Strategies to Improve the HIV Care Continuum Among Key Populations in India
Phase: NA
Conditions: HIV Infections
Sponsor: Johns Hopkins University

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 1 of 44 
 
 
 
Strategies to Improve the HIV Care Continuum among Key Populations in India: a Cluster 
Randomized Trial 
 
 
 
 
Sponsored by: 
 
US National Institute on Drug Abuse 
Indian National AIDS Control Organisation 
Elton John AIDS Foundation 
 
 
 
ClinicalTrials.gov Protocol Number: 
NCT02969915 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Co-Chairs: 
Gregory M. Lucas, MD, PhD 
Shruti H. Mehta, PhD 
 
 
 
 
 
Version 2.0 
20 October 2022 
 
 
 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 2 of 44 
 
 
1. TABLE OF CONTENTS 
2. KEY ROLES 
5 
3. LIST OF ABBREVIATIONS 
7 
4. PROTOCOL SUMMARY 
8 
5. INTRODUCTION 
11 
5.1 BACKGROUND INFORMATION 
11 
5.2 RATIONALE 
11 
5.3 STUDY HYPOTHESES 
13 
6. OBJECTIVES 
13 
6.1 PRIMARY OBJECTIVE 
13 
6.2 SECONDARY OBJECTIVES 
13 
6.3 EXPLORATORY OBJECTIVES 
13 
7. STUDY DESIGN 
14 
8. STUDY POPULATION 
14 
8.1 INCLUSION/EXCLUSION CRITERIA 
15 
8.1.1 PARTICIPANT INCLUSION CRITERIA 
15 
8.1.2 PARTICIPANT EXCLUSION CRITERIA 
15 
8.2 RECRUITMENT PROCESS 
16 
8.3 PARTICIPANT RETENTION 
16 
9. INTERVENTIONS 
17 
9.1 CONTROL CONDITION 
18 
9.2 INCENTIVE INTERVENTION 
18 
10. STUDY PROCEDURES/EVALUATIONS 
19 
10.1 CLINICAL EVALUATIONS AND PROCEDURES 
19 
10.2 LABORATORY EVALUATIONS 
20 
11. ASSESSMENT OF SAFETY 
21 
11.1 SAFETY ASSESSMENT OVERVIEW 
21 
11.2 DEFINITIONS 
21 
11.2.1 DEFINITION OF ADVERSE EVENTS (AE) 
21 
11.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
22 
11.3 REPORTING REQUIREMENTS FOR THIS STUDY 
22 
12. CLINICAL MANAGEMENT 
23 
12.1 CLINICAL MANAGEMENT OF ADVERSE EVENTS 
23 
12.2 CRITERIA FOR DISCONTINUATION 
23 
12.2.1 CRITERIA FOR PERMANENT INTERVENTION DISCONTINUATION FOR AN INDIVIDUAL 
PARTICIPANT 
23 
12.2.2 CRITERIA FOR PREMATURE STUDY DISCONTINUATION FOR AN INDIVIDUAL PARTICIPANT 23 
13. STATISTICAL CONSIDERATIONS 
23 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 3 of 44 
 
13.1 OVERVIEW AND GENERAL DESIGN ISSUES 
23 
13.2 STUDY ENDPOINTS 
24 
13.2.1 PRIMARY ENDPOINT 
24 
13.2.2 SECONDARY ENDPOINTS 
24 
13.2.3 EXPLORATORY ENDPOINTS 
25 
13.3 STUDY OBJECTIVES AND HYPOTHESES 
26 
13.4 SAMPLE SIZE CONSIDERATIONS 
27 
13.5 STUDY SITE SELECTION AND PAIR MATCHING 
28 
13.6 RANDOMIZATION AND MASKING PROCEDURES 
29 
13.7 PARTICIPANT ENROLLMENT AND FOLLOW-UP 
30 
13.8 DATA AND SAFETY MONITORING 
30 
13.9 ANALYSIS PLAN 
31 
13.9.1 ANALYSIS PLAN FOR PRIMARY OUTCOME 
31 
13.9.2 SECONDARY OUTCOMES 
32 
13.9.3 EXPLORATORY OUTCOMES 
32 
14. DATA HANDLING AND RECORDKEEPING 
35 
14.1 DATA MANAGEMENT RESPONSIBILITIES 
35 
14.2 ESSENTIAL/SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
35 
14.3 QUALITY CONTROL AND QUALITY ASSURANCE 
36 
14.3.1 PROCEDURES TO ENSURE THE VALIDITY AND INTEGRITY OF THE DATA 
36 
14.3.2 PROCEDURES TO GUARANTEE THE ACCURACY AND COMPLETENESS OF THE DATA 
36 
15. CLINICAL SITE MONITORING 
36 
16. HUMAN SUBJECTS PROTECTIONS 
36 
16.1 INSTITUTIONAL REVIEW BOARDS 
36 
16.2 VULNERABLE PARTICIPANTS 
37 
16.2.1 PREGNANT WOMEN AND FETUSES 
37 
16.2.2 PRISONERS 
37 
16.2.3 CHILDREN 
37 
16.2.4 ILLITERATE PARTICIPANTS 
37 
16.3 INFORMED CONSENT 
37 
16.3.1 INFORMED CONSENT PROCESS 
37 
16.3.2 ASSENT PROCESS 
38 
16.3.3 DOCUMENTATION OF INFORMED CONSENT 
38 
16.4 RISKS 
38 
16.5 SOCIAL IMPACT EVENTS 
39 
16.6 BENEFITS 
40 
16.7 COMPENSATION 
40 
16.8 PARTICIPANT PRIVACY AND CONFIDENTIALITY 
40 
16.9 CERTIFICATES OF CONFIDENTIALITY 
41 
16.10 STUDY DISCONTINUATION 
41 
16.11 POST-TRIAL ACCESS 
41 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 4 of 44 
 
16.12 COMMUNITY ADVISORY BOARD AND OTHER RELEVANT STAKEHOLDERS 
41 
17. ADMINISTRATIVE PROCEDURES 
41 
17.1 PROTOCOL REGISTRATION 
41 
17.2 REGULATORY OVERSIGHT 
41 
17.3 STUDY IMPLEMENTATION 
41 
17.4 CLINICALTRIALS.GOV 
41 
18. REFERENCES 
41 
19. APPENDICES 
42 
APPENDIX I. SCHEDULE OF PROCEDURES AND EVALUATIONS FOR COHORT PARTICIPANTS 
FOLLOWED IN CLUSTER RANDOMIZED TRIAL 
43 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 5 of 44 
 
2. KEY ROLES 
Co-Chairs 
Shruti Mehta, PhD MPH 
Professor & Deputy Chair of Epidemiology  
Department, Bloomberg School of Public 
Health 
Johns Hopkins University 
615 N Wolfe Street, E6546 
Baltimore, MD 21205 
Phone: 443-287-3837 
Email: smehta@jhu.edu   
 
Gregory M. Lucas, MD PhD 
Professor of Medicine 
Johns Hopkins University 
1830 E. Monument St, Room 435A 
Baltimore, MD 21287 
Phone: 410-614-0560 
E-mail: glucas@jhmi.edu 
 
Co-Investigators 
Sunil Suhas Solomon, MBBS PhD MPH 
Associate Professor  of Medicine 
Johns Hopkins University 
1830 E. Monument Street, Room 444 
Baltimore, MD 21287  
Phone: 443-287-9596 
E-mail: sss@jhmi.edu  
 
David Celentano, ScD MHS 
Professor & Director of Epidemiology  
Department, Bloomberg School of Public 
Health  
Johns Hopkins University 
615 N Wolfe Street, W6041 
Baltimore, MD 21205 
Phone: 410-955-3286 
E-mail: dcelent1@jhu.edu 
 
 
 
 
 
 
 
John B. Wong, MD 
Professor of Medicine 
Tufts University School of Medicine 
800 Washington St, Suite 302 
Boston, MA 02111 
Phone: 617-636-5695 
E-mail: jwong@tuftsmedicalcenter.org 
 
Biostatistican 
Allison McFall, MHS, PhD 
Johns Hopkins Bloomberg School of Public 
Health  
615 N Wolfe Street, E6546 
Baltimore, MD 21205 
Phone: 410-955-3578 
E-mail: amcfall2@jhu.edu  
 
Budget and implementation 
Katie Zook, CCRP 
Research Program Manager 
Johns Hopkins University School of 
Medicine 
1830 E. Monument Street, Room 8032 
Baltimore, MD 21287 
Phone: 410-614-2938 
E-mail: kcook7@jhmi.edu   
 
India Principal Investigator 
M. Suresh Kumar, MD MPH 
YRGCARE  
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-44-2254-2929 
E-mail: msuresh1955@gmail.com  
 
 
 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 6 of 44 
 
Project Coordinator 
Aylur Kailasom Srikrishnan, BA 
YRGCARE  
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-44-2254-2929 
E-mail: krish@yrgcare.org  
 
Project Administrator 
Aylur Kailasom Ganesh, BA MPH 
YRGCARE  
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-44-3910-6600 
E-mail: ganesh@yrgcare.org  
 
Data Manager 
Santhanam Anand, BS
Laboratory Manager  
Shanmugam Saravanan, PhD 
YRGCARE  
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-44-3910-6600 
E-mail: saravanan@yrgcare.org  
 
Study Clinician/Quality Control 
Rifa Tazyeem Khan, MBBS MPH 
YRGCARE  
15 (New No: 34) East Street, 
Kilpauk Garden Colony, 
Chennai 600010 
Tamil Nadu, India 
Phone: 91-44-3910-6600 
E-mail: rifa@yrgcare.org 
YRGCARE 
Voluntary Health Services 
Taramani, Chennai 600113 
Tamil Nadu, India 
Phone: 91-98-8456-5413 
E-mail: a2consultancy2018@gmail.com  
 
 
 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 7 of 44 
 
3. LIST OF ABBREVIATIONS 
AE 
 
 
 
Adverse event 
AIDS  
 
 
Acquired immunodeficiency syndrome 
ART  
 
 
Antiretroviral therapy 
CD4 
 
 
 
Cluster of differentiation 4 
DALY  
 
 
Disability-adjusted life years 
eCRF  
 
 
Electronic case report forms 
GCLP  
 
 
Good clinical laboratory practice 
GCP  
 
 
Good clinical practice 
GDP  
 
 
Gross domestic product 
JHM  
 
 
Johns Hopkins Medicine 
JHU 
 
 
 
Johns Hopkins University 
HCV  
 
 
Hepatitis c virus 
HIV 
 
 
 
Human immunodeficiency virus 
ICC 
 
 
 
Integrated care center 
IDI 
 
 
 
In-depth interview 
ICER  
 
 
Incremental cost-effectiveness ratio 
INR 
 
 
 
Indian National Rupee 
JHU 
 
 
 
Johns Hopkins University 
LMIC  
 
 
Low and middle income countries 
MI 
 
 
 
Motivational interview 
MSM  
 
 
Men who have sex with men 
NACO  
 
 
National AIDS Control Organisation (India) 
NIDA  
 
 
National Institute on Drug Abuse 
OAT  
 
 
Opioid agonist treatment 
PrEP  
 
 
Pre-exposure prophylaxis 
PWID  
 
 
People who inject drugs 
RDS  
 
 
Respondent driven sampling 
SAE 
 
 
 
Serious adverse effect 
STI 
 
 
 
Sexually transmitted infection 
SSP 
 
 
 
Syringe Service Program 
TB 
 
 
 
Tuberculosis 
USD  
 
 
United States Dollar 
WHO  
 
 
World Health Organization 
YRGCARE 
 
 
Y.R. Gaitonde Centre for AIDS Research and Education

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 8 of 44 
 
4. PROTOCOL SUMMARY  
Strategies to Improve the HIV Care Continuum among Key Populations in India: a Cluster 
Randomized Trial 
 
Purpose: 
People who inject drugs (PWID) and men who have sex with men (MSM) have a high HIV 
prevalence in India. In prior work, we found that key population-specific integrated care centers 
(ICCs), which provide HIV testing, risk reduction services, and assistance linking HIV-positive 
persons to government HIV clinics, increased HIV testing rates and were popular and acceptable 
to PWID and MSM. However, by itself, the ICC intervention was not associated with 
improvements in the HIV care continuum among HIV-positive persons. The purpose of this trial 
is to evaluate the effectiveness of non-cash HIV care incentives – a demand creation strategy – to 
improve progress on the care continuum among HIV-positive PWID and MSM in India. 
 
