir/emtricitabine) which is highly effective.  
However, it is not known if the use of lubricant during RAI will interfere with the efficacy of 
PrEP for HIV prevention.   
 
Design: To address the impact of a popular, over-the-counter gel lubricant use in MSM on 
PrEP, investigators at Emory University will collaborate with the Centers for Disease Control 
and Prevention (CDC) to conduct a randomized clinical trial of 90 MSM.  Men will be 
randomized into a 3-arm study as follows:  (1) daily oral Truvada® only, (2) daily gel lubricant 
applied rectally only or (3) oral Truvada® plus rectal gel lubricant application daily.  This study 
will entail 4 study visits at the Emory University Hope Clinic.  During the first visit (time 0), all 
men will be screened for eligibility and undergo written informed consent, physical 
examination, rapid HIV testing, phlebotomy for screening laboratories, and randomization.  
During study visit 2 prior to the initiation of study product (time 1-6 weeks), participants will 
undergo phlebotomy, collection of rectal secretions, and rectal biopsy via rigid sigmoidoscopy 
for establishment of baseline values.  During study visit 3 (time 4-16 weeks), men will be 
dispensed and instructed on the at-home application of rectal lubricant and/or oral Truvada.  
During study visit 4 (time 5-26 weeks), men will return after 7 consecutive days of study 
product use for repeat phlebotomy, collection of rectal secretions, and rectal biopsy via rigid 
sigmoidoscopy.  After collection, biologic specimens will be immediately transported by courier 
to CDC (laboratory of Clyde Hart) for processing.  Specimens will be processed immediately 
for ex vivo laboratory assays that will include PrEP drug concentrations, inflammatory cytokine 
levels, HIV target cell measurement and characterization by flow cytometry, and in vitro HIV 
infection assays.  Comparison of assay results among the 3 study arms should determine if 
rectal lubricant usage reduces PrEP drug concentrations, increases inflammation, or increases 
the proportion or susceptibility of HIV target cells in the rectal mucosa. 
Duration: The duration of this study is 2 years. Participants will be considered ‘on-study’ for no 
more than 26 weeks.   
 
Sample size: For this protocol we will recruit 90 HIV-negative MSM who meet eligibility criteria 
outlined in the protocol. 
 
Population:  The population to be studied in this protocol is HIV negative MSM who meet 
eligibility criteria and are willing to perform study procedures.  These men will be recruited from 
existing databases of MSM who have agreed to be contacted for future studies, and from 
internet and paper advertisements currently used routinely by the Hope Clinic for study 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
4 
 
recruitment.  


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
5 
 
LAY SUMMARY 
 
Men who have sex with men (MSM) continue to be disproportionately affected by HIV. Over 
60% of new HIV infections in the US occur among MSM.  The majority of HIV infections among 
MSM occur through exposure to the rectal mucosa during receptive anal intercourse (RAI).  
During RAI, products such as lubricants are often used to reduce friction.  However, lubricants, 
especially hyperosmolar lubricants, have been shown to cause inflammation in the rectum.  
Pre-exposure prophylaxis (PrEP) is a new HIV prevention method that is recommended by 
CDC and WHO for MSM at risk of HIV infection.  PrEP entails taking an anti-HIV medication 
(Truvada; tenofovir/emtricitabine) on a daily basis to prevent HIV infection.  However, it is 
unclear whether the inflammation caused by rectal lubricant usage during RAI will result in 
rectal tissues with increased numbers of HIV target cells, or reduced PrEP drug levels, such 
that PrEP is no longer able to prevent HIV infection for MSM using rectal lubricants.  This study 
is designed to examine whether the use of rectal lubricants could affect the efficacy of PrEP for 
MSM.   
 
For this protocol, we will recruit HIV-negative MSM aged 18-49 who are willing to adhere to 
study procedures.  There will be 4 study visits conducted over a maximum 6-month period. 
The first visit will be a screening visit where eligibility is determined, written informed consent is 
obtained, screening tests are performed, and men will be randomized to one of three study 
groups:  1.  Use of rectal over the counter gel lubricant alone; 2. Use of oral Truvada alone; or 
3. Use of rectal gel lubricant and oral Truvada.  The second study visit will occur 1-6 weeks 
after the screening visit.  During the second study visit, men will undergo a blood draw and 
rigid sigmoidoscopy for collection of baseline rectal secretions and biopsies. The third study 
visit will occur at least 3 weeks after the second study visit (4-16 weeks after the screening 
visit).  During the 3rd study visit, men will be given lubricant and/or Truvada and instructed on 
their use for 7 consecutive days before study visit 4. Study visit 4 will occur at least 4 weeks 
after study visit 2 (5-26 weeks after the screening visit).  During study visit 4, men will again 
undergo a blood draw and undergo a rigid sigmoidoscopy for collection of rectal secretions and 
biopsy samples post use of product(s) for 7 days just prior to visit.  All specimens will be 
transported directly to the laboratory of Clyde Hart, PhD at CDC where multiple immune 
assays are planned to determine if the use of lubricant may affect how well PrEP works.   
 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
6 
 
