A Cluster Randomized Trial of Integrated Care Centers to Improve Access to HIV Prevention, Testing, and Treatment Services Among High-Risk Vulnerable Populations in India
Phase: NA
Conditions: HIV Infection
Sponsor: Johns Hopkins University

 
 
Integrated Care Centers to Improve HIV Outcomes in Vulnerable Indian Populations 
 
 
 
 
 
 
 
 
 
 
 
ClinicalTrials.gov Protocol Number: 
NCT01686750 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
14 November 2016 
 
 

 
1
Design of the Indian NCA study (Indian National Collaboration on AIDS): A cluster 
1 
randomized trial to evaluate the effectiveness of integrated care centers to improve HIV 
2 
outcomes among men who have sex with men and persons who inject drugs in India 
3 
 
4 
Sunil S Solomona, b, c  
 
 
 
 
sss@jhmi.edu  
 
 
 
5 
Gregory M Lucasa 
 
 
 
 
 
glucas@jhmi.edu 
6 
David D Celentanob 
 
 
 
 
 
dcelent1@jhu.edu 
7 
Allison M McFallb 
 
 
 
 
 
amcfall2@jhu.edu 
8 
Elizabeth Ogburnb 
 
 
 
 
 
eogburn@jhu.edu 
9 
Lawrence H. Moultonb 
 
 
 
 
lmoulto1@jhu.edu 
10 
Aylur K Srikrishnanc  
 
 
 
 
krish@yrgcare.org 
11 
M Suresh Kumarc 
 
 
 
 
 
msuresh1955@gmail.com 
12 
Santhanam Anandc 
 
 
 
 
 
anad@yrgcare.org 
13 
Suniti Solomonc 
 
 
 
 
 
suniti@yrgcare.org 
14 
Shruti H Mehtab* 
 
 
 
 
 
smehta@jhu.edu 
15 
 
16 
Author affiliations:  
17 
aJohns Hopkins School of Medicine, 1830 E Monument St, Baltimore, MD 21205 
18 
bJohns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205 
19 
cYR Gaitonde Centre for AIDS Research and Education (YRGCARE), Chennai, India 
20 
 
21 
 
22 
*Corresponding Author: 
23 
Prof Shruti H Mehta 
24 
Johns Hopkins Bloomberg School of Public Health 
25 
Department of Epidemiology 
26 
615 N. Wolfe Street, Rm. E6537 
27 
Baltimore, MD 21205 USA 
28 
Phone: 443-287-3837 
29 
Fax: 410-955-0863 
30 
Email: smehta@jhu.edu 
31 
 
 
32 

 
2
ABSTRACT 
33 
 
34 
Background 
35 
Globally, men who have sex with men and people who inject drugs remain disproportionately 
36 
affected by HIV, but they have not been the focus of prevention and treatment interventions in 
37 
many resource-limited settings. 
38 
Methods/ Design 
39 
This cluster-randomized trial (conducted from June 2012 to June 2017), evaluates whether 
40 
single-venue, integrated delivery of core HIV services to vulnerable high-risk populations 
41 
improves service utilization and consequently, HIV testing and other outcomes along the HIV 
42 
care continuum. Core services include: HIV counseling and testing, information, education and 
43 
communication, condom distribution, needle and syringe exchange programs, opioid agonist 
44 
therapy, management of sexually transmitted infections, tuberculosis screening, diagnosis, and 
45 
treatment, and antiretroviral therapy. Stratified restricted randomization was used to allocate 22 
46 
Indian cities (10 men who have sex with men and 12 people who inject drugs sites) at a 1:1 ratio 
47 
to either the intervention or control condition. Integrated care centers were scaled-up and 
48 
implemented in the 11 intervention cities and outcomes will be assessed by pre- and post-
49 
intervention surveys at intervention and control sites. As men who have sex with men and people 
50 
who inject drugs are hidden populations, with no sampling frame, respondent-driven sampling 
51 
will be used to accrue samples for the two independent cross-sectional surveys.  
52 
Discussion 
53 
For an AIDS-free generation to be realized, prevention, care and treatment services need to reach 
54 
all populations at risk for HIV infection. There is a clear gap in access to services among men 
55 

 
3
who have sex with men and people who inject drugs. Trials need to be designed to optimize 
56 
utilization of services in these populations.  
57 
Trial registration: ClinicalTrials.gov Identifier: NCT01686750 
58 
Date of Registration: September 13, 2012 
59 
 
60 
Word count: 260 
61 
Keywords: HIV/ADS; men who have sex with men; people who inject drugs; India 
62 

 
4
BACKGROUND 
63 
Study Rationale 
64 
India has an estimated 2.3 million HIV-infected persons [1]. The HIV epidemic in India 
65 
has historically been driven by heterosexual transmission [1] with the exception of the Northeast 
66 
where injection drug use is the primary driver [2-4]. Recent evidence suggests that the HIV 
67 
epidemic in India has stabilized and may even be declining [1, 5] attributable to reductions in 
68 
HIV prevalence among high-risk heterosexual populations (e.g., female sex workers, truck 
69 
drivers, women attending antenatal clinics) who have been targeted by interventions since the 
70 
mid 1980s. By contrast, men who have sex with men (MSM) and people who inject drugs 
71 
(PWID) have not been targeted by interventions until recently, and represent two key populations 
72 
with highest HIV burden in India currently [1, 6, 7].  
73 
The National AIDS Control Organization (NACO), India has estimated there are 2.35 
74 
million ‘high-risk’ MSM living in India [8]; however, estimates of prevalence of same-sex 
75 
behavior among men are as high as 9%, translating to as many as 45 million MSM [9, 10]. As in 
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several other resource-limited settings, anal intercourse is a crime punishable by law in India 
77 
[11]. Consequently, most MSM remain hidden and frequently marry women to conceal their 
78 
MSM behavior [12]. HIV prevalence among MSM ranges between 7-41%, with cities in the 
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south reporting higher burden of infection [13-18].  
80 
India is home to the largest number of opiate users in the world (~3 million) [19] and ~ 
81 
1.1 million PWID  [20, 21]. Historically, drug use in India was described in the Northeastern 
82 
states due to their proximity to the ‘Golden Triangle’ – Burma, Laos, Thailand and Vietnam. 
83 
Later, reports of injection drug use emerged from large metropolitan cities across India [22-25] 
84 
and more recently, reports of increases in drug use have been reported from cities in the 
85 

 
5
Northwestern states of India [26-29], which border the ‘Golden crescent’ – Afghanistan and 
86 
Pakistan.  HIV prevalence among PWID ranges from 10-30%, with cities from the Northeastern 
87 
states bearing a higher burden of infection [30-32, 4, 3, 23, 24].  
88 
Although MSM and PWID together account for a minority of HIV cases in India, they 
89 
are major drivers of the epidemic in some regions. MSM and PWID share commonalities that 
90 
make HIV service delivery challenging: (1) both behaviors are punishable by law, discouraging 
91 
people from seeking prevention and treatment services [11, 12]; (2) high levels of experienced 
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stigma from the general and medical communities have been reported by both [33-35]; and (3) 
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prevention and treatment services are only accessible via a fragmented service delivery model. 
94 
All of these have contributed to service underutilization.  
95 
Study aims and hypotheses 
96 
This trial evaluates whether single-venue, integrated delivery of core services to MSM 
97 
and PWID improves service utilization and consequently HIV testing and other outcomes along 
98 
the HIV care continuum. Core services recommended by the World Health Organization (WHO), 
99 
United Nations Office on Drug Control (UNODC) and the Joint United Nations Programme on 
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HIV/AIDS (UNAIDS) for PWID (several of which are also applicable to MSM) include: (1) 
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HIV counseling and testing [HCT], (2) information, education and communication (IEC), (3) 
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condom distribution, (4) needle and syringe exchange programs [NSEP], (5) opioid agonist 
103 
therapy [OAT] for opioid users, (6) management of sexually transmitted infections [STIs], (7) 
104 
viral hepatitis vaccination, (8) tuberculosis [TB] diagnosis, prevention and treatment, and (9) 
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antiretroviral therapy [ART] [36]. Further, WHO recommends these services be delivered in an 
106 
affordable, accessible and non-discriminatory manner. Together these interventions can improve 
107 
awareness of HIV status, reduce injection-related and same-sex risk behavior, improve health, 
108 

