Clinical trial NCT02924389
Conditions: HIV
Sponsor: Emory University
Start date: 2016-09-01; Completion date: 2019-09-11
Enrollment: 22 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to find out how well the HIV medication dolutegravir gets into different parts of the body including blood plasma, special blood cells, and rectal tissue. Specifically, investigators want to compare how fast dolutegravir lowers the HIV viral load in these three different sites. In addition, as an exploratory aim, investigators seek to learn if there are any differences in how dolutegravir acts in males and females. Results of this study will provide more information about HIV medications and their limitations. In the future, this could help create better HIV medications that can get into these hard-to-reach places and eventually cure HIV infection.

Detailed description:
Emerging evidence indicates that sites outside of blood plasma, such as peripheral blood mononuclear cells (PBMCs) and gut-associated lymphoid tissue, remain reservoirs for HIV and play critical roles in viral persistence despite long-term potent combination antiretroviral therapy (cART). Suboptimal ARV drug concentrations within these reservoirs are thought to contribute to our inability to fully eradicate HIV. In addition, host factors such as sex have been found to impact ARV drug exposure within these sites and effect key outcomes such as time to virologic suppression. The understanding of reservoir site pharmacology and the impact on sex is limited due to several barriers: 1) Difficulty in sampling reservoir sites intensively and 2) Scarcity of women enrolled in HIV clinical research studies. Optimal drug concentrations are ideally determined early in drug development by dose-ranging studies that require intensive blood plasma sampling; this methodology is impractical to employ within tissue sites. To mitigate these barriers, the researchers propose to study the pharmacology of the integrase strand transfer inhibitor dolutegravir (DTG) within three body compartments: blood plasma, PBMCs, and rectal tissue using a novel integrated population pharmacokinetic-viral dynamic (PK-VD) modeling approach. This PK-VD modeling strategy generates concentration-response relationships with limited sampling and dosing simulations ideally suited to reservoir sites.

The primary aim of this study is to validate the integrated population PK-VD model that quantitatively describes the relationship between dolutegravir (DTG) exposure and HIV viral decay in blood plasma. The second aim of this study is to develop an integrated population pharmacokinetic-viral dynamic (PK-VD) model to describe the relationship between DTG exposure and HIV viral decay in peripheral blood mononuclear cells and rectal tissue reservoir sites. The third aim is exploratory and will investigate sex differences in DTG penetration into blood plasma, peripheral blood mononuclear cells and rectal tissue reservoirs reservoirs as well as its impact on the rectal microbiome.

Arms: arm 1: Males diagnosed with HIV will undergo serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants will be treated with either Triumeq or Truvada with dolutegravir. arm 2: Females diagnosed with HIV will undergo serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants will be treated with either Triumeq or Truvada with dolutegravir.
Interventions: intervention 1: dolutegravir intervention 2: Triumeq intervention 3: Truvada
Intervention descriptions: intervention 1: Tivicay is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. 50 mg of Tivicay (dolutegravir) will be taken orally once a day. intervention 2: Triumeq is a fixed-dose combination drug for the treatment of HIV/AIDS. It is a combination of 600 mg abacavir, 50 mg dolutegravir and 300 mg lamivudine. Triumeq will be taken orally once daily. intervention 3: Truvada is a combination of emtriva and viread, both nucleoside analog HIV-1 reverse transcriptase inhibitors. Truvada is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. One Truvada tablet (containing 200 mg/300 mg of emtricitabine and tenofovir disoproxil fumarate) will be taken orally once daily.

Protocol documents:
Prot_SAP_001.pdf: 
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Defining Antiretroviral Pharmacology Within HIV-1 Reservoirs of Males and Females 
Protocol date: September 8, 2020 
NCT number: NCT02924389 
 
PRINCIPAL INVESTIGATOR 
 
Cecile Delille Lahiri, M.D. 
 
 
 
 
 
Assistant Professor of Medicine 
 
 
Division of Infectious Diseases 
 
 
 
Emory University School of Medicine 
 
 
 
 
 
 
 
CO-INVESTIGATORS 
 
 
 
 
 
 
 
 
Ighovwerha Ofotokun, M.D., M.Sc.  
Associate Professor of Medicine  
Division of Infectious Diseases 
Emory University School of Medicine 
 
Anandi Sheth, M.D. 
Assistant Professor of Medicine 
Division of Infectious Diseases 
Emory University School of Medicine 
 
Lisa Haddad, M.D, MS, MPH 
Assistant Professor 
Department of Gynecology and Obstetrics 
Emory University School of Medicine 
 
Lisa Flowers, M.D. 
Professor 
Department of Gynecology and Obstetrics 
Emory University School of Medicine 
 
 


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CONTENTS 
 
Section 
 
 
 
 
 
 
 
Page(s) 
 
ABBREVIATIONS 
 
 
 
 
 
 
3-4 
 
ABSTRACT 
 
 
 
 
 
 
 
5 
 
LAY SUMMARY 
 
 
 
 
 
 
6 
 
1.  Study Aims & Hypotheses  
 
 
 
 
7 
 
2.  Introduction 
 
 
 
 
 
 
8-9 
 
3.  Study Design 
 
 
 
 
 
 
10-13 
 
4.  Selection/Enrollment of Participants 
 
 
 
13-15 
 
5.  Clinical and Laboratory Evaluation 
 
 
 
15-16 
 
6.  Statistical Considerations  
 
 
 
 
16-17 
 
7.  Data Collection & Monitoring 
 
 
 
 
18 
 
8.  Human Subjects 
 
 
 
 
 
 
19-20 
 
9.  Data Safety & Monitoring Plans  
 
 
 
20 
 
10.  Sponsor  
 
 
 
 
 
 
20 
 
11.  Biohazard Containment  
 
 
 
 
20 
 
12.  References 
 
 
 
 
 
 
20-22  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ABBREVIATIONS 
 
AAUCMB = average area under the curve minus baseline 
 
ARV = antiretroviral 
 
AUC = area under the curve 
 
BP = blood plasma 
 
CL/F = oral clearance of drug 
 
Cmax = maximum drug concentration 
 
Cmin = minimum drug concentration 
 
CNS = central nervous system 
 
CSF = cerebrospinal fluid 
 
DTG = dolutegravir 
 
DTG Ct24h = DTG total concentration 24 hours post dosing 
 
Emax = maximum drug effect 
 
EC90 = DTG Ct24h required to produce 90% of the maximum drug effect 
 
EC95 = DTG Ct24h required to produce 95% of the maximum drug effect 
 
HAART = highly active antiretroviral therapy 
 
HPLC-MS/MS = high performance liquid chromatography – tandem mass spectroscopy 
 
INSTI = integrase strand transfer inhibitor 
 
LPV/RTV = lopinavir/ritonavir 
 
PBMCs = peripheral blood mononuclear cells 
 
PK = pharmacokinetic 
 
PD = pharmacodynamic 
 
RT-PCR = real time-polymerase chain reaction 
 
TDF/FTC = tenofovir disoproxil fumarate/emtricitabine 
 
Tmax = time to Cmax 
 
Tmin = time to Cmin 
 


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T1/2 = half life 
 
VD = viral dynamic 
 
WIHS = Women’s Interagency HIV Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ABSTRACT 
Emerging evidence indicates that sites outside of blood plasma, such as peripheral blood mononuclear cells 
(PBMCs) and gut-associated lymphoid tissue, remain reservoirs for HIV and play critical roles in viral persistence 
despite long-term potent combination antiretroviral therapy (cART). Suboptimal ARV drug concentrations within 
these reservoirs are thought to contribute to our inability to fully eradicate HIV. In addition, host factors such as 
sex have been found to impact ARV drug exposure within these sites and effect key outcomes such as time to 
virologic suppression. Our understanding of reservoir site pharmacology and the impact on sex is limited due to 
several barriers: 1) Difficulty in sampling reservoir sites intensively and 2) Scarcity of women enrolled in HIV 
clinical research studies. Optimal drug concentrations are ideally determined early in drug development by dose-
ranging studies that require intensive blood plasma sampling; this methodology is impractical to employ within 
tissue sites. To mitigate these barriers, we propose to study the pharmacology of the integrase strand transfer 
inhibitor dolutegravir (DTG) within three body compartments: blood plasma, PBMCs, and rectal tissue using a 
novel integrated population pharmacokinetic-viral dynamic (PK-VD) modeling approach. This PK-VD modeling 
strategy generates concentration-response relationships with limited sampling and dosing simulations ideally 
suited to reservoir sites. Additionally, we will prioritize the exploration of sex differences by leveraging our 
extensive research infrastructure, including the clinical core of the Emory Center for AIDS Research (CFAR), the 
Atlanta Clinical and Translational Science Institute (ACTSI), and the motivated cohort of the Atlanta Women’s 
Interagency HIV Study (WIHS). We hypothesize that integrated population PK-VD modeling will show that 
optimal drug doses needed to suppress HIV will be higher in PBMC and rectal tissue reservoirs compared to 
blood plasma and will be different between males and females.  
 
Our proposed aims are: 1) Compare descriptive data generated from our DTG PK-VD blood plasma model to 
existing dose-ranging study data for validation, 2) Extend the development of DTG PK-VD models to PBMC and 
rectal tissue reservoirs, and 3) Investigate sex differences in DTG PK-VD in all three body sites.  To accomplish 
this, 20 HIV-infected males and 20 HIV infected females (total n = 40) will be enrolled in a 168 day (6 month) 
longitudinal study whereby blood plasma, PBMCs, and rectal tissue will be serially sampled during six (6) study 
visits to measure DTG concentrations, HIV-1 RNA viral load, and perform 3 different assays to measure the HIV 
reservoir, including total cell-associated HIV DNA,  2-LTR unintegrated HIV DNA circles, and a modified rapid 
low cell quantitative viral outgrowth assay (QVOA). From these data, integrated population PK-VD models will 
be constructed and dosing simulations used to determine optimal drug exposure needed to attain virologic 
suppression at all three sites within males and females. With support from a multi-disciplinary team of mentors, 
completion of this work will uniquely position me for an independent research career integrating pharmacologic 
interventions within HIV cure stratagems. 
 
Duration 
Enrollment is expected to take 36 months, with completion of all study visits in 40 months.  Data collection will 
be completed after sample collection of the last enrolled participant at their Day 168 visit. 
Sample size 
A sample size of 20 HIV-infected women and 20 HIV-infected men will be enrolled in this study. 
 
Population 
HIV-1 infected women enrolled in the Emory Women’s Interagency HIV Study (WIHS), Ponce de Leon Center, 
or other community HIV clinic and men enrolled at the Ponce de Leon Center or other community HIV clinic. 


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LAY SUMMARY 
 
Even with strong HIV medications, there is no known cure for HIV infection.  When a person is infected with HIV, 
studies have shown that the virus enters many different parts of the body, including the brain, lymph nodes, the 
gut (including the rectum), and special cells in the blood.  HIV medications are very good at getting into blood 
plasma and killing the virus, but may have limited ability to get into some of these other places.   In sites such as 
special blood cells and the gut, the virus can hide from HIV medications. 
 
