Evaluation of Multiple Interventions to Improve HIV Treatment Outcomes Among People Who Inject Drugs in India: a Randomized Factorial Trial With a Randomized Adaptive Component for Those Experiencing Early Treatment Failure
Phase: NA
Conditions: HIV Infections
Sponsor: Johns Hopkins University

Page 1 of 39 
 
 
 
Evaluation of Multiple Interventions to Improve HIV Treatment Outcomes Among 
People Who Inject Drugs in India: a Randomized Factorial Trial With a 
Randomized Adaptive Component for Those Experiencing Early Treatment 
Failure 
 
PWID Opportunities to Improve TrEat and Retain (POINTER) 
 
Funded by: 
 
The National Institute on Drug Abuse 
 
R01DA049301 
 
 
 
Protocol Chair/Co-Chair:  
 
 
Gregory M. Lucas, MD PhD 
Shruti H. Mehta, PhD MPH 
 
ClinicalTrials.gov Protocol Number:  
NCT05165810 
 
 
 
 
 
 
 
 
 
 
Version Number:  
 
 
 
2.0 
 
 
 
 
 
 
 
Version Day Month Year:  
 
 
27 March 2026 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
1. KEY ROLES............................................................................................................................5 
2. LIST OF ABBREVIATIONS .....................................................................................................8 
3. PROTOCOL SUMMARY .........................................................................................................9 
4. INTRODUCTION...................................................................................................................11 
4.1 Background Information ...................................................................................................11 
4.1.1 Injection drug use is a substantial and expanding problem in India ...........................11 
4.1.2 Poor treatment outcomes persist for PWID living with HIV ........................................11 
4.2 Rationale .........................................................................................................................12 
4.2.1 Rationale for factorial randomized controlled trial in phase-1.....................................12 
4.2.2 Rationale for adaptive, second randomization in phase-2 .........................................12 
5. STUDY DESIGN ...................................................................................................................12 
6. STUDY POPULATION ..........................................................................................................14 
6.1 Study Context and Selection of Study Cities ....................................................................14 
6.2 Inclusion/Exclusion Criteria ..............................................................................................14 
6.2.1 Participant Inclusion Criteria ......................................................................................14 
6.2.2 Participant Exclusion Criteria.....................................................................................15 
6.3 Recruitment Process .......................................................................................................15 
6.4 Participant Retention .......................................................................................................15 
7. INTERVENTIONS .................................................................................................................16 
7.1 Policy Intervention: Standard ART Initiation vs. Same-Day ART ......................................16 
7.2 Structural Intervention: Facility-Based Care vs. Community-Based Care .........................17 
7.2.1 Overview of history with integrated care centers .......................................................17 
7.2.2 Assisted linkage to care in the two study arms ..........................................................17 
7.2.3 Facility-based care arm .............................................................................................17 
7.2.4 Community-based care arm ......................................................................................17 
7.3 Adaptive component (phase-2): routine adherence support vs. adherence-plus for those 
experiencing early treatment failure .......................................................................................18 
7.3.1 Protocol and components of adherence-plus ............................................................19 
7.3.2 Training, supervision, and fidelity monitoring .............................................................19 
8. STUDY PROCEDURES/EVALUATIONS ..............................................................................20 
8.1 Schedule of Procedures/Evaluations ...............................................................................20 
9. SAFETY MONITORING ........................................................................................................21 
9.1 Trial management ............................................................................................................21 

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9.2 Data management ...........................................................................................................22 
9.2.1 Recruitment and screening .......................................................................................22 
9.2.2 Data collection for enrolled participants .....................................................................22 
9.2.3 Data entry methods ...................................................................................................23 
10. CLINICAL MANAGEMENT .................................................................................................23 
10.1 Clinical Management of Adverse Events ........................................................................23 
10.2 Pregnancy .....................................................................................................................24 
10.3 Treatment Failure ..........................................................................................................24 
11. ANALYTICAL CONSIDERATIONS .....................................................................................24 
11.1 Design Overview ...........................................................................................................24 
11.2 Hypotheses ...................................................................................................................24 
11.2.1 Phase-1: Factorial trial ............................................................................................24 
11.2.2 Phase-2: Adaptive trial ............................................................................................24 
11.3 Study Objectives ............................................................................................................25 
11.3.1 Primary Objectives ..................................................................................................25 
11.3.2 Secondary Objectives .............................................................................................25 
11.3.3 Exploratory Objectives ............................................................................................25 
11.4 Outcome measures .......................................................................................................27 
11.5 Sample Size Considerations ..........................................................................................29 
11.6 Enrollment/Stratification/Randomization/Blinding Procedures ........................................30 
11.7 Participant Enrollment and Follow-up ............................................................................30 
12. DATA HANDLING AND RECORDKEEPING .......................................................................30 
12.1 Data Management Responsibilities ................................................................................30 
12.2 Quality Control and Quality Assurance ..........................................................................30 
12.2.1. Procedures to ensure the validity and integrity of the data .....................................30 
12.2.2. Procedures to guarantee the accuracy and completeness of the data ....................31 
13. HUMAN SUBJECTS PROTECTIONS .................................................................................31 
13.1 Institutional Review Board/Ethics Committee .................................................................31 
13.2 Vulnerable Participants ..................................................................................................31 
13.2.1 Pregnant women and fetuses ..................................................................................31 
13.2.2 Prisoners .................................................................................................................31 
13.2.3 Illiterate participants ................................................................................................32 
13.3 Informed Consent ..........................................................................................................32 
13.3.1 Informed consent process .......................................................................................32 
13.3.2 Documentation of informed consent ........................................................................32 

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13.4 Risks .............................................................................................................................32 
13.4.1 PWID participants in randomized trial ......................................................................32 
13.5 Social Impact Events .....................................................................................................33 
13.6 Benefits .........................................................................................................................33 
13.7 Compensation ...............................................................................................................33 
13.7.1 PWID participants in randomized trial ......................................................................33 
13.8 Participant Privacy and Confidentiality ...........................................................................33 
13.9 Certificates of Confidentiality .........................................................................................34 
13.10 Critical Event Reporting ...............................................................................................34 
13.11 New Findings ...............................................................................................................34 
13.12 Study Discontinuation ..................................................................................................34 
13.13 Ancillary Protection ......................................................................................................35 
14. ADMINSTRATIVE PROCEDURES .....................................................................................35 
14.1 Protocol Registration .....................................................................................................35 
14.2 Study Implementation ....................................................................................................35 
14.2.1 Coordinating Center ................................................................................................35 
14.2.2 Contact information .................................................................................................35 
14.2.3 Federalwide assurance (FWA) ................................................................................36 
14.2.4 Protocol version and amendments ..........................................................................36 
 
 
 

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1. KEY ROLES 
 
Co-Chairs 
Gregory M. Lucas, MD PHD 
Professor of Medicine 
Johns Hopkins University School of Medicine 
600 N. Wolfe Street, Carnegie Rm 382  
Baltimore, MD 21287 
Phone: 410-614-0560 
Email: glucas3@jh.edu  
 
Shruti H. Mehta, PhD MPH 
Professor & Chair of Epidemiology  
Johns Hopkins Bloomberg School of Public Health 
615 N Wolfe Street, Ste W6041 
Baltimore, MD 21205 
Phone: 443-287-3837 
Email: smehta@jhu.edu  
 
Biostatistician 
Allison McFall, PhD MS 
Johns Hopkins Bloomberg School of Public Health 
615 N Wolfe St, Rm E6648 
Baltimore, MD 21205 
Phone: 410-955-3578 
Email: amcfall2@jhu.edu  
 
Investigators 
Sunil S Solomon, MBBS PhD MPH 
Johns Hopkins School of Medicine 
615 N Wolfe St, Ste E6518 
Baltimore, MD 21205 
Phone: 443-287-9596 
Email: sss@jhmi.edu  
 
Carl Latkin, PhD MS 
Johns Hopkins Bloomberg School of Public Health 
2213 McElderry St, Rm M231 
Baltimore, MD 21205 
Phone: 410-502-5368 
Email: carl.latkin@jhu.edu  
 
David Celentano, ScD MHS 
Johns Hopkins Bloomberg School of Public Health 
615 N Wolfe St 
Baltimore, MD 21205 
Phone: 410-955-3286 
Email: dcelent1@jhu.edu  
 
Julie Evans, PhD MPA 

Page 6 of 39 
 
Johns Hopkins Bloomberg School of Public Health 
615 N Wolfe St 
Baltimore, MD 21205 
Phone: 410-955-3227 
Email: jevans64@jh.edu  
 
Talia Loeb, MHS 
Johns Hopkins Bloomberg School of Public Health 
615 N Wolfe St 
Baltimore, MD 21205 
Phone: 410-955-3227 
Email: tloeb2@jh.edu  
 
Mihili Gunaratne, MPH 
Johns Hopkins Bloomberg School of Public Health 
615 N Wolfe St 
Baltimore, MD 21205 
Phone: 202-384-3608 
Email: mgunara2@jhmi.edu  
 
International Investigators 
Aylur K Srikrishnan, BA 
YRGCARE 
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-44-2254-2929  
Email: krish@yrgcare.org 
 
Pradeep Amrose, MBBS 
YRGCARE 
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-44-3910-6600 
E-mail: pradeep@yrgcare.org 
 
M Suresh Kumar, MD MBBS DPM MPH 
YRGCARE 
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-44-3910-6600  
Email: msuresh1955@gmail.com 
 
Jiban J Baishya, MBBS MHA 
YRGCARE 
15 (New No: 34) East Street, 

Page 7 of 39 
 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-85-2796-3652 
Email: jbaishy1@jhmi.edu  
 