 
6
reduce mortality, and decrease the infectiousness of HIV-infected persons in the community 
109 
through effective viral suppression.  We will evaluate the community-level effectiveness of 
110 
MSM//PWID-focused integrated care centers (ICCs), which will provide core and group-specific 
111 
HIV prevention and treatment services at a single venue utilizing a cluster-randomized trial 
112 
design in 22 sites across India.   
113 
 
114 
Our hypotheses are:  
115 
1) Establishing ICCs will increase access to HCT and knowledge of HIV status among MSM and 
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PWID. 
117 
2) In the subset of HIV-infected MSM and PWID, ICCs will increase access to care, use of ART 
118 
and will decrease community viral load. 
119 
3) Establishing ICCs will decrease transmission risk behaviors and HIV incidence among MSM 
120 
and PWID via improved access to prevention services (NSEP, OAT, IEC). 
121 
 
122 
METHODS/ DESIGN 
123 
Study design 
124 
The study design is a cluster-randomized trial with parallel MSM and PWID strata.  ICCs 
125 
were scaled-up and implemented at sites allocated to the intervention arm, and outcomes will be 
126 
assessed by pre- and post-intervention surveys at intervention and control sites (Figure 1). As 
127 
MSM and PWID are hidden populations with no sampling frame, respondent-driven sampling 
128 
(RDS) will be used to accrue samples for the two independent cross-sectional surveys. Sites (10 
129 
MSM and 12 PWID sites) were randomized in a 1:1 allocation ratio. The trial is currently 
130 
underway. The pre-intervention survey took place between September 2012 and December 2013; 
131 

 
7
the ICCs were scaled up between June 2014 and February 2015. Post-intervention survey 
132 
commenced in August 2016 and is expected to be complete by April 2017. 
133 
Study sites 
134 
Twenty-seven candidate sites were selected (15 PWID, 12 MSM; Figure 2) of which 22 
135 
were included in the trial. Sites were selected to represent regions of India where there was 
136 
preliminary evidence of high HIV prevalence or high risk of HIV acquisition through discussions 
137 
with the Targeted Interventions (TI) Division of NACO, India.  We ensured sufficient distance 
138 
between sites to minimize potential overlap (contamination) between intervention and control 
139 
sites. MSM sites were selected to represent cities with established HIV epidemics among MSM, 
140 
smaller cities in high prevalence states and cities with anecdotal reports of HIV among MSM but 
141 
no published reports [1]. PWID sites were selected to represent varying stages of drug use 
142 
epidemics (established drug use epidemics, large metropolitan cities, cities with documented 
143 
emerging drug use epidemics and cities with anecdotal evidence of emerging drug use) [1].    
144 
Design of the intervention 
145 
The intervention is vertically integrated delivery of HIV prevention and treatment 
146 
services in stand-alone venues – called ICCs -- to disenfranchised high-risk groups. These 
147 
centers will provide services critical to HIV prevention and essential outpatient services for HIV-
148 
infected persons. The core services at MSM ICCs are: HCT, condom promotion and distribution, 
149 
diagnosis and treatment of STIs, testing services for spouses, HIV and risk reduction counseling 
150 
services as well as counseling for substance use and depression. In addition, PWID ICCs will 
151 
also include NSEP and OAT (using medically managed buprenorphine).  Finally, in both PWID 
152 
and MSM ICCs, we established linkages with local government centers to deliver treatment for 
153 
HIV (ART) and tuberculosis. All ICC services are currently available in India but are typically 
154 

 
8
provided by independent and insulated service organizations. The keystone of the ICC 
155 
intervention is vertically integrated service delivery to disenfranchised high-risk groups.  
156 
ICCs are based on the premise that interventions that combine approaches and address 
157 
multiple levels (e.g., community-, network-, and individual-levels) can lead to sustainable 
158 
change [37-42]. At the core of our model is a structural intervention that seeks to bring about 
159 
community-level change through provision of integrated services in a non-discriminatory setting 
160 
with nested approaches guided by social and behavioral science theories to induce behavioral 
161 
change at network and individual levels. The structural change (i.e., establishment of ICCs) is 
162 
based on the Andersen and Aday model of health care utilization [43, 44]. The goal is to address 
163 
environmental, predisposing, enabling, and need factors in MSM and PWID that promote or 
164 
inhibit health services use.  To implement this structural change, we rely on the diffusion of 
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innovations [45] and ‘tipping point’ theories [46]. We propose to leverage MSM and PWID 
166 
social networks to disseminate information about the ICCs to improve ICC utilization [47]. Once 
167 
participants visit these centers, we target individual-level behavior change according to the 
168 
Information, Motivation and Behavior (IMB) Skills theoretical framework [48, 49].  
169 
Control condition 
170 
In control sites, all services described above will be locally available. They are provided 
171 
by the government free-of-charge, but delivered in segregated centers that cater to both the 
172 
general population as well as key populations (i.e., there are no MSM or PWID specific centers 
173 
currently in any of the control cities). HCT is delivered by government Integrated Counseling 
174 
and Testing Centers (ICTC) and private laboratories. ART is delivered through government ART 
175 
centers. Tuberculosis care is delivered through government Directly Observed Therapy (DOT) 
176 
centers. STI testing and treatment is provided by government hospitals. For PWID, NSEP and 
177 