The dose of HIV medication needed for good HIV control is decided by studies that look at drug levels in the 
blood plasma of patients.  While the dose of medication may be good enough to control HIV infection in blood 
plasma, it may not be good enough to control HIV infection in these other hard-to-reach sites.   
 
The purpose of this study is to find out how well the HIV medication dolutegravir (DTG/Tivicay), a FDA approved 
HIV medication for the treatment of HIV infections, gets into different parts of the body:  including blood plasma, 
special blood cells, and rectal tissue.  Specifically, we want to compare how fast dolutegravir (DTG) lowers the 
HIV viral load in these three different sites. In addition, we want to see if there are any differences in how 
dolutegravir acts in males and females. Results of this study will give us more information about HIV medications 
and their limitations.  In the future, this could help us create better HIV medications that can get into these hard-
to-reach places and eventually cure HIV infection. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1. STUDY AIMS AND HYPOTHESES 
 
1.1 Aim 1 
 
The primary aim of this study is to validate the integrated population PK-VD model that 
quantitatively describes the relationship between DTG exposure and HIV viral decay in BP.  
 
Twenty (20) HIV-infected women and twenty (20) men will undergo BP sampling for HIV-1 RNA and 
DTG concentrations following first dose oral administration of Triumeq ( DTG 50 mg/Abacavir, ABC 600 
mg/ Lamivudine, 3TC 300 mg) or DTG (50 mg) plus standard dose of co-formulated tenofovir disoproxil 
fumarate (TDF)/ emtricitibine (FTC) on days 14, 42, 168, and repeat intensive sampling over 24 hours 
following observed dosing at day 84 for steady state parameter estimates.  Integrated population PK-
VD modeling and simulation will be used to estimate the EC90, defined as the DTG Ct24h (DTG total 
concentration 24 hours post dosing) required to produce 90% of the maximum drug effect (Emax), and 
other PK-VD parameters.   
 
 
Hypothesis:  A population PK-VD model with exposure-response simulations will show that optimal 
DTG doses needed for virologic suppression are higher in PBMCs and rectal tissue compared to BP.  
 
1.2 Aim 2 
 
The second aim of this study is to develop an integrated population PK-VD model to describe 
the relationship between DTG exposure and HIV viral decay in PBMCs and rectal tissue 
reservoir sites.   
HIV-1 infected subjects initiating therapy with a DTG-based HAART regimen will undergo collection of 
PBMCs at Baseline and on Days 14, 42, 84, and 168.   Rectal tissue will be collected within 7 days of 
ART initiation, and on Days 42, 84, and 168 for DTG concentrations and quantitation of the HIV 
reservoir by measuring HIV RNA, total cell-associated HIV DNA, 2-LTR DNA circles, and by performing 
a modified QVOA.   Integrated population modeling and simulation will be used to estimate EC90 at 
each site.   
Hypothesis:   A population PK-VD model will accurately estimate DTG EC90, Emax (concentration 
required for maximum effect), and optimal dose needed for virologic suppression in BP. 
1.3 Aim 3 
The third aim is exploratory and will investigate sex differences in DTG penetration into blood 
plasma, PBMC and rectal tissue reservoirs as well as its impact on the rectal microbiome.   
Integrated population modeling and simulation will be used to estimate EC90 at each site. 
Hypothesis:  A population PK-VD model with exposure-response simulations will show that DTG 
exposure differs between males and females and is associated with both viral dynamic changes within 
PBMC and rectal tissue reservoirs as well changes within the rectal microbiome.   
 
 
 
 


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INTRODUCTION 
 
1.4 Background 
 
Emerging evidence suggests that sites such as gut tissue and peripheral blood mononuclear cells 
(PBMCs) remain reservoirs for HIV-1 and play critical roles in viral persistence despite combination 
antiretroviral therapy (cART)[1-11].  Leading theories to explain barriers to HIV eradication from 
reservoirs include 1) ongoing proliferation of latently infected cells invulnerable to cART and 2) 
continuing viral replication due to suboptimal antiretroviral (ARV) tissue concentrations[8, 12, 13].  
In response, the HIV cure agenda has focused on strategies such as “shock and kill”, whereby 
latently infected cells are activated (“shocked”), making them susceptible to killing by immune 
attack and/or cART[14].  To achieve killing by cART, drugs must be capable of penetrating 
reservoirs.  This approach requires a clear understanding of drug pharmacokinetics (PK) and HIV 
viral dynamics (VD) specifically in these affected sites.  Drug and host characteristics, including 
factors modulated by patient’s sex [15-18], result in drug distribution and disposition that differs 
between blood plasma (BP) and other body compartments [19, 20]. For example, lower ARV 
concentrations in lymphatic tissues were found to be associated with persistent HIV replication 
[13].  Likewise, sex differences have been noted in PK parameters of multiple ARV drugs within 
BP[21-25] and PBMCs[26-29], with females showing more rapid HIV viral load decay and shorter 
time to plasma virologic suppression than males[25, 29]. Most of these prior studies are limited by 
examination of sex differences only in secondary analyses.  Improved understanding of ARV 
PK-VD within HIV reservoirs of males and females will have far-reaching public health 
implications by informing the development of sex-specific pharmacologic HIV cure 
strategies.   
A key obstacle to reservoir PK-VD assessment is the challenge of repeated tissue sampling, which 
is necessary to establish pharmacologic parameters in traditional dose-ranging studies. This is 
further compounded by paucity of PK-VD data in women who account for >50% of the 36.9 million 
people living with HIV worldwide[30], yet represent < 18% of participants in clinical studies of HIV 
cure[31]. Integrated population PK-VD modeling uses mathematical modeling and dose-ranging 
simulations to simultaneously describe drug exposure and VDs and generate concentration-
response relationships. We have recently shown that a PK-VD modeling and simulation tool can 
accurately predict the PK-VD relationship for a fixed dose of LPV/RTV in a small number of 
patients[32]. We propose to test this novel PK-VD modeling approach to generate concentration-
response relationships using limited tissue sampling combined with dosing simulations for 
dolutegravir (DTG) to test a more practical approach for pharmacologic assessment of deep-
seated reservoirs.  Leveraging our extensive translational research infrastructure supported by the 
clinical core of the Emory Center for AIDS Research, the Atlanta Clinical and Translational Science 
Institute, and access to the motivated female cohort in the Atlanta Women’s HIV Interagency 
Study, we will apply integrated PK-VD models to assess relationships between DTG exposure and 
HIV viral dynamics in 3 compartments, BP, PBMCs, and rectal tissue, in HIV-infected females and 
males.  DTG was chosen because of its potent antiviral activity, excellent safety profile, and 
published robust dose-ranging study data in BP.   
 
1.5 Potential significance 
 
1. We will investigate the utility of a novel strategy, integrated population PK-VD modeling, to predict 
DTG exposure needed for virologic suppression in BP. This model differs from early phase PK-PD 
models in that it utilizes data from participants on fixed-dose drug instead of different doses. In 
place, dosing simulations will be employed to predict optimal dose needed for virologic suppression.  
This approach will complement efforts to generate PK-VD data for clinical decision making for drugs 
where data are lacking.   
 


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2. Applying this model to predict PK-VD parameters in PBMCs and rectal mucosa is innovative. 
 
3. The recruitment of women, via the resources of an established cohort of women in the Atlanta WIHS, 
will be a priority enabling the study of sex differences. This will provide novel PK-VD data on females in 
an area where relevant sex-specific data are not available.   
 
4. Using multiple different assays to measure the HIV reservoir, including HIV RNA, total cell 
associated HIV DNA, 2-LTR DNA circles, and modified QVOAs allows a multi-faceted mechanism to 
evaluate the reservoir so that we can better understand the overall size, replication competence of 
latent virus, and the cell subset origin of latent virus.  Together, this information provides key insight into 
understanding where the viral reservoir is located, which subsets harbor the virus, which latent cells are 
capable of producing replication-competent virus, and differences across tissues and sex. 
 
 
 
2. STUDY DESIGN 
 
3.1  Study design overview 
The primary aim of this study is to determine whether DTG plasma PK-VD parameters can be 
accurately estimated using an integrated population PK-VD model with data derived from subjects 
initiating a uniform dose of a DTG-based HAART regimen compared to a standard dose-ranging study. 
It will be descriptive in nature and will involve HIV-infected women and men prospectively recruited 
from the Atlanta WIHS cohort, the Ponce de Leon Center, and community HIV clinics.  Population PK-
VD modeling will be applied. Subjects will undergo intensive blood sampling over a period of 6 months 
following HAART initiation, as shown in Figure 1. Plasma DTG concentration will be measured by 
HPLC-MS/MS and plasma HIV RNA will be quantified by RNA extraction, reverse transcription 
polymerase chain reaction (RT-PCR), and PCR amplification. DTG concentrations and viral dynamic 
data will be modeled to generate blood plasma DTG EC90, Emax, and other PK-VD metrics of interest.  
DTG was selected because of the abundance of dose ranging PK-PD data available in the literature for 
validation. A 6-month study duration suffices as DTG based HAART regimens are very potent and have 
steep viral decay slopes with most HIV-infected individuals achieving undetectable plasma viral loads at 
or before this time point on DTG-based therapy [33]. 
The second aim will be exploratory:  we will expand the integrated population PK-VD approach to test 
its utility in the estimation of PK-VD parameters including EC90 and Emax in two other reservoir sites: 
PBMCs and rectal tissue. PBMCs will be collected at Baseline and Days 14, 42, 84, and 168. Rectal 
tissue will be collected within 7 days of ART initiation and on Days 42, 84, and 168, as shown in Figure 
1. Intracellular and rectal tissue DTG concentrations and HIV RNA will be quantified using similar 
techniques as for blood plasma, but validated for these tissues. As measurement of HIV RNA only 
provides a very limited view of the total HIV reservoir, we will also measure the reservoir using three 
additional assays:  total cell associated HIV DNA, 2-LTR DNA circles, and a modified QVOA. 
Aim 3 seeks to investigate sex differences in penetration of DTG into blood plasma and PBMC and 
rectal tissue reservoirs, as well as differences in the rectal microbiome. 