Design: 
Matched-pair cluster randomized trial. 
 
Study Population: 
HIV-positive ICC clients who are 18 years of age or older, antiretroviral therapy (ART)-naïve or 
have taken ART for less than 12 months, and do not receive HIV care in the private sector. 
 
Study Size: 
The study will be conducted at 16 sites (clusters) and we aim to enroll up to 150 participants at 
each site (2400 participants overall). 
 
Treatment Regimen: 
Participants at sites randomized to the intervention will (in addition to receiving usual linkage 
services provided by ICCs) be eligible to receive incentives (non-cash vouchers for goods) for 
achieving HIV care milestones, including visiting a government HIV clinic prior to ART 
initiation, initiating ART, attending HIV treatment motivational interview sessions, and 
collecting timely ART refills. 
 
Participants at sites randomized to the control condition will receive usual linkage to care 
services provided by ICCs, including outreach worker assistance with linkage to HIV treatment 
and reminders to remain in care. 
 
 
Study Duration: 
The study duration will be approximately 48-54 months. Ethnography and preparatory work at 
the sites will take 6 months. Participants will be enrolled over 12 months and then followed for a 
24-month intervention phase. Finally, an epidemiologic survey will be conducted at all sites at 
the conclusion of the intervention phase that will extend another 6-12 months. 
 
Primary Objective: 
To determine if HIV care incentives increase survival with viral suppression at 12 months among 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 9 of 44 
 
HIV-positive PWID and MSM, compared with the control condition. The primary endpoint was 
changed from 24 months to 12 months due to the COVID-19 pandemic and the resulting 
suspension of research activities. 
  
Secondary Objectives: 
• To determine if HIV care incentives increase survival with viral suppression at 6, 18, and 
24 months among HIV-positive PWID and MSM, compared with the control condition. 
 
• To determine if HIV care incentives increase the proportion with at least one suppressed 
viral load during study follow-up among HIV-positive PWID and MSM, compared with 
the control condition. 
 
• To determine if HIV care incentives increase other indices of the care continuum among 
HIV-positive PWID and MSM, compared with the control condition, including: 
o Time to ART initiation (among those ART-naïve at baseline) 
o Retention to HIV care during follow-up 
o ART medication possession ratio 
 
• To determine if HIV care incentives reduce mortality among HIV-positive PWID and 
MSM, compared with the control condition. 
 
Exploratory Objectives: 
• To determine if offering HIV care incentives at ICCs increases: 
o HIV testing rates at ICCs 
o New HIV diagnosis rates at ICCs 
 
• To determine whether treatment incentives are acceptable to participant and providers. 
 
• To determine whether treatment incentives affect community-level indicators of 
engagement across the HIV care continuum including: 
o Recent HIV testing (among HIV-negative and unknown HIV-positives) 
o Awareness of status (among HIV-positive) 
o Recent visit with HIV medical provider (among HIV-positive) 
o Current use of ART (among HIV-positive) 
o HIV RNA suppression (among HIV-positive) 
o Prevalence of viremic individuals in the population 
o HIV incidence estimated by multi-assay algorithm 
 
• To assess the incremental cost-effectives ratio of providing HIV care incentives for 
PWID and MSM, compared with the control condition. 
 
Study Sites: 
PWID ICCs based in the following Indian cities: 1) Amritsar, 2) Aizawl, 3) Bilaspur, 4) 
Churachandpur, 5) Delhi, 6) Dimapur, 7) Kanpur, and 8) Ludhiana. MSM ICCs based in the 
following Indian cities: 1) Bangalore, 2) Belgaum, 3) Bhopal, 4) Delhi, 5) Hyderabad, 6) 
Madurai, 7) Vijayawada, and 8) Visakhapatnam.  

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 10 of 44 
 
 
 
Figure 1. Overview of Study Design and Randomization Scheme: 
 
 
 
 
 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 11 of 44 
 
5. INTRODUCTION 
5.1 Background Information 
Ongoing trial among PWID and MSM in India. In 2011, we initiated a cluster-randomized 
trial to evaluate the effectiveness of integrated care centers (ICCs) to improve HIV outcomes 
among marginalized people who inject drugs (PWID) and men who have sex with men (MSM) 
populations across India (1). ICCs provide vertically integrated risk reduction (condoms, OST, 
needle/syringe exchange [NSEP]), HIV counseling and testing, treatment services (CD4 testing, 
sexually transmitted infection [STI] treatment, referral to government centers for antiretroviral 
therapy [ART]), and support services (mental health and substance use counseling, ART 
adherence counseling, and couples counseling) in stand-alone stigma-free venues. The primary 
outcome of this trial was annual uptake of HIV testing in these high risk populations. Of equal 
importance; however, has been the enthusiasm that coalesced around the ICC model as we 
engaged national, local, and community stakeholders in the design and implementation 
processes. Results from the trial showed that ICCs increased rates of recent HIV testing in these 
key populations (2). 
 
Limited impact of ICC intervention on HIV care and treatment outcomes. However, data 
from the ICC trial also showed that, despite increasing the uptake of HIV testing, the ICCs had 
no apparent impact on downstream outcomes in the HIV care continuum (e.g., initiation of ART, 
retention to care, viral suppression) that are critical for reducing HIV-related morbidity, 
mortality, and transmission (2). In contrast with HIV testing, which only requires a single visit to 
the ICC, achieving these downstream outcomes requires a durable commitment to HIV treatment 
and repeated visits to government ART centers. By addressing the supply side of evidence-based 
HIV prevention and treatment services in a supportive environment, the ICCs appear to have 
affected lower-barrier outcomes such as HIV testing. However, longer-term engagement in care, 
particularly among these impoverished populations, will require additional 
interventions/motivation.  
 
 Pilot study of voucher incentives for HIV care. We conducted a pilot trial of voucher 
incentives for HIV care in Chennai, India (3). We randomized 120 ART-naïve, HIV-positive 
PWID to an incentive intervention, which provided vouchers for completing verifiable HIV care 
steps, or to an active control condition, in which participants could win vouchers through prize-
bowl drawings. Over 12 months of follow-up, participants in the incentive arm were more likely 
than those in control arm to visit a government HIV clinic at least once (49% vs. 33%, P=0.002) 
and to start ART (hazard ratio 2.33, 95% CI: 1.15, 4,73). However, viral suppression was not 
significantly different in the two arms  
5.2 Rationale 
Engagement in HIV care begins with risk awareness and HIV testing, but, for HIV-positive 
people, requires long-term commitment, sustained HIV care visits and life-long ART to achieve 
viral suppression, which will reduce HIV transmission within a community. Our ICC 
intervention addresses structural and health service barriers by increasing the supply of vital 
HIV-related services in a non-discriminatory atmosphere. We hypothesize that a supplemental 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 12 of 44 
 
demand-focused intervention will be effective in overcoming individual barriers to engaging in 
HIV care and treatment. Behavioral economic theory suggests that people discount the future in 
favor of current utility. Behaviorists have conceptualized this phenomenon in terms of 
intertemporal discounting; empirical data suggest that people discount the value of things as a 
hyperbolic function of delay time. As a consequence, decision-making related to important issues 
with long-term implications can be disproportionally influenced by factors of much smaller 
importance that have immediacy (e.g., lost time, costs, perceived risks, side effects). Behavioral 
theory and economic principles of demand suggest that incentives may be effective in promoting 
behaviors that have long-term health benefits by providing an offset to the immediate ‘costs’ of 
these behaviors.  
 
Rationale for focusing on PWID and MSM in India. India is home to the third largest number 
of people living with HIV globally. While India’s HIV epidemic is predominantly heterosexual, 
there is a growing burden among PWID and MSM who have not been a major focus of the 
National AIDS Program until recently. India, similar to other low- to middle-income countries 
(LMIC), has seen nearly 50% decline in overall HIV prevalence over the past decade (0.41% to 
0.27% from 2001 to 2011 among adults); however, among PWID and MSM, prevalence remains 
stable, with increasing trends in some regions. India is also home to the largest number of opiate 
users globally and an estimated 1.1 million PWID (4). India is situated between the two largest 
heroin producing regions globally – the ‘Golden Crescent’ and the ‘Golden Triangle’ – which 
has resulted in a geographically diverse epidemiology of drug use. In the Northeast, drug 
injection has been endemic for decades, because of proximity to the ‘Golden Triangle.’  
However, epidemics are emerging in North/Central India because of a shared border with the 
‘Golden Crescent’. In fact, in our survey of PWID in 15 cities, we found the highest HIV 
incidence (by a factor of 2) in the central Indian city of Kanpur (12%). India is also home to an 
estimated 2.35 million high-risk MSM with other estimates suggesting the prevalence of same-
sex behavior among adult men to be as high as 9% - 11% (translating to ~45 million MSM).  
 
Both PWID and MSM have HIV burden that is 15-25 times higher than the general population. 
While HIV care and ART have been available free of charge through government programs since 
2004, data suggest limited uptake of these services by these groups. PWID and MSM in India 
face multidimensional barriers to engaging in optimal HIV care and treatment. Stigma and 
discrimination are pervasive. This and cultural norms in India, which, for example, stipulate 
marriage to women even for MSM, leave many PWID and MSM to live on the margins of 
society. Moreover, in both PWID and MSM, substance use both increases risk behavior and is a 
barrier to successful HIV treatment. In a recent analysis by our group, the primary barrier to viral 
suppression among 443 PWID on ART was active injection drug use (OR: 0.04; 95% CI: 0.01, 
0.11) and similarly among 347 HIV-infected MSM alcohol dependence was the primary barrier 
to viral suppression (OR: 0.26; 95% CI: 0.12, 0.57). Compounding these barriers is poverty; in 
our baseline data, the median monthly income among PWID and MSM was 3 USD/day and 5 
USD/day, respectively, and the majority reported being daily wage earners – 56% of PWID and 
37% of MSM. While our ICC intervention was focused on addressing issues of stigma and 
comorbidity, including substance use, the addition of incentives will help to overcome other 
barriers related to poverty and potential lost wages. 
 
UNAIDS has proposed a “90-90-90” target by 2020, with the aims that 90% of HIV-infected 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 13 of 44 
 
persons become aware of their status, 90% of those aware of their status receive sustained ART, 
and 90% of those receiving ART achieve viral suppression. In India, as in several other LMICs, 
the “90-90-90” target will be unattainable without making substantial inroads in HIV prevention 
and treatment among these hard-to-reach groups. Indeed, controlling HIV among PWID and 
MSM in LMICs has been identified one of the greatest barriers to controlling HIV globally. 
Strategies to identify HIV-infected PWID and MSM in the community, link them to care and 
successfully maintain them on ART are critical to achieving ambitious UNAIDS targets globally. 
5.3 Study Hypotheses 
We hypothesize that non-cash HIV care incentives will improve rates of survival with viral 
suppression in PWID and MSM in India. Providing incentives for achieving verifiable HIV care 
benchmarks is a demand-stimulation approach, in contrast to supply-focused approaches, such as 
efforts to increase accessibility or reduce barriers to services. In prior work, we found that a 
supply-focused intervention – ICCs - was popular and associated with increased HIV testing 
rates but did not have a discernible effect on the HIV care continuum. 
6. OBJECTIVES 
6.1 Primary Objective 
To determine if HIV care incentives increase survival with viral suppression at 12 months among 
HIV-positive PWID and MSM, compared with the control condition. 
6.2 Secondary Objectives 
• To determine if HIV care incentives increase survival with viral suppression at 6, 18, and 
24 months among HIV-positive PWID and MSM, compared with the control condition. 
 