 
9
OST are available free of charge but delivered through different venues. While OST is 
178 
predominantly delivered in the government sector (except in the Northeast where non-
179 
governmental organizations [NGOs] deliver OST), NSEP is almost exclusively delivered by 
180 
NGOs.  
181 
Study outcomes 
182 
The primary and secondary study outcomes are listed in Table 1. They will be assessed 
183 
by both objective laboratory data and self-reported data from behavioral and medical surveys. 
184 
Our primary outcome is HCT in the prior 12 months. Participants will be asked about HIV 
185 
testing in two ways. First, they will be asked whether they have ever had an HIV test and if so 
186 
then to recall the last time they had an HIV test. Interviewers have been extensively trained on 
187 
capturing an accurate response to this question. Participants are asked if they recall the exact date 
188 
that they were tested. If so then the date is captured. If unaware of the exact date, interviewers 
189 
have been trained to work with the participant to arrive at an approximate time frame by using 
190 
personal events such as birthdays and anniversaries as well as cultural and religious events such 
191 
as Christmas and Diwali. Second, persons who report that they have not been tested for HIV or 
192 
that they tested negative at their last test are also asked if they have ever been told by a health 
193 
care professional that they are HIV positive and to recall the last time they were told that they 
194 
were HIV positive. A response to each of these questions is mandatory. In calculating the 
195 
outcome variable, persons who report being HIV positive and being tested more than 12 months 
196 
ago will be excluded from the denominator. Persons will be considered to have the outcome of 
197 
interest if they report either having had an HIV test in the prior 12 months or being told by a 
198 
health care professional that they were HIV positive in the past 12 months.   
199 
Implementation of the trial 
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10
Ethnography 
201 
 Before initiating the baseline assessment, we conducted ethnographic research and 
202 
community preparedness in 27 candidate study sites to: (1) identify potential “seeds” for RDS; 
203 
(2) assess potential for contamination across study sites by exploring mobility; and (3) 
204 
understand regional variation in existing HIV prevention and treatment services. On average, two 
205 
focus group discussions (FGDs) and 6-8 in-depth interviews (IDIs) were conducted in each 
206 
potential study site.    
207 
During this preparatory phase, we also conducted community meetings for a 3-month 
208 
period with peer leaders and outreach workers from the MSM/PWID NGOs in the community to 
209 
inform them of the study. RDS is a peer-driven chain referral strategy that hinges on the ability 
210 
of participants to recruit peers. Injection drug use and same-sex behavior are both stigmatized in 
211 
India and punishable by law. Thus, a key goal of these community meetings was to make the 
212 
target populations aware that they might receive coupons from their peers/friends/sexual or 
213 
injection partners to participate in a study and that this study was not a ploy to harm or arrest 
214 
MSM or PWID but rather to evaluate their access to HIV services and understand the needs of 
215 
the communities.    
216 
Baseline pre-intervention assessment.  
217 
The goal of the baseline assessment, conducted between September 2012 – December 
218 
2013, was to establish baseline prevalence of study outcomes for sites in the trial. We accrued 
219 
samples of ~1000 eligible participants in each candidate study site where we partnered with one 
220 
or more NGOs working with the target population. Sampling was conducted using RDS, a chain-
221 
referral sampling method [50, 51] which approximates a probability sample of populations when 
222 
sampling frames are lacking. It is similar to snowball sampling [52] except the recruitment 
223 

 
11
process is implemented in a systematic way that allows for the calculation of selection 
224 
probabilities. Participants select and provide referral coupons to individuals in their peer network 
225 
[50]. Verbal informed consent was obtained from all participants. 
226 
Eligibility criteria were: 
227 
1) ≥18 years of age 
228 
2) Present a valid RDS referral coupon 
229 
3) Be able to comprehend one of the languages in which the survey would be available  
230 
4) Male gender (MSM) 
231 
5) Oral or anal intercourse with another man in the prior year by self-report (MSM) 
232 
6) History of drug injection in the prior two years by self-report (PWID) 
233 
RDS was initiated at each site with participants (“seeds”) selected during ethnography.  
234 
Two seeds were selected from a list of 10 per site to represent varying demographic, geographic 
235 
(different parts of the city), HIV status, and for MSM sites, sexual identity (insertive vs. 
236 
penetrative vs. versatile) and for PWID sites, drug-related diversity (e.g., heroin vs. other opioid 
237 
injection; daily vs. less frequent injection) in the local population. While the initial plan was to 
238 
select 4-7 seeds, recruitment in nearly all sites proceeded at a rapid pace – therefore, in 25 of 27 
239 
sites no additional “seeds” were added. In one MSM and one PWID site, a third seed was added 
240 
as recruitment was slower than the other sites. In one PWID site (Moreh), recruitment was 
241 
terminated prematurely for safety considerations due to civil unrest.  
242 
“Seeds” and subsequent RDS recruits were asked to provide a scan of their fingerprint. 
243 
The fingerprint image is immediately converted to a unique hexadecimal code and stored; the 
244 
image itself is not stored. This code is linked to a study ID, which is used on participant forms 
245 

 
12
and laboratory samples and is also used to rule out duplicate enrollments within a site and to link 
246 
participation across multiple phases of the study.    
247 
All participants underwent a survey followed by HIV pre- and post-counseling and a 
248 
blood draw. Survey modules and laboratory tests are provided in Table 2. English language 
249 
versions of the surveys used at MSM and PWID sites are available as supplementary files. The 
250 
survey was conducted by trained interviewers who were hired expressly for the pre- or post-
251 
intervention RDS surveys, did not work with or have previous interactions with the target 
252 
population in question, and had no stake in the outcome of the ICC evaluation. Interviewers 
253 
recorded answers to a web-based, secure database via laptops and a local area network. RDS 
254 
interviewers and support staff were trained extensively on visit flow, documentation, 
255 
questionnaires, and laboratory procedures using a single training protocol across sites. Quality 
256 
control for the survey was maintained by programmed logic checks and real-time data 
257 
monitoring algorithms and by site supervisors who monitored 5% of randomly selected 
258 
interviews for proper interviewing technique. Constraints placed on the database required 
259 
interviewers to answer every question on the survey and ensured that missing data was minimal. 
260 
Participants were also asked to recruit up to two members of their sexual (MSM) or drug-
261 
using networks (PWID) who satisfied the study eligibility criteria using bar-coded coupons that 
262 
had a holographic image to hinder replication attempts.  If participants successfully referred 
263 
eligible participants, they received an additional incentive of INR 50 (USD 0.8) per eligible 
264 
person recruited in addition to compensation of INR 250 (USD 4.1) for completing the pre-
265 
intervention assessment.  Participants were recruited in successive RDS waves at each site until 
266 
the desired sample size was accrued.  
267 
 
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13
Randomization. 
269 
 Randomization took place after the pre-intervention assessment was completed. First, we 
270 
selected 12 PWID sites (from 15) and 10 MSM sites (from 12) for randomization.  In the PWID 
271 
stratum, two sites were removed because of logistical challenges that deemed them unsuitable for 
272 
randomization (Moreh, Gangtok). Three additional sites were dropped based on very low HIV 
273 
prevalence (Bhubaneshwar [PWID-stratum], Lucknow and Mangalore [MSM-stratum]).    
274 
We used a restricted stratified randomization approach to randomly distribute the 22 sites 
275 
to either the intervention or control condition [53]. In CRTs, the number of randomized units is 
276 
relatively small and large imbalances between study arms may occur if randomization is 
277 
unrestricted; hence, restricted randomization is often used to ensure reasonable balance between 
278 
study arms in important factors. However, the desire for balance between arms must be balanced 
279 
against leaving a sufficient number of randomization options (e.g., at least 100). 
280 
First, sites were stratified based on risk group (MSM and PWID) and then additional 
281 
restriction criteria were used to ensure balance, first within strata and then overall.  Within strata, 
282 
restrictions were made on the basis of geography, HIV prevalence and the primary outcome: 
283 
HCT in the prior 12 months (Table 3).  Additional restrictions were made on outcomes among 
284 
HIV positive persons. All within-strata restrictions were based on RDS-weighted proportions of 
285 
the outcomes. After strata-specific restrictions were made, the two strata were combined to 
286 
derive a combined set of allocations. Final restrictions were made using the same outcomes with 
287 
the exception that both RDS-weighted and unweighted proportions were considered. 
288 
Restrictions related to geography and HIV prevalence were imposed because both were 
289 
related to the stage of the HIV epidemic in the target population and HIV service availability. 
290 
Further, geographic restrictions were important for political reasons, such that all intervention 
291 