PROJECT DESCRIPTION 
The efficacy reported in clinical studies of daily oral dosing of Truvada® or tenofovir to prevent 
HIV infection in MSM indicates the potential for PrEP to greatly reduce HIV infections within 
these high-risk populations. CDC recently released clinical practice guidelines recommending 
PrEP for MSM at risk of HIV infection.1  However, the impact of rectal lubricant use on factors 
that could impact PrEP effectiveness in MSM is unclear. Recent studies suggest that lubricant 
application can increase epithelial damage and expression of inflammatory makers in human 
rectal tissue explants and epithelial cell cultures, and in macaque monkey rectal models 
without increasing their rates of HIV or SHIV infection, respectively.2-4 In contrast, consistent 
rectal lubricant use has been shown to increase acquisition of non-HIV STDs in a cohort of 
MSM in the USA.5  Additionally, studies from the TDF2 Study have suggested that ratios of 
intracellular tenofovir to natural substrate are reduced in the presence of immune cell 
activation. Together, these studies raise the concern that while MSM taking oral PrEP may be 
protected from HIV acquisition, regular use of rectal lubricants may abrogate the protection 
provided by PrEP due to increased epithelial damage, inflammation and immune activation.   
To address the impact of a popular, over the counter, gel lubricant use in the rectum in MSM 
on PrEP, investigators at Emory University will collaborate with Dr. Clyde Hart at the CDC to 
recruit and randomize 90 MSM into a three-arm study of PrEP and lubricants: (1) daily oral 
Truvada® for 7 days, (2) daily gel lubricant applied rectally for 7 days or (3) oral Truvada® plus 
rectal gel lubricant application daily for 7 days. At CDC, ex vivo laboratory assays will be used 
to evaluate the impact of rectal lubricant use on oral PrEP’s effectiveness.  Blood, rectal 
secretions and rectal biopsies obtained by rigid sigmoidoscopy (at approximately 8 -10 cm 
from the anal verge) will be collected from men in all three study arms at least 21 days prior to 
initiation of treatment and immediately following  7 days of consecutive use of assigned 
product.  Specimens will be processed immediately for ex vivo laboratory assays at CDC.  
Blood plasma and PBMCs will be used to measure extracellular and intracellular drug 
concentrations as well as intracellular concentrations of the natural dNTP substrates to assess 
adherence to oral Truvada® and to compare changes in the ratio of drug to natural substrate in 
peripheral blood.  Rectal secretions from all participants will be analyzed to measure changes 
in soluble immunological cytokines in the presence of gel lubricant usage that may indicate 
associated increases in inflammation.  Rectal lymphocytes will be isolated from the rectal 
biopsies collected from each man and analyzed for concentrations of intracellular tenofovir and 
emtricitabine as well as natural substrates, dATP and dCTP, to evaluate the potential for gel 
lubricant to alter the ratio of antiretroviral drug to natural substrate in the rectal mucosa.  
Additionally, rectal lymphocytes from 10 participants in each arm will be characterized using 
multicolor flow cytometry to observe potential changes in the proportion and activation state of 
HIV target cells within the rectal mucosa.  Rectal lymphocytes from the remaining 10 
participants in each arm will be subjected to in vitro infection with HIV to test for changes in the 
susceptibility to virus infection in the presence of gel lubricant usage.   
These studies should provide important laboratory results to help inform policy and public 
health officials as to usage of hyperosmolar rectal lubricants in concert with oral PrEP.  
Pharmacological analyses will provide important data as to whether lubricant usage diminishes 
the ratio of drug to substrate in HIV target cells in the rectum that may reduce PrEP 
effectiveness.  Immunological studies will help us understand whether lubricant usage 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
7 
 
increases inflammation and the concentrations of HIV target cells in the rectum of men taking 
oral PrEP.  The ex vivo virus infection assays described here will provide a surrogate measure 
of whether lubricant usage increases susceptibility to rectal infection with HIV for men taking 
oral PrEP.  Together the combination of these studies should help determine if rectal lubricant 
usage may abrogate the potential anti-HIV benefits of oral PrEP. 
Public Health Relevance: Information about the impact of rectal lubricant use in men who 
have sex with men will better inform policy makers and the public to make important choices 
regarding the safety of rectal lubricant usage in the presence of pre-exposure prophylaxis.   
Goal:  To determine if PrEP efficacy can be abrogated by use of rectal lubricants in MSM.   
 
STUDY POPULATION  
 A total of 70 HIV-negative MSM aged 18-49 will be recruited from existing Emory University 
study databases of MSM who have agreed to future contact about research opportunities.  We 
will also recruit men from print and on-line advertisements.  Research recruiters at the Hope 
Clinic and the Rollins School of Public Health are experienced in recruiting this population for 
research studies, including those with rectal biopsies, and do not anticipate problems.  Dr. 
Kelley is currently conducting an Emory IRB approved study of the effects of unprotected anal 
intercourse on the rectal mucosa.  This study involves recruiting a similar population to 
undergo repeated rectal biopsy procedures that are timed with sexual intercourse.  We expect 
approximately 10-15% of men will not complete the study, therefore the sample size of 70 men 
will likely result in study completion for 60 men.   
 
INCLUSION CRITERIA FOR MSM 
 
1) HIV-negative man who reports receptive anal sex with another man in the last 6 months 
aged 18-49 years 
2) Male to female transgender women who are not currently taking hormonal therapy or 
plan to take hormonal therapy for the duration of the study 
3) Not currently taking PrEP and no plans to initiate during study 
4) Able to provide informed consent in English  
5) No plans for relocation in the next 6 months 
6) Willing to undergo peripheral blood and rectal biopsy sampling 
7) Willing to use study products as directed 
8) Willing to abstain from receptive anal intercourse 3 days prior to study visit 2 and 10 
days prior to study visit 4. 
9) Willing to abstain from receptive anal intercourse for 1 week after study visits 2 and 4.   
 