• To determine if HIV care incentives increase the proportion with at least one suppressed 
viral load during study follow-up among HIV-positive PWID and MSM, compared with 
the control condition. 
 
• To determine if HIV care incentives increase other indices of the care continuum among 
HIV-positive PWID and MSM, compared with the control condition, including: 
o Time to ART initiation (among those ART-naïve at baseline) 
o Retention to HIV care during follow-up 
o ART medication possession ratio 
 
• To determine if HIV care incentives reduce mortality among HIV-positive PWID and 
MSM, compared with the control condition. 
6.3 Exploratory Objectives 
• To determine if offering HIV care incentives at ICCs increases: 
o HIV testing rates at ICCs 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 14 of 44 
 
o New HIV diagnosis rates at ICCs 
 
• To determine whether treatment incentives are acceptable to participant and providers. 
 
• To determine whether treatment incentives affect community-level indicators of 
engagement across the HIV care continuum including: 
o Recent HIV testing (among HIV-negative and unknown HIV-positives) 
o Awareness of status (among HIV-positive) 
o Recent visit with HIV medical provider (among HIV-positive) 
o Current use of ART (among HIV-positive) 
o HIV RNA suppression (among HIV-positive) 
o Prevalence of viremic individuals in the population 
o HIV incidence estimated by multi-assay algorithm 
 
• To assess the incremental cost-effectives ratio of providing HIV care incentives for 
PWID and MSM, compared with the control condition. 
7. STUDY DESIGN 
This is a phase III, two-arm, matched-pair, cluster randomized trial. The study will be conducted 
at 16 sites across India (8 PWID and 8 MSM). Eligible, HIV-positive PWID or MSM will be 
recruited at each site prior to randomization. In each site pair, one site will be assigned to the 
control condition and the other site to the incentive intervention. 
 
1. 
Control condition – Free-of-charge HIV care and ART available at government HIV 
clinics. ICCs provide HIV counseling, risk reduction services, and peer outreach to support 
HIV treatment linkage, adherence and retention. 
2. 
Incentive intervention – Control condition services plus ICCs offer HIV treatment 
incentives (non-cash vouchers for goods) for completing verifiable HIV care activities. 
 
In addition to the quantitative endpoints from the trial, we will also collect mixed methods data 
to understand how treatment incentives were perceived by different stakeholders. During the 
latter part of the intervention phase, we will conduct an epidemiologic survey among PWID and 
MSM at all study sites using RDS. The survey will provide insight into the community-level 
impact of the intervention and to trends in HIV testing, prevention, and treatment (by comparing 
with results of 2 prior surveys). Finally, a cost-effectiveness evaluation with be conducted. 
 
The study duration will be approximately 48 months. Ethnography and preparatory work at the 
sites will take 6 months. Participants will be enrolled over 12 months and then followed for a 24-
month intervention phase. Finally, an epidemiologic survey will be conducted at all sites at the 
conclusion of the intervention phase that will extend another 6 months. 
8. STUDY POPULATION 
We will recruit cohorts of HIV-positive participants at each ICC site, with roll-out of the study 
arm allocation (incentive intervention or control condition) after or near the conclusion of cohort 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 15 of 44 
 
enrollment. Cohort participants will be followed for 24 months during the intervention phase in 
order to accomplish primary and secondary objectives. The exploratory objectives require i) 
collecting of mixed methods data on HIV care incentives from key stakeholders, ii) conducting 
an RDS survey at each site targeting either PWID or MSM, depending on the site, and iii) 
conducting cost-effectiveness analyses. 
8.1 Inclusion/Exclusion Criteria 
8.1.1 Participant Inclusion Criteria 
Inclusion criteria for cohort participants in cluster randomized trial 
Men and women who meet all of the following criteria are eligible for inclusion as a cohort 
participant: 
• 18 years of age or older 
• Registered client at the local ICC 
• Documented HIV seropositive 
• Is either ART-naïve or has been taking ART less than 12 months 
• Competent to understand the study and provide written informed consent 
• If previously linked to HIV care, willing and able to provide government ART book for 
documentation of care received 
 
Inclusion criteria for mixed methods evaluation of treatment incentives  
Men and women who meet any of the following criteria are eligible for inclusion in the 
qualitative component of the study: 
• 18 years of age or older 
and a or b 
a) ICC client at one of the 8 intervention sites who was participated in the incentive 
program 
or 
b) ICC staff member involved in incentive delivery at one of the 8 intervention sites   
 
Inclusion criteria for the RDS survey  
Men and women who meet all of the following criteria are eligible for inclusion as an RDS 
survey participant: 
• 18 years of age or older 
• Presents a valid RDS recruitment coupon (unless a “seed”) 
• Competent to understand study and provide oral consent 
• Meets key population risk factor specific for the site [a) self-identifies as male and reports 
oral/anal intercourse with another man in the prior 12 months, or b) reports injection drug 
use in the prior 24 months] 
8.1.2 Participant Exclusion Criteria 
Exclusion criteria for cohort participants in cluster randomized trial 
Men and women who meet any of the following criteria are ineligible for inclusion as a cohort 
participants: 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 16 of 44 
 
• Does not speak Hindi, English, or the local language 
• Plans to migrate in the next 12 months 
• Receives HIV care in the private sector 
 
Exclusion criteria for mixed methods evaluation of treatment incentives 
Men and women who meet any of the following criteria are ineligible for inclusion as a cohort 
participants: 
• Does not speak Hindi, English, or the local language 
 
Exclusion criterion for the RDS survey  
Men and women who meet the following criterion are ineligible for inclusion as an RDS survey 
participants: 
• Does not speak Hindi, English, or the local language 
8.2 Recruitment Process 
Recruitment of study cohorts for cluster randomized trial 
We will recruit HIV-positive individuals who access services at the 16 ICCs in this cluster-
randomized trial. Individuals will be recruited into the cohort by referrals from ICC clinical staff. 
Research assistants will meet with individuals who express interest in the study in a private 
office space. In addition, during the enrollment period, in collaboration with local non-
governmental organizations, ICC staff will conduct outreach at local hotspots to identify persons 
from the target population to come to the ICC for HIV testing and potential assessment for 
cohort eligibility.  
 
Recruitment for mixed methods evaluation of treatment incentives 
A quantitative survey will be administered to all participants participating in the cohort study. 
For the qualitative component, the study team will identify persons with specific characteristics 
related to HIV care and provide a list to the ICC Site Coordinator who will then work with other 
study staff to contact these participants and invite them for this additional evaluation. The ICC 
staff will introduce them to a Research Assistant who will provide them with further information 
on the qualitative assessment. The Research Assistant will directly approach ICC staff for the 
staff qualitative assessment.  
 
Recruitment for RDS survey 
We will recruit members of the target populations (PWID or MSM depending on site) via RDS 
at the conclusion of the intervention period (year 4 of the study). RDS is a structured version of 
snowball sampling, where recruitment begins at each site with 2 to 5 “seeds” (representative 
individuals identified through ethnography). Participants who meet eligibility requirements and 
complete the study visit will be given 2 coupons to recruit other members of their network. 
Individuals who come to the study site will meet with a research assistant in a private office 
setting. The research assistant will briefly describe the study and the eligibility assessment. 
8.3 Participant Retention 
Once a participant enrolls in the cohort study, the study site will make every effort to retain 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 17 of 44 
 
him/her for the full study period (24 months), to minimize possible bias associated with loss-to-
follow-up. Retention rates of 80% at 24 months are targeted among non-deceased participants. 
Study site staff are responsible for developing and implementing local standard operating 
procedures to target this goal. Components of such procedures include: 
• Thorough explanation of the study visit schedule and procedural requirements during the 
informed consent process and re-emphasis at each study visit. 
• Collection of detailed locator information at the baseline visit, and active review and 
updating of this information at each subsequent visit. 
• Use of mapping techniques to establish the location of participant residences and other 
locator venues. 
• Use of appropriate and timely visit reminder mechanisms to retain participants. 
• Immediate and multifaceted follow-up on missed visits. 
• Mobilization of trained outreach workers or “tracers” to complete in-person contact with 
participants at their homes and/or other community locations. 
• Regular communication with the study community at large to increase awareness about 
HIV/AIDS and explain the purpose of HIV treatment research and the importance of 
completing research study visits. 
9. INTERVENTIONS 
Study sites (clusters) will be randomly allocated to either the incentive intervention or to the 
control condition (Table 1). All sites will receive a core packet of services provided by 
population-targeted ICCs (either PWID or MSM).  
 
Table 1. Summary of services in control and intervention conditions 
Service/Intervention 
Control 
Condition sites 
(n=8) 
Incentive 
Intervention sites 
(n=8) 
HIV counseling and testing 
X 
X 
Harm reduction services 
 
 
Condoms 
X 
X 
Risk reduction counseling 
X 
X 
Syringe service program (SSP) 
PWID sites 
PWID sites 
Opioid agonist treatment (OAT) 
PWID sites 
PWID sites 
STI screening and syndromic treatment 
X 
X 
TB symptom screening and referral 
X 
X 
Hepatitis C virus (HCV) antibody testing and 
counseling 
PWID sites 
PWID sites 
Services for HIV-positive clients 
 
 
Referral for ART and peer outreach 
X 
X 
Motivational interviewing  
X 
X 
Incentives for achieving HIV treatment 
milestones 
 
X 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 18 of 44 
 
9.1 Control Condition 
This trial incorporates an active control condition. In a prior trial, we evaluated the acceptability, 
feasibility, and effectiveness of PWID- or MSM-focused ICCs (2). The goal of ICCs was to 
provide a menu of population-specific services in non-discriminatory settings. We found that 
ICCs served large numbers of clients (median of 1,500 per ICC over 2 years), were favorably 
reviewed in anonymous client surveys, and increased community level HIV testing rates (2). 
Although the integrated population-focused venue is distinct, the services provided by ICCs are 
consistent with the standard of care in India. At the present time, pre-exposure prophylaxis 
(PrEP) is not endorsed by the National AIDS Control Organisation (NACO) in India and is not 
available in ICCs. In the control condition, the following care package will be routinely available 
• HIV counseling and testing 
• Harm reduction services 
o Condoms 
o Risk reduction counseling 
o SSP (PWID sites only) 
o OAT (PWID sites only) 
• STI screening/syndromic treatment 
• Tuberculosis (TB) symptom screen and referral 
• HCV antibody testing (PWID sites only) 
• Services for HIV-positive clients 
• Referral for ART and peer outreach/support 
• Motivational interviewing for HIV treatment adherence 
9.2 Incentive Intervention 
The incentive intervention will include all services available at control condition sites plus HIV 
care incentives. Cohort participants at intervention sites will be eligible to receive treatment 
incentives (Table 2). Additionally, ICCs assigned to the intervention will offer treatment 
incentives to additional HIV-positive clients (up to a maximum of 300 persons per site). 
 
