Clinical trial NCT02263326
Conditions: HIV Infection
Sponsor: Babafemi Taiwo
Start date: 2014-12-01; Completion date: 2017-09-01
Enrollment: 89 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
HIV-1 infected subjects with CD4 nadir \> 200 cells/mm3, no history of virologic failure and plasma HIV RNA \<50 copies/mL for at least 48 weeks while on any United States Department of Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as confirmed plasma HIV-1 RNA \> 50 copies/mL before or at Week 24

Detailed description:
DESIGN HIV-1 infected subjects with CD4 nadir \> 200 cells/mm3, no history of virologic failure and plasma HIV RNA \<50 copies/mL for at least 48 weeks while on any United States Department of Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as confirmed plasma HIV-1 RNA \> 50 copies/mL before or at Week 24

All subjects will undergo routine monitoring including plasma HIV-1 RNA, CD4/CD8 count, hematology, chemistry and fasting lipids. Resistance testing will be done in all patients who experience virologic failure. Single-copy HIV-1 assay will be done to quantify residual viremia.

DURATION 48 weeks

SAMPLE SIZE 90 subjects

POPULATION HIV-1-infected men and women, 18 years and older, with CD4 nadir \> 200 cells/mm3, no baseline resistance, no history of virologic failure, and HIV RNA \<50 copies/mL for at least 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug regimen

REGIMEN Subjects will be randomized (1:1) to:

Arm 1: dolutegravir 50 mg plus lamivudine 300 mg once daily OR Arm 2: Continue current DHHS recommended or alternative three-drug antiretroviral regimen

Arms: arm 1: dolutegravir 50 mg plus lamivudine 300 mg once daily arm 2: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Interventions: intervention 1: dolutegravir intervention 2: lamivudine intervention 3: Continue current antiretroviral regimen
Intervention descriptions: intervention 1: 50 mg tablet by mouth once daily for 48 weeks intervention 2: 300 mg tablet by mouth once daily for 48 weeks intervention 3: Continue current DHHS recommended or alternative three-drug antiretroviral regimen

Protocol documents:
Prot_SAP_ICF_000.pdf: 
 
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Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce drug Exposure 
(ASPIRE) Study  
 
 
 
 
 
 
 
 
IND Sponsor: 
Babafemi Taiwo, M.B.B.S  
Northwestern University  
IND EXEMPT 
 
 
 
 
 
 
Pharmaceutical Support Provided by: 
 
ViiV Healthcare, Inc.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ASPIRE FINAL Version 2.0  
June 25, 2015   
 
 
 
 
 


 
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CONTENTS 
 
 
 
Page 
 
Sites Participating in the Study .................................................................................................... 4 
 
Protocol Team Roster ................................................................................................................. 4 
 
SCHEMA .................................................................................................................................... 7 
1.0 HYPOTHESIS AND STUDY OBJECTIVES ........................................................................ 8 
 
   1.1        Hypothesis .......................................................................................................... 8 
1.2 
Primary Objective ................................................................................................. 8 
1.3 
Secondary Objectives .......................................................................................... 8 
2.0 INTRODUCTION ................................................................................................................ 9 
2.1 
Background and Rationale ................................................................................... 9 
3.0 STUDY DESIGN ............................................................................................................... 11 
4.0 SELECTION AND ENROLLMENT OF SUBJECTS .......................................................... 11 
4.1 
Inclusion Criteria ................................................................................................ 11 
4.2 
Exclusion Criteria ............................................................................................... 13 
4.3 
Study Enrollment Procedures............................................................................. 14 
5.0 STUDY TREATMENT ....................................................................................................... 14 
5.1 
Regimens, Administration, and Duration ............................................................ 14 
5.2 
Study Product Formulation and Preparation ....................................................... 15 
5.3 
Pharmacy: Product Supply, Distribution, and Accountability .............................. 15 
5.4 
Concomitant Medications ................................................................................... 16 
5.5 
Adherence Assessment ..................................................................................... 16 
6.0 CLINICAL AND LABORATORY EVALUATIONS .............................................................. 17 
6.1 
Schedule of Events ............................................................................................ 17 
6.2 
Timing of Evaluations ......................................................................................... 18 
6.3 
Instructions for Evaluations ................................................................................ 19 
7.0 CLINICAL MANAGEMENT ISSUES ................................................................................. 24 
7.1 
Toxicity Management (Grades 1, 2, 3, 4) ........................................................... 24 
7.2 
Rash .................................................................................................................. 25 
7.3 
Nausea/Vomiting................................................................................................ 26 
7.4 
AST/ALT Elevations ........................................................................................... 26 
 
7.5 
Creatinine  ......................................................................................................... 27 
7.6 
Allergic reaction ................................................................................................. 28 


 
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7.7. 
Suicidal Ideation or Behaviors………………………………………………………..28 
7.8 
Pregnancy ......................................................................................................... 29 
8.0 CRITERIA FOR DISCONTINUATION ............................................................................... 29 
8.1 
Permanent Treatment Discontinuation ............................................................... 29 
8.2 
Premature Study Discontinuation ....................................................................... 29 
9.0 STATISTICAL CONSIDERATIONS .................................................................................. 30 
9.1 
General Design Issues ....................................................................................... 30 
9.2 
Endpoints ........................................................................................................... 30 
9.3 
Randomization and Stratification ........................................................................ 30 
9.4       Sample size and Accrual ................................................................................... 30 
9.5 
Monitoring - Data Safety Monitoring Committee ................................................. 31 
            9.6       Analyses………………………………………………………………………………..31 
10.0 PHARMACOLOGY PLAN ............................................................................................... 32 
11.0 DATA COLLECTION AND MONITORING AND ADVERSE EVENT REPORTING ......... 32 
11.1 
Records to Be Kept ............................................................................................ 32 
11.2 
Role of Data Management ................................................................................. 32 
11.3 
Clinical Site Monitoring and Record Availability .................................................. 32 
11.4 
Expedited Adverse Event Reporting................................................................... 33 
12.0 HUMAN SUBJECTS ....................................................................................................... 33 
12.1 
Institutional Review Board (IRB) Review and Informed Consent ........................ 34 
12.2 
Subject Confidentiality ....................................................................................... 34 
12.3 
Study Discontinuation ........................................................................................ 34 
13.0 PUBLICATION OF RESEARCH FINDINGS .................................................................... 34 
14.0 BIOHAZARD CONTAINMENT ........................................................................................ 34 
 
15.0   REFERENCES…………………………………………………………………………………..35                   
 APPENDIX I: SAMPLE INFORMED CONSENT……………………………………………………38 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Sites and Investigators Participating in the Study  
 
Northwestern University, Chicago, IL  (Babafemi Taiwo, M.B.B.S., Amesika Nyaku, M.D.) 
Brigham and Women’s Hospital, Boston, MA (Paul Sax, M.D.) 
University of Cincinnati, Cincinnati OH (Carl Fichtenbaum, M.D.)  
University of California – San Diego, CA ( Connie Benson, M.D.) 
The Ohio State University, Columbus OH (Susan Koletar, M.D.) 
Emory University, Atlanta, GA (Vincent Marconi, M.D.)  
 
Protocol Team Roster 
 
Chair 
Babafemi Taiwo, M.B.B.S.  
Division of Infectious Diseases  
Northwestern University 
645 N. Michigan, Suite 900 
Chicago, IL 60611 
Telephone: 312-695-0009 
Fax: 312-695-5088 
Email: b-taiwo@northwestern.edu 
 
Co-Chair 
Paul Sax, M.D 
Brigham and Women’s Hospital 
75 Francis Street 
Boston, MA 02115 
Telephone: 617-732-7460 
Fax: 617-732-6829 
Email: psax@partners.org 
 
Investigators 
Carl Fichtenbaum, M.D.  
Univ. of Cincinnati CRS 
405
 3223 Eden Avenue, Room 3114
 
Cincinnati OH 45267-0405   
Telephone: 513-584-6361   
Fax: 513-584-6040  
Email:carl.fichtenbaum@uc.edu 
 
Connie Benson,  M.D. 
University of California San Diego (UCSD)  
Antiviral Research Center 
200 W. Arbor Dr.  MC 8208 San Diego, CA 92103-8208 
Telephone: 619-543-8080  
Fax: 619-543-5066 
E-Mail: cbenson@ucsd.edu  
 
 


 
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Susan Koletar, M.D. 
The Ohio State Univ. AIDS CTU   
Division of Infectious Diseases   
N-1135 Doan Hall   
410 West 10th Avenue   
Columbus OH 43210-1282
 U 
Telephone: 614-293-5667   
Fax: 614-293-4556  
Email: susan.koletar@osumc.edu  
 
Vincent Marconi, M.D.  
Emory University 
The Ponce de Leon Ctr.  
Ponce de Leon Avenue 
 Room 345 
 
Atlanta GA 30307   
Telephone: 404-616-0673   
Fax: 404-616-0592  
Email: vcmarco@emory.edu 
  
Amesika Nyaku, M.D. 
Division of Infectious Diseases  
Northwestern University 
645 N. Michigan, Suite 900 
Chicago, IL 60611 
Phone: 312-695-5085 
Fax: 312-695-5088 
Email: a-nyaku@northwestern.edu 
 
Patrick A. Ryscavage, MD 
University of Maryland 
Institute of Human Virology 
725 W. Lombard Street, S320 
Baltimore, MD 21201 
Telephone: 410-706-0400  
Fax: 410-706-1992  
Email: PRyscavage@ihv.umaryland.edu 
 
Virologist 
Jonathan Li, M.D 
Brigham and Women's Hospital  
Department of Infectious Diseases   
65 Landsdowne St., Room 435 
Boston MA 02139   
Telephone: 617-768-8381 
Fax: 617-768-8738  
Email: jli22@partners.org  
 
 


 
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Research Manager 
Baiba Berzins, M.P.H. 
Division of Infectious Diseases  
Northwestern University  
645 N. Michigan Avenue, Suite 900  
Chicago, IL  60611 
Phone: (312) 695-5012 
FAX: (312) 695-5088 
E-Mail: baiba@northwestern.edu 
 
 
Data Manager 
Rachelle Price, M.P.H. 
Division of Infectious Diseases  
Northwestern University  
645 N. Michigan Avenue, Suite 900  
Chicago, IL  60611 
Phone: (312) 695-5055 
FAX: (312) 695-5088 
E-Mail: rachelle.price@northwestern.edu  
 
 
ASPIRE Team (Site PIs) email group:  aspire-team@googlegroups.com (note hyphen) 
 
ASPIRE Protocol (Site Staff and Team) email group: ASPIREprotocol@googlegroups.com 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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SCHEMA 
 
DESIGN 
HIV-1 infected subjects with no history of virologic failure and plasma HIV 
RNA <50 copies/mL for at least 48 weeks while on any United States 
Department of Health and Human Services (DHHS) recommended,  
alternative, or other three-drug antiretroviral regimen will be randomized 
to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their 
current regimen (Arm 2) for 48 weeks.  The primary endpoint is virologic 
failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL before or 
at Week 24 
 
All subjects will undergo routine monitoring including plasma HIV-1 RNA, 
CD4/CD8 count, hematology, chemistry and fasting lipids. Resistance 
testing will be done in all patients who experience virologic failure. Single-
copy HIV-1 assay will be done to quantify residual viremia.  
 
Plasma and serum samples will be stored for possible future exploration 
of the impact of switching on markers of immune activation, inflammation, 
bone and renal toxicity. PBMCs will be stored in the subset of patients 
enrolled at Northwestern University to explore the impact of switching on 
HIV reservoir size.                          
 
DURATION 
 
48 weeks  
 
SAMPLE SIZE 
90 subjects 
 
POPULATION 
HIV-1-infected men and women, 18 years and older, with no baseline 
NRTI resistance, no history of virologic failure, and HIV RNA <50 
copies/mL for at least 48 weeks prior to study entry while on any DHHS 
recommended,  alternative, or other three-drug regimen  
 
 
REGIMEN 
Subjects will be randomized (1:1) to:  
 
Arm 1: dolutegravir 50 mg plus lamivudine 300 mg once daily  
OR  
Arm 2: Continue current DHHS recommended or alternative three-drug 
antiretroviral regimen  


 
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1.0 
HYPOTHESIS AND STUDY OBJECTIVES 
1.1 
Hypothesis 
 
HIV-infected patients with no history of virologic failure, and HIV RNA <50 copies/mL for at least 
48 weeks on any DHHS recommended,  alternative, or other three-drug regimen will maintain 
viral suppression after switching to DTG + lamivudine.  
Note: All DHHS recommended,  alternative, or other baseline regimens contain a  boosted 
protease inhibitor or non-nucleoside reverse transcriptase inhibitor or integrase inhibitor plus two 
nucleos(t)ide reverse transcriptase inhibitors, one of them lamivudine or emtricitabine. 
  