Ashwini Kedar, MD 
YRGCARE 
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-84-4792-7387 
Email: ashwini.kedar@yrgcare.org  
 
Laboratory Representative 
Jayaseelan Boobalan, PhD 
YRGCARE 
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-95-0018-4200 
Email: boobalan@yrgcare.org  
 
 
 
 

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2. LIST OF ABBREVIATIONS 
 
AE 
 
 
Adverse Event 
ART 
 
 
Antiretroviral Therapy 
CD4 
 
 
Cluster of differentiation 4 
CFIR  
 
Consolidated Framework for Implementation Research 
DSMB  
 
Data Safety Monitoring Board 
DSMP  
 
Data Safety Monitoring Plan 
FWA  
 
Federalwide Assurance 
GEE 
 
 
Generalized estimating equations 
HCV 
 
 
Hepatitis C Virus 
HIV 
 
 
Human Immunodeficiency Virus 
HPTN 074 
 
HIV Prevention Trials Network 074 
ICC 
 
 
Integrated Care Centre 
ICF 
 
 
Informed Consent Form  
IDIs 
 
 
In-depth interviews 
INR 
 
 
India Rupee 
IRB 
 
 
Institutional Review Board 
JHM 
 
 
Johns Hopkins Medicine 
JHU 
 
 
Johns Hopkins University 
LMIC  
 
Low- and Middle-Income Countries 
MOP  
 
Manual of Procedures 
MOU  
 
Memorandum of Understanding 
MOUD  
 
Medication for opioid use disorder 
MSM  
 
Men who have sex with men 
NACO  
 
National AIDS Control Organisation 
NGO  
 
Non-governmental organization 
NIH 
 
 
National Institutes of Health 
OAT 
 
 
Opioid Agonist Treatment 
ORW  
 
Outreach worker 
PWH  
 
People living with HIV 
PWID  
 
People who inject drugs 
POC 
 
 
Point of care 
RDS 
 
 
Respondent-driven sampling 
RNA 
 
 
Ribonucleic acid 
SACS  
 
State AIDS prevention and control societies 
SSP 
 
 
Syringe Services Program 
STI 
 
 
Sexually Transmitted Infection 
TB 
 
 
Tuberculosis 
TDF 
 
 
Tenofovir 
TLD 
 
 
Tenofovir disoproxil fumarate /lamivudine /dolutegravir 
USD 
 
 
United States Dollar 
WHO  
 
World Health Organization 
YRGCARE 
 
Y.R. Gaitonde Centre for AIDS Research and Education 
 
 
 

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3. PROTOCOL SUMMARY 
 
Full Title:  
Evaluation of Multiple Interventions to Improve HIV Treatment Outcomes 
Among People Who Inject Drugs in India: a Randomized Factorial Trial 
With a Randomized Adaptive Component for Those Experiencing Early 
Treatment Failure 
 
Short Title:  
PWID Opportunities to Improve TrEat and Retain (POINTER) 
 
Sample Size: 
800 
 
Study  
Population: 
PWID living with HIV, 18 years or older, who are either ART-naive or 
defaulted from ART for greater than 60 days, and have HIV RNA of 1,000 
c/mL or higher 
 
Participating  
 
 
Sites: 
YR Gaitonde Centre for AIDS Research and Education (YRGCARE), 
Chennai, Tamil Nadu, India 
 
Study Design: 
Non-blinded, randomized, factorial trial (phase-1) with a secondary 
adaptive randomization (phase-2), designed to assess the effectiveness 
of three interventions (relative to standard care) to increase viral 
suppression among PWID living with HIV in India 
 
Study Duration: 
The study will last 5 years. Research participants will be asked to 
complete screening plus 5 study visits (baseline, 3, 6, 12, and 18 months) 
 
Study Regimen/ 
Intervention: 
Three interventions will be implemented among participants treated with 
antiretroviral therapy (ART) for HIV. 
 
1) Same-day ART initiation vs. standard ART initiation 
 
2) Community-based care (integrated HIV and PWID care) vs. facility-
based care (centralized government-based HIV care) 
 
3) Adherence-plus: Enhanced adherence support for participants who 
experience treatment failure at 6 months (vs. routine adherence 
support) 
 
Primary  
Objectives: 
Phase-1 – To determine whether same-day ART initiation (compared with 
standard ART initiation) or whether community-based care (compared 
with facility-based care) increases the proportion of PWID living with HIV 
with viral suppression at 6 months. 
 
Phase-2 – To determine whether adherence-plus, compared with routine 
adherence support, increases the proportion with viral suppression at 6 
months (12 months from beginning Phase I) among participants that 

Page 10 of 39 
 
experience treatment failure at the end of phase-1. 
 
 
 
 
Primary Endpoint: 
Phase-1: Viral suppression at 6 months. 
 
Phase-2: Viral suppression 6 months following the second randomization 
(12 months from enrollment in phase-1) 
 
 
Study Schema: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1. Study design 
 
 
*Boxes with yellow highlight are the experimental arms 

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4. INTRODUCTION 
 
People who inject drugs (PWID) are at high risk for HIV infection and experience worse 
antiretroviral therapy (ART) outcomes than other key populations, particularly in low- and 
middle-income countries (LMIC). India has the largest number of people who use opioids in the 
world, and new injection drug epidemics have emerged in the North and Central regions of the 
country. We will enroll people living with HIV who are 18 years of age or older who report recent 
injection drug use, are ART-naïve or who have defaulted from ART for greater than 60 days, 
and have HIV RNA of 1,000 c/mL or higher 
 
In phase-1, we will evaluate two structural interventions to improve treatment outcomes among 
PWID living with HIV in India. First, same-day ART (initiating ART on the day of HIV 
diagnosis/confirmation rather than waiting until standard evaluations are completed in an HIV 
clinic), was found to increase 12-month viral suppression rates in three African studies but has 
not been evaluated in PWID. The second intervention is community-based care. At present, all 
publicly financed HIV treatment is provided at centralized government ART centers (facility-
based care). In prior work, we found that PWID-centric integrated care centers (ICCs) were 
effective at engaging the population, increasing HIV testing uptake, and were rated favorably by 
clients in anonymous surveys. ICCs linked HIV-positive PWID to facility-based care at 
government clinics, but did not provide on-site ART. However, ICCs can be scaled-up to provide 
ART on-site (community-based care) and we hypothesize this will improve initiation and 
retention to ART among PWID. We will use a randomized factorial design to determine the 
individual and joint effects of same-day ART and community-based care. The primary outcome 
of the phase-1 trial is viral suppression at 6 months, with longer term follow-up to 18 months.  
 
In phase-2, we will evaluate a psychosocial/navigation intervention (adherence-plus) among 
participants who experience treatment failure during the first trial phase, defined as HIV RNA 
≥1,000 c/mL at the 6-month visit. These participants will be randomly assigned (in a second 
randomization) to adherence-plus or routine adherence support. The primary outcome of phase-
2 will be viral suppression 6 months following the second randomization (12 months from 
enrollment in phase-1). 
 
4.1 Background Information 
 
4.1.1 Injection drug use is a substantial and expanding problem in India 
 
Located between the “Golden Triangle” and the “Golden Crescent”, the leading producers of 
opium globally, India has a large number of opioid users. By one estimate, there are 167,882 
current opioid users in the state of Punjab alone.1 In the northeast region of India, which borders 
Myanmar, injection drug use has been endemic since the 1970s and has always been the major 
driver of the HIV epidemic in this region. However, in recent years, there has been an epidemic 
of injection drug use in the north (bordering Pakistan) and central regions of India that has 
attracted news and political coverage.2-4 In a community survey of adolescents and young adult 
men in a rural district of Punjab, 21% report past-year heroin use, with two-thirds of those 
reporting injection.5 In 2017 we conducted systematic respondent-driven sampling (RDS) 
surveys of PWID in 12 Indian cities (~1000 per city). We found an average HIV prevalence of 
20% and an average HIV incidence of 4.57 per 100 person-years.6 These data highlight a 
growing epidemic of injection drug use in India with high HIV prevalence and incidence. 
 
4.1.2 Poor treatment outcomes persist for PWID living with HIV 

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HIV care continuum outcomes are worse in PWID than in other key populations,7,8 and this 
disparity appears to be larger in LMICs.9-12 In a recent survey of 2,906 PWID living with HIV in 
15 Indian cities, we found that only 41% were aware of their HIV-positive status, 31% were 
linked to ART, and 15% had a suppressed viral load.13 There is no “quick-fix” to this challenge. 
This is illustrated by the fact that in three well-conducted clinical trials aimed at improving HIV 
treatment outcomes among PWID, no study arm achieved viral suppression above 50%.14-16 
Moreover, we presented data comparing progress along the HIV care continuum among men 
who have sex with men (MSM) and PWID in India between 2013 and 2017. We found that, over 
this 4-year period, MSM increased use of ART by 33 percentage points (95% CI: 15, 52) more 
than PWID did over the same period. Similarly, viral suppression rates increased 15 percentage 
points (95% CI: 0, 31) more among MSM than PWID over the observation period (CROI 2020). 
These data support the need to identify tiered approaches to improve treatment outcomes 
among PWID in India. 
 
4.2 Rationale 
 
4.2.1 Rationale for factorial randomized controlled trial in phase-1 
 
We aim to simultaneously evaluate two potentially feasible and scalable interventions to 
improve treatment and retention outcomes among PWH who inject drugs. Under the 
assumption of no effect modification between the outcomes, a factorial design offers the 
potential to efficiently evaluate the main effects of more than one intervention.17 We will assess 
interventions at different levels: policy (same-day ART) and structural (community-based care).  
 