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3.2  Study entry and initial screening 
 
• 
If a person agrees to participate and provides informed consent, a screening evaluation will occur at 
the clinical core of the Emory Center for AIDS Research (CFAR) at the Grady IDP or at the Grady 
Hospital CRN, a core equipped with state-of-the-art facilities for clinical research. Screening will include 
informed consent, a review of medical and medication history, and assessment for eligibility. HIV status 
will be verified with documentation of HIV ELISA test confirmed with western blot or plasma HIV-RNA. 
Screening laboratory tests, if not already available within 90 days prior to screening, will be conducted 
at the Grady clinical laboratories on a fee-for-service basis and will include complete blood count (CBC) 
with platelet and differentials, and full chemistry. Consecutive potential participants in the Atlanta WIHS 
cohort will be screened until 40 eligible participants are enrolled (20 females and 20 males).  
Participants will receive $20 in compensation after completion of the screening visit.  A preliminary 
consent-only visit may also be conducted if necessary. 
• 
It is important to know that for this study, the study drug, dolutegravir (DTG/Tivicay) is FDA approved 
for the treatment of HIV infections and can be given in combination with other antiretrovirals (ARVs), as 
a standard therapy for HIV. It is also important to know that this study will not provide nor will the study 
pay for the study medication. Participants will receive from their provider a prescribed supply of the 
drug, Tivicay® (dolutegravir/DTG), with either Triumeq, or Truvada or Descovy as determined by their 
primary HIV provider. It will be taken by mouth as prescribed and its dose and its administration will be 
determined by your provider. Participants will also be responsible for bringing these medications with 
them to their study visits. 
3.3 Study visits 
Visit 1:  Baseline, Pre-dose  
This visit will take place at the Grady IDP clinic and will involve a targeted history and physical, review 
of reproductive and sexual history, urine dipstick pregnancy test (women) and pre-dose collection of 
blood plasma, PBMC sampling, and HIV RNA quantification. Subjects will initiate HAART regimen with 
either Triumeq, DTG 50 mg daily plus Truvada (tenofovir disoproxil fumarate/emtricitabine, TDF/FTC) 


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300/200 mg daily, or DTG 50 mg daily plus Descovy (emtricitibine/tenofovir alafenamide) 200/25 mg 
daily. Eligibility to start these regimens will be determined by their primary HIV provider and participants 
are responsible for acquiring the medication and bringing them to the study visits.   Specimens will be 
processed within one hour to separate the plasma component and PBMCs and stored at -80°C until 
analyzed for DTG drug concentrations.     
In addition, either at this visit or within 7 days of ART initiation, participants will undergo anoscopy with 
rectal tissue sampling.  Rectal mucosa fluid will be collected first using two dry sterile cotton swabs and 
stored at -80°C for future rectal microbiome analysis using 16S sequencing. Any digital image of the 
biopsy site may also be taken during the anoscopy procedure to follow healing of the site over time.  
These de-identified images may be shared with investigators not listed on the study. 
 Four (4) to 8 pieces of rectal tissue will be collected via punch biopsy during anoscopy for 
measurement of DTG concentrations, HIV-1 RNA, total cell associated HIV DNA, 2-LTR DNA circles, 
and modified QVOA. Half of the rectal tissue will be flash-frozen in liquid nitrogen and cryopreserved at 
-80°C until analysis.  The other half will be placed fresh in phosphate-buffered saline and transported to 
the Laboratory of Biochemical Pharmacology (under the supervision of Drs. Gavegnano and Schinazi) 
at room temperature within 24 hours of collection for processing and analysis.   
Participants will receive $30 for the blood draw and $50 for the rectal biopsy, for a total of $80 
compensation for their time and inconvenience if they complete all procedures. 
The Screening and Baseline visits can occur on the same day if acceptable to the participant. 
 
Visits 2, 3 :  Post-dose population sampling of blood plasma, PBMCs, and rectal tissue. 
Visit 2 will occur 14 days after visit 1. 
Visit 3 will occur 42 days after visit 1. 
During visits 2-3, participants will have a focused history and physical exam.  Participants will undergo 
post-dose population sampling of blood plasma and PBMCs at visits 2-3.  Rectal mucosa fluid and 
tissue will be collected at visit 4 for future rectal microbiome analysis and measurement of DTG 
concentrations, HIV-1 RNA, total cell-associated HIV DNA, 2-LTR DNA circles, and modified QVOA.  
Participants will receive $30 for visits requiring only a blood draw, and an additional $50 in 
compensation at any visit with rectal tissue collection (up to 8 punch biopsies), for a total of $80. A 
digital image of rectal biopsy sites may be taken during the anoscopy procedure to examine healing of 
the site and these images may be shared with investigators not listed on the study. 
Visit 4: Steady state 24 hour PK-VD sampling 
Visit 4 will occur 84 days (12 weeks) after visit 1. 
This visit will involve an 8-hour stay either at the Grady or the Emory site of the Georgia Clinical and 
Translational Science Alliance (CTSA) for intensive blood plasma and PBMC sampling for ARV 
concentrations and HIV RNA quantification. 
During visit 4, participants will have a focused history and physical exam and provide urine for 
pregnancy testing and blood for CD4+ T cells (add-on: CD3), CBC (add-ons: BI smear w/diff; RBC 
morphology) with differential and comprehensive chemistries. 
Visit 4 will represent steady-state PK. DTG has an elimination half-life of 14 hours [34], therefore steady 
state plasma concentration is achieved after 5 days of oral administration. Adherence to previous DTG 
doses will be documented. Participants are responsible for bringing in their prescribed medication. 
Blood samples will be drawn 15 minutes prior to DTG administration (time 0) and 1, 2, 3, 4, 6, 8 and 24 
hours following observed drug intake to provide steady-state PK-VD data. HIV-RNA sampling will be 
done once as subjects are expected to be virologically suppressed in the blood plasma at this stage of 
HAART therapy. In addition, each participant will undergo PBMC and rectal mucosa fluid collection and 


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tissue sampling (up to 8 punch biopsies) 24 hours post-dose for measurement of rectal microbiome, 
DTG concentrations,HIV-1 RNA, total HIV-associated HIV DNA, 2-LTR DNA circles, and modified 
QVOA. Participants will be compensated $150 for this visit. 
Visit 5: 
Visit 5 will occur 168 days (6 months) after visit 1. During visit 5, participants will have a focused history 
and physical exam.  Participants will undergo post-dose population sampling of blood plasma and 
PBMCs.  Rectal mucosa fluid and tissue will be collected for future rectal microbiome analysis and 
measurement of DTG concentrations, HIV-1 RNA, total cell-associated HIV DNA, 2-LTR DNA circles, 
and modified QVOA.  A digital image of rectal biopsy sites may be taken during the anoscopy 
procedure to examine healing of the site and these images may be shared with investigators not listed 
on the study. 
Participants will be compensated $30 for the blood draw and $50 for the rectal biopsy, for a total of $80 
compensation if they complete all procedures. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 1 illustrates the schedule of events during each study visit: 
 
Table 1. SCHEDULE OF EVENTS 
 
Screening 
visit 
Baseline 
Visita  (pre-
dose) 
Day 14 
Day 42 
Day 84 (24 hr 
visit, steady 
state) 
Day 168 
Screening and Baseline Evaluation 
Informed 
consent 
 
 
 
 
 
 
Documentation 
of HIV status 
 
 
 
 
 
 
Targeted H&P 
 
 
 
 
 
 
Chem 14c 
 
 
 
 
 
 
CBC w/ diffc (add-
ons: BI smear w/diff; 
RBC morphology) 
 
 
 
 
 
 
CD4 T cell count 
(add-on: CD3) 
 
 
 
 
 
 
Determine DTG EC90 in blood plasma 
Plasma DTG 
concentration 
 
 
 
 
 
 
 
 
 
Plasma HIV-1 
RNA  
 
 
 
 
 
 
 
 
 
 
Determine DTG EC90 in PBMCs and rectal tissue (RT)b 
DTG 
concentrations 
 
 
 
 
 
 
 
 
 
HIV-1 RNA 
 
 
 
 
 
 
 
 
 
 
Total cell-
associated DNA 
 
 
 
 
 
 
 
 
 
2-LTR DNA 
circles 
 
 
 
 
 
 
 
 
 
Modified QVOA 
 
 
 
 
 
 
 
 
 
Examine rectal mucosa microbiome 
Rectal mucosa 
microbiome 
analysis 
 
 
 
 
 
 
 
 
 
 
aDay = Number of days since initiation of cART with DTG-based regimen.  Day 0 = day of 1st dose cART 
bRectal tissue assays will be performed in all participants within 7 days of first dose, and on Days 42, 84, and 168. 
cCBC with diff and Chem 14 will only be done at screening visit if they have not been done in last 90 days. 
 
NOTE: Pregnancy tests will continue to be performed at each visit. 
 
4.  SELECTION AND ENROLLMENT OF PARTICIPANTS 
 
4.1 Inclusion criteria 
• 
Age ≥ 18 years 


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• 
No ARVs in the last 6 months (from date of screening)  
• 
No documented or suspected resistance to integrase inhibitors (dolutegravir, elvitegravir, 
raltegravir, or bictegravir).  
• 
Creatinine Clearance >50 mL/min, as calculated by the Cockcroft-Gault equation within 90 days 
of screen 
• 
Liver function testing, including alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), and alkaline phosphatase < 5 times upper limit of normal within 90 days of screen 
• 
Intact gastrointestinal tract 
• 
Able and willing to give informed consent 
• 
Willing and eligible to initiate ARV therapy with Triumeq, DTG + Truvada (TDF/FTC), or DTG + 
Descovy (FTC/TAF) 
• 
Agree to receive from their provider and pay for a prescribed supply of the drug, Tivicay® 
(dolutegravir/DTG), with either Triumeq, or Truvada or Descovy as determined by their primary 
HIV provider. 
o Agree to take the prescribed medication by mouth. 
o Agree that they (the participant) is responsible for bringing these medications with them 
to their study visits. 
• 
Willing to undergo serial blood and rectal tissue sampling 
• 
Female participants’ must be willing to have a pregnancy test done at each visit.  
Female participants of childbearing potential (FCB) must agree to either commit to continued 
abstinence from heterosexual intercourse or to use a reliable form of birth control such as oral 
contraceptive pills, intrauterine device, Nexplanon, DepoProvera, permanent sterilization, or 
another acceptable method, as determined by the investigator for the duration of the study.  
FCB are defined as sexually mature women who have not undergone hysterectomy or bilateral 
oophorectomy or have not been naturally postmenopausal for at least 24 consecutive months 
(i.e have had menses at any time in preceding 24 months) 
 
4.2 Exclusion criteria 
• 
Pregnant or attempting to conceive now or during the course of the study 
• 
Self-reported or documented current anal or rectal disease prohibiting safe anoscopy and 
biopsies, in investigator’s opinion. 
• 
Taking concurrent medications that interfere with DTG (see Table 2) 
• 
Bleeding diathesis 
• 
Platelet count <50,000 mm3 
• 
Medical condition that interferes with conduct of study, in investigator’s opinion 
 
4.3 Study enrollment procedures 
 
The study protocol and protocol consent form will be approved by the Emory University institutional 
review board (IRB) and the Grady Health System Research Oversight Committee prior to 
implementation of this study. 
 
Candidates will be notified of the study via a flier (Appendix A).  Once a candidate has been 
identified, the details of the study will be carefully discussed with them.  Prior to undergoing any 
study procedure, the candidate will be asked to read and sign the study protocol consent form that 
was approved by the Emory IRB.  The subject will be given a copy of the signed informed consent 
form for their records, and a second copy will be kept in the subject’s research record. 
 