 
14
sites were not restricted to one region or state. Additional covariates used in the restriction 
292 
process represented the primary and secondary outcomes.  Of a total 232,848 possible 
293 
allocations, 596 allocations remained after all restrictions. Across all combinations, there were 
294 
only two sites that had >75% chance of being randomized to the same arm [53]. Three 
295 
individuals independent from the study who were blinded to the allocation sequence associated 
296 
with each of the possible numbers chosen (e.g., 001 to 596) were asked to draw numbered balls 
297 
from an opaque container to arrive at the final 3 digit number, corresponding to a numbered 
298 
randomization combination. A recording of the randomization is available at: 
299 
https://www.youtube.com/watch?v=vmHYHgv_uS0. The final allocation is shown in Figure 2.  
300 
 
301 
Intervention implementation.  
302 
Venue selection.  In each intervention site, venues were selected for scale-up following 
303 
discussions between the State AIDS Control Society, NGO leaders, MSM/PWID community 
304 
members and study investigators. In all cities, only one site was selected for scale up unless 
305 
mobility within the city was restricted due to distance or unsafe circumstances, in which case 
306 
more than one ICC was scaled-up (e.g., Imphal – 3 , Chandigarh – 2, Bilaspur – 2). For the 
307 
PWID sites, ICCs were distributed between the private sector (Imphal, Dimapur and Aizawl) and 
308 
the government sector (Chandigarh, Ludhiana and Bilaspur). For the MSM sites, four ICCs were 
309 
nested within existing government facilities – only the Hyderabad ICC was situated within an 
310 
NGO. ICCs were scaled up between July 2014 and February 2015.       
311 
Service delivery. Core services (HCT, STI testing and treatment, condoms and individual 
312 
and group counseling) are available on-site at the ICCs. PWID ICCs also provide daily OST (7 
313 
days a week) and NSEP; in addition, most ICCs also conduct field-based NSEP using outreach 
314 

 
15
workers from the ICCs. ART and anti-tuberculosis therapy (ATT) are operating through a link 
315 
model, in which medications and testing support are provided through government centers, but 
316 
service delivery and patient follow-up takes place at ICCs. All pre-treatment work-up (e.g., CD4, 
317 
clinical examination, etc.) is performed at the ICC prior the patient’s referral to the government 
318 
center to initiate ART. Following the initial visit to initiate ART at the government ART center, 
319 
the patient is able to collect his/her monthly refills from the ICC (the “link”). He/she undergoes 
320 
monitoring, monthly medication dispensing and clinical exams, as required, at the ICC and 
321 
results are provided semi-annually to the government ART centers to update their records. Thus, 
322 
the patient will only have to visit the government ART center once for registration and semi-
323 
annually thereafter. For each visit to the government center, participants are accompanied by an 
324 
ICC peer-health worker. 
325 
For tuberculosis care, samples for screening and diagnosis are collected at the ICC, with 
326 
confirmatory testing taking place at government centers. If a participant is diagnosed with TB, 
327 
he/she is linked to the government DOT center most convenient to him/her for treatment 
328 
initiation and follow-up. There are over 400,000 DOT centers in India ensuring easy access to all 
329 
populations with excellent retention rates. Peer-health workers from the ICCs follow up with 
330 
clients diagnosed with TB to ensure completion of the DOT program.  
331 
 
Client tracking. Peers and community health workers are responsible for tracking clients 
332 
(via telephone and home/field visits) with respect to use of HIV services. Those who receive an 
333 
HIV test and tested HIV negative are tracked within one year for repeat testing. Those who are 
334 
HIV positive and not yet eligible for ART (CD4 >350 cells/μl) are tracked if they miss a 
335 
quarterly visit with the on-site clinician and finally HIV positive clients on ART who miss 
336 
picking up a refill (every thirty days) are tracked.  
337 

 
16
 
Intervention fidelity. Fidelity is assessed at regular intervals through direct observation 
338 
(visits by study PIs, investigators and overall research coordinator), monthly review of ICC 
339 
process indicators and client satisfaction surveys administered to a convenience sample of 500 
340 
participants per site by staff not involved in delivery of services at the ICC.  
341 
Evaluation post-intervention assessment.  
342 
A post-intervention assessment will be conducted in all 22 intervention and control sites 
343 
approximately 24 months after the establishment of the ICCs (beginning in August 2016).  RDS 
344 
will be used to accrue samples of 1000 persons in each site using identical eligibility criteria as 
345 
the baseline pre-intervention assessment.  An additional module will be added to the survey to 
346 
collect data on utilization and perceptions of the ICCs. Participants will undergo a blood draw 
347 
and laboratory testing as in the pre-intervention assessment.  
348 
An important consideration is the selection of seeds for the post-intervention RDS. We 
349 
will select either the same seeds, if possible (i.e., if the seeds are alive, residing in the same 
350 
community and still regarded as peer leaders in the community) or seeds that are as similar as 
351 
possible to the seeds used in the pre-intervention RDS (e.g., age, area of town they reside, 
352 
marital status, sexual preference, drug of choice, etc.).  
353 
Data management systems. 
354 
 For the pre- and post-intervention assessments, we developed software in-house that 
355 
references features of RDS coupon manager software and tracks recruitment and coupon 
356 
numbers, links coupons of recruiters and recruits, tracks non-eligible referrals and determines 
357 
reimbursements.  The software also incorporates biometric data capture (fingerprint images) 
358 
allowing storage of system-generated unique non-identifiable reference keys that are linked to 
359 
study identification numbers. This biometric information is used to identify duplicate 
360 

 
17
recruitments within and across sites in the pre- and post-intervention assessments. This 
361 
information will also be used to identify participants who participated in both the pre- and post-
362 
intervention assessments and utilized an ICC. 
363 
Electronic surveys for the pre- and post-intervention interviews were developed using the 
364 
Lime Survey Open Source Tool embedded with JAVA Scripts that includes logic checks, skip 
365 
patterns and data constraints. The interview data is linked to the information captured in the in-
366 
house coupon manager software using the coupon ID.  We utilize PHPMYADMIN with a secure 
367 
password-protected encrypted database to store all data in a cloud.  All data is exported from the 
368 
individual sites via a Virtual Private Network tunnel to the central database maintained at 
369 
YRGCARE in Chennai. When the local sites are connected to the internet, fingerprint–generated 
370 
codes from all sites are pushed from the central server to the fingerprint database at each site. 
371 
Storing this data centrally allows for the identification of duplicates in real-time within and 
372 
across sites. 
373 
Laboratory testing and specimen storage.  
374 
 
Laboratory specimens for the pre- and post-intervention surveys are collected on-site and 
375 
processed and transported daily via courier to the central YRGCARE lab in Chennai for further 
376 
testing and long-term storage. Only rapid HIV testing is performed on site where the data 
377 
collection takes place. Additional CD4, HIV RNA, syphilis and HSV-2 testing are performed at 
378 
YRGCARE. Indeterminate HIV results were resolved using Western Blot testing at YRGCARE. 
379 
Remaining plasma and serum specimens are being stored at -700C at YRGCARE.  
380 
Regulatory oversight and participant safety.  
381 
The trial is being conducted under regulatory review by institutional review boards at 
382 
YRG CARE, Johns Hopkins School of Medicine, and Johns Hopkins Bloomberg School of 
383 