4.2.2 Rationale for adaptive, second randomization in phase-2 
 
In phase-2, our objective is to use an adaptive trial design18,19 to evaluate the effectiveness of 
the adherence-plus intervention among participants who experience treatment failure at 6 
months of phase-1. Adherence-plus is a psychosocial/navigation intervention that addresses 
patient-level barriers and builds on prior work14-16 and theories, including social cognitive and 
maintenance theories.20,21 While the effectiveness of behavioral interventions for HIV treatment 
adherence have been mixed,14-16,22,23 the HIV Prevention Trials Network (HPTN) 074 study 
demonstrated the effectiveness of a psychosocial/systems navigation intervention on HIV viral 
suppression and mortality among PWID living with HIV.16 By virtue of our study design, we are 
asking a different question than was addressed in HPTN 074, where the intervention was 
evaluated up front. In the current trial, we are asking whether more selective use of the 
intervention, specifically only in those experiencing treatment failure in the short-term, can 
improve subsequent treatment outcomes compared with routine adherence support. This 
question is relevant because adherence-plus is relatively resource intensive with dedicated staff 
who must be trained and supervised. If the intervention is successful when tailored only to those 
experiencing difficulties, it may be more feasible to implement. 
 
 
5. STUDY DESIGN 
 
This is a non-blinded, randomized, factorial trial (phase-1) with a secondary adaptive 
randomization (phase-2), designed to assess the effectiveness of three interventions (relative to 
standard care) to increase viral suppression among PWID living with HIV in India. 

Page 13 of 39 
 
In phase-1 of the trial, we will evaluate the individual and joint effectiveness of 2 interventions: i) 
same-day ART and ii) community-based care (orange boxes, Figure 1). Each intervention will 
be compared against standard of care in India, standard ART initiation and government facility-
based HIV care, respectively. Following recruitment and screening, participants will be 
randomized in 1:1:1:1 ratio to 1 of 4 arms, in which they may receive neither intervention 
(double control), one intervention or the other, or both interventions. Participants experiencing 
virologic failure at the 6-month visit will undergo a second randomization to either adherence-
plus or routine adherence support. Follow-up visits will be at 3, 6, 12, and 18 months. 
 
 
 
 
 
Figure 1. Study design 
 
 
*Boxes with yellow highlight are the experimental arms 

Page 14 of 39 
 
 
6. STUDY POPULATION 
 
The target population is PWH who inject drugs, are 18 years or older, and ART-naïve or have 
been off ART for a prolonged period. 
 
6.1 Study Context and Selection of Study Cities 
 
This study will be conducted in the context of PWID-focused epidemiological and 
implementation research in the study cities since 2013. This background work was funded by 
research grants from the US National Institutes of Health, Elton John AIDS Foundation and 
support from the National AIDS Control Organization (NACO), India. 
 
Our prior work includes robust epidemiologic assessments of PWID populations in 15 Indian 
cities. We found substantial city-to-city variability in HIV prevalence/incidence and in the care 
continuum among PWID living with HIV.13,24 These background data allow us to select cities for 
the trial where injection drug use is on the rise,2 HIV burden is high, and care continuum 
outcomes are poor. Table 1 shows 2017 data from PWID in the proposed study cities. 
Percentages are weighted for respondent-driven sampling (RDS). The estimated PWID 
population sizes are based on a biometrically-based capture-recapture method.25 HIV incidence 
was estimated using a validated multi-assay algorithm.26 
 
6.2 Inclusion/Exclusion Criteria 
 
6.2.1 Participant Inclusion Criteria 
 
Randomized factorial trial (phase-1) 
Inclusion criteria: 
1. 
18 years of age or older 
2. 
Reports injection drug use in prior 24 months 
3. 
Documented HIV positive status 
4. 
Antiretroviral therapy status (a or b) 
a. 
Antiretroviral therapy naïve 
OR 
Table 1. Survey data from PWID recruited by RDS in in 2017 
Characteristic 
Kanpur 
New Delhi 
Surveyed, n 
999 
999 
Estimated PWID population 
size, n 
18,537 
10,448 
Female, n 
1  
3 
Age, median (IQR) 
35 (28, 43) 
32 (27, 38) 
Injected in prior 6 months, % 
94 
98 
Shared prior 6 months, % 
33 
44 
HIV prevalence, % 
21 
38 
HIV RNA >500 c/mL,% 
91 
95 
HIV incidence, % 
11.1 
18.5 
 

Page 15 of 39 
 
b. 
Antiretroviral experienced, defaulted from care, and has not taken 
antiretroviral therapy in >60 days 
5. 
HIV RNA ≥1,000 c/mL 
6. 
If previously linked to HIV care, able and willing to provide government ART book for 
documentation of care received 
 
Randomized adaptive trial (phase-2)  
Inclusion criteria: 
1. 
Enrolled in phase-1 trial 
2. 
Experiences treatment failure (HIV RNA ≥1,000 c/mL) at 6 months 
 
6.2.2 Participant Exclusion Criteria 
 
Randomized factorial trial (phase-1) 
Exclusion criteria: 
1. 
Pregnant (if female) 
2. 
Breastfeeding (if female) 
3. 
Does not speak English, Hindi, or local language 
4. 
Plans to migrate in next 12 months 
5. 
Not competent to participate in the study or provide written informed consent 
 
Randomized adaptive trial (phase-2)  
Exclusion criteria: 
Not applicable 
 
6.3 Recruitment Process 
 
Our research team has nearly 15 years of experience working with PWID in the target cities, 
which will facilitate study recruitment. We will meet with PWID groups, NGOs, State AIDS 
Control Societies, and other stakeholders to disseminate information about the trial to potential 
participants. Additionally, we will be in the process of completing respondent-driven sampling 
(RDS) surveys in the target cities. These are the third serial surveys in the target surveys. From 
prior surveys we learned that RDS surveys are effective in identifying PWID living with HIV who 
are either unaware of their status or have not engaged in HIV treatment. Finally, word-of-mouth 
referrals are an important component of recruitment efforts.    
 
6.4 Participant Retention 
 
Retention to follow-up is a challenge among PWID, and loss-to-follow-up is particularly 
challenging in New Delhi. Standard retention measures will be used to ensure that participants 
adhere to their study visits. 
 
Detailed locator/contact information will be collected/updated in the electronic database at the 
time of enrollment, including information on mobile phone number, alternate phone numbers, 
home address, hangout locations (injection venues), and addresses and phone numbers of two 
to three contacts. Each client will be asked whether study staff may contact these individuals 
regarding appointment reminders.  
 
For study visits, site coordinators will generate weekly reports to identify clients who are due for 
study visits over the next two weeks.    

Page 16 of 39 
 
 
Once a visit is missed, outreach workers will make at least three attempts to contact participants 
using different approaches and different times of the day. The first attempt will be  
via their mobile phone (if provided). Additional attempts will include a visit to their home and/or 
other designated locations and/or contacts and hang out locations as needed. Outreach staff will 
continue to contact participants for up to one month after the missed study visit.  
 
All tracking attempts (including the results of each attempt) will be recorded in the database.  
 
Instances of migration (permanent or transient) will be documented.  
 
Mortality rates are high in this population (PWID living with HIV) in India. Reports of participants’ 
deaths will be investigated by outreach workers. Information on death and cause (via verbal 
autopsy) will be recorded where possible. Deaths will be considered verified if one of the 
following applies: i) hospital records or death certificate, ii) confirmation of death by a family 
member, or iii) confirmation of death from an eyewitness (usually another PWID). Reports of 
migration and incarceration will be noted, but we will continue to track these individuals. 
 
 
7. INTERVENTIONS 
 
7.1 Policy Intervention: Standard ART Initiation vs. Same-Day ART 
 
Clinical trials conducted in Africa (2 clinic-based and 1 field-based) have found rapid (same-day) 
ART initiation to be associated with significant increases in 12-month viral suppression 
compared with standard ART initiation.27-30 Subsequently, same-day ART initiation has been 
implemented in several African settings.31,32 The same-day ART strategy is low cost and has the 
potential to integrate well with outreach methods to identify unlinked (unaware of status or out of 
care) PWID living with HIV. However, same-day ART has never been evaluated outside of 
Africa or among PWID.  
 
In the standard ART initiation arm, participants will receive counseling and a referral card (either 
to facility-based or community-based care, according to randomization). A standard ART 
initiation protocol33 will be used in both facility-based and community-based settings, namely a 
baseline visit (history, physical, and laboratory assessments) and typically one follow-up visit in 
7-14 days with ART counseling and initiation. Universal treatment (irrespective of CD4 count) is 
standard care across India.   
 
In the same-day ART initiation arm, participants will receive the same counseling and referrals 
as the standard ART initiation arm, but in addition, staff will provide focused ART counseling 
and an informational pamphlet. The study clinician will conduct a health assessment to screen 
for any conditions that might affect management/selection of antiretroviral medication, 
specifically history of kidney disease, tuberculosis treatment/symptoms, or history of adverse 
reactions to antiretroviral drugs. We will use a modified SLATE II pre-ART screening 
approach.34 Participants who have a positive screen will not be started on ART until medical 
evaluation is completed. Women will be tested for pregnancy and screened for breastfeeding at 
enrollment. Pregnancy and breastfeeding are exclusion criteria for the trial because specialist 
treatment and monitoring is required to ensure proper care of both the woman and child. 
Women who are pregnant or breastfeeding will be linked to a government ART center 
immediately for specialist care per national guidelines. After counseling, review of medical 

Page 17 of 39 
 
history, and a physical exam, participants will be given a 30-day supply of ART and follow-up 
instructions (either at a government ART clinic [facility-based care] or to the community-based 
care site, per randomization). We will dispense the same antiretroviral medications and 
formulations for same-day ART initiation as are used in the government ART centers for first-
line treatment. Currently, the regimen of dolutegravir-based therapy (combined with TDF and 
lamivudine) is the national standard in India, consistent with the World Health Organization 
(WHO) 2018 guidelines for first-line ART.  
 