4.4 Prohibited and precautionary medications 
 


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Any participant actively taking any of the prohibited or precautionary medications listed in Table 2 
will not be eligible to participate in this study. 
 
Table 2:  Prohibited and precautionary medications 
 
Concomitant drug 
class:  drug name 
Effect of concentration 
on Dolutegravir and/or 
concomitant drug 
Clinical comment 
HIV antiviral agents 
Non-nucleoside 
reverse transcriptase 
inhibitor (NNRTI): 
etravirine 
 Dolutegravir 
Do not coadminister 
without also giving 
darunavir/ritonavir, 
atazanavir/ritonavir, or 
lopinavir/ritonavir 
NNRTI:  Efavirenz 
 Dolutegravir 
Dose adjustment of 
DTG to 50 mg bid for 
treatment naïve  
NNRTI:  Nevirapine 
 Dolutegravir 
Avoid coadministration:  
insufficient data for 
dosing 
recommendations  
 
Protease inhibitors:  
Fosamprenavir/ritonavir 
Tipranavir/ritonavir 
 Dolutegravir 
Dose adjustment of 
DTG to 50 mg bid for 
treatment naïve 
Other agents 
Psychotropic agents: 
Oxcarbazepine 
Phenytoin 
Phenobarbital 
Carbamazepine 
St. John’s Wort 
 Dolutegravir 
Avoid coadministration:  
insufficient data for 
dosing 
recommendations 
Medications with 
polyvalent cations: 
Cation-containing 
antacids or laxatives 
Sucralfate 
Buffered medications 
 Dolutegravir 
Must administer 
Dolutegravir 2 hours 
before or 6 hours after 
these medications 
Hypoglycemic: 
Metformin 
 Metformin 
Consider metformin 
dose reductions 
Antibiotic: 
Rifampin 
 Dolutegravir 
Dose adjustment of 
DTG to 50 mg bid for 
treatment naïve 
Adapted from Table 5 in Tivicay (dolutegravir) [package insert]. ViiV Healthcare:  Research Triangle Park, 
NC; 2014 [34]. 
 


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5. Definitions for Schedule of Events- timing of study visits 
 
5.1.1 Screening Visit 
Screening evaluations will determine eligibility and will occur prior to the participants’ enrollment into 
the study. 
5.1.2 On Study Visits 
The first on-study visit will occur after the screening visit, but within a month (30 days) of screening 
visit (unless otherwise specified). All other on-study visits that occur after the first on-study visit will 
occur 14 days, 42 days, 84 days, and 168 days after the first visit. 
The window period for visits on day 14 can be +/- 3 days. 
The window period for visits on day 42 and 84 can be +/- 7 days. 
The window period for the visit on day 168 can be +/- 14 days. 
Please see Table 1 for schedule of clinical and laboratory evaluations. 
 
5.2 Definitions of evaluations 
5.2.1 Consent Form 
A signed and dated consent form approved by the Emory IRB is required prior to 
participation in this study. 
 
5.2.2 Documentation of HIV 
HIV-1 infection, as documented by any licensed serologic test confirmed by western blot or 
by positive plasma HIV-1 RNA performed by any laboratory that has a CLIA certification. 
 
5.2.3 Medication History 
Current medications will be recorded from the patient’s self-report and medical record 
including doses, dosing frequency, and duration of treatment. 
 
5.2.4 Screening Clinical Assessment  
Screening clinical assessment will include a review of medical diagnoses, current 
medications, and eligibility criteria.   
 
5.2.5 Screening Laboratory Evaluations 
At screening, most recent HIV-1 RNA PCR (if available) and CD4 T-cell counts will be 
recorded from the medical record.  Absolute CD4+/CD8+ counts and percentages 
performed by flow cytometry at a CLIA-certified or equivalent laboratory will be recorded.  
Study eligibility will be determined based on medical history review and laboratory testing as 
described below:   
• 
Urine collected at this visit in all female participants will be tested by dipstick for beta-
hCG to assess for pregnancy.  If this test indicates pregnancy, the patient will be 
notified and referred to their primary care provider in the clinic for further evaluation.   
• 
Platelet count within the last 90 days will be reviewed from the medical record.  
Participants with platelets <50,000 are not eligible to participate. 
• 
Renal and liver function testing within the last 90 days will be reviewed from the 
medical record.  Participants with creatinine clearance <50 mL/min by Cockcroft-


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Gault equation or AST, ALT, alkaline phosphatase > five (5) times upper limit of 
normal are not eligible to participate. 
 
5.2.6 HIV-1 RNA in plasma, PBMCs, and rectal tissue 
 
HIV-1 RNA will be quantified in cryopreserved plasma, PBMCs, and rectal tissue by RNA 
extraction, reverse transcription polymerase chain reaction (RT-PCR), and PCR 
amplification using assays validated for each site at the Emory CFAR virology core on a fee-
for-service basis. 
 
5.2.7 HIV-1 total cell associated DNA, 2-LTR DNA circles, and modified QVOA in PBMCs and 
rectal tissue 
Total-cell associated HIV DNA , 2-LTR DNA circles, and modified rapid-low cell QVOA will 
be quantified by Dr. Christina Gavegnano within the Laboratory of Biochemical Pharmacology 
under the supervision of Dr. Raymond Schinazi on a fee-for-service basis.  For total HIV DNA 
and 2-LTR DNA circle assays, PBMCs, at a minimum of 1.0 x 105 cells, will be subjected to total 
cell lysis with an NP-40 based detergent while rectal tissue will be homogenized and then 
dissolved.  Quantitation of 2-LTR DNA circles will be performed using real-time PCR and 
Taqman technology (Applied Biosystems), as previously described.  Plasmids containing LTR 
sequences will be used as standards for quantitation (NL4-3, subtype B).  Total-cell associated 
HIV DNA will be performed using the Abbott Real-time HIV-1 DNA assay.  The modified rapid-
low cell QVOA is a culture-based assay that detects the outgrowth of replication-competent 
virus. Ex-vivo PBMCs will be subjected to density gradient centrifugation to obtain total PBMC 
populations and sorted using fluorescent activated cell sorting (FACS).  For PBMCs from tissue, 
cells will be subjected to tissue homogenization and purification of live, single cell supsensions 
using existing methods in the BSL 2/3 Laboratory of Biochemical Pharmacology (OctoMacs Pro; 
Miltenyi Biotec methodology).  Sorted cells are cultured with EC99 of cART (Raltegravir/(-)-
FTC/efavirenz) for 72 hours to prevent virus harbored in sorted cells from spreading.  
CD3/CD28 and IL-15 are added to induce activation of latent virus from sorted memory cultures; 
24 hours post reactivation, cells are stained with anti-p24 fluorescein isothiocyanate mAb and 
non-dividing p24+ cells are quantified with FACS to measure reservoir size.  Supernatant is 
harvested and virus is quantified with p24 ELISA prior to infection with naïve PBMCs at limiting 
dilutions of inoculates to determine replication competence.   
Total cell-associated HIV DNA and 2-LTR DNA circles quantitation will be performed on 
cryopreserved PBMCs and rectal tissue.  The modified QVOA will be performed in both 
cryopreserved PBMCs and fresh rectal tissue.  Fresh rectal tissue will be placed in phosphate-
buffered saline and transported at room temperature to the Laboratory of Biochemical 
Pharmacology within 24 hours of collection for processing.   
5.2.8 Dolutegravir concentrations in plasma, PBMCs, and rectal tissue 
DTG concentrations will be measured from blood plasma, PBMCs, and rectal tissue under  
Dr. Edward Acosta’s supervision at the University of Alabama-Birmingham Antiviral 
Laboratory using HPLC-MS/MS, as previously described [35]. To decrease variability, 
samples will be analyzed in duplicate and resulted as the average. 
 
5.2.9 Any Digital images of biopsy sites will be examined from 2 consecutive visits with digital 
imaging analysis software.  The percentage of the biopsy that has healed over time will be 
calculated as an exploratory analysis to better understand mucosal healing after injury.   
 
5.2.10 Rectal fluid microbiome  
Rectal microbiome analysis will be performed at a future date using 16S sequencing. 


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6. STATISTICAL CONSIDERATIONS 
 
6.1 Primary endpoint 
To estimate the EC90 of dolutegravir in blood plasma using an integrated Pharmacokinetic (PK) – 
Viral Dynamic (VD) model. 
 
6.2 Secondary endpoints 
To estimate the EC90 of dolutegravir in PBMCs and rectal tissue using an integrated 
Pharmacokinetic (PK) – Viral Dynamic (VD) model. 
 
To compare the PK-VD determined EC90 of dolutegravir in blood plasma, PBMCs, and rectal tissue 
between males and females. 
 
6.3 Sample size justification 
 
For our primary endpoint, we plan to enroll a total of 40 HIV-1 infected persons (20 men and 20 
women into this study.  As our primary endpoint is descriptive, our goal is to attain an accurate 
parameter estimate by achieving a sufficiently narrow confidence interval.  Based on a coefficient 
of variation of 25% [36], a sample size of 17 HIV-1 infected women gives us 80% certainty that the 
90% confidence interval for DTG EC90 will be no wider than 0.20 units [37].   
 
 
6.4 Analyses 
6.4.1 Demographic and clinical characteristics 
Baseline demographic and clinical characteristics will be summarized by descriptive 
statistics. 
 
6.4.2 Primary objective analysis:  Estimate EC90 of DTG in blood plasma using integrated PK-VD 
modeling 
 
Pharmacokinetics:  PK data will be used to plot plasma concentration-time curves for DTG 
at steady-state to determine total drug exposure (AUC) and other PK parameters, including 
peak concentration (Cmax), minimum concentration (Cmin), time to Cmax (tmax), time to Cmin 
(tmin), half-life (t1/2), and estimated clearance (CL/F).  
 
Viral dynamics:  Viral dynamic determinant of response will be AAUCMB, defined as the 
decrease in log10 time-averaged under the viral load-time curve from 0 to Day 168 (AUC0-
week-12) minus baseline.  
 
PK-VD Modeling:  Population analysis will be used to develop the overall PK-VD model.  
Because this is a longitudinal study with repeated measures, an expectation-maximization 
algorithm will be used on a parametric non-linear mixed-effects model to determine 
maximum likelihood estimates for model parameters, as developed by Shumitzky and 
Walker [38, 39].  This will be implemented using ADAPT software (version 5, MLEM module) 
[40]. Baseline covariates, including age, race, body mass index, menstrual cycle, and use of 
hormonal contraception will be evaluated for their ability to explain inter-individual variability 
in base model parameters. Prediction-corrected visual checks [41] will be used for model 
evaluation. 
 