 
 
 
 
 
 
 
 
 
 
 
Similar to our approach in a pilot trial in Chennai (3), vouchers will be redeemable for food, 
clothing, household goods, and specialty items at the ICC or from collaborating stores. Non-cash 
incentives support a drug- and alcohol-free lifestyle and were acceptable and effective in the 
pilot trial. Some items that will be stocked at ICCs for voucher redemption are toothpaste, soap, 
Table 2. HIV treatment incentive schema  
Target 
Eligibility 
Incentive 
criteria 
Value 
Frequency 
available 
Maximum 
possible over 
24 months 
Pre-ART 
retention 
ART-naïve 
Attend visit at 
govt. HIV clinic 
INR 250 
(USD 3.60) 
Once every 6 
months 
INR 1000 
(USD 14.30) 
ART initiation  
ART naive 
Initiate ART at 
govt. HIV clinic 
INR 500 
(USD 7.10) 
Once 
(non-repeatable) 
INR 500 
(USD 7.10) 
ART persistence 
Initiated 
ART 
Timely monthly 
refills 
INR 150 
(USD 2.10) 
Once every 
month 
INR 3600 
(USD 51.40) 
Internal 
motivation 
All 
MI counseling 
at ICC 
INR 100 
(USD 0.70) 
Once every 3 
months 
INR 800 
(USD 11.40) 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 19 of 44 
 
shampoo, biscuits, tea, coffee, rice (1kg, 5kg), lentils, wheat flour (1kg packs), shirts, sweaters, 
and backpacks. Each site will decide on the options for incentives based on local 
experience/needs. Participants may choose to save incentives in an account to redeem for larger 
gifts (e.g., mobile phone). 
 
Incentives will be given for verified activities, not self-report alone. Governmental HIV clinics 
record visits, laboratory results, and dispensations of antiretroviral drugs in notebook that 
patients keep (government ART book). Entries in the government ART book (and if needed 
verification by records at the clinic) will be used to verify incentivized activities. Incentives for 
ART refills will be given if the refill is no more than 3-days late, following a typical 30-day 
prescription.  
10. STUDY PROCEDURES/EVALUATIONS 
10.1 Clinical Evaluations and Procedures 
Clinical evaluations and procedures for study cohorts in cluster randomized trial 
Eligible participants who meet inclusion criteria and provide written informed consent will be 
enrolled in the local cohort. Cohort participants will complete a baseline study visit, most often 
on the day of screening, and will be asked to complete follow-up visits at 6 months, 12 months, 
18 months, and 24 months, for a total of 5 study visits. However, due to delays from the COVID-
19 pandemic, not all participants were able to complete the 18- and 24-month visits. Detailed 
information on the evaluation and procedures of study visits are shown in Appendix I. Study 
visits will include the following evaluations: 
• Biometric capture (fingerprint) to confirm identity 
• Blood draw, laboratory assessments described below 
• Collection of contact and locator information 
• Interviewer-administered survey covering the following domains 
o Demographics 
o Quality of life 
o Engagement/experience with HIV care 
o ART adherence 
o Beliefs about ART 
o Alcohol and drug use 
o Injection- and sex-related risk behaviors 
o Depression symptoms 
o Health care utilization 
o Fentanyl and overdose (from 18 months onward) 
• Abstraction of information from government ART book 
 
Clinical evaluations and procedures for mixed methods evaluation of treatment incentives 
We will query cohort participants at incentive sites about their experiences with and perceptions 
of treatment incentives in the 24-month visit interview. Additionally, individuals eligible for the 
qualitative component will be invited to participate in in-depth interviews (IDI). IDIs will use a 
semi-structured format to address the following domains: 
 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 20 of 44 
 
IDIs with ICC clients at intervention sites 
• Perceived purpose of the incentive program 
• Process of learning about the incentive program  
• Experiences with receiving incentives 
• Opinions about the value of incentives and how frequently incentives could be earned 
• Impact of incentive program on client opinions and beliefs about HIV care 
 
IDIs with ICC staff 
• Familiarity with the incentive program 
• Perceived purpose of the incentive program 
• Challenges with implementing the incentive program 
• Good and bad things about the incentive program 
• Opinions about how the program affected HIV-positive clients’ behaviors 
 
Clinical evaluations and procedures for RDS survey 
The RDS survey will be a cross-sectional assessment of PWID or MSM populations in each 
study city. Beginning with 2-5 “seed participants,” eligible participants who complete a one-time 
study visit are eligible to recruit up to 2 network members to the study with coupons (described 
above). Participants will be reimbursed both for completing the study visit and for each eligible 
participant that they refer to the study (up to 2). RDS participants who present with a valid 
recruitment coupon will be asked to undergo the following procedures: 
• Biometric scan (fingerprints) to assure individual has not already participated in the study 
• Rapid HIV counseling and testing, described below 
• Interviewer-administered survey covering the following domains 
o Demographics 
o Peer network information 
o Substance use (including alcohol)  
o Drug-related and sexual risk behavior 
o HIV treatment literacy 
o HIV care continuum outcomes (e.g., experience with HIV testing, HIV care and 
HIV treatment) 
o General utilization of health care including hospitalizations, physician and non-
physician outpatient visits, medications, productivity (full-time, part-time work), 
out of pocket medical costs, and time and wages lost due to medical appointments 
including travel as well as utilization of harm reduction services (OAT, syringe 
service program [SSP]) 
o Depression 
o Quality of Life  
o Social Support 
o Stigma 
10.2 Laboratory Evaluations 
Laboratory evaluations for the study cohort in the cluster randomized trial  
• HIV RNA will be measured from plasma at all cohort study visits by the central 
laboratory (YR Gaitonde Centre for AIDS Research and Education [YRGCARE]) in 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 21 of 44 
 
Chennai, India using RealTime HIV-1 (Abbott Laboratories, Abbott Park, IL, USA). The 
HIV RNA result at the 24-month visit will be shared with participants  
• CD4 cell counts will be measured at baseline by flow cytometry in a local or regional 
laboratory. The CD4 test result will be shared with participants. 
• At the 6-month, 12-month, and 18-month cohort visits we will measure serum glucose, 
serum creatinine, and a liver function panel, respectively. These assays will be conducted 
at local or regional laboratories. Results from these tests will be shared with participants 
as a value-added benefit of participating in the trial. 
 
Laboratory evaluations for mixed methods evaluation of incentives 
None 
 
Laboratory evaluations for RDS survey 
• Rapid HIV testing - This point-of-care testing will be used to test all RDS participants. 
The rapid testing protocol includes the use of 3 rapid test kits in an algorithm: Alere 
Determine HIV-1/2 (Alere Medical, Chiba, Japan), First Response HIV Card test 1-2.0 
(Premier Medical Corporation, Daman, India), and Signal Flow Through HIV 
1+2/Immunodot Test Kit (Span Diagnostics, Surat, India). 
• HIV-1 RNA - HIV RNA will be measured from plasma in HIV-positive survey 
participants by the central laboratory (YRGCARE) in Chennai, India, using RealTime 
HIV-1 (Abbott Laboratories, Abbott Park, IL, USA). 
• CD4 cell count - CD4 cell counts will be measured in all HIV-positive participants by the 
central laboratory (YRGCARE) in Chennai, India using Flow Cytometry (EPICs XL-
MCL, Beckman Coulter, Inc., USA.  
• Recent HIV infection - Recent HIV infection will be assessed using a validated multi-
assay algorithm in all HIV-positive survey participants. The algorithm testing includes 
Limited Antigen (LAg) Avidity EIA (Maxim Biomedical Inc, Rockville, MD, USA) and 
the JHU-modified Bio-Rad Avidity assay (Bio Rad Laboratories, Hercules, CA, USA). 
Individuals are characterized as having recent infection if CD4 count >50 cells/mm3, HIV 
RNA >400 copies/mL, LAg avidity <2.9 OD-n, and JHU-modified Bio-Rad avidity 
index<85% (5). 
11. ASSESSMENT OF SAFETY 
11.1 Safety Assessment Overview 
This section provides information on the definition of adverse events (AE), serious adverse 
events (SAE) and the procedures for reporting. Procedures for prompt reporting of AE and SAE 
will be standardized across the field sites.  
11.2 Definitions 
11.2.1 Definition of Adverse Events (AE) 
An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or diagnosis that occurs in a study participant during the conduct of the study 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 22 of 44 
 
regardless of the attribution (i.e., relationship of event to medical treatment/study product/device 
or procedure/intervention). This includes any occurrence that is new in onset or aggravated in 
severity or frequency from the baseline condition.  
11.2.2 Definition of Serious Adverse Events (SAE) 
An SAE is defined as any untoward medical occurrence that: 
 
 
• Results in death 
• Is life-threatening  
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity  
• Is a congenital anomaly/birth defect 
• Is an important medical event that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the patient or may require intervention to 
prevent one of the other outcomes listed in the definition above). 
11.3 Reporting Requirements for this Study 
The research procedures in our study include 1) qualitative work (interviews with key 
informants), 2) study visits with cohort participants, and 3) a RDS surveys. These research 
procedures are minimal risk (involve only a blood draw), and do not include a drug or medical 
device. Furthermore, study sites (or clusters) are the unit of randomization, not individual 
participants. Participants at intervention sites have access to the intervention (non-cash HIV 
treatment incentives), but are not required to seek or accept the intervention. Finally, the study 
population, HIV-positive PWID and MSM have substantially higher risks of morbidity and 
mortality than person in the general population. Given these considerations, our reporting 
obligations for the trial focus only on events that are more likely than not to be associated with i) 
study procedures, or ii) participation in the intervention. Two types of events will be reportable: 
 
1. Unanticipated problems involving risks to participants or others will be reported to the 
YRGCARE and JHM IRBs within 10 working days (unless the event is death, in which case 
# 2 applies).  Such events are defined as: 
a. The information is unexpected in terms of nature, severity, or frequency, given: 
i. The research procedures described in the protocol and informed consent 
document; and 
ii. The characteristics of the subject population being studied 
b. The information indicates that the participants or others are at greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized. 
2. Deaths of study participants in close association with study procedures will be reported to the 
IRB within 3 working days. 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 23 of 44 
 
12. CLINICAL MANAGEMENT 
12.1 Clinical Management of Adverse Events 
Research staff will interact with participants at study visits and during the intervention 
(dispensing non-cash incentives). Research staff will refer participants to a clinic or hospital for 
medical conditions that arise. 
12.2 Criteria for Discontinuation 
12.2.1 Criteria for Permanent Intervention Discontinuation for an Individual Participant 
Potential reasons for permanent or premature discontinuation of intervention are: 
• Request by the participant to stop. 
• Request of site coordinator if s/he thinks the intervention is no longer in the best interest of 
the participant. 
• At the discretion of the IRB/Ethics Committee, Office for Human Research Protections 
(OHRP), other government agencies as part of their duties, or investigator 
12.2.2 Criteria for Premature Study Discontinuation for an Individual Participant 
Potential reasons for permanent or premature discontinuation of study are: 
• Request by the participant to withdraw. 
• Request of site coordinator if s/he thinks study participation is no longer in the best 
interest of the participant. 
• At the discretion of the IRB/Ethics Committee, Office for Human Research Protections 
(OHRP), other government agencies as part of their duties, or investigator 
13. STATISTICAL CONSIDERATIONS 
13.1 Overview and General Design Issues 
The primary objective of this study is to determine whether offering non-cash HIV care 
incentives increases survival with viral suppression among HIV-positive PWID and MSM. Key 
secondary endpoints include engagement in HIV treatment and retention to care as mediators of 
survival with viral suppression, qualitative evaluation of treatment incentives, and costs and cost 
effectiveness. We will address these objectives with a phase III, two-arm, matched-pair, 16-site 
cluster randomized trial. We selected a cluster randomized as opposed to an individually 
randomized trial for two reasons. First, the cluster randomized design minimizes the likelihood 
of contamination effects that might occur if incentives were being offered to some but not to 
other participants at the same site. Second, we hypothesize that offering incentives will have 
favorable off-target effects at the ICCs, such as encouraging more key population members to 
visit for HIV-testing. This can be meaningfully assessed in a cluster randomized design, but not 
in an individually randomized design. Participants who are HIV-positive and have limited or no 
prior ART exposure will be enrolled and followed for 24 months at the 16 study sites. The 
control condition includes linkage and support services provided by ICCs and standard HIV 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 24 of 44 
 
treatment provided free-of-charge by government HIV clinics.  
 