7.2 Structural Intervention: Facility-Based Care vs. Community-Based 
Care 
 
7.2.1 Overview of history with integrated care centers 
 
In a recently completed cluster-randomized trial, we developed and evaluated PWID-focused 
integrated care centers (ICCs) that co-located HIV testing, counseling, and linkage to care with 
key PWID risk-reduction services (MOUD and SSP). These centers were not equipped to 
provide ART directly as the National AIDS Control Organisation (NACO) in India has historically 
followed a strictly centralized model for providing free ART in the public sector. However, NACO 
is explicitly exploring decentralized/differentiated care models for HIV, given its assessment that 
current ART facilities are “overloaded and understaffed.”35 Our ongoing experience with ICCs, 
suggests they can be scaled to provide and monitor first-line ART for PWID. We hypothesize 
that greater accessibility in a PWID-focused setting care will lead to higher linkage and retention 
to ART in the community-based vs. the facility-based model. This is supported by favorable ICC 
client satisfaction data.6  
 
7.2.2 Assisted linkage to care in the two study arms 
 
After randomization, in both arms, an outreach worker will be offered to support each 
participant. Outreach workers will have the goal of linking participants to care, defined as being 
assigned a medical ID number. Outreach workers will accompany participants to their assigned 
treatment sites and assist them in getting a verified HIV-positive test result (if needed). The goal 
of providing linkage assistance in both arms is to prevent minor administrative barriers from 
interfering with linkage in either arm. Outreach workers will assist with linkage for a maximum of 
15 days.        
 
7.2.3 Facility-based care arm 
 
Study staff will refer participants assigned to facility-based care to government ART centers, 
which are managed and supplied by NACO. Clients with a documented HIV positive status can 
walk-in to any government ART facility and register for care. At the registration visit, a history 
and a physical exam (including screening for TB/STIs) are conducted by a physician, and a 
blood sample is drawn for baseline laboratories (CD4 cell count, chemistry panel, hemogram, 
hepatitis B surface antigen). Patients are typically asked to return to clinic in 1-2 weeks to 
review laboratory results, receive additional counseling, and (usually) initiate first-line ART. 
Following ART initiation, patients return to clinic in 2 weeks, followed by monthly ART refill visits 
thereafter. Longer ART dispensations (2- or 3-months) may be used for stable patients and 
these longer dispensations were used extensively during the COVID-19 pandemic. 
 
7.2.4 Community-based care arm 
 

Page 18 of 39 
 
Study staff will refer participants assigned to community-based care to an integrated care center 
(ICC). In each city we will scale-up an existing ICC to enable independent ART management. 
We established the ICC model for PWID in 2013 and have maintained them in multiple cities 
with funding/support from NIH (research), NACO (HIV testing supplies, staffing and medication 
for opioid use disorder (MOUD), SSP supplies, etc.) and the Elton John AIDS Foundation 
(charity). ICCs routinely provide HIV and HCV testing, counseling services (substance abuse, 
depression, adherence to HIV care, etc.), STI and TB screening and referrals, MOUD (mostly 
buprenorphine), and clean needles/syringes provided by outreach workers. Currently ICCs are 
staffed by i) a site coordinator (record keeping, staff oversight), ii) a counselor, iii) a nurse 
(additional nurses are provided by the government solely for MOUD management), iv) a 
phlebotomist, and v) outreach workers. To scale-up ICCs for ART management we will hire a 
part-time physician with ART experience/training in each ICC. We will establish a supply chain 
for ART with the assistance of government ART centers. ART will be stored with buprenorphine 
and STI treatment packs in secure double-locked storage facilities. The scaled-up ICCs will 
provide HIV care that is consistent with Indian guidelines and treatment provided in the 
government sector.33 ICCs will use the same HIV and routine adherence counseling materials , 
HIV record-keeping forms, and clinical and laboratory monitoring protocols. ICCs will stock first-
line antiretroviral therapy and first-line alternate therapy. Currently, the single-pill regimen that is 
universally used as first-line treatment in LMICs is dolutegravir /tenofovir disoproxil fumarate 
/lamivudine. In the government sector standard laboratory monitoring includes kidney and liver 
function tests, a hemogram, CD4 testing, and viral load testing every 6 to 12 months, depending 
on patient stability.  
 
The community-based clinics will follow standard Indian practices for prevention of HIV-
associated conditions. Participants will initiate daily cotrimoxazole preventive therapy (CPT) for 
prevention of Pneumocystis jirovecii and bacterial infections. Participants will be eligible for 
CPT, in conjunction with ART, if they have WHO stage 3 or 4 disease, or have a CD4 cell count 
<350 cells/mm3 at presentation. CPT may be discontinued when participants are clinically well 
and have two consecutive CD4 cell count >350 cells/mm3 (separated by at least 6 months). 
Isoniazid preventive therapy (IPT) is used in people living with HIV to reduce the risk of TB. 
Daily IPT is generally started 3 months after ART initiation if a chest X-ray is clear and the 
participant does not have 4S symptoms. IPT is given for 6 months and then discontinued. Clinic 
physicians will refer participants with serious symptoms to government hospitals for emergency-
level care. If government practice changes during the trial period, community-based care will 
revise treatment protocols to match standard care. Community-based care clinics will refer 
participants who meet criteria for second-line (generally protease inhibitor-based regimens) to 
government ART centers. We anticipate the such situations will be relatively rare because of the 
durability of dolutegravir-based treatment.36 Participants randomized to the community-based 
care arm will be free to seek HIV care in the government or private sector. 
 
7.3 Adaptive component (phase-2): routine adherence support vs. 
adherence-plus for those experiencing early treatment failure  
 
In phase-2, participants who experience treatment failure (HIV RNA ≥1000 c/mL) at 6 months 
will undergo randomization to either routine adherence support (provided at their assigned site) 
or to the adherence-plus intervention (provided at the research site). Routine adherence support 
includes administering standardized adherence counseling at the clinic. The adherence-plus 
intervention includes two components: 1) navigation and 2) psychosocial support and 
counseling. These components may be provided by a single individual, but we anticipate that 
peer outreach workers will focus on tracking/outreach while trained counselors will provide the 

Page 19 of 39 
 
psychosocial/navigation component. The objectives of adherence-plus are to educate, provide 
psychosocial support, and build skills needed for treatment independence. Counselors will seek 
to achieve these goals through a motivational interviewing (MI) (or strengths-based case 
management)14,16 framework, in which participants are guided to identify internal motivations 
and strengths and apply them to HIV and substance use treatment. Counselors will have 
sufficient education and aptitude to learn MI methods and core information about HIV and its 
treatment, acquire a detailed knowledge of local PWID resources, and to accurately document 
services provided.  
 
7.3.1 Protocol and components of adherence-plus  
 
Adherence-plus will be a tailored intervention that will last a maximum of 6 months. Under the 
guidance of Prof. Carl Latkin, who led the development, piloting, and operationalization of the 
HPTN 074 psychosocial/navigation intervention,16 we will assemble counselor training curricula 
and detailed scripts for content sessions. Counselors/navigators will conduct individual sessions 
with participants that cover topics relevant to PWID living with HIV (Table 2). The content for 
these sessions will be revised and further developed in a manual of procedures (MOP). At the 
end of the session the counselor will provide the participant with a mutually agreed upon action 
plan. We anticipate that sessions will be 30-45 minutes in duration, and sessions may be 
repeated. Field activity will be strongly emphasized in the intervention. The navigator function is 
to provide material support to remove barriers to care (e.g., assistance with transportation).  
 
Facilitators will be used when participants attend scheduled counseling sessions. Potential 
facilitators include: clean syringes, bleach packets, condoms, bus passes to attend clinics, 
mobile phone minutes, food supplements, and outreach worker (ORW) support attending 
medical or substance use appointments. We anticipate making adherence-plus flexible, so that 
attention may be reduced for people making progress and intensified for those continuing to 
have difficulties. 
 
 
  
 
7.3.2 Training, supervision, and fidelity monitoring  
Table 2 Likely session components of adherence-plus intervention 
Number / Session title 
 
Description 
1) Introduction to 
adherence-plus 
 
Needs assessment (depression, substance abuse, sustenance needs, 
etc.); Social / geospatial assessment (social support network, where 
does s/he spend time); Client goals 
2) HIV treatment – basics 
 
Basics of HIV (not curable, highly treatable); HIV treatment – adherence, 
side-effect management, lifelong treatment; Meaning of CD4 and viral 
load 
3) Drug and alcohol use 
 
Inventory of drug and alcohol use, and resulting social harms; Motivation 
to change assessment; Treatment options; Successful HIV treatment 
with active substance abuse 
4) Dyad counseling with 
supporter 
 
Identify treatment supporter for dyad counseling; Risk reduction 
strategies; Strategies to support index in HIV treatment and OAT (if 
appropriate) 
5) Injection- and sex-
related risk reduction 
 
Clean needles – SSP resources; Drug splitting strategies to minimize 
risk; Overdose; Safe sex; Discussing HIV status with sex partner; sex 
partner HIV testing; Role of effective HIV treatment in reducing 
transmission risk 
6) Opioid agonist treatment 
 
Experience with OAT or preconceptions about OAT; Stabilization; 
Chronic disease model of opioid use disorder 
7) HIV treatment for the 
long run 
 
Re-engaging in care after a lapse; Treatment continues even when you 
feel well; Strategies for remaining engaged; Side-effect management 

Page 20 of 39 
 
 
Navigators will complete a curriculum modeled after HPTN 074.16 Training will include MI 
strategy, role-playing, and didactic instruction on HIV and substance use. It is anticipated that 
navigators will manage a patient load of no more than 15 at one time. Navigators will liaise with 
both government ART clinics (facility-based care) and ICCs (community-based care), according 
to participants’ treatment assignments. Experienced counselors from YRGCARE will supervise 
the work of navigator /outreach worker teams and meet with them as a group monthly to discuss 
cases, challenges, and strategies. The supervisor will sit-in on a subset of counseling sessions 
and use a check-list to score the session. The supervisor will review the checklist with the 
counselor for quality control and fidelity.  
 