1.2 
Primary Objective 
 
Among HIV patients with no history of virologic failure and HIV RNA <50 copies/mL for at least 
48 weeks prior to entry, we will compare virologic failure rate, defined as confirmed HIV RNA >50 
copies/mL before or at Week 24 between those who continue their current regimen versus those 
who switch to DTG + lamivudine 
 
1.3 
Secondary Objectives are to determine the impact of switching on:  
 
1.3.1. CD4 count at Weeks 24 and 48  
 
1.3.2   Rates of HIV-1 viremia >20, >50, and >200 copies/mL at Weeks 24 and 48  
 
1.3.2. HIV resistance among those with confirmed viral rebound to > 50 copies/mL 
 
1.3.3. Incidence of clinical and/or laboratory toxicities.  
The safety and tolerability measures will include time to discontinuation of any study 
medication due to adverse events (AEs), proportion of Grade 3 or Grade 4 clinical AEs, 
proportion of Grade 3 or Grade 4 laboratory abnormalities, and summaries of all treatment-
related AEs.  
 
1.3.4. Change in HIV-1 detection by the single-copy assay from baseline to Weeks 24 and 48 
 
1.3.5. To collect and store samples for possible future exploration of the impact of switching 
on: 
a. Other measures of the HIV reservoir size e.g total/integrated DNA and cellular RNA 
in PBMC (substudy in patients enrolled at Northwestern University) 
b. Soluble and cellular markers of immune activation and inflammation: e.g. CRP, IL-
6, sCD14, sCD163, d-dimer and TNFR-2 
c. Markers of bone turnover and renal tubular toxicity 
d. Stored samples may also be used for targeted pharmacokinetic evaluations if 
needed to explain study results 
 
 
 
 


 
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2.0 
INTRODUCTION 
2.1 Background and Rationale 
 
Antiretroviral therapy with fewer than three drugs is an option for some HIV-infected patients 
Current HIV treatment guidelines recommend the use of three active agents with the goal of 
maintaining HIV viral suppression below 50 copies/mL (cpm)1,2 However, long-term combination 
antiretroviral therapy (ART) has limitations including adverse effects, drug-drug interactions, and 
cumulative cost. Each constituent compound of ART may have an additive effect on these limitations. 
For example, two of the most common components of modern ART regimens are the nucleos(t)ide 
reverse transcriptase inhibitors (NRTI), abacavir and tenofovir, each of which has potential adverse 
effects. Tenofovir is associated with renal/bone toxicity while abacavir has been associated with 
hypersensitivity syndrome, and perhaps cardiovascular effects)3-8. Adverse effects of NRTIs may 
overlap with those of protease inhibitors (PI) and/or non-nucleoside reverse transcriptase inhibitors 
(NNRTI).4,9,10 The global move towards early ART initiation11,12has amplified the impetus to discover 
novel therapeutic strategies that will avoid long-term toxicity and curtail cost while maintaining 
virological suppression. One potential strategy is reductive ART, defined as treatment with fewer than 
three ARV drugs per day in a patient who is virologically suppressed on a three-drug regimen.13 Other 
terms that have been used to describe this strategy include ART de-intensification and ART 
simplification. Crucially, the most successful reductive ART strategies must select both appropriate 
patient candidates and an optimal ART regimen that provides potential benefits in toxicity and cost 
while maintaining virologic suppression. 
The optimal patients for reductive ART are likely to be those with relatively low viral reservoirs 
during three-drug ART.  Nadir CD4 count may be useful in identifying such patients since CD4 count 
is readily accessible clinically and has been shown to be predictive of reservoir size during successful 
ART. This was demonstrated in a study of patients who had been virally suppressed for a mean 
duration of 3.2 years.14 In multivariate analysis, only nadir CD4 count was significantly associated with 
HIV proviral DNA (reservoir size). Duration of viral suppression may also be a useful parameter to 
identify those likely to have a low reservoir size since longer duration of suppression below 50 cpm 
has been associated with reduced risk of viral rebound,15-17 Moreover, viral reservoirs tend to diminish 
with increased time on ART.18 In an observational study of 664 patients receiving ritonavir boosted PI 
(PI/r) monotherapy after initial viral suppression with three agents, both nadir CD4 count <200 
cells/mm3 and a shorter duration of viral suppression prior to regimen simplification were associated 
with virologic failure.19  In summary, patients with a higher nadir CD4 count and longer duration of 
suppressive ART may have lower HIV reservoirs and thus may be more likely to experience a 
favorable response to a reductive ART regimen. 
 
The integrase strand transfer inhibitor (INSTI) class of antiretroviral drugs has attributes that 
are desirable in a reductive ART regimen; namely, reliable potency, long-term tolerability, and limited 
resistance in treatment naïve patients. Dolutegravir (DTG) is especially attractive since resistance to 
DTG occurs less commonly (discussed in the section below) than resistance to the earlier INSTIs in 
patients with virologic failure20-22, suggesting a higher barrier to resistance with DTG. Raltegravir has 
been studied as part of NRTI-sparing regimens in ART switch studies, demonstrating improvements in 
some toxicities such as bone mineral density, but with mixed results in terms of virologic efficacy.20,23-
25. Elvitegravir is less attractive both because it requires pharmacologic boosting and is available in 
the United States only as a component of a single tablet regimen. We hypothesize that the 
combination of DTG plus another potent well-tolerated agent will constitute an effective regimen for 
reductive ART. 
 
Dolutegravir  


 
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DTG was FDA approved in 2013 for the treatment of HIV-1 infection in antiretroviral-naïve and 
experienced patients. In early studies, monotherapy with DTG 50 mg once daily for 10 days resulted 
in a mean viral load decline of 2.46 log10 and 7/10 (70%) of the subjects achieved viral load < 50 
copies/mL .26 DTG’s chiral, non-racemic structure fits loosely into its intasome binding pocket, 
allowing it to retain binding capacity despite mutational changes in pocket structure, and to dissociate 
from integrase-DNA complexes more slowly than other members of the INSTI class.27 Resistance 
passage experiments demonstrated no development of significant DTG phenotypic resistance after 
112 days, whereas >5 fold phenotypic resistance to raltegravir occurred by day 28.28 As noted above, 
the resistance profile of DTG appears to be higher than earlier INSTIs, as no mutation emerged in 
large clinical trials of treatment naïve individuals.29,30 The R263K mutation was later identified in a few 
highly treatment experienced patients salvaged with DTG-containing ART. R263K confers very low 
resistance to DTG but it also compromises viral fitness.31,32 Other mutations described in association 
with DTG (e.g G118R and H51Y) also damage viral replicative fitness, which may explain the rarity of 
DTG-related mutations in clinical trials.33 The reduced replicative fitness of viruses selected by DTG is 
consistent with recent findings that integrase mutations selected by DTG impair the emergence of 
resistance to RTIs such as lamivudine and nevirapine.31 Furthermore, the metabolic, renal, bone, and 
drug-drug interaction profile of DTG is highly favorable compared to many antiretroviral agents 
currently in wide use.34  DTG is approved for both once- and twice-daily dosing, depending on 
concomitant medications, or presence of INSTI resistance mutations with or without severe renal 
disease. The recommended DTG dose in the absence of INSTI mutations or concomitant use of 
potent UGT1A/CYP3A inducers is 50 mg once daily. Dolutegravir is also available in a fixed- dose 
combination that includes 50 mg of DTG, 600 mg abacavir, and 300 mg lamivudine, known as 
Triumeq®. 
Lamivudine 
 
Lamivudine has long been known to have excellent tolerability, and importantly has low in vitro 
and in vivo mitochondrial toxicity.35 It possesses good CNS penetration,36 and concentrates in the 
male and female genital tract.37 Lamivudine received FDA approval for treatment of HIV-1 infection in 
1995 and has remained a core component of many first line ART regimens worldwide.1,38 The 
important role of lamivudine in combination ART was recently further demonstrated in the GARDEL 
study, which found that initial dual therapy with lamivudine plus lopinavir/r was as effective and better 
tolerated than the combination of lopinavir/r, lamivudine and a second NRTI in treatment naïve 
patients.39 
 
Dolutegravir + lamivudine is an ideal regimen to evaluate for reductive ART  
Early trials of reductive ART primarily employed PI/r monotherapy13. More recent trials have 
explored lamivudine plus PI/r including two recent randomized studies (OLE, SALT), which found non-
inferiority of regimen simplification from standard three-active drug treatment to PI/r +.lamivudine 40,41 
These results differ from those of several PI/r monotherapy switch studies which demonstrated 
inconsistent efficacy and a higher rate of low-level viremia in those receiving PI/r alone.42-46 The two-
drug regimen of DTG +lamivudine has several potential advantages over PI/r + lamivudine; these 
include two constituent pharmacologic agents as opposed to three, a lower pill burden, a favorable 
effect on lipids, reduced drug-drug interactions, and lower rate of gastrointestinal side effects. In 
addition DTG achieves potent concentrations in the CNS 47 which may not the case for some PIs.48,49 
Taken together, evidence suggests that DTG + lamivudine will be a highly potent and safe regimen 
with a sufficiently high resistance barrier to maintain virologic suppression, making it an ideal regimen 
to investigate for reductive ART. This strategy has a high probability of success if utilized in a 
population of suppressed patients who have clinical parameters associated with relatively low viral 
reservoirs and long-term adherence.  
 


 
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3.0 
STUDY DESIGN 
 
ASPIRE  is a prospective, open-label, randomized, multicenter, 48-week  study to explore whether 
HIV-infected subjects with no history of virologic failure, and HIV RNA <50 copies/mL for at least 48 
weeks on any DHHS recommended,  alternative, or other three-drug regimen will maintain viral 
suppression after switching to DTG + lamivudine.   Subjects must have a pre-treatment genotype of 
the reverse transcriptase and protease genes documenting no NRTI resistance mutations.     
 
Subjects (N=90) will be randomized to DTG + lamivudine (Arm 1) or continuation of their DHHS 
recommended,  alternative, or other regimen (Arm 2) for 48 weeks.  
Each subject will be evaluated at screening, entry, and at Weeks 4, 12, 24, 36, and 48.  All subjects 
will undergo routine monitoring including plasma HIV-1 RNA, CD4/CD8, hematology, chemistry, and 
fasting lipid profiles.  
 
HIV-1 RNA single-copy assay will be performed to quantify changes in residual viremia from baseline 
to Weeks 24 and 48.  Plasma and serum samples will be stored for possible evaluation of changes in 
soluble and cellular markers of inflammation and immune activation as well as changes in markers of 
bone turnover and renal tubular toxicity and for targeted pharmacokinetics studies.  PBMCs will be 
stored in the patient subset enrolled at Northwestern University to further explore the dynamics of HIV 
reservoir size with the experimental reductive strategy.   
 
Subjects with suspected virologic failure (defined as plasma HIV-1 RNA > 50 copies/mL at any time 
after study entry up to Week 48) will have a confirmatory viral load obtained within 35 days after 
receipt of the results of the initial sample. Resistance testing will be attempted on the confirmatory HIV 
RNA in all patients with confirmed virologic failure. Subjects with confirmed virologic failure on the 
study regimen may be switched to alternative combination ART at the discretion of their HIV care 
provider. The HIV care provider may elect to continue DTG + lamivudine if there is evidence that 
virologic failure was caused by a lapse in adherence. At the end of the study, subjects will be 
managed at the discretion of their primary HIV providers.  
 
All subjects will be followed through Week 48 regardless of treatment modification, discontinuation or 
adherence.   
 
4.0 SELECTION AND ENROLLMENT OF SUBJECTS 
4.1 
Inclusion Criteria 
 
4.1.1 HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or 
chemoiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and 
confirmed by a licensed Western blot or a second antibody test by a method other than 
the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. 
 
NOTE: The term “licensed” refers to a United States FDA-approved kit. 
 
WHO (World Health Organization) and CDC (Centers for Disease Control and 
Prevention) guidelines mandate that confirmation of the initial test result must use a 
test that is different from the one used for the initial assessment. A reactive initial rapid 
test should be confirmed by either another type of rapid assay or an E/CIA that is 
based on a different antigen preparation and/or different test principle (eg, indirect 
versus competitive), or a Western blot or a plasma HIV-1 RNA. 