To provide context for the results from the cluster randomized trial, we will conduct a mixed 
methods evaluation of treatment incentives and cost-effectiveness analyses. In addition, near the 
conclusion of the trial intervention phase, we will conduct a concurrent epidemiologic survey of 
PWID or MSM at all study sites using RDS. The survey will provide insight into the community-
level impact of the intervention and to trends in HIV testing, prevention, and treatment (by 
comparing with results of 2 prior surveys conducted in the same cities). 
 
Protocol revisions due to COVID-19: Cohort study participant enrollment was completed in 
October, 2018. Study activities (follow-up visits and incentive intervention) were suspended 
indefinitely in March 2020. At the time research activities were suspended, all participant visit 
windows had closed for the 6- and 12-month follow-up visits. However, 65 and 959 participants 
had not completed the 18- and 24-month visits, respectively, but had not reached or were within 
the visit window. Because of this, in Protocol Version 2.0 we revised the primary endpoint from 
24 months to 12 months. Data that was collected at 18 and 24 months will be considered in 
secondary and sensitivity analyses. 
13.2 Study Endpoints 
Primary and secondary study endpoints will be assessed at follow-up cohort visits on the basis of 
laboratory testing, structured interviews, and external sources of data, including government HIV 
clinic treatment records and death reports from family and friends. Exploratory endpoints will be 
assessed on the basis of i) costing data collected during the study, ii) qualitative IDIs, and iii) 
RDS surveys conducted in the key populations near the conclusion of the intervention phase. 
13.2.1 Primary Endpoint 
Survival with suppressed viral load, defined as HIV RNA <150 copies/mL in plasma or serum, at 
12 months. 
13.2.2 Secondary Endpoints 
• Survival with suppressed viral load at 6, 18, and 24 months. 
• Proportion with at least one suppressed viral load during study follow-up (6, 12, 18, or 24 
months). 
• Time to ART initiation, recorded from government HIV treatment records, among cohort 
participants that were ART-naïve at baseline. 
• Retention to HIV care during follow-up, defined as having 1 or more visits to a 
government ART clinic in each 6-month period of study follow-up. 
• ART possession ratio (a measure of medication adherence), defined as the time in 
possession of ART divided by the follow-up time. Follow-up time will commence at 
enrollment for ART-experienced participants and at ART initiation for ART-naïve 
participants. Follow-up time will be censored at the end of trial follow-up, death, or loss-
to-follow-up. The amount of time in possession of ART will be determined from ART 
dispensation logs maintained by government HIV clinics.  
• Mortality, defined as a report of a participant’s death from a family member or a close 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 25 of 44 
 
friend. Death records are not maintained by local, state, or national governments in India. 
13.2.3 Exploratory Endpoints 
• Rate of HIV testing in ICCs, defined as number of HIV tests performed in an ICC per 
unit time. This is an ICC-level endpoint. The number of HIV tests and the testing results 
are recorded in a computerized ICC database. For each matched site pair, follow-up will 
commence on the date that the intervention is rolled-out at the intervention site in the 
pair. Follow-up will end at the conclusion of the active intervention period.  
• New HIV diagnosis rate in ICCs, defined as the number of persons testing newly HIV-
positive in the ICC per unit time. This is an ICC-level endpoint. For each matched site 
pair, follow-up will commence on the date that the intervention is rolled-out at the 
intervention site in the pair. Follow-up will end at the conclusion of the active 
intervention period. 
• Mixed methods evaluation of treatment incentives obtained by i) survey questions of 
cohort participants at the final (24-month) study visit (quantitative component), and ii) 
IDIs with ICC clients and ICC staff (qualitative component). 
• Community-level effects will be assessed by an end-of-study RDS survey among PWID 
or MSM (according to site). RDS is a network-based sampling method, in which 
participants recruit people from their social networks with a coupon tracking system. 
Sampling weights are generated that provide unbiased estimates of characteristics of 
interest in the underlying population. Our team has experience using RDS to assess the 
community-level impact of a structural intervention (1). In this trial, we will use RDS 
estimates to 1) assess for community-level impact of the incentive intervention compared 
with the control condition, and 2) to assess epidemiologic trends in HIV prevention, care 
continuum, HIV prevalence, and HIV incidence by comparison with prior surveys 
conducted in these cities. Endpoints to be assessed in the RDS survey include:   
o Recent HIV testing, defined as the proportion that self-report HIV testing in the 
prior 12 months among all survey participants, except those who are aware of 
their HIV-positive status and report diagnosis more than 12 month previously. 
o Awareness of HIV-positive status, defined as the proportion that self-report HIV-
positive status in interview among participants subsequently determined to be 
HIV seropositive. 
o Recent HIV care visit, defined as the proportion of HIV-positive participants who 
report a visit with an HIV care provider in the prior 6 months. 
o Current ART use, defined as the proportion of HIV-positive participants who 
report ART use in the prior 30 days. 
o HIV RNA suppression, defined as the proportion of HIV-positive participants 
with measured HIV RNA <150 copies/mL   
o Prevalence of viremic individuals in the population, defined as the proportion of 
all participants (HIV-negative and HIV-positive) with a measured HIV RNA 
≥150 copies/mL 
o HIV incidence, estimated with a validated multi-assay algorithm (5) measured in 
HIV-seropositive participants. 
• Cost-effectiveness of the incentive intervention versus control condition using the 
primary and secondary outcome measures, for example, the cost per additional cohort 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 26 of 44 
 
participant with viral suppression. 
13.3 Study Objectives and Hypotheses 
We hypothesize that non-cash HIV care incentives will improve rates of survival with viral 
suppression in PWID and MSM in India. Providing incentives for achieving verifiable HIV care 
benchmarks is a demand-stimulation approach, in contrast to supply-focused approaches, such as 
efforts to increase accessibility or reduce barriers to services. In prior work, we found that a 
supply-focused intervention – ICCs - was popular and associated with increased HIV testing 
rates, but did not have a discernible effect on the HIV care continuum. In a pilot trial, we found 
that treatment incentives were associated with increased access of HIV care and initiation of 
ART (3). Our objectives for the current trial are as follows: 
 
Primary Objective 
To determine if HIV care incentives increase survival with viral suppression at 12 months among 
HIV-positive PWID and MSM, compared with the control condition. 
 
Secondary Objectives 
• To determine if HIV care incentives increase survival with viral suppression at 6, 18, and 
24 months among HIV-positive PWID and MSM, compared with the control condition. 
 
• To determine if HIV care incentives increase the proportion with at least one suppressed 
viral load during study follow-up among HIV-positive PWID and MSM, compared with 
the control condition. 
 
• To determine if HIV care incentives increase other indices of the care continuum among 
HIV-positive PWID and MSM, compared with the control condition, including: 
o Time to ART initiation (among those ART-naïve at baseline) 
o Retention to HIV care during follow-up 
o ART medication possession ratio 
 
• To determine if HIV care incentives reduce mortality among HIV-positive PWID and 
MSM, compared with the control condition. 
 
Exploratory Objectives 
• To determine if offering HIV care incentives at ICCs increases: 
o HIV testing rates at ICCs 
o Rates of identifying out-of-care HIV-positive persons at ICCs 
 
• To determine whether treatment incentives are acceptable to participant and providers.   
 
• To determine whether treatment incentives affect community-level indicators of 
engagement across the HIV care continuum including: 
o Recent HIV testing (among HIV-negative and unknown HIV-positives) 
o Awareness of status (among HIV-positive) 
o Recent visit with HIV medical provider (among HIV-positive) 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 27 of 44 
 
o Current use of ART (among HIV-positive) 
o HIV RNA suppression (among HIV-positive) 
o Prevalence of viremic individuals in the population 
o HIV incidence estimated by multi-assay algorithm 
 
• To assess the incremental cost-effectives ratio of providing HIV care incentives for 
PWID and MSM, compared with the control condition. 
13.4 Sample Size Considerations 
We calculated power for comparing the primary endpoint within matched cluster pairs, survival 
with suppressed viral load, defined as HIV RNA <150 copies/mL in plasma or serum, at 24 
months, among the cohorts of HIV-positive study participants. Cluster-randomized designs 
require consideration of the between-cluster coefficient of variation (k), a measure of variation 
between clusters. In general, the more variability in outcome between clusters, the larger the 
sample size required to detect a given difference. The coefficient of variation in a matched study 
needs to take into account the matching correlation (km), in other words how much of a reduction 
in pair variability is accomplished by matching. More successful matching is associated with 
lower km values. We calculated the km using baseline RDS data from a prior trial for a 
hypothetical set of matched pairs based on the proposed matching criteria for this trial as 
described above. The values of km ranged from 0.08 to 0.15 when considering RDS-II weighted 
and unweighted estimates of the outcome of interest. In addition to consideration of km, we also 
considered other factors specified by the sample size formula from Hayes at al. (6): 
 
 
where 0 and  1 are the true population proportions in the absence and presence of the 
intervention, respectively, n is the number of individuals within each cluster, z/2 and zβ are the 
standard normal distribution values corresponding to the upper tail probabilities of /2 and β, 
respectively and km is the coefficient of variation within matched pairs.  
 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 28 of 44 
 
Within our calculations, we varied the km from 0.10-0.20 based on our preliminary data, the 
sample size per cluster from 50-150 to account for varying levels of loss to follow-up, and the 
outcome prevalence in 
control condition clusters 
from 25-45%. The number of 
cluster pairs needed was 
relatively insensitive to the 
prevalence of outcome in the 
control group and the cluster 
size as long as the sample 
size was >70 per cluster. 
Figure 2 shows the number 
of cluster pairs needed (y-
axis) to provide 80% power 
to detect differences of 0.05 
to 0.30 (x-axis) across a 
range of km values (different 
colored lines) assuming a 
sample size of 150 per 
cluster, two-sided 
alpha=0.05, and 25% 
outcome prevalence in the 
control clusters. With 8 cluster pairs, we will have 80% power to detect differences of 8 
percentage points (risk ratio = 1.32) if the km is 0.10, and 10 percentage points (risk ratio = 1.4) if 
the km is 0.15. If the prevalence in control clusters is 40% then the detectable difference is 10 
percentage points (risk ratio = 1.4) if the km is 0.10.  
13.5 Study Site Selection and Pair Matching 
Study sites (cities) are the units of randomization in the current trial. In a prior cluster 
randomized trial that concluded in June 2017, we evaluated the effectiveness of ICCs for 
increasing rates of HIV testing among PWID and MSM in 22 sites across India 
(ClinicalTrials.gov identifier: NA00047702) (1, 2). From the sites in the prior trial, we selected 
16 well-characterized sites for the current trial. The site selection criteria included 1) large 
estimated number of HIV-positive key population members (PWID or MSM depending on the 
site), 2) poor HIV care continuum indicators (low awareness of HIV status, low linkage to care 
and ART, and low prevalence of viral suppression), and 3) ability to match the site with another 
site (see below).  
  
Close matching of characteristics of interest in matched pairs can increase the efficiency of 
cluster randomized trials (6). To match sites, we considered data from RDS surveys of PWID or 
MSM conducted in 2012/2013 and again in 2016/2017 (n~1000 participants per site), but also 
drew from our research team’s prolonged experience at the sites. Absolute matching criteria 
included the key population (PWID sites could only be paired with PWID sites and MSM sites 
could only be paired with MSM sites) and whether or not the site was an intervention site (ICC) 
or usual care site in the prior trial - former intervention sites already had ICCs up and running, 
but new ICCs needed to be launched in former usual care sites (former intervention sites were 
Figure 2. Number of matched pairs needed to detect 
differences. Red dotted line indicates 8 pairs of clusters 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 29 of 44 
 
paired only with other former intervention sites and former usual care sites were paired only with 
former usual care sites). These strata resulted in the categorization shown in Figure 3.   
 