 
18
Public Health.  Additional trial oversight is provided by a data safety monitoring board (for the 
384 
PWID stratum) and an advisory board (for the MSM stratum), both comprised of expert 
385 
members external to the investigators’ organizations.  
386 
Statistical power 
387 
We calculated power for comparing the primary outcome (HCT in prior 12 months) in 
388 
intervention and control clusters at the post-intervention RDS survey [53]. We calculated the 
389 
number of clusters needed assuming an outcome prevalence at the post-intervention RDS in 
390 
control clusters of 10-40%, a range of 350-1000 persons in each cluster for HIV-negative 
391 
outcomes, an RDS design effect of 2, a two-sided α of 0.05, power=0.80 and a within-stratum 
392 
coefficient of variation ranging from 0.10 to 0.40. We incorporated the RDS design effect 
393 
(relative to simple random sampling) by doubling the sample size required per cluster after 
394 
calculating power. For the primary outcome, with 11 intervention and 11 control clusters, we 
395 
will have 80% power to detect an absolute difference of 12% in the prevalence of the primary 
396 
outcome in intervention and control clusters (e.g., 42% and 30%, respectively) with a within-
397 
stratum coefficient of variation of 0.25 and 1000 participants in each cluster. 
398 
Our trial was powered to be able to detect differences in the primary outcome, but we 
399 
also calculated power for secondary outcomes. Power for secondary outcomes that include the 
400 
full sample (e.g., proportion of PWID reporting sharing injection equipment in the prior 6 
401 
months) was similar to that for primary outcomes as the methods and the range of outcome 
402 
prevalence in control clusters was within the range of what was considered for the primary 
403 
outcome. Power was relatively insensitive to the within-cluster sample size so our ability to 
404 
detect outcome differences for outcomes where only HIV positive subjects are considered is 
405 
similar to outcomes where the full RDS sample is used. For outcomes restricted to HIV-positive 
406 

 
19
subjects, we assumed a sample size of 100-300 persons per cluster. Power remained insensitive 
407 
to the cluster sample size down to a sample size of 100 per cluster. For example, with all other 
408 
assumptions held constant and an RDS sample size of 150, if the baseline prevalence of the 
409 
outcome is 30%, we will be able to detect a difference of 14 percentage points (e.g., 30% vs. 
410 
44%). For outcomes with lower baseline prevalence, we would be able to detect a smaller 
411 
difference  (e.g., if 20% of HIV infected patients are engaged in care in the control sites, we 
412 
would have adequate power to detect a difference of 9 percentage points [20% vs. 29%]).  
413 
 
414 
Analysis plan 
415 
Community level.  
416 
The primary analysis will be to compare the prevalence of community-level outcomes 
417 
across intervention and control clusters, adjusting for pre-intervention prevalence levels. For a 
418 
given outcome, we will first log-transform the 22 cluster-level proportions obtained from the 
419 
post-intervention RDS. Then, via weighted least squares linear regression, these will be 
420 
regressed on a dummy term for the control arm (vs. intervention), another for the MSM stratum 
421 
(vs. PWID), and a term for the log-transformed cluster-level pre-intervention proportions. The 
422 
exponentiated coefficient for the control arm term is thus the prevalence risk ratio (PRR), and (1-
423 
PRR)×100% is the percentage increase in service utilization associated with the intervention. 
424 
The primary analyses will be conducted using the RDS-II weighted cluster-level proportions 
425 
from both pre- and post-intervention RDS samples. These RDS-II weights, which account for 
426 
personal network size (number of PWID or MSM seen in the past 30 days) will be calculated 
427 
using the RDS Analyst Software Version 0.5 (http://hpmrg.org). For secondary outcomes that are 
428 
continuous (e.g., community viral load) we will use a similar regression approach. 
429 

 
20
We will conduct several sensitivity analyses for the primary and all secondary outcomes 
430 
First, we will repeat analyses using unweighted cluster-level proportions from both the pre-and 
431 
post intervention RDS surveys. Second, we will consider adjustment for demographic covariates 
432 
(age, sex, marital status and educational attainment) measured at the post-intervention RDS that 
433 
are associated with the outcome and are differentially distributed across intervention and control 
434 
clusters. We will consider adjustment for these factors if the p values for associations with the 
435 
outcome and the intervention vs. control clusters are <0.05 and the OR is >2 or < 0.5. A two-
436 
stage approach will be used when adjusting for individual-level covariates: at the first stage, for a 
437 
prevalence outcome, individual responses are modeled with a logistic regression model adjusting 
438 
for all relevant covariates except the dummy term for control vs. intervention. In the second 
439 
stage, observed and expected prevalence counts for each cluster are calculated, followed by t-
440 
test-like analyses of log-transformed ratios of observed to expected [53]. We will also consider 
441 
an approach that models the difference in outcome prevalence between the pre- and post- 
442 
intervention surveys using the same cluster-level comparison approach. We will also consider 
443 
individual-level analyses using multi-level random effects regression approaches (Stata 
444 
GLLAMMs program) to account for dependence of responses within clusters [54-56]. These 
445 
models allow inclusion of fixed effects (e.g., intervention), random effects (e.g., clusters), 
446 
adjustment for pre-intervention covariates at the individual and cluster level, and incorporation 
447 
of scaled RDS weights as sampling weights. Finally, we will conduct descriptive analyses of the 
448 
HIV care continuum, before and after the intervention phase of the study, in which completion of 
449 
earlier steps are assumed to be necessary to complete later steps. Additionally, we will consider 
450 
sensitivity analyses of outcomes in the HIV care continuum, where biologic markers such as 
451 

 
21
HIV RNA and serum antiretroviral drug testing, are used to supplement self-reported data on 
452 
access to care. 
453 
Several subgroup analyses are also planned. First, we will analyze all outcomes 
454 
separately within each stratum (PWID and MSM). Using the combined sample of MSM and 
455 
PWID sites, we will further compare all outcomes within subgroups defined by age, marital 
456 
status, educational attainment, substance use (drug and alcohol use), and personal network size 
457 
(number of persons in risk group [PWID or MSM] known and seen in the prior 30 days). Using 
458 
only the PWID sites, we will also analyze subgroup differences by age, sex, marital status, 
459 
educational attainment, substance use (including alcohol use), personal network size and region. 
460 
In the MSM sites, we will also analyze subgroup differences by age, sexual identity, marital 
461 
status, educational attainment, substance use (including alcohol use), personal network size and 
462 
region. We also plan subgroup analyses by HIV serostatus and awareness of status for risk 
463 
behaviors, HIV testing of spouses, substance use, stigma, and depression. 
464 
 
465 
Network- and individual-levels.  
466 
Network effects will be ascertained by comparing utilization of ICCs and services within 
467 
ICCs across networks as defined by RDS. For example, we will examine utilization patterns 
468 
across recruiters and recruits in the evaluation RDS. We will also ascertain whether utilization of 
469 
ICCs varied by wave of RDS. Individual-level comparisons will draw on data from post-
470 
intervention RDS participants in the intervention clusters, in which extra questions will address 
471 
participants’ use of ICC services. In addition, biometric data at the post-intervntion RDS will be 
472 
linked with the biometric data from the ICCs to determine utilization. Individual analyses will 
473 
use descriptive statistics and log-binomial regression to compare the level of each outcome (e.g., 
474 

 
22
proportion accessing HCT in prior 12 months) by the main exposure of interest (visiting an ICC).  
475 
We will adjust for individual-level confounders including demographic characteristics.  Analyses 
476 
will use multi-level random effects regression approaches to account for dependence of 
477 
responses within personal networks [56]. In addition, using the biometric data to link persons 
478 
between the pre-and post intervention RDS samples, we will conduct exploratory within-
479 
individual comparisons of the primary outcome and secondary outcomes. For example, 
480 
restricting the sample to persons who participated in both the pre- and post intervention RDS 
481 
samples and are eligible for the outcome, we will compare across control and intervention 
482 
clusters the proportions of person who transition from not having the outcome to having it and 
483 
vice versa. 
484 
 