 
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4.1.2. HIV-1 RNA  <50 copies/mL on all measurements within 48 weeks prior to study entry 
while on any DHHS recommended, alternative or other three-drug antiretroviral 
regimen. A history of switching for simplification and/or tolerability is allowed.  
At least two measurements within the previous 48 weeks are required prior to study 
screening. 
4.1.3 No history of virologic failure, defined as consecutive HIV RNA > 50 copies/mL after 12 
months of initiating ART.   
NOTE: An isolated (non-consecutive) HIV RNA > 50 copies/mL (but less than 400 
copies/mL) is permitted after 12 months of initiating ART but not in the 48-week 
window prior to study entry. 
4.1.4 Screening plasma HIV RNA < 20 copies/mL using the COBAS AmpliPrep/COBAS 
TaqMan HIV-1 Test, v2.0, obtained within 45 days prior to study entry 
4.1.5.  Pretreatment genotype of the protease and reverse transcriptase genes 
documenting no nucleos(t)ide (NRTI) mutations  according to the 2014 IAS-USA drug 
resistance mutations list (available at https://www.iasusa.org/sites/default/files/tam/22-
3-642.pdf  ) 
 
4. 1.6. No known resistance to integrase inhibitors [Note:  pre-treatment resistance testing for 
integrase inhibitors is not required.] 
  
4.1.7. 
Laboratory values obtained within 45 days prior to study entry:  
• 
ANC ≥750/mm3 
• 
Hemoglobin ≥10 g/dL   
• 
Platelets ≥50,000/mm3 . 
• 
Calculated creatinine clearance (CrCl) ≥50 mL/min, as estimated by the Cockcroft-
Gault equation 
 
4.1.8 Negative serum or urine pregnancy test at screening and within 48 hours of study entry 
for women with reproductive potential (defined as women who have not been 
postmenopausal for at least 24 consecutive months, i.e., who have had menses within 
the preceding 24 months, or have not undergone surgical sterilization [e.g., 
hysterectomy, bilateral oophorectomy, or salpingectomy]) .The urine test must have a 
sensitivity of ≤50 mIU/mL. 
 
4.1.9 If participating in sexual activity that could lead to pregnancy, female subjects with 
reproductive potential must use one form of contraceptive as listed below while 
receiving protocol-specified medications and for 60 days after stopping the 
medications. At least one of the following methods MUST be used appropriately: 
• 
Condoms (male or female) with or without a spermicidal agent. Condoms are 
recommended because their appropriate use is the only contraception method 
effective for preventing HIV transmission. 
• 
Diaphragm or cervical cap with spermicide 
• 
IUD (intrauterine device) 


 
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• 
Hormone-based contraceptive. Some medications alter the metabolism of 
hormone-based contraceptives. This interaction may make hormone-based 
contraceptives less effective. Therefore, an alternative or an additional 
contraception method may be required. Oral contraceptives containing 
norgestimate and ethinyl estradiol can be used without an additional contraception 
method. 
Subject-reported history is acceptable documentation of sterilization, other contraception 
methods, menopause, and reproductive potential. 
 
4.1.10 Men and women age ≥18 years. 
 
4.1.11 Ability and willingness of subject to provide informed consent 
4.1.12 Ability to continue current regimen (i.e., have uninterrupted access) 
4.1.13  Negative hepatitis B surface Ag within 45 days of entry   
4.2   Exclusion Criteria 
 
4.2.1 Serious illness or AIDS-related complication within 21 days of screening requiring 
systemic treatment and/or hospitalization until candidate either completes therapy or is 
clinically stable on therapy, in the opinion of the site investigator, for at least 7 days 
prior to study entry.  Need for systemic therapy for malignancy currently or anticipated 
during the study period.  
 
NOTE: vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses 
(as judged by the site investigator) have no restriction. .  
 
4.2.2 Treatment within 30 days prior to study entry with immune modulators such as 
systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-
CSF), erythropoietin, or any investigational therapy. Vaccination within 7 days 
NOTE:  Subjects receiving stable physiologic glucocorticoid doses (defined as 
prednisone ≤15 mg/day [or equivalent] as a stable or tapering dose) are 
permitted.  
4.2.3 Pregnant women or women of childbearing potential who wish to become pregnant 
during the study period, or Breast-feeding 
4.2.4    Active HCV treatment or anticipated need for treatment within study period. HCV 
infection alone is not exclusionary (see 4.2.5, 4.2.6 and 4.2.9)  
4.2.5 Unstable liver disease (as defined by the presence of ascites, encephalopathy, 
coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), 
known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic 
gallstones)  
4.2.6 Severe hepatic impairment (Class C) as determined by Child-Pugh classification  
 4.2.7 Known allergy or hypersensitivity to DTG or lamivudine.  


 
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4.2.8 Active drug or alcohol use or dependence that could interfere with adherence to study 
requirements 
4.2.9 ALT (alanine aminotransferase) >5 x ULN (upper limit of normal) OR ALT >3 x ULN 
and total bilirubin >1.5 x ULN  (with 35% direct bilirubin) within 45 days of entry 
 
NOTE: If the potential subject is taking an atazanavir-containing regimen at the time of 
screening, total bilirubin <5 x ULN is acceptable 
4.3 Study Enrollment Procedures 
 
4.3.1 Prior to implementation of this protocol, sites must have the protocol and the protocol 
consent form approved by their local institutional review board (IRB). 
Once a candidate for study entry has been identified, details will be carefully discussed 
with the subject. The subject will be asked to read and sign the approved protocol 
consent form.  
 
4.3.2 Registration/Randomization 
Subjects who meet enrollment criteria will be randomized on the day of study entry 
according to the study treatment that has been randomly assigned to the Patient 
Number on the site-specific Randomization List held by the local site 
pharmacist.   For subjects from whom informed consent has been obtained, but who 
are deemed ineligible or who do not enroll into the protocol, the Eligibility Checklist  
must be completed with the reason(s) for screen failure and faxed to the Data 
Management Center.   
 
5.0 
STUDY TREATMENT 
5.1 Regimens, Administration, and Duration 
 
 
Subjects will be randomized (1:1) to either:  
 
Arm 1: DTG 50 mg orally once daily plus lamivudine 300 mg orally once daily  
 
OR  
 
Arm 2: Continue current DHHS recommended or alternative three- drug 
antiretroviral regimen 
 
 
  
Study treatment duration is 48 weeks.  
5.1.1 Regimen 
 
Subjects must begin study treatment within 72 hours after entry (see Section 6.0) and 
continue on study treatment for 48 weeks. 
The pharmacist will dispense the amount of study-provided study products at the entry 
visit (day 0) and Weeks 4, 12, 24, 36 to last to the next study visit.  


 
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At the Week 48 visit, subjects must return any remaining study-provided study 
products. 
5.1.2 Administration 
 
DTG will be administered orally as one 50 mg tablet once daily with or without food.  
 
DTG should be taken at least 2 hours before or 6 hours after taking cation containing 
antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or 
buffered medications. Alternatively, DTG and supplements containing calcium or iron 
can be taken together with food. 
 
Lamivudine will be administered orally as one 300 mg tablet once daily with or without 
food   
 
5.2 Study Product Formulation and Preparation 
 
5.2.1    Dolutegravir  (Tivicay) 50 mg tablets. Store at 25°C (77°F); excursions 
permitted to 15°C - 30°C (59°-86°F).  Each bottle contains a 30 day supply.   
 
Lamivudine (Epivir) 300 mg tablets. Store at 25C (77F); excursions permitted to 15 to  
30C (59 to 86F).  Each bottle contains a 30 day supply.  
 
 
5.3 Pharmacy: Product Supply, Distribution, and Accountability 
 
5.3.1 Study Product Supply/Distribution 
DTG and lamivudine for Arm 1 will be supplied by ViiV.       
Subjects must have the ability to continue procuring current regimen if randomized to 
continue their present treatment (Arm 2) 
5.3.2 Study Product Accountability 
The site pharmacist is required to maintain complete records of all study products 
received. All unused study products must be returned to the site (or as otherwise 
directed by the sponsor) after the study is completed or terminated.  
5.4 Concomitant Medications 
 
Below are lists of selected concomitant medications. These lists are only current as of 
the date of this protocol. Therefore, whenever a concomitant medication or study agent 
is initiated or a dose changed, investigators must review the concomitant medications’ 
and study agents' most recent package inserts, and Investigator’s Brochures to obtain 
the most current information on drug interactions, contraindications, and precautions. 
5.4.1 Required Medications: None.  
5.4.2 Prohibited Medications 
 
 
Prohibited medications with DTG 


 
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The following are prohibited while the subject is on study drugs: 
• Systemic cytotoxic chemotherapy 
• Dofetilide (or pilsicainide [available in Japan]) is prohibited as DTG may inhibit its 
renal tubular secretion resulting in increased dofetilide concentrations and potential 
for toxicity 
NOTE: Vaccinations are contraindicated within 7 days of study visits in Arms 1 and 2  
 
 
5.4.3 Precautionary Medications 
Whenever a concomitant medication or study agent is initiated or a dose changed, 
investigators must review the concomitant medications’ and study agents' most recent 
package inserts, Investigator’s Brochures to obtain the most current information on 
drug interactions, contraindications, and precautions. 
 
 
Precautionary medications with DTG 
• antacids or laxatives that contain aluminum, magnesium, sucralfate (CARAFATE®), 
or buffered medicines. DTG should be taken at least 2 hours before or 6 hours after 
these medicines are ingested. 
• iron or calcium supplements. Supplements including multivitamins containing calcium 
or iron may be taken at the same time with DTG if taken with food. Otherwise, DTG 
should be taken at least 2 hours before or 6 hours after these medicines. 
• anti-seizure medicines: oxcarbazepine (TRILEPTAL®), phenytoin (DILANTIN®, 
DILANTIN®-125, PHENYTEK®), phenobarbital (LUMINAL®), carbamazepine 
(CARBATROL®,  QUETRO®, TEGRETOL®, TEGRETOL®-XR, TERIL®, EPITOL®) 
• St. John’s wort (Hypericum perforatum) 
• a medicine that contains metformin 
• rifampin (RIFATER®, RIFAMATE®, RIMACTANE®, RIFADIN®) as DTG dose  must 
be adjusted 
 
 
5.5 Adherence Assessment 
 
Adherence to all study drugs will be monitored by self-report. Sites will provide adherence 
reinforcement, according to local standard practice, throughout the study. Subjects with poor 
adherence will be provided counseling by the site. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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6.0 
CLINICAL AND LABORATORY EVALUATIONS 
6.1 Schedule of Events 
 
 
Evaluation 
VISITS 
 
 
Scre
ening  
  
Entry  
 
Wk 
4 
 
Wk 
12 
 
Wk 
24 
 
Wk 
36 
 
Wk 
48 
 
Confirma
tion of 
Virologic 
Failure  
Premature 
Study or 
Treatment 
Discontinu
ation   
Complete Physical Exam 
 
 X  
    
  
  
  
  
  
  
Targeted Physical Exam, 
Adverse Event Assessment 
 X  
  
 X  
 X  
 X  
 X  
 X  
 X  
 X  
Informed Consent, Medical 
History, Eligibility Criteria 
Review 
 X  
  
  
  
  
  
  
  
  
Study Evaluations (Clinical 
Assessment, Concomitant  
Medications) 
 X  
 X  
 X  
 X  
 X  
 X  
 X  
 X  
 X  
Pharmacy Dispensing  
  
 X  
 X  
 X  
 X  
 X  
  
  
  
Adherence Assessment 
 
 
X 
X 
X 
X 
X 
X 
X 
Hematology 
 X  
 X  
 X  
 X  
 X  
 X  
 X  
  
 X  
Chemistry and Liver Function 
Tests 
 X  
 X  
 X  
 X  
 X  
 X  
 X  
    
 X  
Fasting Lipid Panel 
    
 X  
  
    
 X  
    
 X  
  
  
Pregnancy Testing 
 X  
 X 
 If pregnancy is suspected  
Hepatitis B Surface Antigen  
 X  
  
  
  
  
  
  
  
  
Hepatitis C Antibody 
 
 X 
 
 
 
 
 
 
 
CD4/CD8 
  
 X  
  
  
 X  
  
 X  
   
 X  
CD4 Nadir 
 
 X 
 
 
 
 
 
 
 
HIV-1 RNA (Cobas Taqman v2) 
 X  
 X  
 X  
 X  
 X  
 X  
 X  
 X  
 X  
Urinalysis 
 X  
  
  
  
  
  
  
  
  
PBMC Processing and Storage 
(Northwestern only) 
  
 X  
  
  
 X  
  
 
 X  
 X  
Plasma Storage 
 X  
 X  
 X  
 X  
 X  
 X  
 X  
 X  
 X  
Serum Storage 
  
 X  
  
  
  
  
 X  
 X  
 X  
                                                      
Single-copy HIV 1 RNA 
 
X 
 
 
X 
 
X 
   
 X 
                                                      
HIV Genotype  
 
  
 
 
   
 
  
X 
 
 
 
 
 
 
 
 
 
 


 
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6.2 
Timing of Evaluations 
 
6.2.1 Screening Evaluations  
 
Screening evaluations must occur prior to the subject starting any study medications, 
treatments, or interventions. 
Screening 
Screening evaluations to determine eligibility must be completed within 45 days prior to 
study entry, unless otherwise specified. The site may use documentation of HIV 
infection and the HIV resistance genotype obtained pre-treatment.   
In addition to data being collected on subjects who enroll into the study, reason(s) for  
screening failures will be captured on the Eligibility Checklist and faxed to the Data 
Management Center (will not be entered directly in REDCap).   
 