 
EXCLUSION CRITERIA 
 
1) History of inflammatory bowel disease or other inflammatory, infiltrative, infectious or 
vascular condition involving the lower gastrointestinal tract that, in the judgment of the 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
8 
 
investigators, may be worsened by study procedures or may significantly distort the 
anatomy of the distal large bowel 
2) Significant laboratory abnormalities at baseline visit for rectal biopsies, including but not 
limited to:  
a) Hgb ≤ 10 g/dL 
b) PTT > 1.5x ULN or INR > 1.5x ULN 
c) Platelet count <100,000 
3) Any known medical condition that, in the judgment of the investigators, increases the 
risk of local or systemic complications of endoscopic procedures or pelvic examination, 
including but not limited to:  
a) Uncontrolled or severe cardiac arrhythmia 
b) Recent major abdominal, cardiothoracic, or neurological surgery 
c) History of uncontrolled bleeding diathesis 
d) History of colonic, rectal, or vaginal perforation, fistula, or malignancy 
e) History or evidence on clinical examination of ulcerative, suppurative, or 
proliferative lesions of the anorectal or vaginal mucosa, or untreated sexually 
transmitted disease with mucosal involvement   
4) Continued need for, or use during the 14 days prior to enrollment, of the following 
medications:  
a) Aspirin or more than 4 doses of NSAIDs 
b) Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation 
inhibitors, or fibrinolytic agents 
c) Any form of rectally administered agent besides products lubricants or douching 
used for sexual intercourse 
5) Continued need for, or use during the 90 days prior to enrollment, of the following 
medications:  
a) Systemic immunomodulatory agents 
b) Supraphysiologic doses of steroids 
c) Experimental medications, vaccines, or biologicals 
 
6) Intent to use HIV antiretroviral pre-exposure prophylaxis (PrEP) during the study, 
outside of the study procedures  
7) Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain, 
discharge, bleeding, etc.) 
8) Current use of hormonal therapy 
9) Any other clinical condition or prior therapy that, in the opinion of the investigator, would 
make the patient unsuitable for the study or unable to comply with the study 
requirements. 
 
 
PROCEDURES 
 
Recruitment procedures 
We will recruit subjects for this protocol from 2 existing databases of MSM who have 
consented to be re-contacted for future research opportunities (see below).  We will also 
recruit men with print and on-line (e.g. Facebook) advertisements as have been utilized for 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
9 
 
other studies conducted by the Emory investigative team.  We will submit all print and online 
advertisement copy to the Emory IRB for approval prior to launching these activities.   
 
1) The Hope Clinic at Emory University maintains a large study database of research 
participants that have agreed to be re-contacted for future research studies.  Due to the 
nature of ongoing studies at the Hope Clinic, a large proportion of these participants are 
MSM.  We will utilize this study database to recruit both MSM who are engaging in 
URAI and men who have never engaged in anal sex.  Men will be contacted by phone 
or email and screened by phone with the eligibility criteria for this protocol.  Men who 
are eligible will be scheduled for a screening visit.   
   
2) PRISM Health (research group in the Rollins School of Public health, Dr. Kelley is a 
member of this group) maintains large study databases of MSM who have participated 
in previous research studies and have consented for future contact. Men will be 
contacted by phone or email and screened by phone with the eligibility criteria for this 
protocol.  Men who are eligible will be scheduled for a screening visit.   
 
 
Study visits 
 
Visit 1 (screening):  
 
This study will be comprised of 4 study visits over a minimum 6 week period and maximum 6 
month period.   
 
During the screening visit, eligible MSM will provide written informed consent after all their 
questions are answered in a private exam room at the Hope Clinic. Subjects will also receive 
an approved HIPAA statement and will be informed about the way their protected health 
information will be used and stored. Copies of the consent/HIPAA form for this project will not 
be placed in individuals’ medical records since this study collects sensitive information such as 
HIV status and sexual orientation.   
 
After provision of informed consent, a medical history and physical examination will be 
conducted by the PI to evaluate for exclusion criteria. A rapid HIV test with finger stick whole 
blood (OraQuick or INSTI) will be performed by the PI or study coordinator who will be certified 
in HIV counseling and testing to confirm eligibility.  Peripheral blood will be drawn for a 
complete blood count and coagulation tests.  Finally, MSM will be randomized to one of three 
study arms:   
 
Arm 1.  Use of rectal gel lubricant alone for 7 days prior to study visit 4.   
 
Arm 2. Use of PrEP alone for 7 days prior to study visit 4  
  
Arm 3. Use of both rectal gel lubricant and PreP for 7 days prior to study visit 4.   
 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
10 
 
This study will not be blinded, so both investigator and participant will be aware of 
randomization assignment.   Participants will be asked to abstain from receptive anal 
intercourse for at least 3 days prior to study visit 2.    
 
Visit 2: 
 
Study visit 2 will occur 1-6 weeks after the screening visit.  During visit 2, the participant will 
undergo a 60mL peripheral blood draw.  All blood specimens will be coded with a unique 
numeric identifier such that the CDC laboratories that receive the specimens will be unable to 
link them back to the study participants.  Finally, rigid sigmoidoscopy (described further below) 
will be performed and, rectal secretions will be collected with Dacron swabs, and 8-12 rectal 
biopsies will be collected. An additional swab will be collected for testing for gonorrhea, 
chlamydia, and HSV-2 DNA to be performed by CDC.  If positive for gonorrhea or chlamydia, 
men will be referred for care at their private physician’s office, the health department, or AID 
Atlanta for treatment. HSV-2 results will not be returned to participants given the unclear 
clinical utility of HSV-2 serology in the absence of active disease.   All men will be instructed to 
place nothing in the rectum and to abstain from sex for 7 days after the procedure to allow the 
mucosa to heal.  Men will be given a follow-up appointment for visit 3 which will occur 3-16 
weeks after visit 2.  
 