Figure 3. Stratification of sites for pair matching 
 
 
 
Treatment condition in trial ending 2017 
 
 
Former ICC site 
Former usual care site 
Key population 
PWID  
• Aizawl 
• Bilaspur 
• Dimapur 
• Ludhiana 
• Amritsar 
• Churachandpur 
• Delhi 
• Kanpur 
MSM 
• Bangalore 
• Belgaum 
• Hyderabad 
• Visakhapatnam 
• Bhopal 
• Delhi 
• Madurai 
• Vijayawada 
 
Within the above stratification, we considered PWID/MSM population size, geography, and 
HIV-related community characteristics - HIV prevalence, viral suppression, and prevalence of 
viremia - when evaluating potential pair matches. Final criteria that were considered in the 
matching process in order of prioritization were: 1) proportion of HIV-positive persons with viral 
suppression; 2) HIV prevalence; and 3) prevalence of viremic persons, 4) estimated size of the 
target population. Final pair matching is listed in Figure 4: 
 
Figure 4. Site pairs, by key population 
PWID 
MSM 
Pair 1:  Aizawl and Bilaspur 
Pair 1:  Bangalore and Visakhapatnam 
Pair 2:  Churachandpur and Amritsar 
Pair 2:  Belgaum and Hyderabad 
Pair 3:  New Delhi and Kanpur 
Pair 3:  Bhopal and Vijayawada 
Pair 4:  Dimapur and Ludhiana 
Pair 4:  Madurai and New Delhi 
13.6 Randomization and Masking Procedures 
In cluster-randomized trials with a relatively low number of sites (clusters), substantial 
imbalances between study arms can emerge easily by chance. To reduce the likelihood of large 
study arm imbalances for key variables, we restricted the pool of potential allocation 
combinations by removing combinations with large baseline imbalances. With no restrictions, 
there were a total of 16 potential allocations (i.e., 42) within each stratum (PWID/MSM), or 256 
overall allocations. First, to reduce large imbalances within the strata, randomization allocations 
were dropped (n=8, 4 in each stratum) due to imbalances in prevalence of viremic persons or 
viral suppression (i.e., all sites with higher/lower prevalence were allocated to one arm). This 
resulted in 12 allocations for each stratum. These allocations crossed (PWID x MSM), resulted in 
144 potential allocations (i.e., 122). Then, an additional overall restriction was placed in which 
allocations were dropped (n=36) due to imbalances in prevalence of viremic persons or viral 
suppression (i.e., higher/lower prevalence 6:2 pair ratio in different arms). This resulted in a total 
of 108 potential allocations. We checked across all these potential allocations for sites that either 
always or never appeared in the same study arm. No sites always or never appeared in the same 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 30 of 44 
 
arm - with the exception matched sites, which, by definition, never appeared in the same arm. 
 
Of the 108 allocation combinations that remained after site pairing and restriction, one allocation 
was selected in a ball drawing ceremony on January 3, 2018 that was refereed by two 
statisticians who were independent of the study. The ceremony was video recorded and is 
available at https://youtu.be/UmXBG2CluNA. Because of the cluster randomized design, 
masking participants or research staff was not feasible. However, the randomization team 
withheld the randomization results for each site pair until cohort recruitment was complete or 
nearly complete at both sites in the pair. The implementation teams in India recruited cohorts at 
each site without knowing whether the site would be intervention or control.     
13.7 Participant Enrollment and Follow-up 
Cohort participants will be assessed for eligibility and enrolled at ICCs as described above. 
These participants will complete a baseline study visit as soon as possible after screening and 
will be asked to complete follow-up research visits at 6, 12, 18, and 24 months. Participants in 
the qualitative evaluations will be enrolled at ICCs and be asked to complete an in-depth 
interview. There will be no follow-up visits in the qualitative evaluation. Participants in the RDS 
survey will be enrolled after being recruited by network members using a coupon system as 
described above. RDS survey participants will be asked to compete a single study visit with no 
follow-up.  
13.8 Data and Safety Monitoring 
Procedures to ensure the validity and integrity of the data 
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. All staff will undergo a three-day training program on the study protocol and the 
standard operating procedures, followed by a one-day one-on-one training session for staff who 
will be administering and/or recording information on tablet PCs/netbooks (RDS) or study case-
report forms (ICCs). Mock interviews will also be included.  If new staff members are hired 
during the course of the trial, they will undergo similar training prior to coming into contact with 
study participants.  
 
Lab technicians/phlebotomists at YRGCARE have undergone training on research ethics and 
good clinical laboratory practices (GCLP).  The YRGCARE ID 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 Trial Group and Abbott 
Laboratories Inc, US. GCLP are monitored by Johns Hopkins, Family Health International, and 
PPD. 
 
Procedures to guarantee the accuracy and completeness of the data 
Our primary mode of data collection will be through the cohort and RDS surveys. In addition, 
some process measure data will be collected in the ICCs. We have chosen to use a laptop data 
entry system rather than paper case report forms. Given the large number of surveys/study visits 
that will be conducted (16,000 in RDS and ~8,000 in cohort), the electronic data collection 
method has advantages over the paper method, including 1) immediate data upload to the central 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 31 of 44 
 
server, 2) increased portability for multiple sites, 3) reduced need to transport paper forms, and 
4) logic checks and field restrictions can be built into the program to minimize data capture 
errors. Finally, the ability to upload data from the field to a central server in real time will help us 
identify potential overlap between sites (i.e., participants who are recruited at more than one 
site). The central database will include the unique alphanumeric codes that will be obtained from 
fingerprint images. Therefore, once a survey is completed the code will be centrally available, 
enabling us to quickly identify individuals recruited at multiple sites. 
13.9 Analysis Plan 
The analysis plan has five components. First, we will compare primary and secondary endpoints 
in cohort participants at sites randomized to the intervention or the control condition. Second, we 
will assess whether the intervention, in comparison with the control condition, was associated 
with “off-target” effects at ICCs (number of unique persons tested for HIV and number of HIV-
positive persons diagnosed). Third, we will conduct a mixed methods evaluation of the HIV care 
incentives. Fourth, we will evaluate the impact of the HIV care incentives on PWID and MSM 
community-level outcomes with a dedicated RDS survey. Fifth, we will evaluate the cost-
effectiveness of the HIV treatment incentive intervention. 
13.9.1 Analysis plan for primary outcome 
In the primary analysis, we will use an intent-to-treat, missing equals failure approach. The 
primary outcome will be the proportion of participants who have survived with a suppressed 
viral load (HIV RNA <150 c/mL) at the 12-month cohort follow-up visit. Participants that die 
prior to the 12-month visit or miss the 12-month visit will be considered failures in the analysis. 
The primary analysis will be at the site-level and will use a two-stage procedure beginning with 
fitting an individual-level logistic regression model with terms for each matched pair and 
individual-level viral suppression at the baseline visit (HIV RNA <150 copies/mL), but ignoring 
the intervention effect. The model computes the expected number of events in each cluster. The 
observed and expected number of events in the two clusters in each matched pair are compared 
and if there is no intervention effect these values will be the same. An adjusted prevalence ratio 
and 95% confidence interval will be calculated by estimating the mean within-pair difference of 
the natural log transformed adjusted prevalences by arm. The exponentiated difference is the 
ratio and a paired t-test will be used for significance testing. An adjusted prevalence difference 
and 95% confidence interval will be calculated in a similar manner, estimating the mean within 
pair difference of the non-transformed prevalences by arm. Analysis of the primary outcome will 
also be stratified by viral suppression status at baseline (HIV RNA <150 copies/mL). In this site-
level one-stage approach, we will calculate the difference in the proportion with suppressed viral 
load within each matched pair among strata defined by baseline viral suppression. We will 
calculate the unweighted mean of the pair-wise difference with a 95% confidence interval and 
use a paired t-test to test the hypothesis that within each stratum the observed difference is 
statistically different from zero. We will further explore whether there is statistically significant 
interaction by baseline viral suppression status and intervention effect.   
 
Primary outcome sensitivity analyses 
We will conduct several supplemental analyses to assess whether inferences are sensitive to 
different analytic specifications. First, we will conduct an analysis in which participants who 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 32 of 44 
 
miss the 12-month visit (but are not known to be deceased) will be excluded (missing ignored), 
and death or non-suppression of the HIV RNA at month 12 will be considered failure. Second, 
we will conduct an analysis that includes only individuals that complete the 12-month visit 
(deaths and missing ignored) and non-suppression of the HIV RNA at month 12 will be 
considered failure. In a third sensitivity analysis, we will consider adjusting for additional 
potential confounders using the same two-stage procedure described above (6). We will only 
consider factors measured at the baseline visit (no post-randomization measures) that have a 
large (odds ratio >2 or <0.5) and statistically significant (p<0.05) association with the 
intervention status and the outcome. Fourth, we will conduct pre-specified analyses that are 
stratified by key population (PWID and MSM).  
13.9.2 Secondary outcomes 
Secondary binary outcomes including i) survival with suppressed viral load at other time points 
(6, 18, and 24 months), ii) proportion with at least one suppressed viral load during follow-up, 
iii) proportion retained to HIV care (defined as the proportion with at least one visit to the ART 
center per 6-month follow-up interval), and iv) mortality will be analyzed similarly resulting in 
pair-wise differences in proportions with a two-stage procedure for confounder adjustment, if 
appropriate (criteria for confounders outlined in prior section). 
 
For two other secondary outcomes, we will use similar pair-matched cluster approaches with a 
two-stage procedure for confounder adjustment. First, we will compare risk of initiating ART at 
intervention vs. control sites (among the subset that is ART-naïve at baseline) using a Cox 
proportional hazards model. Second, we will compare ART possession ratio (defined as number 
of days covered by ART dispensations divided by the number of days under observation) by 
calculating a mean difference between intervention and control conditions. 
13.9.3 Exploratory outcomes 
Intervention effects on HIV testing and diagnosis at ICCs 
We will assess whether the intervention, when compared with the control condition, is associated 
with off-target effects at ICCs. We hypothesize that treatment incentives for HIV-positive clients 
may also attract more people to the ICC for HIV testing, and subsequently, lead to more newly 
diagnosed HIV-positive persons. We will use a similar two-stage procedure as described above 
to calculate the mean pair-wise differences in rates. 
 
Analysis plan for mixed methods evaluation of HIV care incentives 
The mixed methods evaluation will include a quantitative and qualitative component. The 
quantitative component comprises close-ended questions about perceptions of and experiences 
with incentives that will be included in the questionnaire for the final (24-month) study visit at 
the 8 incentive sites. These data will be summarized to quantify overall and site-level variability 
in perceptions about treatment incentives. 
 
Qualitative data will be obtained by in-depth interviews as described. Transcribed interviews will 
be translated from the local language and entered into Atlas.ti, a free-text organizing program 
and analyzed using content analysis. We will identify core consistencies and meanings in the 
data through careful repeated reading of interview texts. Coding involves labeling sections of 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 33 of 44 
 
text based on themes and particular domains of interest related to the study aims. We will use an 
“open coding” procedure whereby the beginning phases of data analysis will involve an 
inductive approach to elucidate patterns and themes in the data to generate codes for analysis. 
New themes can be generated from the analysis in addition to those established a priori. Early 
coding will be followed by a more deductive process whereby relevant text from the remaining 
interviews is coded using Atlas.ti within the framework established early on. The outputs of the 
coded text will then be reviewed for similarities and differences and synthesized using matrices 
structured by the main themes of the analysis. Quotes representing each theme will be reviewed 
again within the context of the full text of the interview to contextualize and confirm 
interpretation. Results will be summarized/presented by main themes. We will focus on 
codes/themes related to barriers to using the ICCs, perceived quality, and perceptions about 
incentives. 
 