6.2.2 Entry Evaluations 
Entry evaluations must occur at least 24 hours after screening evaluation and be 
completed prior to the initiation of study medications.  
6.2.3 Post-Entry Evaluations 
On-Treatment Evaluations 
Evaluations should occur +/- 14 days of the scheduled visit.    
 
Visit to Confirm Virologic Failure  
Subjects with a suspected virologic failure should have a sample for confirmatory viral 
load obtained within 35 days after receipt of the results of the initial sample and other 
Confirmation of Virologic Failure visit evaluations. If the initial sample was 
collected during a treatment interruption, sites are encouraged to address toxicity or 
adherence issues before taking the confirmatory sample  
 
NOTE: Virologic failure is defined as confirmed plasma HIV-1 RNA > 50 copies/mL at 
any time after study entry up to Week 48 
 
If the Confirmation of Virologic Failure visit coincides with a regularly scheduled visit, 
the evaluations should be combined.  
 
If virologic failure is confirmed, sites must inform the protocol team by sending an email 
to  aspire-team@googlegroups.com .  Management of subsequent ART will be left to 
the discretion of the site investigator. If stopping study treatment, the subject will 
complete the Premature Treatment Discontinuation evaluations per section 6.2.4 and 
continue to be followed on study/off study treatment. . 
 
6.2.4 Discontinuation Evaluations 
 
Evaluations for Registered Subjects Who Do Not Start Study Treatment 


 
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Subjects who do not begin study treatment should have screening and entry forms 
completed and entered in the database. Beyond the entry visit, no further evaluations 
are required. These subjects will be replaced. 
 
Premature Treatment Discontinuation Evaluations  
Subjects who discontinue the study medications before the end of the study (Week 48) 
should have the Premature Treatment Discontinuation evaluations done within 14 days 
after stopping study drugs. They will be encouraged to continue to attend all study 
visits and receive study evaluations as per section 6.1 through Week 48.   
 
Premature Study Discontinuation Evaluations  
All subjects who prematurely discontinue participation in the study should have the 
Premature Study Discontinuation evaluations done. 
 
6.3 Instructions for Evaluations 
 
All clinical and laboratory information required by this protocol must be present in the source 
documents. 
All stated evaluations are to be recorded on the CRF and keyed into the REDCap database 
unless otherwise specified. 
6.3.1 Documentation of HIV-1 
Section 4.1.1 specifies assay requirements for HIV-1 documentation. HIV-1 
documentation is not recorded on the CRF.  
 
6.3.2 Medical History 
The medical history must include all diagnoses identified by the ACTG criteria for 
clinical events and other diagnoses. In addition to reporting all diagnoses within the 
past 30 days prior to study entry, the following diagnoses should be reported 
regardless of when the diagnosis was made: 
• 
AIDS-defining conditions 
• 
Bone fractures (verbal history accepted) 
• 
Coronary heart disease 
• 
Cancer (exclusive of basal/squamous cell skin cancer) 
• 
Diabetes 
• 
Tuberculosis 
 
Any allergies to any medications and their formulations must also be documented.  
 
         6.3.3 
Medication History 
A medication history must be present in the history and recorded in the source 
documents:  
 
 


 
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Medication History Table 
Medication Category 
Complete History or Timeframe 
Record in 
CRFs 
Antiretroviral therapy 
Complete (start date of initial 
ART regimen, estimated time 
on each drug) 
Yes 
Immune-based therapy 
Within 30 days prior to entry  
Yes 
Prescription drugs for 
treatment or prophylaxis of 
opportunistic infections 
(OIs) 
Within 30 days prior to entry  
Yes 
Other prescription drugs 
Within 30 days prior to entry 
Yes 
Non-prescription drugs  
Within 30 days prior to entry 
No 
Complementary and 
alternative medicines 
Within 30 days prior to entry 
No 
 
 
6.3.4. Nadir CD4+ 
 
The subject’s prior nadir CD4+ cell count (absolute value and date) should be 
documented with a copy of the nadir CD4+ cell count report or clinician’s 
documentation of the CD4 nadir in the subject’s medical record.  If documentation is 
not available, patient’s recall of CD4 nadir can be recorded.    
 
 
6.3.5 Clinical Assessments 
 
Complete Physical Exam 
A complete physical examination performed at any time between screening and the 
entry evaluation is to include at a minimum an examination of the skin, head, mouth, 
and neck; auscultation of the chest; cardiac exam; abdominal exam; and examination 
of the lower extremities for edema. The complete physical exam will also include signs 
and symptoms, diagnoses, height, weight, and vital signs (temperature, pulse, 
respiration rate, and blood pressure). 
Targeted Physical Exam 
A targeted physical examination is to be performed at screening and after the entry 
visit and will be driven by any previously identified or new signs or symptoms including 
diagnoses that the subject has experienced since the last visit. This examination 
includes weight and vital signs (temperature, pulse, respiration rate, and blood 
pressure). 
Signs and Symptoms  
At entry, record on the CRFs all signs/symptoms occurring within 30 days prior to 
entry. 
 
After entry, record all Grade ≥3 signs/symptoms, any signs/symptoms regardless of 
grade that lead to a change in treatment, or that meet EAE, SAE, or ICH guidelines.   
 


 
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Diagnoses 
At screening, record diagnoses in the medical history per section 6.3.2. At study entry 
and thereafter, record all new diagnoses since the last study visit identified by the 
ACTG criteria for clinical events and other diseases.  
 
Concomitant Medications 
Record any immune-based therapies and other prescription medications taken since 
the last study visit, including actual or estimated start dates and stop dates in the CRF. 
Current non-prescription, alternative and traditional medications are recorded in the 
source documents only.  
 
Study Treatment  
Record all study treatment (DTG + lamivudine or continued ART)  modifications, 
including initial doses, subject-initiated and/or protocol-mandated modifications, and 
inadvertent and deliberate interruptions of more than 7 days total or 3 or more 
consecutive days since last visit. Record any permanent discontinuation of treatment. 
 
6.3.6 Laboratory Evaluations 
Sites must refer to the DAIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014, which can 
be found at http://rsc.tech-
res.com/safetyandpharmacovigilance/gradingtables.aspx.   
Record all protocol-required laboratory values, regardless of grade, obtained at 
screening and entry on the CRFs.  
After entry, record all laboratory values Grade ≥3. All laboratory values that lead to a 
change in study treatment, and all renal (serum creatinine and blood urea nitrogen) 
and liver function tests (AST, ALT, alkaline phosphatase, total and direct bilirubin) 
regardless of grade, must be recorded. Also record all lipid values regardless of grade 
on the CRF. 
 
Hematology 
Hemoglobin, hematocrit, white blood cell count (WBC), with differential, absolute 
neutrophil count (ANC), and platelet count.   
 
Liver Function Tests 
AST (SGOT), ALT (SGPT), alkaline phosphatase, total and direct bilirubin  
 
Blood Chemistries 
Electrolytes (Na+, K+, Cl-, HCO3/CO2), glucose, creatinine, phosphate, and blood urea 
nitrogen,   
 
Fasting Lipids 
Total, HDL, and LDL cholesterol, triglycerides. 
 
Subjects should be instructed to fast for 8 hours prior to this test. Fasting is defined as 
no food or drink, except for sips of water with medications. If the subject has not been 
fasting, the visit does not need to be rescheduled.  Record the non-fasting status on 
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Hepatitis B Surface Antigen  
Documentation of negative hepatitis B surface antigen within 45 days prior to study 
entry  
 
Hepatitis C Antibody 
Documentation of hepatitis C antibody status  
NOTE: HCV antibody testing is not needed if there is documented positive HCV 
antibody status ANY TIME prior to study entry OR a negative HCV antibody test within 
90 days prior to study entry  
 
 
Urinalysis 
Dipstick or microscopic exam may be done; if dipstick results are abnormal, 
microscopic exam is required.  
 
Pregnancy Test 
All women with reproductive potential must have a negative serum or urine beta-
human chorionic gonadotropin (β-HCG) pregnancy test result at screening and within 
48 hours prior to initiating protocol-specified medications and any time thereafter when 
pregnancy is suspected. (The urine test must have a sensitivity ≤50 mIU/mL).  
 
6.3.7 Immunologic Studies 
 
CD4+/CD8+ 
Evaluations for CD4+/CD8+ cell counts and percentages should be performed at the 
same laboratory, if possible, for all on-study evaluations. The laboratory must have 
CLIA certification, or its equivalent.  
 
Because of the diurnal variation in CD4+/CD8+ cell counts, determinations for 
individual subjects should be obtained consistently in either the morning or the 
afternoon throughout the study, if possible. 
 
6.3.8 Virologic Studies 
Plasma HIV-1 RNA  
Screening HIV-1 RNA must be performed within 45 days prior to study entry. All on-
study HIV-1 RNA assays including the screening measurement must be done using the 
COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0, lower quantification limit of 20 
copies/mL  (Roche Molecular Systems, Inc.) at a CLIA certified local laboratory as 
specified in the Laboratory Processing Chart.  
 
Subjects with suspected virologic failure should have a sample for confirmatory viral 
load obtained within 35 days after receipt of the results of the initial sample. 
 
 
 
 
 
 


 
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Genotype 
Pre-treatment - Pre-treatment RT/protease genotype must be documented prior 
to study entry.  [Note:  pre-treatment integrase genotype is not required] 
 
Virologic failure - When a subject is suspected to have virologic failure, a 
confirmatory plasma HIV-1 RNA and a plasma sample for genotyping will be 
collected.  If failure is confirmed, plasma from the Virologic Failure 
Confirmation Visit should be sent to Northwestern for real-time genotyping at 
Quest Diagnostics. RT/protease + integrase if in Arm 1; RT/protease only if in 
Arm 2. See details in the Laboratory Processing Chart (LPC). 
                       Stored Plasma for Virology: Single Copy HIV-1 Assay:  
Plasma samples will be stored to measure HIV-1 by single copy assay at Entry, Week 
24, Week 48, and at time of study premature discontinuation. HIV-1 single copy assay 
will be performed at premature discontinuation only if HIV RNA is < 20 copies/mL  
 
Samples should be stored at each site and batch shipped to the laboratory of Dr. 
Jonathan Li at two time-points: 1) after all subjects at the site complete Week 24 and; 
2) after all subjects at the site complete Week 48.  See details in the LPC.  
   
PBMCs (Substudy in patients enrolled at Northwestern University) 
PBMCs will be processed and stored for possible evaluation of HIV reservoir dynamics 
e.g by measuring changes in total and integrated DNA in PBMC 
 
6.3.9 Adherence Assessment  
 
 
 
Adherence to all study medications will be assessed by self-report.   Sites will provide 
adherence reinforcement, according to local standard practice throughout the study. 
Subjects with poor adherence will be provided counseling by the site.   
 
Time of last dose of study medications and time of plasma collection will be recorded at 
the study visits where adherence assessments  are completed.   
 
 
6. 3.10  Storage of Plasma and Serum for potential future studies 
 
Plasma and serum samples will be stored for possible evaluation of changes in soluble 
and cellular markers of inflammation, immune activation, bone turnover and renal 
tubular toxicity, and for possible targeted pharmacokinetic studies. The specific 
biomarkers are to be determined. Date and time of samples collected and last dose of 
study drugs will be recorded.  The samples will be shipped and stored at the study 
repository at Northwestern University. 
 
 
 
 
 
 
 
 
 


 
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7.0 
CLINICAL MANAGEMENT ISSUES 
7.1 
Toxicity Management 
 
Criteria for subject management, dose interruptions, modifications, and discontinuation of 
study treatment will be mandated only for toxicities attributable to study-provided drugs (i.e., 
DTG and lamivudine in Arm 1). If any individual study-provided drug must be interrupted or 
discontinued due to toxicity, then the entire regimen must be interrupted or discontinued. 
Toxicities that occur in subjects randomized to continuation of their ART regimen (Arm 2) will 
be managed according to standard practice by the site investigator. If the site investigator 
intends to substitute one or more drugs in Arm 2 for toxicity management, the ASPIRE study 
team must be consulted for approval at aspire-team@googlegroups.com ,  
 
The grading system for drug toxicities is the DAIDS Table for Grading the Severity of Adult and 
Pediatric Adverse Events, Version 2.0, November 2014,  located at                              
http://rsc.tech-res.com/safetyandpharmacovigilance/gradingtables.aspx.  NOTE: The 
ASPIRE protocol team must be notified by e-mail regarding toxicities that result in regimen 
interruption or discontinuation. Email: aspire-teamgooglegroups.com.    
 