Visit 3: 
 
Study visit 3 will occur a minimum of 3 weeks (maximum 16 weeks) after study visit 2 in order 
to allow full healing of the rectal mucosa after biopsy and some flexibility in clinic scheduling.  
During visit 3, the study group assignment will be reviewed and participants will be provided 
applicators pre-filled with 5ml of a popular, over the counter gel lubricant and/or Truvada. 
Truvada will be dispensed through the Emory Investigational Drug Service.  MSM assigned to 
study arms 1 and 3 will be instructed to insert 5mL of rectal lubricant with the study-provided 
pre-filled applicator once daily for 7 consecutive days prior to their scheduled study visit 4.  
MSM assigned to study arms 2 and 3 will be dispensed 7 days of Truvada from the Emory 
Investigational Drug Service and instructed on daily dosing for 7 consecutive days prior to their 
scheduled study visit 4.  Of note, MSM in study group 3 will use rectal gel lubricant and 
Truvada during the same 7-day period.  MSM will be requested to abstain from receptive anal 
intercourse while on study product (Truvada and/or lubricant). 
 
Visit 4: 
 
Study visit 4 will occur a minimum of 1 week after study visit 3 and a maximum of 26 weeks 
from the screening visit.  As above, men will be provided an appointment for study visit 4 
during study visit 3.  They will be instructed to use study product based on arm assignment for 
7 consecutive days prior to the study visit 4 appointment.  During study visit 4, the participant 
will undergo a 60mL peripheral blood draw.  A urine sample will be collected from participants 
randomized to an arm containing Truvada.  This sample will be used to at CDC to develop an 
assay to detect Truvada in the urine.  All specimens will be coded with a unique numeric 
identifier such that the CDC laboratories that receive the specimens will be unable to link them 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
11 
 
back to the study participants.  Finally, rigid sigmoidoscopy (described further below) will be 
performed and, rectal secretions will be collected with Dacron swabs, and 8-12 rectal biopsies 
will be collected. An additional swab will be collected for testing for gonorrhea, chlamydia, and 
HSV-2 DNA to be performed by CDC.  If positive for gonorrhea or chlamydia, men will be 
referred for care at their private physician’s office, the health department, or AID Atlanta for 
treatment. HSV-2 results will not be returned to participants given the unclear clinical utility of 
HSV-2 serology in the absence of active disease.   All men will be instructed to place nothing 
in the rectum and to abstain from sex for 7 days after the procedure to allow the mucosa to 
heal. 
 
Contingency visit: 
 
Attempts to ensure adherence to the study visits will be made with telephone and/or email 
reminders to the participant.  However, if screening laboratory results are lost or are 
inconclusive or if a participant has been unable to adhere to study protocol, he may be 
rescheduled for a future date where the above visit procedures will be performed.  These 
additional visits will be scheduled within the above visit windows.   
 
Phone calls/retention contacts: 
 
While on study, periodic phone calls, texts, or email reminders will occur between study staff 
and participants to ensure proper retention and adherence to study protocol.   
 
Rectal biopsy procedures 
 
Dr. Kelley or a to-be-named mid-level provider who is trained and supervised by Dr. Kelley 
(see below) will be performing all rectal biopsies utilizing a disposable rigid sigmoidoscope, 
light source, and jumbo biopsy forceps.  Dr. Kelley was trained in office based rectal biopsy 
procedures by Dr. Robin Rutherford, an experienced gastroenterologist at Emory University. 
All biopsy procedures will be performed in an examination room at the Hope Clinic with 
assistance from the project coordinator or clinical research nurse.  Dr. Kelley has personally 
completed more than 50 rectal biopsy procedures for another Emory IRB approved study 
protocol at the Hope Clinic with zero complications. Briefly, without the administration of any 
previous enemas or other preparation, 8-12 adequate ~1.0 mm thick biopsy specimens will be 
taken from normal-appearing rectal mucosa 10 cm above the external anal aperture using a 
rigid sigmoidoscope and flexible sigmoidoscopic forceps mounted on a semi-flexible rod.  All 
biopsy specimens will be coded with a unique numeric identifier such that the CDC 
laboratories that receive the specimens will be unable to link them back to the study 
participants. Specimens will be transported directly to CDC after the study visit.   
Twenty-four to forty-eight hours after the procedure, study personnel will interview the subjects 
who donated rectal biopsy samples and inquire about symptoms, complications, or adverse 
events related to study procedures. Subjects who report symptoms suggestive of any 
significant complications will receive advice on seeking care, and will be given referrals to 
appropriate healthcare professionals as needed. This follow-up may be completed over the 
phone or through electronic communication.      


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TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
13 
 
 
Blood sample collection 
The most common risks of blood sample collection are pain at the puncture site, bruising, and 
a feeling of lightheadedness. To minimize these risks, blood draws will be performed by trained 
personnel, and will be performed in a secure environment with access to first aid equipment, 
bandages, and trained healthcare professionals.  
 