485 
Dissemination 
486 
 
This trial represents a public-private partnership and collaboration between investigators 
487 
at the Johns Hopkins University (Schools of Medicine and Public Health), investigators and 
488 
research staff at the YR Gaitonde Centre for AIDS Research and Education (YRGCARE), the 
489 
Targeted Intervention Division of the National AIDS Control Organization, India and several 
490 
local State AIDS Control Organizations and local non-governmental organizations.  Prior to and 
491 
during the implementation of the trial, quarterly community meetings have been held to keep the 
492 
community and relevant stakeholders informed on the conduct of the study. Meetings will 
493 
continue past the end of the trial to inform the communities of the finding. A meeting will also 
494 
be held with the representatives of the National AIDS control Organization to disseminate the 
495 
findings. Once the trial is complete, depending on the findings, key stakeholders will decide on 
496 
whether to adopt the ICC model as a whole or certain aspects of the model as the standard of 
497 

 
23
care. This will require a consideration of the demonstrated effectiveness and cost. If they choose 
498 
not to adopt the model, clients in sites with ICCs will be transferred back to the relevant 
499 
government centers and NGOs for services (e.g., ART and OST).  
500 
 
501 
DISCUSSION 
 
502 
 
Dramatic progress has been made in the management and prevention of HIV since the 
503 
first report in 1981. Yet, key challenges remain.  First, implementation strategies need to be 
504 
identified that can take demonstrated efficacious interventions at an individual level (e.g., ART, 
505 
OST) and improve their effectiveness in the real-world [37-40, 42]. Second, while ART roll-outs 
506 
and expanded prevention services have led to overall declines in HIV prevalence across all 
507 
settings [5], these declines have not been as apparent among key populations such as MSM and 
508 
PWID [5, 57, 58]. In several countries where HIV epidemics are driven by drug use, HIV 
509 
prevalence has at best stabilized if not increased over the past decade [5]. Resurgence in reports 
510 
of both STIs and high-risk behavior have been noted globally among MSM [57]. These two 
511 
populations are particularly difficult to target because a large majority of them remain hidden 
512 
and no sampling frame exists making achieving a representative sample challenging. Our trial is 
513 
unique in its utilization of RDS to evaluate the effectiveness of a community-level intervention 
514 
in hard to reach populations.  
515 
 
Conversations about the end of AIDS and an AIDS-free generation have begun [59, 60]. 
516 
However, for this goal to be realized, prevention, care and treatment services need to reach all 
517 
populations at risk for HIV infection particularly those that are hardest-to-reach. There is a clear 
518 
gap in access to services among MSM and PWID. Trials need to be designed to optimize 
519 

 
24
utilization of services in these populations. We believe that this represents one of the first trials 
520 
aimed at improving the HIV care continuum among MSM and PWID populations.  
521 
 
522 
 
523 
 
524 
 
525 
 
526 
 
527 
 
528 
 
529 
 
530 
 
531 
 
532 
 
533 
 
534 
 
535 
 
536 
 
537 
 
538 
 
539 
 
 
540 

 
25
LIST OF ABBREVIATIONS: 
541 
Anti-tuberculosis therapy (ATT) 
542 
Antiretroviral therapy (ART) 
543 
Directly Observed Therapy (DOT) 
544 
Focus group discussions (FGD) 
545 
HIV counseling and testing (HCT) 
546 
Integrated care centers (ICC) 
547 
In-depth interviews (IDI) 
548 
Men who have sex with men (MSM) 
549 
Needle and syringe exchange programs (NSEP) 
550 
Non-governmental organizations (NGO) 
551 
Opioid agonist therapy (OAT) 
552 
People who inject drugs (PWID) 
553 
Respondent-driven sampling (RDS) 
554 
Sexually transmitted infections (STI) 
555 
 
556 
ETHICS APPROVAL AND CONSENT TO PARTICIPATE: 
557 
This study was approved by the Johns Hopkins and YR Gaitonde Centre for AIDS Research and 
558 
Education Institutional Review Boards. The reference number for the Johns Hopkins Institutional 
559 
Review Boards is NA_00047702. With IRB approval, informed consent was obtained verbally, 
560 
as this study was considered minimal risk. 
561 
 
562 
AVAILABILITY OF DATA AND MATERIAL: 
563 
This is a protocol paper and so there are no data associated with the paper.  
564 
 
565 
COMPETING INTERESTS:  
566 
The authors declare that they have no competing interests. 
567 
 
568 
CONSENT FOR PUBLICATION: 
569 
Not applicable. 
570 
 
571 

 
26
FUNDING: 
572 
This work was supported by the National Institutes of Health, [R01 MH 89266, R01 DA 032059] 
573 
and the Elton John AIDS Foundation. Additional support was provided by the Johns Hopkins 
574 
University Center for AIDS Research, the National Institute on Drug Abuse and the National 
575 
Institute on Allergy and Infectious Diseases [P30 AI094189 and K24 DA035684, T32 AI102623 
576 
respectively]. The funding bodies did not play a role in design, in the collection, analysis, and 
577 
interpretation of data; in the writing of the manuscript; and in the decision to submit the 
578 
manuscript for publication. 
579 
 
580 
AUTHOR CONTRIBUTIONS: 
581 
Sunil Solomon, Gregory Lucas, David Celentano, Shruti Mehta, Suniti Solomon, M Suresh 
582 
Kumar and Aylur K Srikrishnan were responsible for the original design of the study and oversee 
583 
implementation. Allison McFall, Elizabeth Ogburn and Lawrence Moulton contributed to the 
584 
statistical aspects of the design including randomization, statistical power and proposed analyses. 
585 
Santhanam Anand designed all of the data collection systems for the study. All authors read and 
586 
approved the final manuscript. 
587 
 
588 
ACKNOWLEDGEMENTS 
589 
We thank Jungen Yi for assistance with manuscript preparation and the National AIDS Control 
590 
Organization (NACO), India, all of our partner non-governmental organizations throughout 
591 
India, and the countless participants, without whom this research would not have been possible. 
592 
 
 
593 

 
27
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784 
 
785 
57. Beyrer C, Baral SD, van Griensven F, Goodreau SM, Chariyalertsak S, Wirtz AL et al. Global 
786 
epidemiology of HIV infection in men who have sex with men. Lancet. 2012;380(9839):367-77.  
787 
 
788 
58. Beyrer C, Abdool Karim Q. The changing epidemiology of HIV in 2013. Curr Opin HIV AIDS. 
789 
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790 
 
791 
59. Fauci AS. AIDS: let science inform policy. Science. 2011;333(6038):13. 
792 
 
793 

 
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60. De Cock KM, Jaffe HW, Curran JW. Reflections on 30 years of AIDS. Emerg Infect Dis.  
794 
 
795 
61. Saunders JB, Aasland OG, Babor TF, de lF, Jr., Grant M. Development of the Alcohol Use Disorders 
796 
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797 
Alcohol Consumption--II. Addiction. 1993;88(6):791-804.  
798 
 
799 
62. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J 
800 
Gen Intern Med. 2001;16(9):606-13.  
801 
 