 
8. STUDY PROCEDURES/EVALUATIONS 
 
8.1 Schedule of Procedures/Evaluations 
 
The schedule of follow-up visits and associated data collection is listed in Table 3. We will 
develop an electronic interviewer-administered survey that will capture information on 
demographics, risk assessment and adherence assessment. We will use standardized surveys 
that we have used among PWID in India since 2004. To maximize retention, we will capture and 
update detailed locator information at all study visits for tracking. At the enrollment visit, we will 
capture biometric data (either an iris scan and/or a fingerprint scan) to verify the identity of the 
participant. No biometric images will be stored – the images will be converted into unique 
hexadecimal codes, and these codes will be stored. At all subsequent visits, the biometric 
verification will be performed prior to initiation of visit procedures. We have used biometric 
tracking among PWID in India since 2013 and it is highly acceptable to participants. 
 

Page 21 of 39 
 
 
 
9. SAFETY MONITORING 
 
Safety monitoring is described in greater detail in the Data Safety and Monitoring Plan (DSMP). 
This trial also has a Data Safety Monitoring Board (DSMB), summarized in the DSMB Charter.  
 
9.1 Trial management 
 
This study will be coordinated by the YR Gaitonde Centre for AIDS Research and Education 
(YRGCARE) in Chennai, Tamil Nadu, India, with oversight from investigators at the Johns 
Hopkins Bloomberg School of Public Health and the Johns Hopkins School of Medicine. 
YRGCARE will oversee all day-to-day aspects of the trial including participant recruitment, data 
collection, laboratory testing, biological sample storage, and data management. YRGCARE was 
established in 1993 with joint missions in HIV service and research. Over the years, YRGCARE 
has also developed a broad research portfolio including clinical trials, cohort and cross-sectional 
studies related to the epidemiology, prevention and management of HIV disease.  
 
Of relevance to the current proposal, YRGCARE has a proven track record of promoting change 
through public-private partnerships and has substantial prior experience with large randomized 
Table 3. Schedule of monitoring events in factorial (phase 1), adaptive (phase 2) trial 
 
Screening 
Enrollment 
3 m 
6 m 
12 m 
18 m 
Oral screening consent 
X 
 
 
 
 
 
Rapid HIV test (if needed) 
X 
 
 
 
 
 
Pregnancy test (if female) 
X 
 
 
 
 
 
Biometric duplicate check 
X 
 
 
 
 
 
Biometric registration 
X 
 
 
 
 
 
Screener questionnaire 
X 
 
 
 
 
 
Biometric verification 
 
X 
X 
X 
X 
X 
Locator information 
 
X 
X 
X 
X 
 
Written informed consent 
 
X 
 
 
 
 
Phase 1 randomization 
 
X 
 
 
 
 
Study questionnaire 
 
X 
X 
X 
X 
X 
   Demographics 
 
X 
 
 
 
 
   Drug & alcohol use 
 
X 
X 
X 
X 
X 
   Risk behaviors 
 
X 
X 
X 
X 
X 
   Depression PHQ-9 
 
X 
X 
X 
X 
X 
   Quality of life 
 
X 
X 
X 
X 
X 
   Harm reduction services 
 
X 
X 
X 
X 
X 
   Social support 
 
X 
X 
X 
X 
X 
   Stigma 
 
X 
X 
X 
X 
X 
   Hepatitis B and C 
 
X 
X 
X 
X 
X 
   Healthcare utilization 
 
X 
X 
X 
X 
X 
   HIV care continuum 
 
X 
X 
X 
X 
X 
   Adverse effects 
 
X 
X 
X 
X 
X 
   Adherence 
 
X 
X 
X 
X 
X 
   Self-efficacy  
 
X 
X 
X 
X 
X 
Phase 2 randomization 
 
 
X 
 
 
 
HIV RNA 
X 
 
X 
X 
X 
X 
CD4 cell count 
X 
 
 
 
 
 
Urine drug test 
X 
 
X 
X 
X 
X 
Blood storage 
 
X 
X 
X 
X 
X 
Interventions close out 
 
 
 
 
 
X 
 

Page 22 of 39 
 
trials. YRGCARE is a site for numerous multisite trials and is a clinical research site for AIDS 
Clinical Trials Group (ACTG). The proposed trial will be conducted in two cities in which we 
have documented large HIV epidemics among PWID and poor treatment outcomes: 
 
• 
New Delhi, National Capitol Territory 
• 
Kanpur, Uttar Pradesh 
 
Study activities will take place at three locations in each city: a research site (for recruitment, 
screening, and data collection at study visits), a PWID-focused community-based care center 
(i.e., the ICC), and one or more government ART centers. 
 
9.2 Data management 
 
9.2.1 Recruitment and screening 
 
Potential participants joining POINTER will come from several sources. It is expected that the 
majority of participants will be referred to POINTER via their participation in a respondent driven 
sampling (RDS) survey that is taking place in each site at the same time. Other potential 
participants will be referred from the local ICC, MOUD clinics, other NGOs, enrolled peers, local 
injecting venues/hotspots, and other sources.  
 
Our group has previously shown that RDS surveys are an effective method to identify more 
difficult-to-reach populations and to identify PWID living with HIV who are unaware of their 
status or unlinked to care.  
 
All participants screened for eligibility into POINTER will undergo the following procedures: 
• 
COVID-19 pre-screen (if not completed already on same day) 
• 
Oral consent 
• 
Biometric registration 
• 
Screening questionnaire   
• 
Complete an HIV point of care (POC) rapid test (if needed to confirm HIV positive 
status),  
• 
A POC HIV RNA test (GeneXpert) among persons with confirmed HIV positive status. 
• 
Collect biometric data (fingerprint or iris scan) to prevent duplicate enrollment and for 
clinical trial tracking. The software converts images into 1024-digit alphanumeric codes 
that are encrypted with proprietary software into a unique identifier. The biometric 
scanning systems protect participant confidentiality because the images are not saved in 
the system and codes cannot be used to reconstruct fingerprint images.  
 
9.2.2 Data collection for enrolled participants 
 
Trial participants will be followed for up to 18 months and will be asked to complete a total of 5 
study visits, including the entry visit. Table 1 shows the planned monitoring schedule.  
 
The following data will be collected and stored: 
• 
Written informed consent documents 
• 
Survey modules 
o Demographics    
o Substance use (including alcohol)  

Page 23 of 39 
 
o Harm reduction service use 
o Drug-related and sexual risk behavior 
o Depressive symptoms 
o Social support 
o Stigma 
o Quality of life 
o Self-efficacy 
o Hepatitis C and B testing and medication 
o Healthcare utilization 
o HIV care continuum outcomes via verified medical record abstraction and self-
report (e.g., experience with HIV testing, HIV care and HIV treatment) 
• 
HIV test results 
• 
HIV RNA test results (GeneXpert) 
• 
Detailed contact and locator information 
• 
CD4 count (in local laboratory) 
• 
HIV resistance testing 
 
9.2.3 Data entry methods 
 
Data from the clinical trial cohort will be collected using tablets on which we will program an 
electronic data collection application. The survey will be downloaded onto the tablets with 
participant data routinely pushed to a secure web cloud server. The interviewer will read out the 
questions and enter the appropriate answers into the tablet in a private area. Logic checks and 
field restrictions will be built into the survey to maximize accuracy/integrity of data collected as 
there will be no paper copies of the survey. All interviewers will be adequately trained on the use 
of the tablets for capturing data prior to coming into contact with study participants.   
    
The database management system will provide a confidential and secure database with 
accurate records.  Data files will be maintained in two computer systems and routine backups 
conducted to protect against data loss. Laboratory data from the YRG CARE laboratory will be 
merged into the study database on a regular basis by study ID. The lab has a network server 
(HP E2000) and a backup tape device (SUREDAT) for storage of data. Data confidentiality will 
be maintained by storing signed consent forms in double-locked filing cabinets on-site at the 
research site and electronic data forms with personal identifiers will be available on the tablet for 
local research site staff but all identifiers will be removed before export to JHU. Data will be 
imported into Stata and R where further editing and checks will be performed prior to data 
analyses. 
 
 
10. CLINICAL MANAGEMENT 
 
10.1 Clinical Management of Adverse Events 
 
The objective of community-based care is to provide first-line ART in a setting that welcomes 
PWID and provides other relevant services for them. Based on prior experience with this 
population we anticipate high rates of AEs and SAEs. The medical team will manage common 
health issues such as bandaging skin wounds, providing symptomatic treatment for diarrhea 
and upper respiratory tract infections, and evaluating fevers. Participants with confirmed or 
suspected TB will be referred to one of many TB diagnosis, treatment, and support resources, 

Page 24 of 39 
 
managed by National TB Elimination Program (NTEP). Participants needing urgent care will be 
referred and accompanied to the nearest public sector hospital.    
 
10.2 Pregnancy 
 
Pregnant women are excluded from joining this study as they require specialized HIV 
management. Women who become pregnant while already enrolled in the study, will be referred 
to specialized government clinics for HIV treatment. In such cases, women may continue to be 
followed in the trial if they wish. 
 