 
Risks of Truvada for PrEP 
In clinical trials of PrEP for MSM, the drug was well tolerated6.  Nausea was more common 
among participants taking the medication than among those taking placebo (9% vs. 5%).  
There were no differences in severe or life-threatening adverse laboratory events between the 
active and placebo group.  Adverse events associated with tenofovir can include a transient 
decrease in renal function and slight decreases in bone mineral density.  Both of these effects 
occur with prolonged use of the medication and are not expected to occur with the limited 7-
day dosing in this protocol.1   
 
Acquisition of HIV drug resistance is a theoretic concern for those taking Truvada for PrEP.   
However, clinical trials have shown this to be a very rare event except in those who were 
‘acutely’ infected with HIV at the time of study enrollment.  In the iPrex study, there was no 
drug resistant virus detected in 100 MSM who became infected after enrollment.  Of the ten 
men who were identified retrospectively to be acutely infected with HIV at enrollment, drug 
resistance was detected in 2/2 of men in the active drug arm and 1/8 of men in the placebo 
arm6.  For this protocol, we will test men for HIV at study entry and monitor clinically for high-
risk behavior or any signs of acute HIV infection at study visits.  If high risk behavior (e.g. 
unprotected anal intercourse with a man of unknown HIV status) or symptoms of acute HIV 
infection are reported, and HIV antibody test will be repeated and the participant will be 
counseled about the need for any follow-up testing.  Clinical signs and symptoms of acute HIV 
infection that will be queried include: fever, fatigue, malaise, skin rash, swollen glands, 
oral/genital ulcers, myalgia/arthralgia1.  Dr. Kelley will review all reports of clinical 
signs/symptoms to determine appropriate follow-up and linkage to care as necessary.  If a 
diagnosis of acute HIV infection is thought to be possible or determined by repeat HIV testing, 
the participant will be discontinued from the study. 
 
Men will be asked to abstain from receptive anal intercourse while using PrEP and/or lubricant 
during the study protocol in order to limit additional exposures (e.g. semen, douching, 
additional lubricants) to the rectal mucosa.  Men taking PrEP will be counseled that they 
should not expect to achieve protection from HIV infection by taking PrEP during this study as 
it is a limited, 7-day course.  All men included in the study have a interest in taking PrEP for 
HIV prevention, will be referred to an area PrEP provider at the termination of the study.  The 
Hope Clinic has compiled a resource sheet of area providers that will be distributed to 
interested participants.   
 
 
Risks of rectal lubricant application 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
14 
 
Personal lubricants are commonly used during sexual intercourse to reduce friction between 
body parts.  Multiple lubricants are available over the counter in local pharmacies.  The FDA 
designates personal lubricants as medical devices, therefore there is no requirement for 
human safety testing prior to marketing.4 There have been a handful of studies that suggest 
personal lubricants, particularly hyperosmolar lubricants (e.g. Astroglide brand), can damage 
human tissues and potentially increase susceptibility to HIV or other STDs.2,3,5 Clearly, more 
research is needed into this question of lubricant safety and HIV transmission.  This study is 
designed to answer some of these outstanding questions. To minimize the risk of rectal 
lubricant application, we will counsel all participants about the possibility of tissue damage with 
the use of lubricants and recommend use of condoms for all sexual acts to reduce 
transmission of HIV and other STDs.  In addition, we will ask men to abstain from receptive 
anal intercourse for the one week period when they are using study product and for 1 week 
after both rectal biopsy procedures (visits 2 and 4).   
 
 
Rigid sigmoidoscopy and biopsies 
Risks associated with lower gastrointestinal endoscopy include colitis from chemicals for 
endoscope sterilization, bowel perforation, bleeding, diverticulitis, and infection. All procedures 
will be performed by Dr. Kelley or a mid-level provider trained and supervised by Dr. Kelley. 
Non-physician medical providers have performed endoscopic procedures for diagnostic and 
therapeutic procedures for years.  Many of these require mastery of flexible sigmoidoscopes, 
detailed anatomy of the full colon, and familiarity with sedation procedures.7,8 Procedures 
utilizing flexible instruments that access a deeper area of the colon and may or may not require 
sedation are more complicated and risky than the procedure detailed in this protocol which 
utilizes a rigid sigmoidoscope and only accesses the sigmoid colon a maximum of 15-20 cm 
from the anal verge.  Therefore, it is appropriate for a licensed mid-level provider to perform 
the procedure after completing a training period under the supervision of Dr. Kelley.  The 
training period for the mid-level provider will include a minimum of 10 directly observed (by Dr. 
Kelley) rectal biopsy procedures.   
 
All procedures will utilize disposable rigid sigmoidoscopes, forceps, and guides to reduce risk 
of infection and obviate the need for instrument sterilization between participants.  To minimize 
risks, rigid proctoscopy, rather than flexible sigmoidoscopy or full colonoscopy, will be used in 
this study and the number of biopsies taken will be limited to 12.  Colonoscopy has been 
shown to be associated with a still low, but significantly greater risk of complications than 
rectosigmoidoscopy9.  The frequency of serious complications after flexible sigmoidoscopy is 
extremely low and complications from rigid sigmoidoscopy are presumably even lower, but 
unknown.  In two large studies9,10 including a combined 144,832 clinically indicated 
procedures, the incidence of serious complications ranged from 0.06 to 0.8% utilizing flexible 
sigmoidoscopy. Obtaining biopsies may be associated with an increased risk of complications. 
The best available data on the risk of multiple biopsies comes from studies of dysplasia 
surveillance among patients with long-standing inflammatory bowel disease, in whom large 
numbers of “blind” biopsies are obtained throughout the colon for early detection of malignant 
transformation. In two such studies11,12 including a combined 3,011 procedures and a median 
of eight12 and 17 biopsies11, respectively, there was only one serious complication, for an 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
15 
 
incidence of approximately 0.33%. More relevant to the present protocol, in a study of subjects 
undergoing endoscopic procedures exclusively for research purposes13, including 64 flexible 
sigmoidoscopies with a mean of 25 biopsies obtained from the rectosigmoid, there were no 
major complications. Thirteen subjects experienced minor symptoms (self-limited bleeding and 
pain), which were not related to the number of biopsies. Thus, the risk of serious complications 
from the proposed study procedures, even with up to 12 biopsy specimens, is expected to be 
very low.  
 