EC90 estimate:  To estimate EC90, exposure-response simulations using a wide range of 
DTG doses will be conducted:  The DTG Cmin (exposure) will be linked to the VD 


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determinant of response, AAUCMB. Median estimates will be reported in ng/mL with 
interquartile range.  90% confidence intervals will be constructed for the EC90 parameter 
using the bootstrap method, as described by Miller [42]. 
6.4.3 Secondary objectives analyses:  Estimate EC90 of DTG in PBMCs and rectal tissue using 
integrated PK-VD modeling 
 
Analyses similar to those described in 6.4.2 for the primary objective will be used here. 
 
7.  DATA COLLECTION AND MONITORING 
 
7.1 Records to be kept 
Case report forms (CRFs) will be provided for each subject to collect demographic, clinical, and 
laboratory data at study entry, and additional clinical data at study visits. These data will be 
collected from the screening clinical assessment, the subject’s medical record, the study entry 
physical examination, and the subject’s medication diary.  Subjects will not be identified by name on 
any CRFs.  Subjects will be identified by the participant identification number (PID), which will be 
provided by the study investigator upon registration. 
 
7.2  Role of Data Management 
 
7.2.1  Instructions regarding the recording of study data on CRFs will be provided by the study 
investigator 
 
7.2.1  The study investigator will be responsible for assuring the quality of computerized data.  
This role extends from protocol development to generation of the final study databases. 
Data will be entered into Emory Redcap, a secure web application for building and 
managing online surveys and databases.   
 
7.3  Clinical Site Monitoring and Record Availability 
7.3.1  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. 
 
7.3.2 The investigator 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. 


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8.   HUMAN SUBJECTS 
 
8.1 Responsibilities of the Investigator 
In implementing this protocol, the investigators will adhere to the basic principles of “Good Clinical 
Practice” as outlined in CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 
CFR 21, part 50 and CFR 21, part 56 and Section 4 of ICH Harmonized Tripartite Guideline for 
GCP.   
 
8.2  IRB Review and Informed Consent 
This protocol and the informed consent document and any subsequent modifications will be 
reviewed and approved by the Emory University IRB. A signed and dated, Emory IRB-approved 
consent form will be obtained from the subject (or parent, legal guardian, or person with power of 
attorney for subjects who cannot consent for themselves). The consent form will describe the 
purpose of the study, the procedures to be followed, and the risks and benefits of participation. A  
copy of the signed consent form will be given to the subject, parent, or legal guardian, and this will 
be documented in the subject’s record. 
8.3  Subject Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records that leave the site will be 
identified only by coded number to maintain subject confidentiality. All records will be kept locked. 
All computer entry and networking programs will be done with coded numbers only. Clinical 
information will not be released without written permission of the subject, except as necessary for 
monitoring by IRB or the OHRP. 
8.4  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. 
8.5 Risks to Human Subjects 
The risks to study participants include side effects of Triumeq, DTG and TDF/FTC or DTG and 
FTC/TAF, risk of venipuncture for blood sampling, and risk of rectal tissue biopsies.  DTG was 
approved by the FDA for use in combination with other ARV agents for treatment of HIV-1 infection 
in treatment-experienced or ARV-naïve persons in 2013.  Subjects will be initiating a DTG-based 
regimen as part of treatment for HIV-infection and therefore will not assume additional ARV-related 
risk above and beyond standard of care.  Clinical evaluation and safety laboratory testing will be 
performed to monitor participants for development of ARV-related adverse events.  Recently, DHHS 
guidelines have released updated recommendations for the use of DTG in females of child-bearing 
potential (FCB) due to the potential risk of neural tube defects in infants born to women taking DTG-
based regimens[43]. Given this new information, FCB must agree to either commit to continued 
abstinence from heterosexual intercourse or to use a reliable form of birth control such as oral 
contraceptive pills, intrauterine device, Nexplanon, DepoProvera, permanent sterilization, or 
another acceptable method, as determined by the investigator for the duration of the study.  
Pregnancy tests will continue to be performed each study visit.  Common risks of venipuncture 
include discomfort, bleeding, and bruising.  When repeated blood draws are necessary, it will be 
attempted through peripheral IV to minimize venipuncture.   


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Common risks of rectal biopsies include discomfort and bleeding.  Rare (<1%) complications of 
anoscopy with rectal biopsies include infection, anal tears, or colonic perforation.  
Adverse events will be reported per Emory IRB protocol. 
9.  Data safety and monitoring plans 
 
Grade 3 and 4 adverse events and study conduct will be reviewed regularly by study investigators.  
Standard Emory IRB guidelines for reporting adverse events will be followed.  Adverse Events and 
Serious Adverse Events will be reported to the IRB per Emory’s guidelines for reportable events.  
 
 
10. SPONSORS 
 
The NIH/NIAID is sponsoring this study. 
 
 
11. BIOHAZARD CONTAINMENT 
 
As the transmission of HIV and other 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. 
 
 
 
 


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ICF_000.pdf: 
Page 1 of 17 
Version Date: V9: 09/08/2020 
IRB Form 06162020 
Defining Antiretroviral Pharmacology Within HIV-1 Reservoirs of Males and 
Females 
NCT02924389 
Date: September 8th, 2020 
IRB00089025 


Page 2 of 17 
Version Date: V9: 09/08/2020 
IRB Form 06162020 
You Are Being Asked to Be in a Research Study 
Concise presentation of key concepts 
You are being asked to be in a research study. A research study is designed to answer a 
scientific question. If you agree to be in the study you will be one of 40 people who are being 
studied, at Emory. 
Why is this study being done? 
This study is being done to is to find out how well dolutegravir (DTG/Tivicay), a FDA approved 
HIV medication for the treatment of HIV infections, gets into different parts of the body: 
including blood plasma, special blood cells, and rectal tissue.  Specifically, we want to compare 
how fast dolutegravir lowers the HIV viral load in these three different sites. In addition, we 
want to see if there are any differences in how dolutegravir acts in males and females. Results 
of this study will give us more information about HIV medications and their limitations.  In the 
future, this could help us create better HIV medications that can get into these hard-to-reach 
places and eventually cure HIV infection.   
Do you have to be in the study?  
It is your decision to be part of this research study. You do not have to be in it. Your choice will 
not affect your access to medical care for your condition. Before you make your decision, you 
should take time to learn about the study. 
What do I have to do if I choose to participate in this study? 
If you are eligible and want to be part of the study, you will be asked to begin a regimen of 
Triumeq, Dolutegravir and Descovy, or Dolutegravir and Truvada. You will need to get the 
prescription from your provider. Your participation is voluntary and will not influence the care 
you receive from Grady or Emory.  During this study, you will have 5 study visits over 6 months: 
one 8-hour visit at Grady Hospital and 4 visits at the Grady Ponce IDP Clinic. Study procedures 
at each of the Ponce visits will take about 1-2 hours.  We would ask you some questions, perform 
a physical examination, collect some blood, and perform a rectal biopsy at the 8-hour visit at 
Grady Hospital and during three of the visits at the Ponce clinic. There is no cost to you for any 
of the study procedures. 
It is important to know that for this study, the study drug, dolutegravir (DTG/Tivicay) is FDA 
approved for the treatment of HIV infections and can be given in combination with other 
antiretrovirals (ARVs), as a standard therapy for HIV. It is also important to know that this study 
will not provide nor will the study pay for the study medication. Your HIV medication will be 
determined by your primary HIV provider you will be responsible for obtaining it and bringing it 
to the study visits. 


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How is this study going to help you?  
If you are in the study, you will be helping the researchers answer the study question how well 
the HIV medication Dolutegravir gets into different parts of the body including blood plasma, 
special blood cells, and rectal tissue. 
What are the risks or discomforts I should know about before making a decision?   
The study will take time. All studies have some risks.  Some risks are relatively small, like being 
bored or losing time, feeling uncomfortable answering some questions, some discomfort or 
bruising from the blood draw and mild discomfort or minimal bleeding from the anus during 
and after the rectal biopsy procedure.  An addition risk is new information regarding STI and 
pregnancy status. For these procedures, experienced staff will perform the tests and provide 
necessary counselling. A full list of expected risks, their frequency and severity are in the 
“What are the possible risks and discomforts?” section of this document. 
Alternatives to Joining This Study 
Since this is not a treatment study, the alternative is not to participate. 
Costs 
You WILL NOT have to pay for any of the study procedures. The study will not be paying any 
additional evaluations or follow up care needed after completion of study activities or related 
to a finding that requires follow up with your provider or a referred to Clinician/Specialist.  
What Should I Do Next? 
Read this form, or have it read to you.  Make sure the study doctor or study staff explains the 
study to you. Ask questions (e.g., about exact time commitment, about unfamiliar words, 
more details on specific procedures, etc.) Make sure you understand the expectation of the 
study and if you can commit to participating in them.  Take time to consider this, and talk 
about it with your family and friends. 


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IRB Form 06162020 
Emory University and Grady Health System 
Consent to be a Research Subject / HIPAA Authorization 
Title: Defining Antiretroviral Pharmacology Within HIV-1 Reservoirs of Males and Females 
IRB #: 00089025 
Short Title: Dolutegravir in Reservoirs 
Principal Investigator: Cecile Delille Lahiri, MD 
Sponsor:  National Institutes of Health (NIH) 
Introduction 
You are being asked to be in a medical research study. This form is designed to tell you everything you need to think about 
before you decide if you want to be a part of the study.  It is entirely your choice.  If you decide to take part, you can 
change your mind later on and withdraw from the research study. The decision to join or not join the research study will 
not cause you to lose any medical benefits.  If you decide not to take part in this study, your doctor will continue to treat 
you. 
Before making your decision: 
•
Please carefully read this form or have it read to you
•
Please listen to the study doctor or study staff explain the study to you
•
Please ask questions about anything that is not clear
You can take a copy of this consent form, to keep. Feel free to take your time thinking about whether you would like to 
participate. You may wish to discuss your decision with family or friends. Do not sign this consent form unless you have 
had a chance to ask questions and get answers that make sense to you.  By signing this form, you will not give up any legal 
rights. 
What is the purpose of this study? 
Even with strong HIV medications, there is no known cure for HIV infection.  When a person is infected with HIV, studies 
have shown that the virus enters many different parts of the body, including the brain, lymph nodes, the gut (including 
the rectum), and special cells in the blood.  HIV medications are very good at getting into blood plasma and killing the 
virus, but may have limited ability to get into some of these other places.   In sites such as special blood cells and the gut, 
the virus can hide from HIV medications. 
The dose of HIV medication needed for good HIV control is decided by studies that look at drug levels in the blood plasma 
of patients.  While the dose of medication may be good enough to control HIV infection in blood plasma, it may not be 
good enough to control HIV infection in these other hard-to-reach sites.   
The purpose of this study is to find out how well dolutegravir (DTG/Tivicay), a FDA approved HIV medication for the 
treatment of HIV infections, gets into different parts of the body:  including blood plasma, special blood cells, and rectal 
tissue.  Specifically, we want to compare how fast dolutegravir lowers the HIV viral load in these three different sites. In 
addition, we want to see if there are any differences in how dolutegravir acts in males and females. Results of this study 
will give us more information about HIV medications and their limitations.  In the future, this could help us create better 
HIV medications that can get into these hard-to-reach places and eventually cure HIV infection.  It is important to know 
that for this study, the study drug, dolutegravir (DTG/Tivicay) is FDA approved for the treatment of HIV infections and can 
be given in combination with other antiretrovirals (ARVs), as a standard therapy for HIV. It is also important to know that 


 
 
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IRB Form 06162020 
 
this study will not provide nor will the study pay for the study medication. Your HIV medication will be determined by your 
primary HIV provider you will be responsible for obtaining it and bringing it to the study visits. 
 