The general guidelines presented in sections 7.1.1 to 7.1.3 apply to toxicities that are not 
specifically discussed further below. Subjects randomized to continuation of their current 
regimen should be managed according to standard practice by the site investigator.  
 
7.1.1 Grade 1 or 2 Toxicity 
 
Subjects who develop a Grade 1 or 2 adverse events (AE) or toxicity may continue 
DTG and lamivudine without alteration of the dosage. If a subject chooses to 
discontinue study treatment, the site should complete the Premature Treatment 
Discontinuation evaluations, notify the ASPIRE protocol team, and encourage the 
subject to attend all remaining study visits. 
 
7.1.2 Grade 3 Toxicity 
 
Asymptomatic Grade 3 abnormalities must be evaluated and managed by the site 
investigator. It may be necessary to hold all study drugs. Consultation with the ASPIRE 
protocol team is encouraged. The ASPIRE protocol team must be notified by e-mail 
regarding toxicities that result in a change in regimen. Asymptomatic elevations of 
triglycerides or cholesterol do not require treatment discontinuation. If the site 
investigator has compelling evidence that the AE was NOT caused by a study drug, 
dosing may continue. If study drugs are held, the subject should be re-evaluated 
closely until the AE returns to Grade <2, at which time study treatment may be 
reintroduced at the discretion of the site investigator or according to standard practice.  
 
If the site investigator determines that a Grade 3 AE or toxicity is an isolated event, the 
site has the option of confirming the toxicity before holding study treatment. 
 
If the same Grade 3 AE recurs within 4 weeks or reintroducing study drugs, the 
implicated study regimen must be permanently discontinued. If the same Grade 3 AE 
recurs after 4 weeks, but is not thought to be related to DTG or lamivudine, the 
management scheme outlined above may be repeated. 
 
 


 
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Subjects who develop symptomatic Grade 3 AE or toxicity thought to be related to 
study treatment should have both DTG and lamivudine discontinued. If the site 
investigator has compelling evidence that the AE has NOT been caused by DTG or 
lamivudine, dosing may resume when the AE has resolved to Grade ≤2. The ASPIRE 
protocol team must be consulted.   
 
Subjects experiencing Grade 3 AEs requiring permanent discontinuation of study 
treatment should be followed closely until resolution of the AE. The ASPIRE protocol 
team must be notified and the subject should be encouraged to attend all remaining 
study visits and continue other study evaluations according to the protocol. 
 
7.1.3 Grade 4 Toxicity 
 
Subjects who develop a Grade 4 AE or toxicity thought to be related to study treatment 
will have both DTG and lamivudine discontinued. If the site investigator has compelling 
evidence that the AE has NOT been caused by DTG or lamivudine, dosing may 
resume when the AE has resolved to Grade ≤2. The ASPIRE protocol team must be 
consulted.   
 
Subjects experiencing Grade 4 AEs requiring permanent discontinuation of study 
treatment should be followed closely until resolution of the AE to Grade ≤2, and the 
protocol team must be consulted.  The subject should be encouraged to attend all 
remaining study visits and continue other study evaluations according to the protocol.  
 
7.1.4 Discontinuation of DTG  
 
Discontinuation of DTG for suspected drug induced liver injury (DILI), other clinically 
significant liver chemistry elevations, severe skin reaction or hypersensitivity reaction, 
subjects should not restart DTG due to the risk of a recurrent reaction; such subjects 
should be withdrawn from the study treatment and be reviewed for alternative 
antiretroviral therapy.  The subject should be encouraged to attend all remaining study 
visits and continue other study evaluations according to the protocol.     
 
7.2   Rash 
 
Mild to moderate rash may occur with DTG-containing ART, generally occurring within the first 
ten weeks of therapy, and only rarely requiring discontinuation of therapy. The rash tends to 
resolve within two to three weeks. The index case of DTG hypersensitivity, which is the only 
case reported to date, involved a profuse, purpuric and coalescing leukocytoclastic vasculitis 
as well as clinically significant liver chemistry elevations. Other than this case, no other 
instances of serious skin reaction, including Stevens-Johnson Syndrome (SJS), Toxic 
Epidermal Necrolysis (TEN) and erythema multiforme, have been reported for DTG in clinical 
trials. The rash and any associated symptoms should be reported as adverse events and 
appropriate toxicity ratings should be used to grade the events (based on DAIDS toxicity 
gradings). If the etiology of the rash can be definitely diagnosed as being unrelated to study 
drugs and due to a specific medical event or a concomitant non-study medication, routine 
management should be performed and documentation of the diagnosis provided.  
 
7.2.1 Grade 1  
Subjects with an isolated Grade 1 rash may continue DTG at the Investigator’s 
discretion. The subject should be advised to contact the Investigator immediately if 


 
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there is any worsening of the rash, if any systemic signs or symptoms worsen, or if 
mucosal involvement develops. 
 
7.2.2 Grade 2 .  
Subjects may continue study drugs for an isolated Grade 2 rash. However, study drugs 
(and all other concurrent medication(s) suspected in the investigator’s causality 
assessment) should be discontinued for any Grade 2 rash that is associated with an 
increase in ALT. The subject should be advised to contact the physician immediately if 
rash fails to resolve (after more than two weeks), if there is any worsening of the rash, 
if any systemic signs or allergic symptoms develop, or if mucosal involvement 
develops.  
 
7.2.3 Grade 3 or 4  
Subjects should permanently discontinue study drugs (and all other concurrent 
medication(s) suspected in the investigator’s causality assessment) for an isolated 
Grade 3 or 4 rash. Subjects should be treated as clinically appropriate and followed 
until resolution of the AE. 
 
7.3 
Nausea/Vomiting 
 
Nausea/vomiting of any grade may be treated symptomatically with oral antiemetics or 
antiemetic suppositories. For Grade ≥3 nausea or vomiting thought to be secondary to study 
drugs that fails to improve on antiemetics to Grade ≤2, all study drugs must be held until 
Grade ≤2. If Grade ≥3 nausea or vomiting recurs with reinstitution of study drugs or persists 
beyond 14 days despite symptomatic management, then study treatment must be 
discontinued and the protocol team consulted. 
 
7.4 
AST/ALT Elevations 
 
7.4.1 Grade 1 or 2 
  
 
Study treatment may be continued for asymptomatic, isolated Grade 1 or 2 AST/ALT 
elevations, at the discretion of the site investigator.  
 
Careful assessments should be done to rule out the use of alcohol, non-study drug-
related drug toxicity or viral hepatitis as the cause of liver chemistry  elevation. 
Evaluations to be considered (but are not required) include: Viral hepatitis serology 
including: Hepatitis A IgM antibody; Hepatitis B Surface Antigen (HBsAg) and Hepatitis 
B Core Antibody (IgM); Hepatitis C RNA; Hepatitis E IgM antibody; Cytomegalovirus 
IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); Syphilis screening; Drugs of abuse screen 
including alcohol; Serum acetaminophen test; Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH);Anti-nuclear antibody, anti-smooth muscle antibody, 
and Type 1 anti-liver kidney microsomal antibodies; Liver imaging (ultrasound, 
magnetic resonance, or computerized tomography) 
 
7.4.2. Liver Chemistry Stopping and Follow-up Criteria 
 
Liver chemistry threshold stopping criteria have been designed to assure subject safety 
and to evaluate liver event etiology. Study drugs will be stopped if any of the following 


 
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liver chemistry criteria are met: 
- ALT ≥3 x ULN and bilirubin ≥2 x ULN (>35% direct bilirubin; bilirubin fractionation 
required) 
 NOTE: serum bilirubin fractionation should be performed if testing is 
available. If testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver 
injury. If testing is unavailable and a subject meets the criterion of total bilirubin 
≥ 2xULN, then the event meets liver stopping criteria; 
- ALT ≥8 x ULN; 
- ALT ≥3 x ULN (if baseline ALT is < ULN) with symptoms or worsening of acute 
hepatitis or hypersensitivity such as fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, or eosinophilia, OR; 
- ALT ≥3 x baseline ALT with symptoms or worsening of acute hepatitis or 
hypersensitivity such as fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, or eosinophilia; 
- ALT ≥5 x ULN and <8 x ULN that persists > 2 weeks (with bilirubin <2 x ULN and 
no signs or symptoms of acute hepatitis or hypersensitivity); 
- ALT ≥5 x ULN but <8 x ULN and cannot be monitored weekly for >2 weeks;  
 
Subjects who develop ALT ≥5 x ULN should be followed weekly until resolution or 
stabilization (ALT <5 x ULN on 2 consecutive evaluations). 
 
When liver chemistry stopping criterion is met, do the following: 
- Immediately discontinue DTG. Subjects should not restart DTG due to the risk of a 
recurrent reaction.  
- Report the event to the study team within 24 hours of learning its occurrence  
- Complete the GSK Liver Event CRF and SAE CRF where applicable 
- Complete the GSK Liver Imaging and/or Liver Biopsy CRFs if these tests are 
performed; 
- Perform liver event follow up assessments, and monitor the subject twice weekly 
until liver chemistries resolve, stabilize, or return to baseline values;  
- Make every reasonable attempt to have subjects return to clinic within 24 hours for 
repeat liver chemistries, liver event follow up assessments, and close monitoring; 
- A specialist or hepatology consultation is recommended; 
-     Subjects should continue to be followed off study treatment for the duration of         
      the study.  The subject should be encouraged to attend all remaining study   
      visits and continue other study evaluations according to the protocol 
Consider the following to further evaluate the liver event: 
- Tests listed in section 7.4.1 above 
- Record the appearance or worsening of clinical symptoms of hepatitis, or 
hypersensitivity, fatigue, decreased appetite, nausea, vomiting, abdominal pain, 
jaundice, fever, or rash as relevant on the AE report form; 
- Record use of concomitant medications, acetaminophen, herbal remedies, other 
over the counter medications, or putative hepatotoxins, on the concomitant 
medications report form. 
- Record alcohol use on the GSK Liver Event Alcohol Intake CRF.    
 
7.5 
Creatinine 
 
DTG initiation is typically associated with an increase in serum creatinine levels of 
approximately 0.11-0.14 mg/dL, which is attributable to DTG’s inhibition of tubular secretion of 


 
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creatinine. As this change is not associated with an actual decline in glomerular filtration rate 
as measured by iohexol clearance, no treatment change is indicated. Subjects should be 
counseled about this expected increase before initiating study medications. Lamivudine 
requires dose adjustment for calculated creatinine clearance (CrCl) <50 mL/min 
 
Subjects who have an increase in creatinine of one grade should be carefully evaluated for 
causes of change in renal function but may continue on study treatment. 
  
The protocol team must be consulted if a subject has an increase in creatinine of 2 grades or 
more. If the increase in creatinine is considered to be due to causes other than study 
treatment, study treatment may be continued after approval by the team. 
  
If lamivudine is continued despite confirmed calculated CrCl <50 mL/min, dosing will be 
adjusted per the package insert. The protocol team must be consulted if a subject requires 
dialysis while on study. The subject must permanently discontinue study treatment and will be 
encouraged to remain on study/off study treatment. Further evaluation and management 
should proceed at the discretion of the site investigator.   
 
7.6       Allergic Reaction  
 
Subjects may continue study medication for Grade 1 or 2 allergic reactions at the discretion of 
the site investigator. The subject should be advised to contact the investigator immediately if 
there is any worsening of symptoms or if further systemic signs or symptoms develop. 
Antihistamines, topical corticosteroids, or antipruritic agents may be prescribed at the 
discretion of the site investigator.  
 
Subjects with ≥Grade 3 allergic reactions that are considered to be possibly or probably 
related to the study medications should permanently discontinue study medications and 
continue to be followed off-study medications, on-study. Subjects should be treated as 
clinically appropriate and followed until resolution of the AE. 
 
7.7 
Suicidal Ideation or Behaviors 
 
 
If any subject experiences a possible suicidality-related adverse event while 
participating in this study that is considered by the Investigator to meet International 
Conference on Harmonization (ICH)-E2A definitions for seriousness, the Investigator 
will collect information using a GSK Possible Suicidality Related Adverse Event (PSRAE) CRF 
form in addition to reporting the event on an Event CRF form. A PSRAE may include, but is 
not limited to, an event that involves suicidal ideation, a preparatory act toward imminent 
suicidal behaviour, a suicide attempt, or a completed suicide. The investigator will exercise his 
or her medical and scientific judgment in deciding whether an event is possibly suicide-related. 
PSRAE forms should be completed and reported within one week of the investigator 
diagnosing a possible suicidality-related adverse event. 
 