Non-physician medical providers have performed endoscopic procedures for diagnostic and 
therapeutic procedures for years.  Many of these require mastery of flexible sigmoidoscope, 
anatomy of the full colon, and familiarity with sedation procedures.7,8 Procedures utilizing 
flexible instruments that access a deeper area of the colon and may or may not require 
sedation are more complicated and risky than the procedure detailed in this protocol.  
Therefore, it is appropriate for a licensed mid-level provider to perform the procedure after 
appropriate training and under the supervision of Dr. Kelley.  The training period for the mid-
level provider will include a minimum of 10 directly observed (by Dr. Kelley) rectal biopsy 
procedures.   
 
There is theoretical risk of increased acquisition of HIV or other infection if a study participant 
is exposed soon after the rectal biopsy procedure (i.e. while the mucosal surface is damaged).  
Therefore, study subjects will be counseled not to engage in anal intercourse for 1 week after 
the procedure.  
 
Biologic samples will be coded with a unique identifier prior to processing and storage for 
immunologic assays.  Therefore, lab personnel will be unable to link specimens with 
participants.  Only the PI and designated co-investigators/study personnel will be able to 
access information to identify specimens of individual participants.   
 
BREECH OF CONFIDENTIALITY 
All measures will be taken to ensure information provided by participants is kept confidential.  
Identifying paper information will be kept in a separate, locked office and only accessible by 
the PI and study coordinator.  Electronic data will be stored on the Redcap server or the Emory 
School of Medicine HIPPAA compliant server, which will be accessible to the PI and study 
coordinator only.  All study specimens will be labeled with a unique identifier prior to transport 
to CDC.  Identifying information will not be shared with laboratory collaborators at the CDC and 
they will be unable to link the study ID to any identifying information.  Any demographic data 
shared with CDC will also be stripped of HIPPAA identifiers prior to sharing.  In the event that 
confidentiality is accidentally breached, the event will be reported to Emory IRB officials who 
are then required to report to the IRB director and/or the IRB Chair any instances of which they 
are aware that involve a use or disclosure of information in violation of the confidentiality 
obligations set forth in the Confidentiality and Non-Disclosure Agreement, HIPAA Regulations 
or HIPAA Privacy and/or Security Policies.  The IRB Director and IRB Chair shall, in turn, 
report the breach to the Emory University HIPAA Privacy Officer within the Office of Research 
Compliance.  The Emory IRB shall take such steps as are appropriate to mitigate any damage 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
16 
 
that may have been caused by the breach and to take corrective action as necessary in order 
to ensure that a similar breach does not occur in the future. 
 
BENEFITS 
Subjects will not derive direct benefit from this study.  
 
COST 
There is no cost to subjects to participate in this study. 
 
ALTERNATIVE 
The alternative to participating in this study is to decide not to participate. Subjects can 
withdraw their consent at any time. 
 
COMPENSATION 
All participants will be compensated for the time and inconvenience of study participation.   
 
Study participants will be compensated $25 for visits 1 and 3.  They will be compensated $125 
for visits 2 and 4 as these visits contain rectal biopsy procedures.   
 
If a contingency visit is necessary, participants will be compensated $20 for the incomplete 
study visit and the above amount when the missed visit is completed.   
 
There is no charge for parking at the Hope Clinic.   
 
PLAN FOR OBTAINING INFORMED CONSENT 
After being screened for eligibility by the PI or study coordinator, subjects will be informed 
about the study and asked to sign an Emory IRB approved informed consent. The consent 
form will describe the purpose of the study, the procedures to be followed, and the risks and 
benefits of participation. Subjects will be consented in a private exam room.  Subjects will be 
given time to read the consent, ask questions and consider the risks and/or benefits to 
participation in this research study prior to obtaining their signature. All subjects enrolled in the 
study will be given a copy of their signed and dated informed consent document. This 
consenting process will be done by trained research staff at the Hope Clinic. All subjects will 
undergo HIV risk reduction counseling with provision of free condoms.  
 
PROVISIONS FOR SUBJECTS FROM VULNERABLE POPULATIONS 
Non-English speaking subjects or illiterate subjects will not be eligible to participate in this 
study.   
 
PARTICIPATION OF WOMEN AND CHILDREN 
Because this is a study of MSM, women are not eligible.  Children 18-21 will be eligible for this 
study.  It is especially important to include MSM aged 18-21 as young MSM are at highest risk 
of HIV infection and research that may lead to better prevention interventions, including an HIV 
vaccine, are desperately needed for this group.  Children younger than 18 will not be eligible.    
 
SUBJECT PRIVACY AND DATA CONFIDENTIALITY 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
17 
 
All subjects will provide informed consent in a private room at the Hope Clinic. 
 
Case report forms (CRFs) will be provided for each subject to collect demographic, behavioral, 
clinical, and laboratory data at study entry, and additional clinical data at the study visit. These 
data will be collected from the screening clinical assessment, the study entry physical 
examination and screening laboratory tests, and rectal biopsy visits. Subjects will be identified 
by the participant identification number (PID), which will be provided by the study investigator 
upon registration.  All laboratory specimens, evaluation forms, reports, and other records that 
leave the site will be identified by coded number only to maintain subject confidentiality. All 
study samples will be kept in a secure area in a limited-access laboratory facility and only the 
research team will have access to the samples. The samples and data will be identified only by 
code numbers. 
 