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63. Steward WT, Herek GM, Ramakrishna J, Bharat S, Chandy S, Wrubel J et al. HIV-related stigma: 
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adapting a theoretical framework for use in India. Soc Sci Med. 2008;67(8):1225-35.  
804 
 
805 
64. Solomon SS, Mehta SH, McFall AM, Saravanan S, Laeyendecker O, Balakrishnan P et al. 
806 
Community viral load, antiretroviral therapy coverage, and HIV incidence in India: a cross-sectional, 
807 
comparative study. Lancet HIV. 2016.  
808 
 
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65. Martin A, Rief W, Klaiberg A, Braehler E. Validity of the Brief Patient Health Questionnaire Mood 
810 
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811 
 
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814 
 
815 
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818 
 
819 
68. Laeyendecker O, Kulich M, Donnell D, Komarek A, Omelka M, Mullis CE et al. Development of 
820 
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821 
2013;8(11):e78818.  
822 
 
823 
69. Hemelaar J, Gouws E, Ghys PD, Osmanov S, Isolation W-UNfH, Characterisation. Global trends in 
824 
molecular epidemiology of HIV-1 during 2000-2007. AIDS. 2011;25(5):679-89.  
825 
 
 
826 

 
32
 
827 
 
828 
Figure 1. Study Design 
829 
Abbreviations: MSM, Men who have sex with men; PWID, People who inject drugs; RDS, 
830 
Respondent-driven sampling; ICC, Integrated care centers 
831 
 
832 
Figure 2. Study Sites. Panel A. MSM sites represent cities with established HIV epidemics 
833 
among MSM (Chennai, Hyderabad, Bengaluru), smaller cities in high HIV prevalence states 
834 
(Coimbature, Madurai, Vishakapatnam, Vijaywada, Mangalore, Belgaum) and cities with 
835 
anecdotal reports of HIV among MSM but no published reports (New Delhi, Bhopal, Lucknow). 
836 
Panel B. PWID sites represent cities with established drug use epidemics (Aizawl, 
837 
Churchandpur, Dimapur, Gangtok, Imphal, Lunglei, Moreh), large cities (New Delhi, Mumbai) 
838 
cities with documented emerging drug use epidemics (Amritsar, Chandigarh, Ludhiana) and 
839 
cities with anecdotal evidence of emerging drug use epidemics (Bilaspur, Bhubaneswar, 
840 
Kanpur). Note New Delhi has two control sites (one for the MSM stratum and one for the PWID 
841 
stratum). 
842 
 
843 
 
844 
Supplementary files 
845 
 
846 
File name: MSM Baseline Survey 
 
847 
Title of data: MSM Baseline Survey 
848 
This survey was distributed (in local languages) to MSM study sites to gather baseline data on 
849 
HIV status and risk behaviors.  
850 
 
851 
File name: PWID Baseline Survey 
852 
Title of data: PWID Baseline Survey 
853 
This survey was distributed (in local languages) to PWID study sites to gather baseline data on 
854 
HIV status and risk behaviors. 
855 

 
33
Table 1. Outcome definitions for the Indian National Collaboration on AIDS (NCA) study 
 
Outcome 
Data inputs 
Population (denominator) 
Definition 
Primary Outcome 
 
HIV testing 
 
1 
HIV testing in the prior 12 
moths  
Survey 
 
All participants, excluding those that report 
being HIV-positive AND report being tested 
more than 12 months ago. 
 
Either 1 OR 2: 
1. Reports HIV test within the prior 12 
months 
OR  
2. Was told he/she had HIV within the last 
12 months 
Secondary Outcomes 
 
Awareness of HIV status, access to care, and HIV treatment 
2 
Awareness of HIV status 
among HIV-seropositive 
persons 
1. Survey  
2. Serologic HIV 
test 
HIV seropositive participants  
Reports having a positive HIV test OR being 
told by a doctor that he/she had HIV. 
3 
Accessing HIV medical care 
in prior 6 months 
1. Survey 
2. Serologic HIV 
test 
HIV seropositive participants 
Reports seeing a doctor about HIV AND 
reports visit with the indicated doctor in the 
prior 6 months. 
4 
Use of ART among ART-
eligible  
1. Survey 
2. Serologic HIV 
test 
HIV seropositive participants who meet either 
criteria 1 or 2 
1. Reports taking ART at any time in the past 
OR  
2. CD4 <350 cells/µL 
Reports ART use in prior 30 days. 
5 
Use of trimethoprim-
sulfamethoxazole (TMP-
SMX) when indicated 
1. Survey 
2. Serologic HIV 
test 
3. CD4 
HIV seropositive AND CD4 count < 200 
cells/µL 
 
Reports taking TMP-SMX in past 30 days 
 
6 
Viral suppression among 
ART-eligible 
1. Survey 
2. Serologic HIV 
test 
3. CD4 
4. HIV RNA 
HIV seropositive participants who meet either 
criteria 1 or 2 
1. Reports taking ART at any time in the past 
OR  
2. CD4 <350 cells/µL 
HIV RNA <150c/mL  
7 
Viral suppression among HIV-
positive  
1. Serologic HIV 
test 
2. HIV RNA 
HIV seropositive participants 
HIV RNA <150c/mL 
8 
Average CD4 cell count 
among HIV-positive  
1. Serologic HIV 
test 
2. CD4 cell 
count 
HIV seropositive participants 
CD4 cell count 
 
 

 
34
Table 1. Outcome definitions for the Indian National Collaboration on AIDS (NCA) study 
 
Outcome 
Data inputs 
Population (denominator) 
Definition 
Risk behaviors, substance use, and depression 
9 
Unprotected anal intercourse 
with non-main male partner in 
prior 6 months [MSM] 
Survey 
 
Participants at MSM sites 
Does not report “always” using a condom 
during insertive or receptive anal sex with 
non-main (e.g., casual, one-time partner, sex 
worker) male partners in the prior 6 months 
10 
Number of non-main male 
sexual partners in prior 6 
months [MSM] 
Survey  
Participants at MSM sites 
Number of non-main male (e.g., casual, one-
time partner, sex worker) male partners with 
whom the participant reports having 
insertive or receptive anal sex in the prior 6 
months 
11 
Symptoms of sexually 
transmitted infection [MSM] 
Survey 
Participants at MSM sites 
Reports genital/anal discharge, pain, or ulcer 
in prior 6 months  
12 
Syphilis infection 
1. RPR test 
2. TPHA test 
Participants at MSM sites 
Positive for syphilis infection by both RPR 
and TPHA tests 
13 
Shared injection equipment in 
prior 6 months [PWID] 
Survey 
Participants at PWID sites 
Reports sharing (passing or receiving) a 
needle and/or syringe with another 
individual in the prior 6 months 
14 
Shared injection equipment at 
last use among active injectors 
[PWID] 
 
Survey 
Participants at PWID sites that report injection 
of one or more drugs in prior 6 months 
Reports sharing (passing or receiving) a 
needle and/or syringe with another 
individual at last injection 
15 
Reported injection abstinence 
in prior 6 months [PWID] 
Survey 
Participants at PWID sites 
Denies injecting any drug in prior 6 months 
16 
Hazardous alcohol use or 
dependence  
Survey 
All participants  
Score ≥8 (hazardous) or ≥15 on Alcohol Use 
Disorder Identification Test (AUDIT)[61] 
17 
Depression 
Survey 
All participants 
Score ≥ 10 on Patient Health Questionnaire 
(PHQ)-9[62]  
 
 
 
 
 
 
 
 
 
 
 
 