Analysis plan for community-level effects assessed by RDS surveys 
Inferences about the effect of HIV care incentives on community-level outcomes will be based 
on study arm differences in outcomes measured at the evaluation RDS survey, adjusted for 
values of outcomes at the baseline survey (which was done in 2016/2017). Because RDS 
participants are recruited without respect to whether they have accessed services at ICCs, they 
can provide an unbiased estimate of community-level impact. 
 
The primary community-level outcome will be viral suppression among HIV-positive individuals 
in the RDS sample. Using the same approach as the primary outcome analysis, we will calculate 
the difference in the RDS II weighted proportions within each matched pair and then calculate 
the unweighted mean of the pair-wise differences with a 95% confidence interval. Comparisons 
will use RDS-weighted proportions, which will be calculated using the RDS-II estimator (7), 
which accounts for the self-reported network size of each individual in the analysis. With these 
weights, RDS can provide inferences about the prevalence of viral suppression (and other 
outcomes) in the underlying population. RDS weighting is subject to assumptions, some of 
which cannot be validated, therefore we will also compare the unweighted prevalence estimates. 
A paired t-test will test the hypothesis that the observed pair-wise difference is statistically 
different from zero. Adjustment for baseline viral suppression at the baseline survey as a cluster-
level factor will be conducted using the two-stage approach as described in the primary analysis. 
Similar analytic methods will be applied to secondary outcomes that are proportions including 
recent HIV testing, awareness of HIV status, HIV care, current ART use, and prevalence of 
viremic individuals in the community, as well as the HIV incidence rate (unweighted only). 
 
As a sensitivity analysis, we will adjust for demographic factors as confounders (age, sex, 
marital status, educational attainment) using the two-stage procedure if the factor has a large 
(odds ratio >2 or <0.5) and statistically significant (p<0.05) association with the intervention 
status and the outcome. Additional sensitivity analyses will consider other approaches including 
an analysis of the within-cluster difference in outcome prevalence between serial cross-sectional 
studies (baseline RDS and evaluation RDS after 24 months of intervention) and individual-level 
models. These models include fixed effects (e.g., matched pair effect), random effects (e.g., 
clusters), scaled RDS weights as sampling weights, and allow adjustment for baseline covariates 
at the individual and cluster level. Additionally, we will conduct pre-specified analyses that are 
stratified by key population (PWID and MSM). 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 34 of 44 
 
 
Analysis plan for cost-effectiveness 
We will conduct 2 cost-effectiveness analyses from 3 perspectives (patient out-of-pocket costs, 
health care payer (governmental), and societal, combining patient and payer costs). The first 
analysis will compare the cost-effectiveness of HIV care incentives versus the control condition 
using the primary and secondary outcome measures to yield, for example, the cost per additional 
individual surviving with viral suppression at 24 months. Using the same approach, we will also 
explore cost-effectiveness with respect to secondary outcomes including newly identified HIV-
infected persons and HIV incidence.  
 
1. Costing: We will apply standard micro-costing methods from the US Task Force on Cost 
effectiveness Analysis to assess care and intervention costs. The intervention costs will be 
based on fair market value of the non-cash incentives. For individuals, we will focus on the 
following major and readily captured medical and productivity measures: hospitalizations, 
physician and non-physician outpatient visits, medications, productivity (full-time, part-time 
work), out of pocket medical costs, and time and wages lost due to medical appointments 
including travel. We will adhere to recommendations for trial-based economic data collection 
(e.g., identifying resource measures, data collection, baseline cost, pilot testing, validation, 
patient-level costing, national costing and standard reporting). We will consult policymakers 
for the most relevant outcomes of interest to them and for their preferred sources of national 
resource unit costs, e.g., based on India’s National Pharmaceuticals Pricing Policy and 
National Health Accounts of India. 
 
2. Effectiveness: The initial cost-effectiveness analysis will combine the costing analysis from 3 
perspectives (patient, payer and societal) for the 24-month intervention period with the 
primary and secondary outcomes of the cluster-randomized trial using statistical analyses 
delineated above. A second cost-effectiveness analysis will extend the end of trial results to a 
lifetime time horizon. Because induced benefits or costs may extend beyond the time horizon 
of the study (e.g., mortality benefit from viral suppression), we will project the future 
implications on health and on costs using computer simulation models. Markov or Monte 
Carlo simulation models track hypothetical cohort members as some individuals develop 
HIV or as those with HIV infection have stable, improved, or worsened health status or die. 
The computer simulations track the proportion of the cohort that is alive each year until all 
cohort members have died or the desired analytic time horizon has been reached. Consistent 
with WHO recommendations, we will obtain quality of life estimates as disability-adjusted 
life years (DALYs).  
 
Economic model development will include the following steps: (1) systematic literature 
search to identify existing data to estimate model parameters and previously published 
economic models, (2) data synthesis to estimate means and ranges of uncertainty, (3) Markov 
and Monte Carlo simulation model development based on the primary study and literature 
data. Search strategies will include those recommended by Health Technology Assessment, 
supplemented by hand-searching of bibliographies and consultation with experts. Data 
synthesis will apply standard quantitative pooling methods typically used in meta-analysis 
(such as a random effects model) when sample sizes are available. When sample size is not 
available, means or medians of published data will be applied with ranges specified in the 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 35 of 44 
 
literature. The Markov model construction will use standard decision analysis software 
(Decision Maker, DATA by Treeage or equivalent). Because costs are discounted to reflect 
time preferences (money spent now is more valuable than money spent one year from now), 
life expectancy will also be discounted in accordance with cost-effectiveness 
recommendations. Model validation or calibration to external data (comparison and 
adjustment, if necessary, of predicted to observed outcomes) will be performed.  
 
3. Cost-effectiveness analyses: By extending the time horizon for the analysis and by translating 
trial outcomes into DALYs, the cost-effectiveness analysis becomes a cost-utility analysis 
where the outcome is expressed as the incremental cost-effectiveness ratio (ICER) per 
disability-adjusted life-year gained. We will compare of the ICER for the incentive 
intervention with the ICERs of other well-accepted medical interventions. Based on WHO 
criteria, the intervention will be considered “highly cost-effective” if the ICER falls below 
the per capita GDP of the country (~$1500 for India) and “cost-effective” if the ICER falls 
below 3 times the per capita GDP.   
 
Extensive sensitivity analyses will be performed, varying each variable or groups of variables 
over their plausible ranges to determine their impact on the cost-effectiveness of HIV care 
incentives versus the control condition. The translation of the Markov model into a Monte 
Carlo simulation will involve assigning distribution functions for each parameter and 
determining the range of plausible values to capture their uncertainty, and re-evaluating the 
computer simulations with boot strap samples. This will be used to determine cost-
effectiveness acceptability curves, which incorporate all of the uncertainty to estimate the 
likelihood that the intervention will have an ICER that makes it cost-effective or cost-saving.   
14. DATA HANDLING AND RECORDKEEPING 
14.1 Data Management Responsibilities 
This study will be conducted a 16 field sites throughout India, but will be coordinated by a single 
site, 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. Investigators from Johns Hopkins and 
YRGCARE will oversee all aspects of the trial including participant recruitment, data collection, 
laboratory testing, biological sample storage, and data management. Additional details can be 
found in the Data and Safety Monitoring Plan. 
14.2 Essential/Source Documents and Access to Source Data/Documents 
Source documents for this study are i) electronic case report forms (eCRFs), into which data 
from interviews will be directly entered, and ii) government ART treatment books, which will be 
photocopied and stored electronically at each study visit. Additional details can be found in the 
Data Safety and Monitoring Plan.  

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 36 of 44 
 
14.3 Quality Control and Quality Assurance 
14.3.1 Procedures to ensure the validity and integrity of the data 
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 YRGCARE have undergone training on research ethics and 
good clinical laboratory practices (GCLP). The YRGCARE ID 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. 
14.3.2 Procedures to guarantee the accuracy and completeness of the data 
Our primary mode of data collection will be through the EHR at the ICCs and study specific 
eCRFs. Additional details can be found in the Data Safety and Monitoring Plan.  
15. CLINICAL SITE MONITORING 
ICCs are key population-focused sites that provide HIV and HCV testing, STI screening and 
treatment, and (in PWID sites) OST and SSP. They are staffed by a site coordinator, one or two 
nurses, a counselor, a phlebotomist, and a part-time physician. This ICC staff provided clinical 
overview for the site. The current study evaluates a behavioral economic intervention, which is 
minimal risk. No additional clinical monitoring is needed for the current protocol. 
16. HUMAN SUBJECTS PROTECTIONS 
16.1 Institutional Review Boards 
The protocol and informed consent documents are approved by the Institutional Review Boards 
of the Johns Hopkins School of Medicine in the US and YRGCARE in Chennai, India. In 
addition, the study is approved by the Indian Council of Medical Research and the Health 
Ministry Screening Committee. Any subsequent modifications will be reviewed and approved by 
both the Johns Hopkins and the YRGCARE IRBs. IRB continuing review and approval will be 
obtained from both the Johns Hopkins and YRGCARE IRBs once a year. If IRB approval 
expires or lapses, all ongoing research activities will stop unless the PIs determine that it is the 
best interests of already enrolled participants to continue their study-related activities. New 
participants will not be enrolled in the study until the IRB approval to continue the research is 
obtained.  

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 37 of 44 
 
16.2 Vulnerable Participants 
16.2.1 Pregnant Women and Fetuses 
Pregnant women who meet eligibility criteria for inclusion in the PWID stratum of the study may 
be included in any aspect of the study (cohort, mixed methods evaluation, or RDS survey). The 
study does not provide medications or interventions that pose a risk to pregnant women or their 
fetuses. We will not test women for pregnancy as part of this study. 
16.2.2 Prisoners 
It is possible that persons who are enrolled may become prisoners during the course of the study. 
We do not have formal agreements in place to provide the incentive intervention or conduct 
study visits while participants are in prison. We will not conduct any research activities while 
participants are in prison. We will continue to track participants and re-engage them in the study 
when they are released from incarceration if still in the follow-up window. 
16.2.3 Children 
Children younger than 18 years will not be included in any aspect of the study. 
16.2.4 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.  
16.3 Informed Consent 
16.3.1 Informed Consent Process 
Study cohorts: Written informed consent will be used for HIV-positive participants enrolled in 
the cohorts at each ICC. Consent will be obtained by a trained, supervised research assistants in a 
private office setting. Approximately 20 minutes will be allotted for consent. Participants will 
not generally have access to the consent form in advance, but they may take a consent form with 
them if they wish to take more time in making a decision to join the study. The research 
assistants will present the consent form to participants in detail and encourage them to ask 
questions. The research assistants will assess participation understanding of the consent form by 
querying whether 1) identifying information will be collected in the study (yes), and 2) whether 
the study will have any follow-up after the initial visit (yes, we will use locator information to 
locate participants at the end of the study and ask them questions about their HIV care and get a 
sample of blood). Because this study will be conducted in numerous cities across India, multiple 
translations are needed to accommodate local languages. 
 
In-depth interviews: A research assistant will meet with individuals in a private office to describe 
the study and obtain oral consent. The research assistant will read the OCS verbatim to potential 
participants in the relevant language for the study site.  
 
RDS survey: We will use an oral consent script for RDS participants. With the exception of the 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 38 of 44 
 
RDS “seeds” (2 or 3 participants to begin the recruitment chain), individuals must present a valid 
to the study site with a valid referral coupon. A research assistant will meet with such individuals 
in a private office to describe the study and obtain oral consent. The research assistant will read 
the oral consent script verbatim to potential participants in the relevant language for the study 
site. 
16.3.2 Assent Process 
Not applicable 
16.3.3 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 field sites. 
16.4 Risks 
a. Medical risks, listing all procedures, their major and minor risks and expected frequency. 
 