10.3 Treatment Failure 
 
Treatment failure is defined in this protocol as HIV RNA ≥1000 c/mL. Participants experiencing 
treatment failure at the 6-month visit will be enrolled in the adaptive trial, where they will be 
assigned to adherence-plus or routine adherence support. In cases where clinically significant 
drug resistance is suspected (i.e., virologic failure in persons with convincing evidence of high 
adherence), we will refer participants to centers where they can be evaluated for second-line 
treatment. 
 
 
11. ANALYTICAL CONSIDERATIONS 
 
11.1 Design Overview 
 
For phase-1, our design is a 2x2 individual randomized factorial design to evaluate two 
interventions: 1) same-day ART vs. standard ART initiation; and 2) community-based care vs. 
facility-based care. Phase-2 is adaptive and includes participants experiencing treatment failure 
at 6 months in phase-1, who will be randomized a second time to adherence-plus vs. routine 
adherence support.  
 
The primary outcome for both phase-1 and 2 of this trial is viral suppression. For phase-1, viral 
suppression will be assessed at 6 months and for phase-2, viral suppression will be assessed at 
12 months (i.e., 6 months after the second randomization). Please see the statistical analysis 
plan (SAP), a separate document, for detailed analytic approach. 
 
11.2 Hypotheses 
 
11.2.1 Phase-1: Factorial trial  
 
Among PWID living with HIV who are ART-naïve or who have been off ART for a prolonged 
period, and have an HIV RNA ≥1,000 c/mL, same-day ART and community-based care will 
increase the proportion with viral suppression at 6 months, compared with standard ART 
initiation and facility-based care. 
 
11.2.2 Phase-2: Adaptive trial 
 
Use of enhanced navigation and psychosocial support (adherence-plus) for participants who 
experience treatment failure at 6 months will increase the proportion with viral suppression at 12 

Page 25 of 39 
 
months (i.e., 6 months after the second randomization), compared with routine adherence 
support. 
 
11.3 Study Objectives 
 
11.3.1 Primary Objectives 
 
11.3.1.1 Phase-1 – To determine the effects of same-day ART (compared with standard ART 
initiation) and community-based care (compared with facility-based care) on viral suppression at 
6 months following phase-1 randomization, among PWID living with HIV. 
 
 
 
 
 
 
11.3.1.2 Phase-2 – To determine the effect of adherence-plus (compared with routine 
adherence support) on viral suppression at 6 months following phase-2 randomization 
(corresponding to 12 months after phase-1 randomization), among PWID living with HIV who 
experience early virologic failure. 
 
11.3.2 Secondary Objectives 
 
11.3.2.1 Phase-1 – To determine the effects of same-day ART and community-based care on 
viral suppression among PWID living with HIV at 3, 12, and 18 months, relative to their control 
conditions. 
 
11.3.2.2 Phase-2 – To determine the effect of adherence-plus (compared with routine 
adherence support) on viral suppression at 12 months following phase-2 randomization (18 
months following phase-1 randomization), among PWID living with HIV who experience early 
virologic failure. 
 
11.3.2.3 Phase-1&2 – To determine the effects of same-day ART, community-based care, and 
adherence-plus on all-cause mortality among PWID living with HIV, relative to their control 
conditions. 
 
11.3.2.4 Phase-1&2 – To determine the effects of same-day ART, community-based care, and 
adherence-plus on linkage to ART at the clinics at 3 and 6 months among PWID living with HIV, 
relative to their control conditions. 
 
11.3.2.5 Phase-1&2 – To determine the effects of same-day ART, community-based care, and 
adherence-plus on self-reported ART adherence among PWID living with HIV, relative to their 
control conditions. 
 
11.3.2.6 Phase-1&2 – To determine the effects of same-day ART, community-based care, and 
adherence-plus on ART adherence measured by medication possession ratio among PWID 
living with HIV, relative to their control conditions. 
 
11.3.3 Exploratory Objectives 
 
11.3.3.1 Phase-1&2 - To determine the effects of same-day ART, community-based care, and 
adherence-plus on quality of life (QOL) among PWID living with HIV, relative to their control 
conditions. 
 

Page 26 of 39 
 
11.3.3.2 Phase-1&2 - To determine the effects of same-day ART, community-based care, and 
adherence-plus on use of medication for opioid use disorder (MOUD) among PWID living with 
HIV, relative to their control conditions. 
 
11.3.3.3 Phase-1&2 - To determine the effects of same-day ART, community-based care, and 
adherence-plus on HIV- and drug use-related stigma among PWID living with HIV, relative to 
their control conditions. 
 
11.3.3.4 Phase-1&2 - To determine the effects of same-day ART, community-based care, and 
adherence-plus on depression symptoms among PWID living with HIV, relative to their control 
conditions. 
 
11.3.3.5 Phase-1&2 - To determine the effects of same-day ART, community-based care, and 
adherence-plus on HIV treatment self-efficacy among PWID living with HIV, relative to their 
control conditions. 
 
11.3.3.6 Phase-1 - To determine the effects of same-day ART and community-based care on 
the development of new antiretroviral drug resistance among PWID living with HIV, relative to 
their control conditions. 
 
 
 

Page 27 of 39 
 
11.4 Outcome measures 
 
Table 4. Study outcome measures 
Title 
Description 
Time Frame 
Primary Outcomes 
 
 
1) Percentage of participants 
with viral load suppression 
(HIV RNA <1000 c/mL) at 6 
months after phase-1 
randomization 
HIV RNA levels in blood measured with 
GeneXpert 2 module, Xpert HIV-1 Viral Load XC 
Cartridge (Cepheid AB, Sweden). Lower limit of 
quantification 40 copies/mL 
Measured at 6 months 
following phase-1 
randomization 
2) Percentage of participants 
with viral load suppression 
(HIV RNA <1000 c/mL) at 6 
months after phase-2 
randomization 
HIV RNA levels in blood measured with 
GeneXpert 2 module, Xpert HIV-1 Viral Load XC 
Cartridge (Cepheid AB, Sweden). Lower limit of 
quantification 40 copies/mL 
Measured at 6 months 
following phase-2 
randomization (corresponding 
to 12 months after phase-1 
randomization) 
Secondary Outcomes 
 
 
1) Percentage of participants 
randomized in phase-1 with 
viral suppression (HIV RNA 
<1000 c/mL) at non-primary 
time points (i.e., 3, 12, and 18 
months). 
HIV RNA levels in blood measured with 
GeneXpert 2 module, Xpert HIV-1 Viral Load XC 
Cartridge (Cepheid AB, Sweden). Lower limit of 
quantification 40 copies/mL 
Measured at 3, 12, and 18 
months following phase-1 
randomization 
2) Percentage of participants 
randomized in phase-2 with 
viral suppression (HIV RNA 
<1000 c/mL) at non-primary 
time point (18 months). 
HIV RNA levels in blood measured with 
GeneXpert 2 module, Xpert HIV-1 Viral Load XC 
Cartridge (Cepheid AB, Sweden). Lower limit of 
quantification 40 copies/mL 
Measured at 12 months 
following phase-2 
randomization (corresponding 
to 18 months after phase-1 
randomization) 
3) All-cause mortality rate 
Research staff and outreach workers collected 
reports on participant deaths. Verified deaths 
required one of the following: i) hospital records or 
death certificate, ii) confirmation of death from a 
family member, or iii) confirmation of death from 
an eyewitness (usually another PWID). Rate will 
be presented as events per unit observation time. 
Measured up to outer window 
of 18-month visit (21 months) 
4) Percentage of participants 
who link to ART at a clinic by 
3- or 6-months following 
randomization  
Linkage to ART will be defined as collecting one 
or more ART prescriptions from a clinic by 3 
months and 6 months, captured by medical record 
abstraction or, in the absence of medical record 
data, participant self-report of ART collection from 
a clinic. 
Measured at 3 months and 6 
months following phase-1 
randomization and 6 months 
following phase-2 
randomization (corresponding 
to 12 months after phase-1 
randomization) 
5) Percentage of participants 
adherent to ART measured 
by self-report 
Participants will be classified as adherent if they 
report taking ART in the prior 30 days and report 
adherence of 80% or higher using a visual analog 
scale (range: 0% to 100%), with higher numbers 
indicating higher adherence   
Measured at 6 months 
following phase-1 
randomization and 6 months 
following phase-2 
randomization (corresponding 
to 12 months after phase-1 
randomization)   

Page 28 of 39 
 
6) Percentage of participants 
adherent to ART measured 
by medication possession 
ratio (MPR) 
ART fill data will be abstracted from medical 
records. In phase-1, participants will be classified 
as adherent if they have at least one ART refill by 
3 months (91 days) and have an MPR of 80% or 
higher in the period between the first ART fill in 
the clinic and 6 months (182 days).  
 