Our target enrollment consists of 20 women and 20 men for this research study. 
 
Procedures 
Where is the study taking place, and how long will the study last? 
• 
The research procedures will be conducted within the Grady and Emory Health Systems. The sites will include 
− The Grady IDP (Ponce Clinic)  
− Grady Memorial Hospital  
• 
You will be in the study for six study visits over the course of 6 months 
 
What will I be asked to do? 
If you are eligible for this study and do volunteer to take part, you will be asked to do the following: 
1. Sign this combined consent/HIPAA Authorization Form and a medical release form. 
2. Have a screening visit for the study and, if eligible, make 6 additional visits at the Ponce Clinic or Grady Memorial 
Hospital, over a course of 6 months which include: 
a. One 8-hour visit at either Grady Memorial Hospital or Emory University Hospital 
b. 4, 2 -hour visits at the Ponce Clinic.   
3. Undergo thorough medical evaluations. This will include:  
a. Review of your medical records  
b. Comprehensive medical history  
c. Physical examination 
4. Specimen collection including 
a. Blood 
b. Urine 
c. Rectal swab collection  
d. Rectal Biopsy collections during anoscopy procedure. Anoscopy is a procedure that uses a lighted scope 
called an anoscope to look at the anal canal and the lower rectum.  
5. Receive from your provider a prescribed supply of the drug, Tivicay® (dolutegravir/DTG), with either Triumeq, or 
Truvada or Descovy as determined by your primary HIV provider. It will be taken by mouth as prescribed. The 
dose and its administration will be determined by your provider. You will be responsible for bringing these 
medications with you to your study visits. 
 
IF YOU ARE FEMALE:  
Females of childbearing potential (FCB) must agree to either commit to continued abstinence from heterosexual 
intercourse or to use a reliable form of birth control such as oral contraceptive pills, intrauterine device, Nexplanon, 
DepoProvera, permanent sterilization, or another acceptable method, as determined by the investigator for the duration 
of the study.  FCB are defined as sexually mature women who have not undergone hysterectomy or bilateral 
oophorectomy or have not been naturally postmenopausal for at least 24 consecutive months (i.e have had their menses/a 
period at any time in preceding 24 months. A pregnancy test will be done at each visit. 
 
 


 
 
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Study Visits:  
The screening visit will determine whether you are eligible for the study. During this visit, a qualified member of the 
research team will review your medical and medication history to determine your eligibility.  In addition, you will give a 
urine sample for a pregnancy test (if you are a female of child bearing potential) and may have blood collected to check 
your blood counts, liver, and kidney function.   
You should let the study staff know if you have any reason to suspect that you may be pregnant during this visit. 
 
 
A. Screening visit: (Grady IDP/Ponce Clinic)   
• 
You will be evaluated to see if you are eligible for the study based on the study’s criteria. 
• 
You will be asked to sign the informed consent, HIPAA form, and medical release form. 
• 
Your medical record will be reviewed. 
• 
Medical/medication history and demographic characteristics will be recorded. 
• 
Urine will be collected for a pregnancy test (females of child bearing potential). 
 
This visit should last for about 1 hour. 
 
The subsequent six study visits will occur over 6 months and will include one 8-hour long visit at Grady Memorial 
Hospital- CRN (5th Floor), immediately followed by a next morning visit (24 hours) at the Grady IDP/Ponce Clinic. 
 
B. First Study Visit/Baseline (Ponce Clinic) 
• 
This visit will take place at the: 
o Grady IDP Clinic/Ponce Clinic on the 3rd floor. 
• 
Arrive promptly for your scheduled appointment time. 
• 
If you are a female of childbearing potential, a urine sample will be collected for a pregnancy test . 
• 
Medical, sexual, and reproductive history will be collected and a targeted physical exam will be performed by 
qualified study personnel. 
• 
You will come to your study visit with the medication that was prescribed by your primary HIV provider for care.  
o This medication must include Dolutegravir (DTG /Tivicay®), and may be in combination with other drugs 
as determined by your primary HIV provider. 
• 
Once this visit is completed, you will be started on your HIV medications. 
o These medications may  include either: 
i.  Triumeq (a combination medication with Dolutegravir, the study drug, + Abacavir + Lamivudine) 
ii. Or the medications Truvada or Descovy plus Dolutegravir (study drug) 
• 
Up to eight tubes of blood (3 full tablespoons) will be collected. 
• 
At this visit, or within seven (7) days of beginning your HIV medication(s), you will undergo a procedure called 
anoscopy to collect rectal fluid and tissue.  During anoscopy, a small tube is inserted into the anus to look at the 
rectal tissue.   
o Rectal fluid will be collected on two (2) dry sterile cotton swabs to look at the types of bacteria living 
there.   
o Up to eight (8) small punch biopsies will be done at one time point to collect small pieces of rectal tissue 
to measure both HIV viral load and dolutegravir drug concentrations.   
• 
To look at rectal tissue healing over time, digital photographs may be taken during the anoscopy procedure, and 
these images may be shared with investigators not listed on the study. 
 
Your visit should last for about 2 hours.  This visit may occur on the same day as the Screening visit. 
 
 
 


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C. Second through Third Study Visits (Grady IDP/Ponce Clinic) 
o
.
o
Visit 2 occurs 14 days after first visit.
o
Visit 3 occurs 42 days after first visit.
•
These visits will take place at the Grady IDP Clinic, on the 3rd floor.
•
Arrive promptly for your scheduled appointment time.
•
If you are a female of childbearing potential, a urine sample will be collected for a pregnancy test.
•
Targeted medical history and physical will be performed by qualified study personnel.
•
Up to eight tubes of blood (3 full tablespoons) will be collected.
•
At Visit 3/Day 42, you will also undergo anoscopy to collect rectal fluid and tissue, where two (2) swabs of fluid
will be collected and up to eight (8) small punch biopsies will be done.
•
To look at rectal tissue healing over time, digital photographs may be taken during the anoscopy procedure, and
these images may be shared with investigators not listed on the study.
Your visit should last for about 2 hours for the visit that has rectal tissue collection, 
And 1 hour for those studies visits that do not involve rectal tissue collection. 
D. Fourth Study visit:  (Grady Memorial and Grady IDP/Ponce Clinic) 
•
This visit will take place at the:
a.
Grady Memorial Hospital at the Clinical Research Network (CRN), located on the C-wing of the 5th floor
and
b.
Grady IDP Clinic/Ponce Clinic on the 3rd floor.
•
It will occur 84 days (12 weeks) after your initial visit.
•
Arrive promptly for your scheduled early morning appointment time.
•
You will be staying 8 hours at the CRN for this visit (meals will be provide throughout your stay) and then you
will come back the next morning to the Grady IDP Clinic for your final blood collection.
•
If you are female of childbearing potential, a urine sample will be collected for a pregnancy test.
•
Targeted medical history and physical will be performed by qualified study personnel
•
An i.v. line will be placed into a vein for blood collection.
•
You will come to your study visit with the medication that was prescribed by your primary HIV provider for care.
a.
This medication must include Dolutegravir (DTG /Tivicay®), and may be in combination with other drugs
as determined by your primary HIV provider.
•
At the study visit you will take your HIV medications.
a.
These medications may  include either:
i.
Truimeq (a combination medication with Dolutegravir, the study drug, + Abacavir + Lamivudine)
ii.
Or the medications Truvada or Descovy plus Dolutegravir (study drug)
•
At the CRN, your blood will be drawn 15 minutes before you take the first dose of medications and after 1, 2, 3,
4, 6, and 8 hours.
•
You will come back the next morning for your 24 hour blood draw at the Grady IDP Clinic, for a total of 8 blood
draws for study tests.
•
Up to eight tubes of blood (3 full tablespoons) will be collected each time.
•
You will undergo anoscopy to collect rectal mucosa fluid and tissue, where two (2) swabs of fluid will be
collected and up to eight (8) small biopsies will be done at one time point.
•
To look at rectal tissue healing over time, digital photographs may be taken during the anoscopy procedure, and
these images may be shared with investigators not listed on the study.
Your visit should last for about 24 hours (8 hours at the Grady Memorial Hospital CRN and 1 hour at the Ponce Clinic). 


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E. Fifth Study Visit (Grady IDP/Ponce Clinic) 
•
This visit will take place at the:
o
Grady IDP/Ponce Clinic on the 3rd floor.
•
It will occur 168 days (6 months/week 24) after your initial visit.
•
Arrive promptly for your scheduled appointment time.
•
If you are a female of childbearing potential, a urine sample will be collected for a pregnancy test.
•
Targeted medical history and physical will be performed by qualified study personnel.
•
Up to eight tubes of blood (3 full tablespoons) will be collected.
•
You will also undergo anoscopy to collect rectal fluid and tissue, where two (2) swabs of fluid will be collected
and up to eight (8) small punch biopsies will be done.
•
To look at rectal tissue healing over time, digital photographs may be taken during the anoscopy procedure, and
these images may be shared with investigators not listed on the study.
Your visit should last for about 2 hours 
Optional Study Section 1: Genetic Testing 
Investigators are also studying how genes (a patient’s DNA) may affect HIV and other viruses, as well as other outcomes 
that may be of concern in HIV-infected women. If you agree, your stored left over samples may be used as a source of 
DNA for genetic testing that is not yet planned but may be done at a later date. This testing may include studies of HIV, 
studies of other diseases that affect people with HIV, studies of your cells, proteins, and other chemicals in your body, and 
studies of your DNA. Your blood specimen will be used to extract DNA and other biological markers, which will be studied 
for research purposes only. The results of the DNA testing will not be revealed to your health care provider or you either 
during or after the completion of this study. 
Optional Study Section 2: Contact for Future Studies/Research Opportunities 
We would like to contact you in the future for participation in other research studies that you may be eligible for.   
Please take your time to think about it and discuss any questions you may have. 
If you agree, we would like to store your name and contact information in an electronic database, specifically designed 
to contact those who are interested in future opportunities to participate in research. The database will be maintained 
by authorized members of Dr. Lahiri’s team and you may be contacted by Investigators or Research Staff under this 
study.  
Confidentiality of your information will be maintained in the following manner: 
•
Access to the database will be restricted and limited to Investigators or Research Staff under this study.
•
Limited information may be shared with Investigators or Research Staff under this study and other researchers
at Emory University.
•
The following information: name and phone number will be provided to Investigators or Research Staff outside
this study, so they may contact you.
•
Information on your mailing address, HIV status, date of birth and clinic of care will not be shared with
Investigators or Research Staff outside this study.
•
This database will be retained indefinitely and if destroyed it will be done to ensure your privacy and
confidentiality are kept.
•
The information in the database may be inspected by an Emory University Research Ethics Board to ensure that
your information is being collected and maintained in an ethical manner.
Your decision to allow your information to be in the database is completely voluntary.  While there may be no benefit to 
you, your information will help researchers to quickly identify individuals who may be suitable for a particular research 
study.  If you change your mind after agreeing to this, your information can be removed from the database.  You will not 
be penalized in any way if you refuse to participate, or if you change your mind and ask that your information be 
removed. 