Study procedure 
Medical Risks 
Frequency Severity 
HIV-positive ICC 
cohort participant 
Pain from phlebotomy 
Most 
Minor 
 
Phlebitis or skin infection from 
phlebotomy 
< 1% 
Minor to 
moderate 
In-depth interviews 
None 
 
 
Baseline/Evaluation 
RDS 
Pain from phlebotomy 
Most 
Minor 
 
Phlebitis or skin infection from 
phlebotomy 
< 1% 
Minor to 
moderate 
 
Psychological discomfort from 
questions about personal behaviors 
< 20% 
Minor 
 
Anxiety about HIV testing 
Most 
Minor 
 
b. Steps taken to minimize the risks. 
The proposed study poses only minimal medical risks. We will minimize the risk of 
phlebotomy-associated adverse events by using trained and experienced phlebotomists and 
by adhering to sterile practice. We will minimize the risk of participant discomfort with 
personal questions by a) training interviewers to query and respond in non-judgmental 
manner and b) to inform participants that they may skip questions they are not comfortable 
answering. Finally, we will minimize anxiety about HIV testing by using trained HIV testing 
counselors. 
 
c. Plan for reporting unanticipated problems or study deviations. 
The Indian co-investigator (Aylur Srikrishnan) 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 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 39 of 44 
 
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. 
 
d. Legal risks such as the risks that would be associated with breach of confidentiality. 
We will collect self-reported information on illicit drug use and sexual practices that may 
pose legal risks to participants if confidentiality is breached. Regarding the HIV-positive ICC 
cohort participants, we will collect identifying information in these subjects, including name, 
address, and contacts. These data will be maintained at the sites on password-protected 
laptops that will be brought home by study staff each night. As with the RDS, data will be 
uploaded each night to an encrypted, internet-based clinical trial database, based at 
YRGACRE in Chennai. Source documents on-site will be maintained in a double-locked file 
cabinet. 
 
Regarding the RDS surveys, we have a multilevel plan to minimize this risk. First, we will 
not collect RDS participants’ names or other identifying information, and we will use oral 
consent to avoid the use of names and signatures on informed consent forms. Second, RDS 
interview data will be uploaded immediately to an encrypted, internet-based clinical trial 
database. RDS interviewers in the field will not have access to participant data in the 
database other than the participant they are currently interviewing. Third, interview and 
laboratory data will be stored and managed at the YRGCARE coordinating center in 
Chennai, India. These data will be password-protected and available only to a defined group 
of data managers and analysts who are working on the trial. 
 
e. Financial risks to the participants. 
This study entails no financial risks to participants. 
16.5 Social Impact Events 
Individuals enrolled in this study may experience personal problems resulting from the study 
participation. Such problems are termed social impact events. Although study sites will make 
every effort to protect participant privacy and confidentiality, it is possible that participants' 
involvement in the study could become known to others, and that participants may experience 
stigmatization or discrimination as a result of being perceived as being HIV-infected. For 
example, participants could be treated unfairly, or could have problems being accepted by their 
families and/or communities. Problems may also occur in circumstances in which study 
participation is not disclosed, such as impact on employment related to time taken for study visits. 
 
In the event that a participant reports a social impact event, every effort will be made by study 
staff to provide appropriate assistance, and/or referrals to appropriate resources. Social impact 
events are documented and reviewed on a scheduled basis by the protocol team leadership with 
the goal of reducing their incidence and enhancing the ability of study staff to mitigate them when 
possible. Social impact events that are judged by the designee to be serious, unexpected, or more 
severe or frequent than anticipated, will be reported to the overseeing IRBs in accordance with the 
IRB’s reporting policy. 
 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 40 of 44 
 
16.6 Benefits 
Participants in the HIV-positive ICC cohorts, have the potential to benefit if the intervention 
leads to improved HIV treatment outcomes and retention to care. Persons who participate in the 
RDS may benefit from HIV counseling and testing and learning their HIV status. No benefits are 
anticipated for those who participate in in-depth interviews. The study has the potential to benefit 
society if the tested intervention is found effective and are adopted in routine service delivery.   
16.7 Compensation 
HIV-positive cohort participants will receive 250 Indian Rupees (4.17 USD) for successfully 
completing each study visit (maximum of 5 visits). For the last 2 visits (18-month and 24-month 
visits) we will offer a bonus of 200 Indian Rupees (3.33 USD), in addition to the base 
reimbursement, for participants who complete the visits in a +/- 14 day window around the 
scheduled visit date. The maximum possible reimbursement for ICC cohort participants is 1650 
Indian Rupees (27.50 USD) for those who complete all 5 study visits and complete the last 2 
visits within the specified window. 
 
Compensation for time and travel will be provided to in-depth interview participants – 150 
Indian Rupees (2.50 USD). 
 
Compensation will be provided to RDS participants. They will receive 250 Indian Rupees (4.17 
USD) for completing the survey and phlebotomy. They will also be eligible to receive an 
additional payment for each coupon returned by an eligible participant up to 2 coupons 
maximum (50 Indian Rupees or 0.83 USD per coupon). Thus, the maximum possible 
compensation for RDS participants will be 350 Indian rupees (6.83 USD). 
16.8 Participant Privacy and Confidentiality 
All participant-related information including eCRFs, laboratory specimens, evaluation forms, 
reports, etc., will be kept strictly confidential. All paper records will be kept in a secure, double-
locked location and only research staff will have access to the records. For electronic records, an 
encrypted network-based data collection storage system will be used. Trained interviewers will 
conduct face-to-face interviews with participants and enter responses directly onto a laptop 
computer or tablet. Information will be routed directly to a central server via a local network. 
Encrypted data will then be transferred over the internet (a minimum of once daily) to the central 
data storage at YRGCARE where it is stored and backed-up every 24 hours. Data will be cleaned 
at YRGCARE and de-identified before being encrypted and transferred via a secure internet 
portal to the analytical team at Johns Hopkins. Human specimens (blood) will be labeled using 
study specific ID numbers only, with no personal identifying information on the tube or 
paperwork. Samples will be shipped under specified conditions and time frames to YRGCARE 
for laboratory testing. The biometric system that will be used generates a unique and 
reproducible hexadecimal code when a fingerprint is scanned or rescanned. The software does 
not store fingerprint images and hexadecimal codes cannot be back-converted to a fingerprint 
image.  
 
Only the field teams delivering care to participants will have access to identifying information of 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 41 of 44 
 
study participants. Any data that is sent to US investigators for analysis will be deidentified. 
Upon request, participant records will be made available to the study sponsor, the sponsor’s 
monitoring representative and applicable regulatory entities. 
16.9 Certificates of Confidentiality 
This study is protected by a Certificate of Confidentiality for data stored in the U.S. Certificates 
of confidentiality are not recognized by the Indian Government.  
16.10 Study Discontinuation 
The study may be discontinued at any time by the IRB or NIDA as part of their duties to ensure 
that research participants are protected. 
16.11 Post-Trial Access 
Not relevant 
16.12 Community Advisory Board and Other Relevant Stakeholders 
Community advisory boards are already present in each of the study field sites as part of ongoing 
research activities and they will continue to be engaged throughout this protocol. Community 
meetings will occur quarterly.  
17. ADMINISTRATIVE PROCEDURES 
17.1 Protocol Registration 
Not applicable 
17.2 Regulatory Oversight 
Not applicable 
17.3 Study Implementation 
Additional details can be found in the Study standard operating procedures (SOP) 
17.4 ClinicalTrials.gov 
This trial is registered with ClinicalTrials.gov – NCT02969915 
18. REFERENCES 
1. 
Solomon SS, Lucas GM, Celentano DD, McFall AM, Ogburn E, Moulton LH, et al. 
Design of the Indian NCA study (Indian national collaboration on AIDS): a cluster randomized 
trial to evaluate the effectiveness of integrated care centers to improve HIV outcomes among 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 42 of 44 
 
men who have sex with men and persons who inject drugs in India. BMC Health Serv Res. 
2016;16(1):652. 
2. 
Solomon SS, Solomon S, McFall AM, Srikrishnan AK, Anand S, Verma V, et al. 
Integrated HIV testing, prevention, and treatment intervention for key populations in India: a 
cluster-randomised trial. Lancet HIV. 2019;6(5):e283-e96. 
3. 
Solomon SS, Srikrishnan AK, Vasudevan CK, Anand S, Kumar MS, Balakrishnan P, et 
al. Voucher incentives improve linkage to and retention in care among HIV-infected drug users 
in Chennai, India. Clin Infect Dis. 2014;59(4):589-95. 
4. 
Aceijas C, Friedman SR, Cooper HL, Wiessing L, Stimson GV, Hickman M. Estimates 
of injecting drug users at the national and local level in developing and transitional countries, and 
gender and age distribution. Sex TransmInfect. 2006;82 Suppl 3:iii10-iii7. 
5. 
Laeyendecker O, Konikoff J, Morrison DE, Brookmeyer R, Wang J, Celum C, et al. 
Identification and validation of a multi-assay algorithm for cross-sectional HIV incidence 
estimation in populations with subtype C infection. J Int AIDS Soc. 2018;21(2). 
6. 
Hayes RJ, Moulton LH. Cluster Randomised Trials. Baco Raton, FL: Chapman & Hall / 
CRC; 2009. 
7. 
Volz E, Heckathorn DD. Probability Based Estimation Theory for Respondent Driven 
Sampling. Journal of Official Statistics. 2008;24(1):79-97. 
 
19. APPENDICES 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 43 of 44 
 
Appendix I. Schedule of procedures and evaluations for cohort participants followed in cluster 
randomized trial 
Procedures/Evaluations 
Screening 
Baseline 
visit 
Follow-up evaluations and intervention 
6 mo. 
12 mo 
18 mo 
24 mo 
Interim 
visits 
Screening questionnaire 
X 
 
 
 
 
 
 
Enrollment informed consent 
X 
 
 
 
 
 
 
Register biometric code (fingerprint based) in database 
 
X 
 
 
 
 
 
Abstract HIV treatment data from govt. ART books 
X 
 
X 
X 
X 
X 
X 
Locator information 
 
X 
X 
X 
X 
X 
X 
Study interview 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
Quality of  life 
 
X 
X 
X 
X 
X 
 
HIV care continuum 
 
X 
X 
X 
X 
X 
 
ART use & adherence 
 
X 
X 
X 
X 
X 
 
Beliefs about ART 
 
X 
X 
X 
X 
X 
 
Drug & alcohol use 
 
X 
X 
X 
X 
X 
 
Drug related risk behaviors 
 
X 
X 
X 
X 
X 
 
Sexual risk behaviors 
 
X 
X 
X 
X 
X 
 
Depressive symptoms 
 
X 
X 
X 
X 
X 
 
Healthcare utilization  
 
X 
X 
X 
X 
X 
 
Laboratory tests 
 
 
 
 
 
 
 
Rapid HIV test 
X 
 
 
 
 
 
 
CD4 cell count 
 
X 
 
 
 
 
 
HIV RNA 
 
X 
X 
X 
X 
X 
 
Blood glucose 
 
 
X 
 
 
 
 
Creatinine 
 
 
 
X 
 
 
 
Hepatic panel  
 
 
 
 
X 
 
 
Study visit compensation 
 
X 
X 
X 
X 
X 
 
HIV care incentives provided (intervention sites only) 
 
 
X 
X 
X 
X 
X 

 
 
Protocol Number NCT02969915 
 
 
Draft Version 2.0 
 
 
October 20, 2022 
 
Page 44 of 44