7.8. 
Pregnancy 
 
If a subject becomes pregnant after study entry, the IND Sponsor (Dr. Babafemi Taiwo) should 
be notified as soon as the site investigator becomes aware of this development using the GSK 
Pregnancy Notification Form. The IND Sponsor will forward the completed GSK Pregnancy 
Notification Form to ViiV within 7 days of receipt. Study medications must be discontinued and 
arrangements made for alternative ART, which should be prescribed at the discretion of the 


 
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site investigator. The pregnant subject should come in for a premature discontinuation of study 
treatment visit within 14 days after stopping study medications. Pregnant subjects who choose 
to stay on study will continue to be followed on study/off study treatment, but do not require 
blood draws for stored samples. They also will not have to complete the adherence 
questionnaire.  
 
The pregnancy must be followed up to determine outcome (including premature termination) 
and status of mother and child, which must also be reported to the IND Sponsor using the 
GSK Pregnancy Follow-up Form. Pregnancy complications and elective terminations for 
medical reasons must be reported as an AE or EAE. Spontaneous abortions must be reported 
as an EAE. Any EAE occurring in association with a pregnancy brought to the investigator’s 
attention after the subject has completed the study and considered by the investigator as 
possibly related to the investigational product, must be promptly reported to the IND Sponsor.   
 
If a woman has completed the study or chooses to discontinue from the study before the end 
of the pregnancy, site staff should request permission to contact her regarding pregnancy 
outcomes at the end of pregnancy. If the information is obtained, pregnancy outcomes will be 
submitted on a CRF at the end of the pregnancy.   
 
Pregnancies that occur on study should be reported to The Antiretroviral Pregnancy Registry 
as well. Intrapartum complications and/or pregnancy outcome should be recorded on the 
CRFs up to week 48 and also reported to The Antiretroviral Pregnancy Registry. More 
information is available at www.apregistry.com. Phone: 800-258-4263; Fax: 800-800-1052. 
 
8.0 
CRITERIA FOR DISCONTINUATION 
8.1 Permanent Study Treatment Discontinuation 
 
• 
Drug-related toxicity requiring permanent study treatment discontinuation (see section 7.0) 
• 
Requirement for prohibited concomitant medications (see section 5.4) 
• 
Requirement to start hepatitis C treatment 
• 
Pregnancy 
• 
Breast-feeding  
• 
Completion of treatment as defined in the protocol 
• 
Request by subject to terminate treatment 
• 
Clinical reasons believed life threatening by the physician, even if not addressed in the 
toxicity section of the protocol 
• 
Failure by the subject to attend 2 consecutive clinic visits 
 
8.2 Premature Study Discontinuation 
 
• 
Request by the subject to withdraw 
• 
Request of the primary care provider or investigator if s/he thinks the study is no longer in 
the best interest of the subject 
• 
Subject judged by the investigator to be at significant risk of failing to comply with the 
provisions of the protocol as to cause harm to self or seriously interfere with the validity of 
the study results 
• 
At the discretion of the IRB, FDA,  IND sponsor,  or pharmaceutical supporters  
 


 
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9.0 
STATISTICAL CONSIDERATIONS 
 
9.1 General Design Issues 
ASPIRE is a prospective, open-label, randomized, multicenter, 48-week study to explore whether 
HIV-infected subjects with  no history of virologic failure, and HIV RNA <50 copies/mL for at 
least 48 weeks on any DHHS recommended,  alternative, or other three-drug regimen will 
maintain viral suppression after switching to DTG + lamivudine.   Subjects must have plasma 
HIV-1 RNA levels less than 20 copies/mL within 45 days of study entry and a pretreatment 
genotype documenting absence of any NRTI mutation. .     
  
 
9.2 Endpoints 
 
9.2.1 Primary Endpoint:  
 
Virologic failure defined as confirmed viral load >50 copies/mL before or at Week 24  
. 
9.2.2 Secondary Endpoints 
 
9.2.2.1  Change in CD4 count from baseline to Weeks 24 and 48. 
 
9.2.2.2  Confirmed viral rebound to >20 copies/mL, >50 copies/mL and >200 copies/mL 
at any time up to or including Week 48   
 
9.2.2.3   Drug resistance associated mutations in subjects with virologic failure    
 
9.2.2.4  Laboratory Toxicities or clinical adverse events of Grade 3 or higher, or of any 
grade which led to a permanent change or discontinuation of study treatment 
regimen. 
 
9.2.2.5. Change in residual viremia as measured by single copy assay 
 
9.2.2.6  Adherence measured by self-report of missed doses  
 
9.2.2.7 Potential exploratory studies if primary hypothesis is proven: 
-Change in markers of inflammation/activation.  
 -Change in reservoir size  
 
 
 
 -Change in markers of bone turnover and renal tubular toxicity  
  
9.3 
Randomization and Stratification – 
 
Subjects will be randomized 1:1 to DTG plus lamivudine (Arm 1) or continuation of their 
current regimen (Arm 2) for 48 weeks.   
 
9.4  
Sample size and Accrual 
 
With a sample size of 41 subjects/arm, the study will have 80% power to show non-
inferiority of DTG + lamivudine compared to DHHS regimen using a 12% non-inferiority 
margin.  The following assumptions are used in the sample size calculation:  
 
I. Non-inferiority will be assessed with a one-sided 5% type I error rate.  


 
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II. The cumulative probability of virologic failure by Week 24 is estimated to be 5% for 
both arms. 
 
   Assuming a lost to follow-up rate of 10% for each arm, the target sample size is   
  45 subjects/arm or 90 in total.  
 
 
 
It is anticipated that the study will meet its accrual target in 3 to 6 months.  
 
9.5 
Monitoring 
 
An independent Data Monitoring Committee will evaluate virologic and safety data after 
the first 45 patients reach week 12.   
 
9.6 
Analyses 
 
9.6.1  Primary Anaysis 
Among suppressed HIV patients with no history of virologic failure, and HIV RNA <50 
copies/mL for at least 48 weeks on any DHHS recommended, alternative, or other 
three-drug regimen, we will compare virologic failure rate, defined as confirmed HIV 
RNA >50 copies/mL by week 24 between those who continue their DHHS regimen 
versus those who switch to DTG + lamivudine 
 
For primary analysis, we will use the FDA snapshot approach in which a subject is 
considered a failure if any of the following occurs during the analysis period: virologic 
failure (i.e., confirmed viral load > 50 copies/mL); loss to follow up; or 
discontinuation/modification of randomized treatment. A secondary analysis will also be 
conducted, wherein a subject is considered censored at the time of loss to follow-up or 
discontinuation/modification of study treatment.  
9.6.2 Secondary Analyses  
 
For secondary analyses, we will compare between Arm 1 and Arm 2: 
9.5.2.1 Change in CD4 count from baseline to weeks 24 and 48  
 
9.5.2.2  Proportion of subjects with HIV RNA >20, >50, and >200 copies/mL at weeks 
24 and 48. The proportion of subjects with these levels of viremia will be plotted by 
time over the course of the study  
 
9.5.2.3 HIV resistance among those with confirmed viral rebound to > 50 copies/mL 
 
9.5.2.4 Incidence of clinical and/or laboratory toxicities.  
The safety and tolerability measures will include: 
-  
Time to discontinuation of any study medication due to adverse events (AEs), -- 
Proportion of Grade 3 or Grade 4 clinical AEs,  
-  
Proportion of Grade 3 or Grade 4 laboratory abnormalities,  
-  
Summaries of all treatment-related AEs.  
 
9.5.2.5 Subject-specific changes in HIV-1 viremia using single-copy assay from 
baseline to weeks 24 and 48. Correlations between viremia detected by the single copy 
assay and protocol defined virologic failure as well as viral rebound to >20 copies/mL, 


 
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20-50 copies/mL and > 200 copies/mL will be determined 
 
9.5.2.6 Descriptive statistics of the number of missed doses (over the past 4 days) at 
weeks 4, 12, 24, 36, 48 
 
9.5.2.7 (Possible future analyses) 
a. Other measures of the HIV reservoir size  
b. Soluble and cellular markers of immune activation and inflammation 
c. Markers of bone turnover and renal tubular toxicity 
 
10.0 
PHARMACOLOGY PLAN 
 
Not applicable. 
 
11.0 
DATA COLLECTION AND MONITORING AND ADVERSE EVENT REPORTING 
11.1 
Records to Be Kept 
 
CRFs will be provided for each subject. Subjects must not be identified by name on 
any CRFs. Subjects will be identified by the Patient Number and Screening Number 
provided upon registration. 
11.2 
Role of Data Management 
 
11.2.1 Instructions concerning the recording of study data on CRFs will be provided by the 
central data management team at Northwestern University. The Research Electronic  
Data Capture (REDCap)  data management system will be used.   
11.2.2 It is the responsibility of the central data management team to assure the quality of 
computerized data for the study. This role extends from protocol development to 
generation of the final study databases.  The REDCap data management system will 
be used for data entry, data queries, and data reports.   
11.3 
Clinical Site Monitoring and Record Availability 
 
11.3.1 Site monitors under contract to the Northwestern University will visit participating 
clinical sites to review the individual subject 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 subjects, compliance with the protocol, and accuracy and completeness of 
records. The monitors also will inspect sites’ regulatory files to ensure that regulatory 
requirements are being followed and sites’ pharmacies, and to review product storage 
and management. 
11.3.2 The site investigator will make study documents (e.g., consent forms, drug distribution 
forms, CRFs) and pertinent hospital or clinic records readily available for inspection by 
the local IRB, the site monitors, the FDA, the OHRP, and the pharmaceutical 
supporter(s) or designee for confirmation of the study data.  


 
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11.4 
Expedited Adverse Event Reporting  
 
The adverse events (AEs) that must be reported in an expedited fashion to the IND Sponsor 
(Dr. Babafemi Taiwo at Northwestern University)  are all serious adverse events (SAEs) as 
defined by International Conference on Harmonization (ICH) guidelines regardless of 
relationship to the study agent(s).   
 
SAEs as defined by ICH guidelines are: deaths, life-threatening events, events that require 
hospitalization or prolongation of hospitalization, events that result in persistent or significant 
disability or incapacity, and congenital anomalies or birth defects. Important medical events as 
assessed by medical and scientific judgment may also be considered SAEs by the investigator 
and should be reported in an expedited fashion.  Possible drug-induced liver injury is also 
considered an SAE in this study and requires expedited reporting. 
The study agents that must be considered in determining relationships of AEs requiring 
expedited reporting to the IND Sponsor are DTG and lamivudine.  
 
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE 
Grading Table), Version 2.0, November 2014, must be used and is available at 
http://rsc.tech-res.com/safetyandpharmacovigilance/gradingtables.aspx.    
 
Any SAE occurring during the study up to 28 days post the last dose of study drug must be 
documented on the GSK Serious Adverse Events Form with Toxicity Grading and faxed to the 
IND Sponsor, Dr. Babafemi Taiwo, at 1-312-695-5088 within 24 hours of awareness.  The IND 
Sponsor and the ASPIRE Research Manager should be alerted about the faxed form by 
sending an email to b-taiwo@northwestern.edu and baiba@northwestern.edu with the title: 
ASPIRE SAE REPORT. The IND Sponsor will forward the completed SAE Form to ViiV 
immediately upon receipt.  
   
The FDA also requires sponsors to submit a written Safety Report of all serious and 
unexpected AEs to all participating investigators of a trial.  All participating investigators, at all 
sites, will be notified of any unexpected SAEs occurring at other sites, in an IND Safety Report 
from the IND Sponsor.   The IND Sponsor will also notify investigators of any revisions to the 
protocol or to the consent, or study closure. The study investigators in this study have the 
responsibility of promptly reporting all SAEs so that IND Sponsor can comply with these 
regulations. 
 
The protocol-defined expedited event reporting period for this protocol is the entire study 
duration for an individual subject (from study enrollment until study completion or 
discontinuation of the subject from study participation for any reason). 
 
After the end of the protocol-defined reporting period stated above, sites must report serious, 
unexpected, suspected adverse drug reactions if the study site staff becomes aware of the 
event on a passive basis, i.e., from publicly available information. 
 
12.0 
HUMAN SUBJECTS 
12.1 
Institutional Review Board (IRB) Review and Informed Consent 
 
This protocol and the informed consent document (Appendix II) and any subsequent 
modifications will be reviewed and approved by each local IRB or ethics committee 
responsible for oversight of the study. A signed consent form will be obtained from the subject 


 
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(or 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 consent form will be given to 
the subject or legal guardian, and this fact will be documented in the subject’s record. 
 