Any identifiable records will be kept locked accessible only by authorized study personnel. 
Electronic data will be password protected and stored on the Redcap server or the Emory 
School of Medicine HIPPAA compliant server. Biologic samples will be coded with a unique 
identifier and no identifiable behavioral data will be shared with laboratory investigators at 
CDC.  Information about the subject’s participation will not be shared with individuals who are 
not directly involved with the research subjects.  Clinical information will not be released 
without written permission of the subject, except as necessary for monitoring by IRB, the FDA, 
the NIH, or the OHRP. Information about the subject’s participation will not be shared with 
individuals who are not directly involved with the research subjects or as identified in the 
HIPAA consent. 
 
PLANS FOR SUBJECTS AT THE END OF THE PROTOCOL 
Subjects will return to the standard of care at the end of the protocol. 
 
CLINICAL SITE MONITORING AND RECORD AVAILABITLITY 
The Emory University IRB, the OHRP, FDA, or other government regulatory authorities may 
perform clinical site monitoring.  Clinical research sites monitoring may include the review of 
the individual participant records, including consent forms, CRFs, supporting data, laboratory 
specimen records, and medical records (physicians’ progress notes, nurses’ notes, individuals’ 
hospital charts) to ensure protection of study participants, compliance with the protocol, and 
accuracy and completeness of records.  The monitors may also inspect sites’ regulatory files to 
ensure that regulatory requirements are being followed. 
 
The investigators will make study documents (e.g., consent forms, CRFs) and pertinent 
hospital or clinic records readily available for inspection by the local IRB or the OHRP for 
confirmation of the study data. 
ADVERSE EVENT MONITORING AND REPORTING 
 
Adverse events (AEs) will be reported on an expedited basis at the standard level during the 
protocol-defined expedited adverse event (EAE) Reporting Period, which is the entire study 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
18 
 
duration for an individual subject (from study enrollment until study completion or 
discontinuation of the subject from study participation for any reason). 
 
AE Reporting 
 
Any AE that is reported to either the investigators or their designated research associates by a 
study subject or by medical staff caring for the subject and which meets the criteria will be 
documented.   
 
In addition, clinical investigators will monitor subjects for AEs during each study visit. Any AE 
will be reported to the Emory University IRB within 10 days of the event, and any serious 
adverse event (SAE) will be reported to the IRB within 24-48 hours of the event.  The standard 
Emory IRB reporting guidelines for AE and SAE reporting, as documented at 
http://www.emory.edu/IRB/guidelines_adverse_event.php, will be followed.   
 
A SAE is an adverse drug experience that results in any of the following outcomes: 
1. Death. 
2. Life-threatening situation - The subject was at risk of death at the time of the adverse 
event/experience.  It does not refer to the hypothetical risk of death if the AE were more 
severe or were to progress. 
3. Inpatient hospitalization or prolongation of existing hospitalization. 
4. Persistent or significant disability/incapacity - Any AE having an outcome that is 
associated with a substantial disruption of the ability to carry out normal life functions, 
including the ability to work.  This is not intended to include transient interruption of daily 
activities. 
5. Congenital anomaly/birth defects - Any structural abnormality in subject’s offspring that 
occurs after intrauterine exposure to treatment. 
6. Important medical events/experiences that may not result in death, be life-threatening, 
or require hospitalization may be considered a serious adverse event/experience when, 
based upon appropriate medical judgment, they may jeopardize the subject and may 
require medical or surgical intervention to prevent one of the outcomes listed above, 
i.e., death, a life-threatening adverse event/experience, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity, or 
a congenital anomaly/birth defect.  Examples of such medical events/experiences 
include allergic bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or 
the development of drug dependency or drug abuse. 
7. Spontaneous and elective abortions will be reported to the Emory IRB as serious 
adverse events.  
 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
19 
 
8. Severity of AEs will be rated according to the following definitions: 
 
Mild: 
The adverse event is transient and easily tolerated 
by the subject. 
Moderate: 
The adverse event causes the subject discomfort 
and interrupts the subject’s normal activities. 
Severe: 
The adverse event causes considerable 
interference with the subject’s normal activities and 
may be incapacitating or life-threatening. 
 
The following definitions will be used to assess the relationship of the AE to study drugs or 
procedures: 
 
 
 
Probably Related: 
An adverse event has a strong temporal relationship to study drug or 
recurs on re-challenge, and another etiology is unlikely or significantly 
less likely. 
Possibly Related: 
An adverse event has a strong temporal relationship to the study 
drug, and an alternative etiology is equally or less likely compared to 
the potential relationship to study drug. 
Probably Not 
Related: 
An adverse event has little or no temporal relationship to the study 
drug and/or a more likely alternative etiology exists. 
Not Related: 
An adverse event is due to an underlying or concurrent illness or 
effect of another drug and is not related to the study drug (e.g., has no 
temporal relationship to study drug or has much more likely alternative 
etiology). 
 
If the adverse event is in, the investigator’s opinion, possibly or probably related, or not related 
to study drug or procedures, then an alternate etiology will be provided by the investigator. 
It should however be noted that a severe adverse event /experience is not necessarily serious, 
as the term severe is a measure of intensity while a serious adverse event (SAE) is 
determined based on the aforementioned regulatory criteria. 
 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
20 
 
All AEs and laboratory abnormalities will be graded according to the Division of AIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), 
Version 1.0, December 2004, which can be found on the DAIDS RCC Web site: http://rcc.tech-
res.com/tox_tables.htm.  All AEs will be followed to satisfactory clinical resolution. 
 