In phase-2, participants will be classified as 
adherent if they have at least one ART refill by 3 
months (91 days) following the second 
randomization (or prior to the second 
randomization) and have an MPR of 80% or 
higher in the period between the first ART refill (or 
the second randomization if the first ART refill was 
prior to the second randomization) and 6 months 
(182 days following the second randomization). 
Measured at 6 months 
following phase-1 
randomization and 6 months 
following phase-2 
randomization (corresponding 
to 12 months after phase-1 
randomization)   
Exploratory outcomes 
 
 
1) Quality of life (QOL) score 
QOL will be measured with a modified EuroQol 
EQ-5D-3L questionnaire with a visual analogue 
scale. Higher scores on both the EQ-5D-3L (range 
0 to 1) and visual analog scale (range 0 to 100) 
indicate higher QOL  
Measured at 3, 6, 12, and 18 
months after phase-1 
randomization 
2) Percentage of participants 
who use of medication for 
opioid use disorder (MOUD) 
Use of MOUD is captured by self-reported in the 
research visit questionnaire. Participants are 
asked whether they received MOUD in the prior 6 
months and, if they did so, they are asked about 
frequency of MOUD visits.  
Measured at 3, 6, 12, and 18 
months after phase-1 
randomization 
3) Stigma score 
We will measure both HIV-related and drug use-
related stigma as separate constructs using a 
survey 
(https://doi.org/10.1016/j.drugpo.2021.103354). 
Each construct is evaluated by three sub-scales: 
1) anticipated healthcare stigma, 2) enacted 
healthcare stigma, and 3) internalized stigma. All 
stigma subscales will be queried using Likert 
scales that range from 0 to 3, with higher scores 
indicating more stigma. For anticipated and 
enacted stigma, participants will be classified as 
experiencing stigma if the Likert scale is >0 for 
any one item (i.e., analyzed as a dichotomous 
outcome). For the internalized stigma subscale, 
scores will be converted to a continuous mean 
outcome from 0 to 3.0, with higher scores 
indicating more stigma.  
Measured at 3, 6, 12, and 18 
months after phase-1 
randomization 
4) Percentage of participants 
with at least moderate 
depression symptoms 
Depression will be measured with the PHQ-9 
questionnaire. The scoring range is 0 to 27, with 
higher values indicating more depression 
symptoms. Participants will be categorized as 
having at least moderate depression symptoms if 
the score is ≥ 10.   
Measured at 3, 6, 12, and 18 
months after phase-1 
randomization 
5) HIV treatment self-efficacy 
HIV treatment self-efficacy will be measured with 
a modified HIV Treatment Adherence Self-
Efficacy Scale. Items will be averaged to calculate 
a self-efficacy score, ranging from 0 to 100, with 
higher scores indicating higher self-efficacy. 
Measured at 3, 6, 12, and 18 
months after phase-1 
randomization 

Page 29 of 39 
 
6) Percentage of participants 
who acquire drug resistance 
mutations (DRMs) at 12 
months 
New antiretroviral drug resistance will be defined 
as the detection of one or more reverse 
transcriptase or integrase gene DRMs at follow-up 
that was not present at baseline, among 
participants with HIV RNA ≥1000 c/mL at the 12-
month visit. DRMs will be interpreted using the 
online Stanford HIV Database 
(https://hivdb.stanford.edu)  
Measured at baseline and 12 
months after phase-1 
randomization 
 
 
11.5 Sample Size Considerations 
 
For phase, 1, sample size 
calculations were done for the 
primary hypothesis of improved 
viral suppression at 6 months 
for each intervention, assuming 
no interaction between 
interventions (i.e., powered for 
intervention main effects) using 
an intention to treat approach. 
Thus, the effective sample size 
for each of the two comparisons 
is equivalent to the overall 
sample. For example, to assess 
the efficacy of same-day ART, 
we would compare outcomes in 
the 2 arms with same-day ART 
to those in the 2 arms without same-day ART. Assuming a two-sided α=0.05 and a range of 
viral suppression in the standard ART initiation arm of 15-35%, which is consistent with what we 
have observed in this population previously, we calculated sample sizes needed for a range of 
effect sizes (5-30%). The figure reflects the sample size needed per comparator group (e.g., 2 
groups for main effects) assuming equal distribution across arms. We chose a total sample of 
800 (or 200 per 4 intervention arms; 400 per the 2 comparison groups) because we will have 
90% power to detect viral suppression rates of 10-12 percentage points or larger for the main 
effects of same-day ART and community-based care.   
 
For phase-2, sample size 
calculations were done for the 
primary hypothesis of 
improved viral suppression at 
6 months following phase-2 
randomization (corresponding 
to 12 months after phase-1 
randomization) for the 
adherence-plus intervention 
compared to routine 
adherence support. Assuming 
a two-sided α=0.05 and a 
range of viral suppression 
(VS) in the routine adherence 
support arm of 20-50%, we 
 
0
100
200
300
400
500
600
700
800
900
1000
20%
22%
24%
26%
28%
30%
32%
34%
36%
38%
40%
42%
44%
46%
48%
Sample size needed in each comparisoon group
Treatment success in intervention arm
15%
20%
25%
30%
35%
Treatment success in control arm
Differences that 
can be detected 
with main effects 
analysis
Differences that can be detected for 
2 way interactions

Page 30 of 39 
 
calculated power for a range of sample sizes – given the sample size is out of our control due to 
the adaptive design – and effect sizes (i.e., prevalence differences). Sample sizes ranged from 
120 to 200, representing 15%-25% of the 800 enrolled trial participants. The figure reflects the 
total sample size needed assuming equal distribution across the two arms (i.e., 1:1 
randomization). With a total sample size of 125 or more, we will have at least 80% power to 
detect a prevalence difference of at least 25%.  
 
11.6 Enrollment/Stratification/Randomization/Blinding Procedures 
 
Participants enrolling in phase-1 will be randomized to one of four arms (1:1:1:1) according to 
the factorial design. In phase-2, participants meeting the definition of treatment failure at the 6-
month visit will be randomized (1:1) (a second time) to routine adherence support or adherence-
plus. In both phases, randomization allocation lists will be stratified by site and lists will be 
blocked – block sizes of 4, 8, and 12 for phase-1 and sizes 2, 4, and 6 for phase-2.  
 
Randomization lists will be generated at the US data management/analysis site using statistical 
software. Then, site-specific randomization allocations lists will be programmed into the study’s 
electronic data collection application, which will automatically select the next allocation for each 
eligible and enrolled participant and display this for study staff on the tablet. Study site staff will 
not have access to the randomization allocation list; rather, they will only see the allocation for 
the participant currently being randomized. As an additional check on randomization, site staff 
will contact the study coordinator (who will keep a partial allocation list) to check that the most 
recent allocation matches the list.   
 
11.7 Participant Enrollment and Follow-up 
 
We anticipate enrolling 800 (approximately 400 per site) people over a period of 20-24 months 
with an average of 15-20 participants per site per month. Enrolled participants will complete the 
baseline survey and be randomized. Participants will be followed at 3, 6, 12, and 18 months. 
 
 
12. DATA HANDLING AND RECORDKEEPING 
 
12.1 Data Management Responsibilities 
 
Our team will follow previously established data protocols that we used in prior projects. We will 
develop an electronic data collection application for the collection of individual participant data at 
study sites. Site interviewers will record responses to survey questions directly into the tablet. 
The survey will be downloaded onto the tablets with participant data routinely pushed to a 
secure web cloud server. Researchers at Johns Hopkins, led by Allison McFall, PhD, will have 
full access to data on the web cloud server from all recruitment sites via a secure password 
protected web-portal. Study analyses will be conducted by research members at the Bloomberg 
School of Public Health. 
 
12.2 Quality Control and Quality Assurance 
 
12.2.1. Procedures to ensure the validity and integrity of the data 
 

Page 31 of 39 
 
All field staff, interviewers, phlebotomists and clinicians who will come into contact with study 
participants will be required to complete research ethics and good clinical practice (GCP) 
training.  
 
Lab technicians/phlebotomists at YRG CARE have undergone training on research ethics and 
good clinical laboratory practices (GCLP). The YRG CARE Infectious Disease Lab is certified by 
the College of American Pathologists, United Kingdom National External Quality Assurance 
Scheme, and the Virologic Quality Assessment Program, US and by the AIDS Clinical Trials 
Group and Abbott Laboratories Inc, US to perform HIV-1 genotypic resistance testing. GCLP 
are monitored by Johns Hopkins, Family Health International, and PPD. 
 
Additional details can be found in the Data Safety and Monitoring Plan.  
 
12.2.2. Procedures to guarantee the accuracy and completeness of the data 
 
Our primary mode of data collection will be through the electronic data collection application. 
Additional details can be found in the Data Safety and Monitoring Plan.  
 
 
13. HUMAN SUBJECTS PROTECTIONS 
 
13.1 Institutional Review Board/Ethics Committee 
 
As in past studies, we are using JHM templates for the study protocol, informed consent form 
(ICF), and waiver of written consent (oral consent scripts). Once these documents are reviewed, 
approved, and stamped by the JHM IRB, we will submit them to the YRGCARE IRB. Following 
this approval (including the occasional need to go back to JHM IRB with a change required by 
YRGCARE), we will send ICF and other critical documents for translation to Hindi and other 
languages (other than English) that will be needed. Finally, the translated versions and 
certificates of translation will be submitted back to both IRBs. All sites will use the same consent 
forms. 
 
Y.R. Gaitonde Med, Educational & Rsch Foundation IRB #1 (IRB00001423) has reviewed and 
approved an early version of this proposal. They will review all subsequent amendments once 
approved by JHM IRB. 
 
13.2 Vulnerable Participants 
 
13.2.1 Pregnant women and fetuses 
 
Pregnant women are excluded from joining this study as they require specialized HIV 
management. Women who become pregnant while already enrolled in the study, will be referred 
to specialized government clinics for HIV treatment. In such cases, women may continue to be 
followed in the trial if they wish. 
 
13.2.2 Prisoners 
 
It is possible that persons who are enrolled may become prisoners during the course of the 
study. This means that they may become prisoners while they are taking HIV treatment. We do 

Page 32 of 39 
 
not have formal agreements in place to provide medication while participants are in prison. 
However, we will work with the prisons in each of the cities to establish agreements where 
possible. The goal will be to support study participants to continue their treatment while in prison 
by either delivering treatment through peers, family members and other prison staff. However, 
we will not conduct any research activities while study participants are in prison.  
 
13.2.3 Illiterate participants 
 
Some of our research participants will be illiterate. As required by the JHM and YRGCARE IRB, 
all informed consent documents will be read verbatim and participants who cannot sign will be 
asked to provide a thumb print.  
 