12.2 
Subject Confidentiality 
 
All laboratory specimens, evaluation forms, reports, and other records that leave the site will 
be identified by coded number only to maintain subject confidentiality. All records will be kept 
locked. All REDCap entry 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 
the IRB, the FDA, or the IND sponsor.  
12.3 
Study Discontinuation 
 
The study may be discontinued at any time by the IRB, the IND Sponsor, pharmaceutical 
supporters, the FDA, or other government agencies as part of their duties to ensure that 
research subjects are protected.  
13.0 
PUBLICATION OF RESEARCH FINDINGS 
Publication of the results of this trial will be governed by Northwestern University policies. Any 
presentation, abstract, or manuscript will be made available for review by the pharmaceutical 
supporters prior to submission.  
14.0 
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 shipping and 
handling of all specimens for this study, as currently recommended by the Centers for Disease 
Control and Prevention and the NIH. 
All dangerous goods materials, including diagnostic specimens and infectious substances, 
must be transported using packaging mandated by CFR 42 Part 72. Please refer to 
instructions detailed in the International Air Transport Association (IATA) Dangerous Goods 
Regulations.  
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integrase impair the emergence of resistance against reverse transcriptase inhibitors. AIDS 
2014; 28(6):813-9. 
32. Quashie PK, Mesplede T, Han YS, et al. Characterization of the R263K mutation in HIV-1 
integrase that confers low-level resistance to the second-generation integrase strand transfer 
inhibitor dolutegravir. J Virol 2012; 86(5): 2696-705. 
33. Mesplede T, Quashie PK, Osman N, et al. Viral fitness cost prevents HIV-1 from evading 
dolutegravir drug pressure. Retrovirology 2013; 10:22. 
34. Osterholzer DA, Goldman M.Dolutegravir: A Next-Generation Integrase Inhibitor for Treatment 
of HIV Infection. Clin Infect Dis. 2014 Jul 15;59(2):265-71. 
35. Lewis W, Kohler JJ, Hosseini SH, et al. Antiretroviral nucleosides, deoxynucleotide carrier and 
mitochondrial DNA: evidence supporting the DNA pol gamma hypothesis. AIDS. 2006;20:675-
684. 
36. Letendre S, Marquie-Beck J, Capparelli E, et al. Validation of the CNS Penetration-
Effectiveness rank for quantifying antiretroviral penetration into the central nervous system. 
Arch Neurol. 2008 Jan;65(1):65-70. 


 
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37. Else LJ, Taylor S, Back DJ, et al.Pharmacokinetics of antiretroviral drugs in anatomical 
sanctuary sites: the male and female genital tract. Antivir Ther. 2011;16(8):1149-67. 
38. European Guidelines for treatment of HIV infected adults in Europe, version 6.1. 
http://www.europeanaidsclinicalsociety.org/images/stories/EACS-Pdf/EacsGuidelines-v6.1-
2edition.pdf. Accessed 2 May, 2013.  
39. Cahn P, Andrade-Villaneuva J, Arribasa Jose, et al. et al (GARDEL Dual therapy with lopinavir 
and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two 
nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 
infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial. The 
Lancet Infectious Diseases 2014; 14(7): 572 - 580 
40. Gatell J, Arribas J, Girard P, et al. Non-inferiority of dual-therapy (DT) with lopinavir/ritonavir 
(LPV/r) plus lamivudine (3TC) vs. triple-therapy (TT) with LPV/r plus two nucleos(t)ides 
(NRTIs) for maintenance of HIV viral suppression: 48-week results of OLE study. 8th IAS 
Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, 
Melbourne. July 20-25, 2014. Abstract LBPE17.  
41. Perez-Molina J, Rubio R, Rivero A, et al. Switching to dual therapy 
(atazanavir/ritonavir+lamivudine) vs. standard triple therapy (atazanavir/ritonavir+2 
nucleos[t]ides) is safe and effective in virologically suppressed patients: 48-week results of a 
randomized clinical trial (SALT study). 8th IAS Conference on HIV Pathogenesis, Treatment 
and Prevention, June 30-July 3, 2013, Melbourne. July 20-25, 2014. Abstract BPE18. 
42. Vernazza P, Daneel S, Schiffer V, et al. The role of compartment penetration in PI-
monotherapy: the Atazanavir-Ritonavir Mono maintenance (ATARITMO) Trial. AIDS. 
2007;21(10):1309. 
43. Karlström O, Josephson F, Sönnerborg A. Early virologic rebound in a pilot trial of ritonavir-
boosted atazanavir as maintenance monotherapy. J Acquir Immune Defic Syndr. 
2007;44(4):417. 
44. Clumeck N, Rieger A, Banhegyi D, et al. 96 week results from the MONET trial: a randomized 
comparison of darunavir/ritonavir with versus without nucleoside analogues, for patients with 
HIV RNA <50 copies/mL at baseline. J Antimicrob Chemother. 2011 Aug;66(8):1878-85.  
45. Katlama C, Valantin MA, Algarte-Genin M, et al. Efficacy of darunavir/ritonavir maintenance 
monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority 
trial, MONOI-ANRS 136. AIDS. 2010;24(15):2365. 
46. Castagna A, Spagnuolo V, Galli L, et al. Simplification to atazanavir/ritonavir monotherapy for 
HIV-1 treated individuals on virological suppression: the MODAt trial. AIDS. 2014 Jul 23. Epub 
ahead of print. 
47. Letendre S, Mills A, Tashima K, et al. Distribution and Antiviral Activity in Cerebrospinal Fluid 
(CSF) of the Integrase Inhibitor, Dolutegravir (DTG): ING116070 Week 16 Results. 20th 
Conference on Retroviruses and Opportunistic Infections, Atlanta GA 2013, Abstract LB 178. 
48. Best BM, Letendre SL, Brigis E, et al. Low atazanavir concentrations in cerebrospinal fluid. 
AIDS 2009;23(1):83-7 
49. Calcagno A, Yilmaz A, Cusato J, et al. Determinants of darunavir cerebrospinal fluid 
concentrations: impact of once-daily dosing and pharmacogenetics. AIDS 2012;26(12):1529-
33 
 
 
 


 
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APPENDIX I: SAMPLE INFORMED CONSENT: Version 2.0, dated 6/15/2015 
 
Protocol Title:  
Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce drug Exposure (ASPIRE) 
Study  
 
 
Principal Investigator and IND Sponsor:  
Babafemi Taiwo, M.B.B.S. 
Northwestern University 
 
Financial Support provided by: ViiV Healthcare 
 
 
INTRODUCTION 
 
You are being asked to take part in this research study because you have human immunodeficiency 
virus (HIV), the virus that causes AIDS, and are on HIV treatment that is keeping the virus well 
controlled. Dr. Babafemi Taiwo at Northwestern University is the study sponsor with financial support 
provided by ViiV.  The doctor in charge of this study at this site is: (insert name of Principal 
Investigator). Before you decide if you want to be a part of this study, we want you to know about the 
study.  
 
This is a consent form. It gives you information about this study. The study staff will talk with you 
about this information. You are free to ask questions about this study at any time. If you agree to take 
part in this study, you will be asked to sign this consent form. You will get a copy to keep. 
 
WHY IS THIS STUDY BEING DONE? 
 
Recommended treatment regimens for a person with HIV infection contain three active HIV drugs. 
Most people who take these medications regularly have a good result, which is usually determined by 
measuring the amount of HIV in the blood (viral load). The desired response is when the level of HIV 
is reduced to very low levels in the blood. Treatment of HIV is life-long. Since some HIV medications 
have side effects and are costly, there is interest in whether HIV can be successfully controlled with 
fewer than three HIV drugs.  
 
The main purpose of this study is to evaluate how well a combination of two study drugs (DTG plus 
3TC) will keep HIV suppressed in the blood of patients who are currently taking three HIV drugs and 
have a very low viral load. The study will also look at the safety and tolerability of this study drug 
combination, and how well patients are able to take the study drugs on schedule. In addition to a 
standard test used to measure blood HIV levels in the clinic, the study will use a very sensitive 
research test that can detect as little as one HIV virus in each milliliter of blood. This test is called the 
single copy assay and is currently used for research only. This very sensitive test will help to better 
see the effect that changing from three active HIV drugs to the two study drugs has on very low levels 
of HIV in the blood.   
 
The drugs used in this study are dolutegravir (DTG, Tivicay) and lamivudine (3TC, Epivir). 
DTG is an integrase inhibitor (a type of HIV drug) and is approved by the Food and Drug 
Administration (FDA) for HIV treatment. 3TC is a nucleoside reverse transcriptase inhibitor (another 
type of anti-HIV drug) that is also approved by the FDA for HIV treatment. Both DTG and 3TC are 


 
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currently part of recommended regimens for treatment of HIV along with a third active drug. However, 
the two-drug combination has not been tested before, and this is the purpose of this study.  
 
WHAT DO I HAVE TO DO IF I AM IN THIS STUDY? 
 
If you agree to join this study, you will be asked to sign this consent form. After you have signed the 
form, you will be asked some questions and will undergo some tests at a screening visit to see if it is 
safe for you to join the study. The screening visit will take about 30-60 minutes. 
 
Screening 
 
You will have a clinical assessment that will include questions about your health and any 
medicines you have taken in the last 30 days.  About 30 mL (2 tablespoons) of blood will be 
drawn for the following tests: 
• 
Routine blood count and chemistry tests, HIV viral load, and hepatitis B test (a virus that can 
affect your liver).  
• 
10 mL of blood (about 2 teaspoons) will be stored indefinitely for future tests.  
• 
You will be asked to give a urine specimen.   
 
Entry 
 
Only patients who have HIV below a certain level at the screening visit will be able to participate 
in this study. If you have met all the requirements to enter the study, you will come to the clinic 
at least 24 hours after your screening evaluation, but within 45 days of your screening visit, for 
entry evaluations. This visit will last about 30-60 minutes.  
• 
You will be asked about any medicine changes you have had since screening. 
• 
You will have a physical exam.  The clinic staff will check your height and weight, and vital 
signs such as temperature, blood pressure, and pulse.   
• 
You will have about 30 mL (2 tablespoons) of blood drawn for routine blood tests, HIV viral 
load, hepatitis C test, and CD4 and CD8 cell count (marker of how strong your immune 
system is). Lipid tests (blood fats and cholesterol) will be done, so you must not have 
anything to eat or drink, except water and required prescription medications, for at least 8 
hours before coming to the clinic. 
• 
About 30 mL (2 tablespoons) of blood will be drawn for the HIV single copy assay 
• 
About 20 ml (4 teaspoons) will be drawn and stored indefinitely for possible future studies to 
evaluate how changing to the two study drugs affects the immune system, bone, and 
kidneys.  
 
• 
You will be randomly assigned (like the toss of a coin) to one of two study groups: 
o Arm 1: Switch your current HIV treatment to the study drugs:  
DTG plus 3TC.  
o Arm 2: Continue taking your current HIV regimen.  
 
You and your study team will know which treatment arm you are on. There are no placebos 
(dummy pills). The study drugs DTG and 3TC will be given to you at this visit only if you are 
assigned to Arm 1; if you are on Arm 2, you will need to continue to provide your own 
medications. You will remain on the assigned study treatment and be followed to the Week 48 
visit.    
 


 
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You will take dolutegravir and 3TC at the same time once a day by mouth. You can take the 
drugs with or without food. If you are taking some antacids, laxatives, or iron or calcium 
supplements you will need to take the DTG 2 hours before or 6 hours after these medications. 
Alternatively, you may take iron or calcium supplements at the same time as DTG if taken with 
food. It is essential that you disclose all the medications (prescribed or over-the-counter) and 
supplements that you are taking to your site investigator and discuss the best way to take DTG.  
 
After Entry 
 
After you start taking the study drugs, you will be asked to come to the clinic approximately 4, 12, 24, 
36, and 48 later.  Most visits will last about 30 to 60 minutes.  
 
At most visits, you will: 
- 
Be asked about how you are feeling; if needed, a brief physical exam will be done. 
- 
You will also be asked about how you are taking the study drugs and about changes to any 
other medicines that you may be taking.  
- 
 About 30 mL (2 tablespoons) of blood will be collected for routine blood tests, HIV viral 
load, and CD4 and CD8 cell count.  
- 
In addition, about 20 mL (4 teaspoons) of blood will be stored indefinitely for future virology 
and immunology tests.    
- 
At Weeks 24, and 48, you will have an additional 30 mL (about 2 tablespoons) of blood 
drawn for single copy assay, and for lipid tests, so you must not have anything to eat or 
drink, except water and required prescription medications, for at least 8 hours before 
coming to the clinic at those visits.  
 
If at any point during the study your viral load increases above 50 copies/mL, you will be asked to 
come back in for some additional tests within 35 days. You will also have another viral load test to 
make sure the first one was correct. This visit will last about 30-60 minutes. 
• 
You will be asked about any medicine changes you have had since your last visit. 
• 
You will have a brief physical exam.  
• 
You will have about 30 mL (2 tablespoons) of blood drawn for HIV viral load, and resistance 
testing. 
• 
Blood 40 mL (about 3 tablespoons) will be drawn and stored indefinitely for possible future 
virology, immunology, and study drug level tests. 
• 
You will be asked about how well you are remembering to take your study drugs. You may be 
asked to undergo counseling to improve how well you take your medications 
 
If the repeat blood test is again greater than 50 copies/mL, this will be taken to indicate failure of 
treatment. You may be asked to stop taking the study medications at this point. You doctor will 
be responsible for deciding the best course of treatment for you based on the results of 
resistance tests (how well the virus responds to certain drugs) and other factors.   
 