DATA SAFETY MONITORING 
Summaries of adverse events (Grades 3 or 4), and targeted AEs across study groups as well 
as study conduct will be reviewed regularly (in real time and summarized quarterly) by study 
investigators.  Any AE will be reported to the Emory University IRB within 10 days of the event, 
and any SAE will be reported to the IRB within 24-48 hours of the event. The standard Emory 
IRB reporting guidelines for AE and SAE reporting, as documented at 
http://www.emory.edu/IRB/guidelines_adverse_event.php, will be followed.    
Additional safety monitoring will be performed annually by an independent Medical Safety 
Monitor.  Based on the 1 year accrual expectation for the study, it is anticipated that the study 
will undergo 2 reviews by the Medical Safety Monitor.  The first will occur approximately 6 
months after the accrual of the first subject. The safety report will summarize AEs and SAEs by 
study group.  The DCC will work with the Medical Safety Monitor to complete a ‘final 
assessment’ following the review of each safety report.  As part of the final assessment the 
Medical Safety Monitor will conclude ‘the study can continue as no safety concerns have been 
identified at the time of the review’ or ‘the study cannot continue as currently designed’.  The 
final assessment by the Medical Safety Monitor will be provided to the study PI who will make 
the findings available as appropriate to the Emory IRB and the NIH. 
 
STUDY DISCONTINUATION 
A study participant may elect to discontinue participation in the study at any time.  The study 
may be discontinued at any time by the IRB, the OHRP, or other government agencies as part 
of their duties to ensure that research subjects are protected.  
 
BIOHAZARD CONTAINMENT 
 
As the of blood-borne pathogens can occur through contact with contaminated needles, blood, 
and blood products, appropriate blood and secretion precautions will be employed by all 
personnel in the drawing of blood and handling of all specimens for this study, as currently 
recommended by the Centers for Disease Control and Prevention and the National Institutes of 
Health. 
 
All infectious specimens will be transported using packaging mandated in the Code of Federal 
Regulations, 42 CFR Part 72. 
 
BIOSAFETY PLAN 
 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
21 
 
No specific biosafety plan is necessary for this protocol as all planned immunologic and 
genetic assays will fall under the existing biosafety protocols of the Hope Clinic and CDC.   
 
 


TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
 
9/26/16 
 
22 
 
  
REFERENCES 
 
1. 
Service UPH. Pre-exposure Porphylaxis for the Prevention of HIV Infection in the United 
States-2014: A Clincal Practice Guideline. 2014. 
2. 
Dezzutti CS, Brown ER, Moncla B, et al. Is wetter better? An evaluation of over-the-
counter personal lubricants for safety and anti-HIV-1 activity. PloS one 2012;7:e48328. 
3. 
Fuchs EJ, Lee LA, Torbenson MS, et al. Hyperosmolar sexual lubricant causes 
epithelial damage in the distal colon: potential implication for HIV transmission. The Journal of 
infectious diseases 2007;195:703-10. 
4. 
Wolf L. Studies Raise Questions About Safety of Personal Lubircants. Chemical and 
Engineering News 2012;90:46-7. 
5. 
Gorbach PM, Weiss RE, Fuchs E, et al. The slippery slope: lubricant use and rectal 
sexually transmitted infections: a newly identified risk. Sexually transmitted diseases 
2012;39:59-64. 
6. 
Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV 
prevention in men who have sex with men. The New England journal of medicine 
2010;363:2587-99. 
7. 
Society of Gastroenterology Nurses and Associates I. Guideline for the performance of 
flexibile sigmoidscopy by registered nurses for colon cancer screening. 2009. 
8. 
American Society for Gastrointestinal E, Ikenberry SO, Anderson MA, et al. Endoscopy 
by nonphysicians. Gastrointestinal endoscopy 2009;69:767-70. 
9. 
Gatto NM, Frucht H, Sundararajan V, Jacobson JS, Grann VR, Neugut AI. Risk of 
perforation after colonoscopy and sigmoidoscopy: a population-based study. J Natl Cancer Inst 
2003;95:230-6. 
10. 
Levin TR, Conell C, Shapiro JA, Chazan SG, Nadel MR, Selby JV. Complications of 
screening flexible sigmoidoscopy. Gastroenterology 2002;123:1786-92. 
11. 
Koobatian GJ, Choi PM. Safety of surveillance colonoscopy in long-standing ulcerative 
colitis. Am J Gastroenterol 1994;89:1472-5. 
12. 
Rutter MD, Saunders BP, Wilkinson KH, et al. Thirty-year analysis of a colonoscopic 
surveillance program for neoplasia in ulcerative colitis. Gastroenterology 2006;130:1030-8. 
13. 
Yao MD, von Rosenvinge EC, Groden C, Mannon PJ. Multiple endoscopic biopsies in 
research subjects: safety results from a National Institutes of Health series. Gastrointest 
Endosc 2009;69:906-10. 
 
 

SAP_001.pdf: 
TITLE OF PROJECT: PrEP, LUBE, AND THE RECTAL MUCOSA IN MSM AT RISK OF HIV 
Emory IRB00077593 
NCT02401230 
PRINCIPAL INVESTIGATOR: Colleen F. Kelley, MD, MPH 
19Jan2018 
 
 
STATISTICAL ANALYSIS PLAN 
 
Drug and dNTP concentrations were normalized to fmol/million cells and fmol/mg rectal tissue in 
blood and tissue, respectively. Detectable drug and dNTP concentrations as well as immune 
cell proportions were compared between the Truvada, Rectal Gel Lubricant and Rectal Gel 
Lubricant + Truvada study arms using a Wilcoxon Rank Sum Test. Left censoring was observed 
for drug concentration measurements below the limit of detection.