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Who owns my study information and samples? 
If you join this study, you will be donating your samples and study information.  You will not receive any compensation if 
your samples or information are used to make a new product. Your specimens will be kept indefinitely and will only be 
used for research purposes. If you withdraw from the study, data and samples that were already collected may be still 
be used for this study.  Your samples will be kept secure and stored at the local laboratory and will only be used for 
research related to this study.  The samples stored will not have any data written on them or records stored with them 
that could identify you.   
What are the possible risks and discomforts? 
The most common risks and discomforts expected in this study are: 
1.
Questionnaire/Comprehensive Medical Review:
Participation in the mental tasks may lead to fatigue, boredom or frustration. Assessment of sexual behavior will be done 
at each visit using a brief questionnaire. The responses to these questions may make one uncomfortable. 
All interviews will be done in private room, with adherence to protecting the privacy and the confidentiality of data 
through the use of trained interviewers and other study staff 
2.
Physical Exams:
Physical examinations may cause both physical and emotional discomfort. Though mild discomfort may occur, there are 
no known serious adverse effects expected and only experienced health care practitioners will conduct the physical 
examinations. 
3.
Drawing Blood:
The needle used to collect blood may cause a bruise at the insertion site, and in very rare circumstances, an infection may 
develop. Other uncommon risks related to the blood draw include pain, bleeding, blood clots, discomfort, swelling, 
lightheadedness, and fainting. These risks are uncommon. 
4.
Collection of rectal swabs
During the anoscopy procedure to look at the anal canal and the lower rectum we will collect rectal swabs. It is expected 
that you may have some mild discomfort during the procedure.  
5.
Anoscopy with tissue collection/biopsy
During the anoscopy procedure to look at the anal canal and the lower rectum we will collect rectal tissue (biopsy). It is 
expected that you may have some mild discomfort and minimal bleeding from the anus during and after the procedure. 
Less common risks are small anal tears or bleeding for several days with bowel movement.  
Though rare, there is also the possible risk of colonic infection/perforation. However, only trained and experienced health 
care practitioners will conduct these collection procedures. 
Minimization of Risk 
To minimize these risks: 
•
Physical examination, drawing blood, and rectal tissue collection will be performed by experienced health
care practitioners trained and certified in these procedures.
•
To minimize any discomfort you may feel during the rectal tissue collection, you may want to take some
over-the-counter pain medication, such as Tylenol, Motrin, or Aleve, before and/or after the procedure.
Risk of New Information Regarding:  sexually transmitted infections and pregnancy status 


 
 
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If a test result is positive, individuals diagnosed with an STI or vaginitis may experience emotional discomfort upon 
receiving their diagnosis, or upon notifying sexual partners, as this would be recommended by study staff during 
counseling. If you have an infection, a qualified health care practitioner will give participants counseling, and a prescription 
for treatment, or a referral to a clinician for further testing and/or treatment. 
A pregnancy test will be administered to avoid any risk posed to a fetus.  Should a participant be found to pregnant in the 
process of screening or during the study they will be given referrals to medical care and the necessary education. Referrals 
will include: prenatal care, adoption and abortion care services. 
 
Experience health care practitioners will perform all tests, examinations and counseling. Furthermore this study requires 
documentation of HIV infection status. If you have not had a recent test, assessment of status prior to enrollment and 
throughout the course of the study requires the performance of FDA-approved HIV antibody tests. All staff participating 
in these studies is trained in the provision of HIV pre- and post-test counseling in accordance with the standards set out 
in the US department of Health and Human Services HIV Counseling, Testing and Referral Standard and Guidelines. HIV 
test counseling and HIV risk behavior counseling will be provided to all potential participants and to those volunteers 
enrolled in the study. 
 
Risks of Sample Storage 
There are few risks related to storing your samples. The greatest risk is to your privacy.  
 
If you are a woman: to protect against possible side effects of the study drug, women who are pregnant or nursing a child 
may not take part in this study. If you become pregnant, there are known risks to you, the embryo, or fetus. Recently, 
guidelines have indicated that there is an increased potential risk of neural tube defects in infants born to women taking 
DTG-based regimens. Given this new information, FCB must agree to either commit to continued abstinence from 
heterosexual intercourse or to use a reliable form of birth control such as oral contraceptive pills, intrauterine device, 
Nexplanon, DepoProvera, permanent sterilization, or another acceptable method, as determined by the investigator for 
the duration of the study.  For women of childbearing potential, pregnancy tests will continue to be performed at all study 
visits.  You and the study doctor must agree on a method of birth control to use throughout the study.  If you think that 
you have gotten pregnant during the study, you must tell the study doctor immediately.  Pregnant women will be taken 
out of the study. 
 
If you are a man: the effect of the study drug on sperm is not known.  To protect against possible side effects, if you are 
a man you should not get a sexual partner pregnant while taking the study drug.  You and the study doctor should agree 
on a method of birth control to use throughout the study. 
 
If you will be taking the study drug home, keep it out of the reach of children or anyone else who may not be able to read 
or understand the label.  Do not let anyone else take the study drug besides you. 
 
It is possible that the researchers will learn something new during the study about the risks of being in it.  If this happens, 
they will tell you about it. Then you can decide if you want to continue to be in this study or not.  You may be asked to 
sign a new consent form that includes the new information if you decide to stay in the study. 
 
Will I benefit directly from the study?  
This study is not designed to benefit you directly.  This study is designed to learn more about how well the HIV 
medication dolutegravir gets into sites of the body including blood plasma, special blood cells, and rectal tissue. The 
study results may be used to help others in the future. 
Will I be compensated for my time and effort? 


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We consider your participation in this study entirely voluntary, and appreciate your time and commitment to research.  
As compensation for your time, inconvenience, and to assist with the cost of transportation, you will get the following: 
•
Twenty dollars ($20) for completing the screening visit.
•
One hundred and fifty dollars ($150) for the completed 24-hour study visit (week12/Day 84).
•
Thirty dollars ($30) for each completed non-overnight study visit that does not have a rectal biopsy procedure (2
visits).
•
An additional fifty dollars ($50) for each completed non-overnight study visit that has a rectal biopsy procedure
(3 visits)
•
Twenty-five dollars ($25) if you return to the clinic for a repeat procedure from a previous visit.
•
If you complete all six study visits and arrive within 15 minutes of your scheduled appointment time for each visit,
you will be given a $25 gift card at the end of your sixth visit. If you complete the screening and all six study visits
you will receive a total of $495. If you do not finish the study, you will be paid for the visits you have completed.
Please note you will be asked to fill out a tax form, including your Social Security or Taxpayer Identification Number, in 
order to be reimbursed, depending on the amount and method of payment. To comply with this federal mandate the 
researchers are required to obtain your social security number to complete the form. 
What are my other options? 
If you decide not to enter this study, there is care available to you outside of this research.  The alternative to participating 
in this study is to not participate.  There are other available FDA-approved medications to treat people with HIV.  You can 
receive care for your HIV infection at the Ponce de Leon Center, your local health department, or AID Atlanta. The study 
doctor will discuss this with you.  You do not have to be in this study to be treated for HIV-1 infection. 
How will you protect my private information that you collect in this study? 
Whenever possible, a study number, rather than your name, will be used on study records.  Your name and other 
identifying information will not appear when we present or publish the study results. 
Study records can be opened by court order.  They also may be provided in response to a subpoena or a request for the 
production of documents.  
Storing and Sharing your Information 
Your samples, genomic data and health information will be stored and shared with other researchers. The samples and 
information will be available for any research question, such as research to understand what causes certain diseases (for 
example heart disease, cancer, or psychiatric disorders), development of new scientific methods, or the study of where 
different groups of people may have come from.
Medical Record 
If you have been an Emory and Grady Health System patient before, then you already have an Emory and Grady Health 
System medical record.  If you have never been an Emory and Grady Health System patient, you do not have one.   An 
Emory and Grady Health System medical record will be made for you if an Emory and Grady Health System provider or 
facility gives you any services or procedures for this study.   
We will take reasonable steps to keep copies of this form out of Emory and Grady Health System’s medical records 
system.  If we aren’t successful in keeping these forms out, despite our efforts, we will take steps to remove them.  If 
they cannot be removed, we will take steps to limit access to them.  
Emory and Grady Health System may create study information about you that can help with your care.  For example, the 
results of study tests or procedures.  These study results will be put in your Emory and Grady Health System medical 


 
 
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record. Anyone who has access to your medical records will be able to have access to all the study information placed 
there.  The confidentiality of the study information in your medical record will be protected by laws like the HIPAA 
privacy rule.  State and federal laws may not protect the research information from disclosure.  
 
The results of some study tests and procedures will be used only for research purposes and will not be placed in your 
medical record.  For this study, those items include: dolutegravir concentrations, HIV viral loads, and microbiome results. 
 
Tests and procedures done at non-Emory and Grady Health System places may not become part of your Emory and 
Grady Health System medical record. Also, if you decide to be in this study, it is up to you to let your other health 
providers know.  
 
In Case of Injury 
If you get ill or injured from being in the study, Emory and Grady Health System will help you get medical treatment.   
Emory and Grady Health System and the sponsor have not, however, set aside any money to pay you or to pay for this 
medical treatment. The only exception is if it is proven that your injury or illness is directly caused by the negligence of 
an Emory and Grady Health System or sponsor employee.  “Negligence” is the failure to follow a standard duty of care.  
If you become ill or injured from being in this study, your insurer will be billed for your treatment costs.  If you do not 
have insurance, or if your insurer does not pay, then you will have to pay these costs.   
If you believe you have become ill or injured from this research, you should contact Dr. Lahiri at telephone number 404-
616-6306. You should also let any health care provider who treats you know that you are in a research study.   
Costs 
You will have to pay for the items or services for which the study sponsor does not pay. The sponsor will not pay for your 
regular medical care. If you have insurance, Emory will submit claims to your insurance for items and services that the 
sponsor does not cover.  Emory will send in only those claims for items and services that it reasonably believes your 
insurance will pay and that the sponsor has not paid.  
 