 
Early study drug or study discontinuation 
If you stop taking the study drugs before the end of the study, you will be asked to continue to be part 
of the study and attend study visits and complete evaluations for the duration of the study.    
 
If you are taken off study early or decide to leave the study early, you will be asked to return to the 
clinic for a final visit. This visit will last about 30-60 minutes. You will have a brief physical exam, and 


 
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have blood drawn (total of about 60 mL, 4 tablespoons) for routine tests, HIV viral load, CD4 and CD8 
cell count, and future tests.  
 
Other 
 
You will be told the results of HIV viral load tests, CD4 and CD8 cell counts, pregnancy tests, and 
routine blood tests done on this study.  
 
Some of your blood will be stored (with usual steps taken to protect your confidentiality) at the study 
repository at Northwestern University and used for possible future testing to evaluate how changing to 
the two study drugs affects the immune system, bone, and kidneys.  The stored sample may also be 
used for other tests to help understand what we find in the study.    
 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
  
About 90 people will take part in this study. 
 
HOW LONG WILL I BE IN THIS STUDY? 
 
You will be on the study for 48 weeks.  
 
WHY WOULD THE DOCTOR TAKE ME OFF THIS STUDY EARLY? 
 
The study doctor may need to take you off the study early without your permission if: 
• 
The study is cancelled by Northwestern University, FDA, the drug company supporting this study 
(ViiV), or the site’s Institutional Review Board (IRB). (An IRB is a committee that watches over the 
safety and rights of research participants.) 
• 
A safety monitoring committee recommends that the study be stopped early.  
 
The study doctor may also need to take you off the study drug(s) without your permission if: 
• 
Continuing the study drugs may be harmful to you. 
• 
You need a treatment that you may not take while on the study. 
• 
You become pregnant or are breast-feeding.  
• 
You are not able to attend the study visits as required by the study 
 
If I have to permanently stop taking study-provided drug, or once I leave the study, how would the 
drug be provided? 
 
During the study: 
If you must permanently stop taking study-provided drug before your study participation is over, the 
study staff will discuss other options that may be of benefit to you. 
 
After the study: 
After you have completed your study participation, the study will not be able to continue to provide 
you with drug you received on the study. If continuing to take these or similar drugs/agents would 
be of benefit to you, the study staff will discuss how you may be able to obtain them. 
 
 
 
 


 
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WHAT ARE THE RISKS OF THE STUDY? 
 
The drugs used in this study may have side effects, some of which are listed below. Please note that 
these lists do not include all the side effects seen with these drugs. These lists include the more 
serious or common side effects with a known or possible relationship. If you have questions 
concerning the additional study drug side effects please ask the medical staff at your site. 
 
There is a risk of serious and/or life-threatening side effects when non-study medications are taken 
with the study drugs. For your safety, you must tell the study doctor or nurse about all medications 
you are taking (including nutritional supplements and herbal medications) before you start the study 
and also before starting any new medications while on the study. Also, you must tell the study doctor 
or nurse before enrolling in any other clinical trials while on this study. 
 
Risks Associated with the Study Drugs 
 
Dolutegravir (Tivicay®) 
The following serious side effects have been associated with the use of dolutegravir : 
 
Allergic reactions. Call your healthcare provider right away if you develop a rash with dolutegravir. 
Stop taking dolutegravir and get medical help right away if you: 
• 
Develop a rash with any of the following signs or symptoms:  
o Fever 
o Generally ill feeling 
o Extreme tiredness 
o Muscle or joint aches 
o Blisters or sores in mouth 
o Blisters or peeling of the skin 
o Redness or swelling of the eyes 
o Swelling of the mouth, face, lips, or tongue 
o Problems breathing 
• 
Develop any of the following signs or symptoms of liver problems:  
o Yellowing of the skin or whites of the eyes 
o Dark or tea-colored urine 
o Pale-colored stools --  bowel movements 
o Nausea or vomiting 
o Loss of appetite 
o Pain, aching, or tenderness on the right side below the ribs 
o If your healthcare provider informs you of changes in liver tests. People with a history of 
hepatitis B or C virus may have an increased risk of developing new or worsening changes 
in certain liver tests during treatment with dolutegravir. Your healthcare provider may do 
tests to check your liver function before and during treatment with dolutegravir. 
 
The most common side effects of dolutegravir include: 
• 
trouble sleeping 
• 
headache 
 
Lamivudine (3TC, Epivir®) 
The following side effects have also been associated with use of lamivudine: 


 
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If you are infected with both Hepatitis B and HIV, you should be aware that your liver function tests 
may increase, and symptoms associated with hepatitis (an acute inflammation of the liver) may 
worsen if lamivudine is stopped.  Although most of these cases have resolved without treatment, 
some deaths have been reported. 
• 
Headache 
• 
Feeling tired  
• 
Dizziness 
• 
Numbness, tingling, and pain in the hands or feet  
• 
Depression 
• 
Trouble sleeping 
• 
Rash 
• 
Upset stomach, vomiting, nausea, loose or watery stools  
• 
Pancreatitis (inflammation of the pancreas), which may cause death. If you develop 
pancreatitis, you may have one or more of the following: stomach pain, nausea, and vomiting.  
• 
Abnormal pancreatic and liver function blood tests 
 
These are not all the possible side effects of the study drugs. For more information, ask your 
healthcare provider or pharmacist. 
Risks of Drawing Blood 
 
Taking blood may cause discomfort, bleeding, and bruising where the blood is drawn. Occasionally, 
there is swelling in the area where the needle enters the body and there is a small risk of infection. 
There is also a risk of lightheadedness, fainting, and blood clots. 
 
ARE THERE RISKS RELATED TO PREGNANCY? 
 
It is not known whether the drug or drug combinations in this study harm unborn babies. If you are 
having sex that could lead to pregnancy, you must agree not to become pregnant or make someone 
else pregnant. Because of the risk involved, you and your partner must use at least one method of 
birth control. You must continue to use birth control until 2 weeks after the study ends. You must 
choose one of the birth control methods listed below: 
• 
Condoms (male or female) with or without a spermicidal agent 
• 
Diaphragm or cervical cap with spermicide 
• 
IUD 
• 
Hormone-based contraception 
 
Some HIV medications can make oral contraceptives less effective. You should discuss this possibility 
with the study staff as you may need a back-up method. 
 
If you can become pregnant, you must have a pregnancy test before you enter this study and before 
you begin study medications (1 teaspoon of blood or a urine specimen will be collected). You will be 
told the results of the test. The test must show that you are not pregnant.  
 
Breast-feeding 
 
It is unknown whether the study drugs pass through the breast-milk and may cause harm to your 
infant. You must not breast-feed if you are in this study. 
 


 
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WHAT IF I BECOME PREGNANT DURING THIS STUDY? 
 
If you become pregnant or think you may be pregnant at any time during the study, tell your study 
staff right away. You will be asked to come in for a clinical assessment and have blood drawn ( 1 
tablespoon, 15 mL) for a pregnancy test, other routine tests, and an HIV viral load. The study staff will 
talk to you about your choices and refer you to a provider of prenatal care if you do not have one. You 
will be told to stop taking the study medications, and you will be asked to continue to be part of the 
study and attend study visits and complete evaluations for the duration of the study. You will not need 
to have blood draws for storage.    
 
You and your physician will decide what anti-HIV drug combination would be best for you to continue. 
These medications will not be provided by the study. This study will not provide care related to your 
pregnancy, the delivery of your baby, or the care of your baby. You must arrange for your care and 
your baby’s care outside of this study. This study will not provide your baby any anti-HIV drugs. Long-
term follow-up is recommended for a baby whose mother takes anti-HIV drugs during pregnancy. The 
study staff will talk to you about your choices for long-term follow up. The pregnancy will be reported 
to federal monitoring agencies. 
 
ARE THERE BENEFITS TO TAKING PART IN THIS STUDY? 
 
If you take part in this study, there may be a direct benefit to you, but no guarantee can be made. It is 
also possible that you may receive no benefit from being in this study. Information learned from this 
study may help others who have HIV. 
 
WHAT OTHER CHOICES DO I HAVE BESIDES THIS STUDY? 
 
Instead of being in this study, you have the choice of: 
• 
treatment with prescription drugs available to you 
• 
treatment with experimental drugs, if there is another study available to you and  you qualify for 
that study 
• 
no treatment 
 
Please talk to your doctor about these and other choices available to you. Your doctor will explain the 
risks and benefits of these choices. 
 
WHAT ABOUT CONFIDENTIALITY? 
We will do everything we can to protect your privacy. Any publication of this study will not use your 
name or identify you personally.   
 
People who may review your records include the sponsor, Northwestern University,  OHRP, U.S. 
FDA, (insert name of site) IRB,  study staff, study monitors, drug company supporting this study (ViiV 
Healthcare), and their designees.  
 
ClinicalTrials.gov  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov as required by U.S. 
Law. This website will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this Website at any time.  
 
 
 


 
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WHAT ARE THE COSTS TO ME? 
 
DTG and 3TC will be provided by the study.   Clinic visits, evaluations and tests required by the study 
will be provided by the study.  The study will not provide your HIV medications if you are randomly 
assigned to the group that will remain on their current HIV drugs. 
 
Taking part in this study may lead to added costs to you and your insurance company. In some cases 
it is possible that your insurance company will not pay for these costs because you are taking part in a 
research study.   
 
WHAT HAPPENS IF I AM INJURED? 
 
If you become ill or get an injury or illness as a result of study procedures, you should seek medical 
treatment through your doctor or treatment center of choice. You should promptly tell the study doctor 
about any illness or injury.   
 
The hospital [university, researchers] will not pay for medical care required because of a bad outcome 
resulting from your participation in this research study. There is no program for compensation through 
Northwestern University, or ViiV Healthcare.  This does not keep you from seeking to be paid back for 
care required because of a bad outcome. You will not be giving up any of your legal rights by signing 
this consent form. 
 
WHAT ARE MY RIGHTS AS A RESEARCH PARTICIPANT? 
 
Taking part in this study is completely voluntary. You may choose not to take part in this study or 
leave this study at any time. You will be treated the same no matter what you decide. 
 
We will tell you about new information from this or other studies that may affect your health, welfare, 
or willingness to stay in this study. If you want the results of the study, let the study staff know. 
 
WHAT DO I DO IF I HAVE QUESTIONS OR PROBLEMS? 
 
For questions about this study or a research-related injury, contact: 
• 
name of the investigator or other study staff 
• 
telephone number of above  
 
For questions about your rights as a research participant, contact: 
• 
name or title of person on the Institutional Review Board (IRB) or other organization appropriate 
for the site 
• 
telephone number of above 
 
 
 
 
 
 
 
 
 
 


 
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Consent for Future Use of Stored Samples 
Any blood leftover after all required study testing is done may be stored (with no information that will 
identify you) and used for future ASPIRE team-approved research. These blood samples may be 
stored for an unknown period of time. Results of testing done on these samples may not be given to 
you because they will be done in the future. 
  
Please initial below if you agree to have any of your leftover blood used for future ASPIRE-approved 
research. You may change your mind at any time and reasonable efforts will be made to destroy your 
samples, though this may not always be possible. 
  
________ (initial) I agree to have my blood and any of my leftover blood stored and used for future 
ASPIRE-approved research 
________ (initial) I do NOT agree to have any of my blood and any leftover blood stored and used for 
future ASPIRE-approved research 
 
 
____________________________ 
___________________________________ 
Witness’ Name (print) 
Witness’ Signature and Date 
(As appropriate) 
 
 
 
 
 
Additional Consent for Subjects Enrolled at Northwestern University ONLY 
About 20 ml (4 teaspoons) of blood will be obtained and stored at the entry, Week 24 and Week 48 
visits for possible evaluation of changes in the amount of HIV that remain hidden in specific blood 
cells called peripheral blood mononuclear cells (PBMCs). This will give us a clue about how changing 
to the two study drugs may affect the ability of HIV to hide in places called HIV reservoirs.  
 
Please initial one of the following to indicate your choice: 
_____ (initial) I agree to complete the extra visits.   
_____ (initial) I do not agree to complete the extra visits.   
 
SIGNATURE PAGE 
 
If you have read this consent form (or had it explained to you), all your questions have been answered 
and you agree to take part in this study, please sign your name below. 
 
 
____________________________ 
___________________________________ 
Participant’s Name (print) 
Participant’s Signature and Date 
 
 
____________________________ 
___________________________________ 
Study Staff Conducting 
Study Staff’s Signature and Date 
Consent Discussion (print)