 
35
Table 1. Outcome definitions for the Indian National Collaboration on AIDS (NCA) study 
 
Outcome 
Data inputs 
Population (denominator) 
Definition 
Services and stigma 
18 
Spouse HIV testing among 
married participants 
Survey 
Participants who report being married 
Reports spouse has ever been tested for HIV 
19 
Symptoms of sexually 
transmitted infection for 
which participant sought care 
in prior 6 months [MSM] 
Survey 
Participants at MSM sites 
Reports genital/anal discharge, pain, or ulcer 
in prior 6 months AND reports seeking 
medical care for symptom(s) 
20 
Used needle/syringe exchange 
program (NSEP) in prior 6 
months [PWID] 
Survey 
Participants at PWID sites 
Reports NSEP use in prior 6 months 
21 
Used needle/syringe exchange 
program (NSEP) in prior 6 
months among active injectors 
[PWID] 
Survey 
Participants at PWID sites that report injection 
of one or more drugs in prior 6 months 
Reports NSEP use in prior 6 months 
22 
Used opioid agonist therapy 
(OAT) in prior 6 months 
[PWID] 
Survey 
Participants at PWID sites 
Reports OAT in prior 6 months 
23 
Stigma subtypes 
Survey 
All participants 
Summed score from each of four 6-item 
stigma scales (enacted, vicarious, felt 
normative, and internalized stigma)[63]  
Community viral load and HIV incidence 
24 
Prevalence of viremic 
individuals in population 
1. Serologic HIV 
test 
2. HIV RNA 
All participants 
Prevalence of HIV-positive subjects with 
HIV RNA >150c/mL[64] 
25 
Average viral load in HIV-
positive participants 
1. Serologic HIV 
test 
2. HIV RNA 
HIV seropositive participants 
Average (log10) HIV RNA 
26 
HIV incidence 
1. Serologic HIV 
test 
2. HIV RNA 
3. CD4 cell 
count 
4. BED assay 
5. Avidity index 
Participants who meet criteria 1 or 2 
1) HIV-seronegative 
OR 
2) HIV-seropositive participants who meet 
criteria for recent infection by HIV RNA, CD4, 
BED assay, and avidity assay  
Cross-sectional HIV incidence estimated as 
described previously[64, 7, 6] 
 
 

 
36
Table 2. Data Collection 
 
 
MSM 
PWID 
Survey modules 
 
 
Demographics 
x 
x 
Peer network size 
x 
x 
HIV testing, care and medications (HIV care continuum) 
x 
x 
HIV treatment knowledge (including questions on other local HIV testing and 
treatment efforts) 
x 
x 
Substance use (drugs, alcohol), injection-related risk behavior, sexual risk behavior 
x 
x 
Service utilization (NSEP, OST, condom provision) 
x 
x 
Tuberculosis history 
x 
x 
Depressive symptoms (Patient Health Questionnaire-9 [65, 62]) 
x 
x 
Social support 
x 
x 
Stigma (Enacted, vicarious, felt normative, internalized MSM stigma) 
x 
 
Stigma (Enacted, vicarious, felt normative, internalized PWID stigma) 
 
x 
Quality of life (adapted version of EuroQOL [66]) 
x 
x 
Acceptability of novel prevention interventions (early ART, circumcision, PrEP) 
x 
x 
Sexual health (including STI history) 
x 
 
Hepatitis C virus and Hepatitis B virus testing, care and treatment 
 
x 
 
 
 
Laboratory testing 
 
 
HIV8 
Determine HIV 1/2, Alere Medical Co., Ltd., Chiba, Japan 
First Response HIV Card Test 1-2.0, PMC Medical India Pvt, Ltd, 
Daman, India 
Signal Flow Through HIV 1+2 Spot/Immunodot Test kit, Span 
Diagnostics Ltd, Surat, India 
x 
x 
CD4 count* 
Flow cytometry, Epics XL – MCL, Beckman Coulter Inc., USA 
x 
x 
HIV RNA* 
RealTime HIV-1 Assay, Abbott Laboratories, Abbott Park, Illinois, 
USA 
x 
x 
BED assay* 
AwareTM BEDTM EIA HIV-1 Incidence Test (IgG Capture HIV-
EIA), Calypte Biomedical Corporation, Portland, OR, USA 
x 
x 
Avidity[67]* GS HIV-1/HIV-2 PLUS O EIA, Biorad Laboratories, Redmond, 
USA using diethyl amine as the chaotropic agent 
x 
x 
HSV-2 
Anti-HSV-2 (gG2) ELISA (IgG), Euroimmun Medizinische 
Labordiagnostika AG, Lubeck, Germany 
x 
 
Syphilis 
RPR Test Kit, Span Diagnostics Ltd. Surat, India 
Immunotrep TPHA, Omega Diagnostics Limited, Scotland, UK 
x 
 
Abbreviations: NSEP, Needle and syringe exchange programs ; OST, Opioid substitution therapy ;MSM, Men who 
have sex with men; PWID, People who inject drugs; ART, Antiretroviral therapy; PrEP, Pre-exposure prophylaxis; 
STI, Sexually transmitted infections  
*Tests performed only among those who tested HIV positive. Cross-sectional estimation of HIV incidence was 
based on a multi-assay algorithm (MAA) validated for HIV Subtype C[68] – the predominant subtype in India that 
included CD4, HIV RNA, BED and Avidity.[69]  
 
 

 
37
Table 3. Description of Stratum-specific and Overall Restriction Criteria 
 
 
Stratum-specific 
Overall 
 
MSM 
PWID 
 
 
GEOGRAPHICAL RESTRICTIONS 
 
 
 
Tamil Nadu (3) 
3 sites distributed at a 
ratio of 2:1 
(Madurai/Chennai in 
separate arms) 
 
 
Andhra Pradesh (3) 
3 sites distributed at a 
ratio of 2:1 
 
 
Karnataka (2), Bhopal, Delhi 
4 sites distributed 
with at least one site 
in each arm 
 
 
Northeast (5) 
 
5 sites distributed 
at a ratio of 3:2 
 
North (4) 
 
4 sites distributed 
at a ratio of 2:2 
 
West/Central India (3) 
 
3 sites distributed 
at a ratio of 2:1 
 
 
RESTRICTIONS BASED ON 
OUTCOMES 
 
 
 
HIV prevalence  
< 1.5%a 
< 2%a 
< 2%c 
Percentage who had HIV test in the prior 12 
months [PRIMARY OUTCOME] 
< 5%a 
< 5%a 
< 5%c 
Percentage of HIV positive aware of status  
<10%a,b 
< 10%a,b 
< 10%c 
Percentage of HIV positive seen HIV 
provider in past 6 months  
< 10%a,b 
< 10%a,b 
< 10%c 
Percentage of HIV positive currently on 
antiretroviral therapy  
<10%a,b 
< 10%a,b 
< 10%c 
Percentage of HIV positive with undetectable 
HIV RNA  
< 9%a 
< 9%a 
< 9%c 
aRestrictions placed on only RDS-weighted proportions; RDS-I estimator used for PREVALENCE and TEST; RDS-
II estimator used for other outcomes because RDS-I estimator could not be calculated 
bRestriction was across three outcomes (Proportion of HIV positive aware of status, Proportion of HIV positive seen 
HIV provider in past 6 months, Proportion of HIV positive currently on antiretroviral therapy); Only those with 
values >10% in 2 of the three outcomes were excluded  
cRestrictions placed on RDS-weighted and unweighted proportions 
 
 

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