The actual amount that you have to pay depends on whether or not you have health insurance and whether or not that 
insurance will pay for any research study costs. Generally, insurance companies will not pay for items and services that 
are required just for a research study. Some insurance companies will not pay for regular medical treatment or treatment 
for complications if you are in a study.  How much you will have to pay for any co-payments, deductibles or co-insurance 
depends on your plan.  Emory and the sponsor will not pay for these costs. 
 
 It is a good idea to contact your insurance provider and tell them you want to be in this research study.  Ask them what 
they will pay for and what they will not pay for.  You can also ask the study team for help in figuring out what you will have 
to pay.  
 
If you do not have insurance, Emory will review your case as part of its program for low-income patient care.  The 
standard policies of that program will apply.  The program will figure out if you have to pay any costs for taking part in 
the study and what those costs will be. 
 
Withdrawal from the Study 
You have the right to leave a study at any time without penalty.   
The researchers also have the right to stop your participation in this study without your consent for any reason, especially if 
they believe it is in your best interest or if you were to object to any future changes that may be made in the study plan. 


 
 
Page 13 of 17 
 
Version Date: V9: 09/08/2020 
IRB Form 06162020 
 
Authorization to Use and Disclose Protected Health Information 
 
The privacy of your health information is important to us.  We call your health information that identifies you, your 
“protected health information” or “PHI.”  To protect your PHI, we will follow federal and state privacy laws, including the 
Health Insurance Portability and Accountability Act and regulations (HIPAA).  We refer to all of these laws as the “Privacy 
Rules.”  Here we let you know how we will use and disclose your PHI for the main study and for any optional studies in 
which you may choose to participate. 
Main Study 
 
PHI that Will be Used/Disclosed:   
The PHI that we will use or share for the main research study includes: 
• 
Medical information about you including your medical history and present/past medications. 
• 
Results of exams, procedures and tests you have before and during the study. 
• 
Laboratory test results. 
 
Purposes for Which Your PHI Will be Used/Disclosed: 
We will use and share your PHI for the conduct and oversight of the research study.  We will use and share your 
PHI to provide you with study related treatment and for payment for such treatment.  We will also use and 
share your PHI to conduct normal business operations.  We may share your PHI with other people and places 
that help us conduct or carry out the study, such as laboratories, data management centers, data monitors, 
contract research organizations, Institutional Review Boards (IRBs) and other study sites. If you leave the study, 
we may use your PHI to determine your health, vital status or contact information.  
 
Use and Disclosure of Your Information That is Required by Law:   
We will use and disclose your PHI when we are required to do so by law. This includes laws that require us to 
report child abuse or abuse of elderly or disabled adults. We will also comply with legal requests or orders that 
require us to disclose your PHI. These include subpoenas or court orders.   
 
Authorization to Use PHI is Required to Participate: 
By signing this form, you give us permission to use and share your PHI as described in this document. You do not 
have to sign this form to authorize the use and disclosure of your PHI.  If you do not sign this form, then you may 
not participate in the research study or receive research-related treatment.  You may still receive non-research 
related treatment.   
 
People Who will Use/Disclose Your PHI: 
The following people and groups will use and disclose your PHI in connection with the research study: 
 
• 
The Principal Investigator and the research staff will use and disclose your PHI to conduct the study and 
give you study related treatment. 
• 
Emory and Grady Health System may use and disclose your PHI to get payment for study related 
treatment and to run normal business operations.  
• 
The Principal Investigator and research staff will share your PHI with other people and groups to help 
conduct the study or to provide oversight for the study. 
• 
 NIH is the Sponsor of the study.  The Sponsor may use and disclose your PHI to make sure the research 
is done correctly and to collect and analyze the results of the research.  The Sponsor may disclose your 
PHI to other people and groups like study monitors to help conduct the study or to provide oversight for 
the study.   


 
 
Page 14 of 17 
 
Version Date: V9: 09/08/2020 
IRB Form 06162020 
 
• 
The research team and the Sponsor may use and disclose your PHI, including disclosure to insurance 
carriers to administer payment for subject injury.  
• 
The following people and groups will use your PHI to make sure the research is done correctly and 
safely: 
o Emory and Grady Health System offices that are part of the Human Research Participant 
Protection Program and those that are involved in study administration and billing.  These 
include the Emory IRB, the Grady Research Oversight Committee, the Emory Research and 
Healthcare Compliance Offices, and the Emory Office for Clinical Research.  
o Government agencies that regulate the research including:  Office for Human Research 
Protections; Food and Drug Administration. 
o Research monitors and reviewer. 
o Accreditation agencies. 
▪ 
Emory University Center for AIDS Research statisticians 
• 
Sometimes a Principal Investigator or other researcher moves to a different institution. If this happens, 
your PHI may be shared with that new institution and their oversight offices. PHI will be shared securely 
and under a legal agreement to ensure it continues to be used under the terms of this consent and 
HIPAA authorization. 
 
Optional Study/Storage of Data/Specimens for Future Research: 
 
PHI That Will be Used/Disclosed for Optional Study:   
The PHI that we will use and/or disclose (share) for the optional genetic testing and contact for future research 
opportunities includes: 
• 
Medical information about you including your medical history and present/past medications. 
• 
Results of exams, procedures and tests you have before and during the study. 
• 
Laboratory test results 
 
Purposes for which your PHI will be Used/Disclosed for Optional Study: 
We will use and disclose your PHI for the conduct and oversight of the optional or the optional genetic testing 
and contact for future research opportunities, including the administration and payment of any costs relating to 
subject injury. 
 
Authorization for This Use of PHI is Required to Participate in Optional Study, but Not in Main Study: 
You do not have to authorize the use and disclosure of your PHI.  If you do not authorize the use and disclosure 
of your PHI for the optional study, then you may not participate in the optional research study.  You can still be 
in the main research study even if you don’t participate in the optional study.    
 
People Who Will Use/Disclose Your PHI for Optional Study: 
The following people and groups will use and disclose your PHI in connection with the optional l genetic testing 
and contact for future research opportunities: 
• 
The same people and groups who will use and disclose your PHI for the Main Study will also do so in 
connection with the optional genetic testing and contact for future research opportunities. 
 
Expiration of Your Authorization 
Your PHI will be used until this research study ends. 
 


 
 
Page 15 of 17 
 
Version Date: V9: 09/08/2020 
IRB Form 06162020 
 
Revoking Your Authorization 
If you sign this form, at any time later you may revoke (take back) your permission to use your information.  If you want 
to do this, you must: 
 
Cecile Delille Lahiri, M.D. 
Division of Infectious Diseases, 
Department of Medicine,  
 
 
 
 
 
 
At that point, the researchers would not collect any more of your PHI.  But they may use or disclose the information you 
already gave them so they can follow the law, protect your safety, or make sure that the study was done properly and 
the data is correct.  If you revoke your authorization you will not be able to stay in the main study.  
 
Other Items You Should Know about Your Privacy 
Not all people and entities are covered by the Privacy Rules.  HIPAA only applies to health care providers, health care 
payers, and health care clearinghouses.  If we disclose your information to people who are not covered by the Privacy 
Rules, including HIPAA, then your information won’t be protected by the Privacy Rules.  People who do not have to 
follow the Privacy rules can use or disclose your information with others without your permission if they are allowed to 
do so by the laws that cover them. 
To maintain the integrity of this research study, you generally will not have access to your PHI related to this research 
until the study is complete.  When the study ends, and at your request, you generally will have access to your PHI that 
we maintain in a designated record set.  A designated record set is data that includes medical information or billing 
records that your health care providers use to make decisions about you. If it is necessary for your health care, your 
health information will be provided to your doctor.  
 
We may remove identifying information from your PHI.  Once we do this, the remaining information will not be subject 
to the Privacy Rules.  Information without identifiers may be used or disclosed with other people or organizations for 
purposes besides this study.   
 
Contact Information 
Contact the 
 
• 
if you have any questions about this study or your part in it,   
• 
if you feel you have had a research-related injury or a bad reaction to the study drug, or 
• 
if you have questions, concerns or complaints about the research 
 
Contact the Emory University Institutional Review Board at 
 
• 
if you have questions about your rights as a research participant. 
• 
if you have questions, concerns or complaints about the research. 
• 
You may also let the IRB know about your experience as a research participant through our Research Participant 
Survey at http://www.surveymonkey.com/s/6ZDMW75. 
 
If you are a patient receiving care from the Grady Health System and have a question about your rights, 
 
. 
 


Page 16 of 17 
Version Date: V9: 09/08/2020 
IRB Form 06162020 
Consent and Authorization 
Consent and HIPAA Authorization for Optional Study/Studies:  
1.
Please initial below if you opt to participate in and authorize use and disclosure of your PHI in the optional
study/studies previously described:
Genetic testing  ____________Initials 
2.
Please initial below if you opt to participate in and authorize use and disclosure of your PHI in the optional
study/studies previously described:
Contact for future research opportunities   ____________Initials 
TO BE FILLED OUT BY SUBJECT ONLY 
Please print your name, sign, and date below if you agree to be in the main study. By signing this consent and 
authorization form, you will not give up any of your legal rights. We will give you a signed copy of the form to keep. 
Name of Subject 
Signature of Subject (18 or older and able to consent) 
Date   
  Time 
TO BE FILLED OUT BY STUDY TEAM ONLY 
__________________________________________________________ 
Name of Person Conducting Informed Consent Discussion 
Signature of Person Conducting Informed Consent Discussion 
Date   
  Time 


Page 17 of 17 
Version Date: V9: 09/08/2020 
IRB Form 06162020 
APPENDIX A: Consent Comprehension Questions 
At the end of consenting, research staff members will read the questions below and circle participant responses. 
1.
The purpose of this study is to find out how well an HIV medicine Dolutegravir (DTG) gets into different parts of
the body.
True/False
2.
You will be responsible for getting your HIV medication as the study will not cover the cost of your HIV
medication.
True/False
3.
You will be responsible for bringing your medication to the study visits.
True/False
4.
This study asks you to come in for 5 study visits over 6 months.
True/False
5.
You will have one study visit at the Grady CRN that will last approximately 8 hours.
True/False
6.
At your Grady CRN visit, the nurse will place an IV in your arm to collect the multiple blood draws over 8 hours.
True/False
7.
You will have four study visits where the doctor will place a scope in your anal canal and collect 2 anal swab
samples and up to 8 anal biopsy samples.
True/False
8.
We will secure your privacy by using a study number for the samples and data collected.
True/False
9.
You have the right to leave the study at any time and can communicate with the PI or study Coordinator for any
questions you may have.
True/False
10. Women of childbearing potential will have a pregnancy test at each visit.
True/False
_______________________________________________ 
Interviewer   Name      
_________________________________________________________________________________________________________________ 
Interviewer Signature                   
 
 
 
 
 
 
 
 Date 
STUDY STAFF:       Please clarify any question/s theion/s the participant has answered incorrectly.