13.3 Informed Consent 
 
13.3.1 Informed consent process 
 
Potentially eligible participants will complete an oral consent script prior to screening, which 
includes biometric registration, a questionnaire, and a blood draw. Participants who are eligible 
after screening and wish to join the study will be asked to provide written informed consent. 
 
To obtain consent, participants will meet with a research staff member in a private area to 
discuss the research. Any study staff member who obtains informed consent from study 
participants will have completed requisite human subjects training. The research staff will 
present a brief overview of the study and what is being requested of the participant. If 
participants continue to express interest, the research staff will present the study in detail in 
conjunction with the informed consent script or document. Participants will be encouraged to 
ask questions during the consent process. Following this discussion, subjects will be asked 
comprehension questions to gauge the degree to which they have understood the study 
procedures. Participants will then be asked to provide a signature or thumbprint (if illiterate).  
 
Consent documents will be approved by JHU and YRGCARE IRBs. The rights and welfare of 
the participants will be protected by emphasizing to them that the availability of medical care will 
not be affected if they decline to participate in this study. In particular, receipt of non-research 
related services at ICCs is not conditioned upon participation in any aspect of the study. 
 
13.3.2 Documentation of informed consent 
 
Participants who provide written consent will be given a copy of the consent. In addition, a 
signed copy of the consent will be maintained in locked cabinets at each of the study sites. 
 
13.4 Risks 
 
13.4.1 PWID participants in randomized trial 
 
Potential risks to clinical trial participants include loss of confidentiality, minor discomfort from 
blood draw, embarrassment responding to questions about drug or sexual behaviors, and 
anxiety from HIV testing. The likelihood of these risks is moderate, and the potential 
seriousness is minor. Of the 3 interventions being evaluated in the trial, one is policy level 
(timing of ART initiation), another is structural (site of HIV care) and one is psychosocial (patient 
counseling and navigation). The medical risks of these interventions are commensurate with 

Page 33 of 39 
 
standard treatment of HIV infection. Of note, prior work by our group has documented high all-
cause mortality rates among PWID living with HIV in these Indian cities. All trial participants will 
receive HIV treatment and monitoring consistent with HIV treatment guidelines in India.  
 
13.5 Social Impact Events 
 
Legal and social risks are possible because study participants are PWID who engage in illegal 
activities. However, we will take multiple precautions to protect against breaches of 
confidentiality. Identifying information will only be accessible to study site staff. Interviewers will 
be trained to not discuss the participants in the study. Results will be reported in aggregate form 
only. Interview and laboratory data will be stored and managed on a secure web cloud server. 
These data will be password-protected and available only to a defined group of data managers 
and analysts who are working on the trial. 
 
13.6 Benefits 
 
This study has the potential to provide benefits to study subjects if one or more of the 
interventions improves treatment outcomes compared with standard care. Additionally, results 
of HIV viral load testing from baseline and from the 6-month time point will be given to all trial 
participants.  
 
This study will contribute to knowledge about the effectiveness of three interventions designed 
to improve HIV treatment outcomes among PWID in India. 
 
13.7 Compensation 
 
US dollar (USD) values based on exchange rate of India Rupee (INR) 72 per USD 1. 
 
13.7.1 PWID participants in randomized trial 
 
Screening/baseline visit (1 or 2 days) 
Participants who begin screening but are found ineligible after the oral screening questionnaire 
(and do not provide blood and urine samples) will be paid 200 INR (2.78 USD). Participants who 
complete the oral and laboratory screening procedures (requiring a blood sample) will be paid 
300 INR (4.17 USD), irrespective of eligibility or decision to participate. Participants will be 
reimbursed a total of 500 INR (6.94 USD) if they complete screening processes, are determined 
to be eligible, complete the baseline questionnaire, and are enrolled into the study (300 INR for 
screening and 200 INR for additional baseline activities). 
    
Follow-up visits 
Participants will be paid 500 INR (6.94 USD) for each of the four study follow-up visits they 
complete (3 months, 6 months, 12 months, and 18 months). 
 
Consequently, PWID participants in the randomized trial can earn a total of 2,500 INR (34.72 
USD) for screening, completing the baseline procedures and attending all follow-up visits.  
 
13.8 Participant Privacy and Confidentiality 
 
Loss of confidentiality, particularly regarding stigmatizing information or illegal behavior, is a 
potential risk to all participants. To minimize this risk among participants in the randomized trial, 

Page 34 of 39 
 
we will keep informed consent documents in a locked file cabinet in a locked room, separate 
from other study data. Interviewers will be trained to not discuss the participants in the study. In 
electronic databases, identifying information will only be accessible to study site staff, and we 
will use unique study identification numbers in the other working data files. Electronic data will 
be transferred to a secure web cloud sever from study sites at 2-3 times per day via secure, 
encrypted transmission. Blood draws will be conducted by trained phlebotomists. We will 
conduct point-of-care pregnancy tests and screen for breastfeeding in all women assessed for 
trial eligibility.  
 
Safeguards will also be taken to ensure that subjects’ confidentiality is maintained.  These 
measures include: 1) unique study numbers in databases and on specimens; 2) restricting 
access to identifiers to only study site staff with the need to use the information for tracking and 
other study procedures; 3) restricting access to locked files and password protected databases 
to essential study personnel. All data will be reported in aggregate form only without personal 
identifiers.  In the case of an adverse event, policies and procedures are in place to work with 
the subject and to keep the study’s governing bodies informed. 
 
13.9 Certificates of Confidentiality 
 
Certificates of confidentiality are not recognized by the Indian Government. 
 
13.10 Critical Event Reporting 
 
The Indian research coordinators (Drs. Jiban Baishya and Ashwini Kedar) will report 
unanticipated problems and study deviations to the local IRB (YRGCARE IRB). Such events will 
also be communicated with the US investigators and Dr. Lucas (JHU PI) will report to the JHM 
IRB. Dr. Lucas will report unanticipated problems or study deviations that involve risks to 
participants or others promptly to the JHM IRB in accordance with Organization Policy. Minor 
problems and protocol deviations (which pose no risk to subjects or others) will be reported in 
annual protocol continuing review. 
 
13.11 New Findings 
 
If any study-relevant new findings are reported during the course of the study that may impact 
the willingness of participants to continue on study and/or willingness to join the study, the new 
findings will be discussed with study staff and the consent form will be revised and submitted to 
the relevant IRBs. Participants will be reconsented via a consent form that includes discussion 
of the new findings. 
 
13.12 Study Discontinuation 
 
The study may be discontinued at any time by the IRB, DSMB, or NIDA as part of their duties to 
ensure that research participants are protected. 
 
When the study ends or if a participant’s participation in the study ends prematurely, participants 
that were assigned to community-based care at the integrated care centers will either continue 
to receive care there (if a source of support can be identified) or they will be transferred to 
facility-based care at a government ART center (current standard of care). The adherence-plus 
intervention is limited to 6 months; participants will return to routine adherence support after the 
intervention concludes. 

Page 35 of 39 
 
 
13.13 Ancillary Protection 
 
As is required by the Government of India, if a person is injured as a result of being in the study 
s/he will be given immediate treatment of injuries as per YRGCARE’s standard of care. The 
entire cost of health care and compensation due to study related injury or death will be covered 
by YRGCARE through “Clinical Trials Insurance.”   
  
1. In the case of an injury occurring to the clinical trial participant, he or she shall be given 
free medical management as long as required. 
 
2. In case the injury occurring to the trial participant is related to the clinical trial, such 
participant shall also be entitled for financial compensation as per order of the Licensing 
Authority (The Drug Controller General of India) and the financial compensation will be 
over and above any expenses incurred on the medical management of the participant. 
 
3. In the case of clinical trial related death of the participant, his/her nominee(s) would be 
entitled for financial compensation, as per the order of the Licensing Authority and the 
financial compensation will be over and above any expenses incurred on the medical 
management of the participant. 
 
4. Financial compensation shall be paid by the Clinical Trial Insurance (New India 
Assurance Co. Ltd) if the death is due to the reasons specified under the Rule 122 DAB 
of the “Drugs and Cosmetics Rules, 1945” and as per the Order from the “Central Drugs 
Standard Control Organization." 
 
 
14. ADMINSTRATIVE PROCEDURES 
 
14.1 Protocol Registration 
 
This protocol is registered in ClinicalTrials.gov, ID: NCT05165810. 
 
14.2 Study Implementation 
 
14.2.1 Coordinating Center 
 
This clinical trial will be conducted exclusively at sites in India, through a longstanding 
collaboration between researchers at Johns Hopkins University, in Baltimore, MD, USA and the 
YR Gaitonde Centre for AIDS Research and Education (YRGCARE) in Chennai, Tamil Nadu, 
India. JHU will serve as the coordinating center for this study, consistent with previous trials. 
YRGCARE has facilities in multiple cities to support research and service delivery for key 
populations. YRGCARE hires staff at each site and directly oversees activities at each site. 
 
14.2.2 Contact information 
 
The US-based MPIs for this trial (Drs. Lucas and Mehta) have direct contact information for 
supervisors and site-level YRGCARE personnel. 
 

Page 36 of 39 
 
14.2.3 Federalwide assurance (FWA) 
 
Each site has an active FWA: FWA00000672. This FWA provides assurance and oversight for 
components in the candidate cites of New Delhi and Kanpur. 
 
14.2.4 Protocol version and amendments 
 
The most recent version of the protocol and any amendments will be available to all study 
personnel on a shared cloud drive. The senior Indian research coordinator (Dr. Jiban Jyoti 
Baishya) and the Indian Co-PI (Mr. AK Srikrishnan) will be responsible for assuring that 
recruitment sites are using the most up-to-date protocol and ICF. 
 
 
 
 
 

Page 37 of 39 
 
 
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