Improving Antiretroviral Adherence and Persistence Using mHealth Tools in HIV-infected Cocaine Users
Phase: NA
Conditions: HIV/AIDS, Cocaine Use
Sponsor: Yale University

Page 1 of 56 
 
NCT04418076 Study Protocol and SAP 
Date: April 13, 2020 
Title: Improving Antiretroviral Adherence and Persistence Using mHealth Tools in HIV-
infected Cocaine Users 
 
 
 

Page 2 of 56 
 
YALE UNIVERSITY 
  
                                  HUMAN INVESTIGATION COMMITTEE 
 
                                     Application to Involve Human Subjects in Biomedical Research 
100 FR1 (2015-1)  
 
SECTION I: ADMINISTRATIVE INFORMATION 
 
Title of Research Project: Improving Antiretroviral Adherence and Persistence using mHealth Tools in HIV-
infected Cocaine Users  
 
Principal Investigator: Frederick L. Altice 
 
Yale  Academic  Appointment: Professor  of  Medicine, 
Epidemiology and Public Health 
Department: Internal Medicine, Section of Infectious Diseases, AIDS Program 
Campus Address: 135 College Street, New Haven, CT 06510 
 
Campus Phone: 203-737-2883 Fax: 203-737-4051 Pager:  
E-mail: Frederick.altice@yale.edu  
Protocol Correspondent Name & Address (if different than PI): Xin Zhou, 135 College Street, New Haven, 
CT 06519 
  
Campus Phone: 781-266-7983 Fax:  
E-mail: xin.zhou19@yale.edu 
Yale Cancer Center CTO Protocol Correspondent Name & Address (if applicable): 
 
Campus Phone:  
Fax:  
E-mail:  
Business Manager: 
Campus Phone : 
Fax : 
E-mail 
 
Investigator Interests: 
Does the principal investigator, or do any research personnel who are responsible for the design, 
conduct or reporting of this project or any of their family members (spouse or dependent child) 
have an incentive or interest, financial or otherwise, that may affect the protection of the human 
subjects involved in this project, the scientific objectivity of the research or its integrity? Note: 
The  Principal  Investigator  (Project  Director),  upon  consideration  of  the  individual’s  role  and 
degree of independence in carrying out the work, will determine who is responsible for the design, 
conduct, or reporting of the research.  
See  Disclosures  and  Management  of  Personal  Interests  in  Human  Research 
http://www.yale.edu/hrpp/policies/index.html#COI  
Faculty  Advisor:(required  if  PI  is  a  student, 
resident, fellow or other trainee)            NA 
 
Yale Academic Appointment: 
 
Campus Address:  
 
Campus Phone:  
Fax:  
Pager:  
E-mail:  

Page 3 of 56 
 
  Yes 
  
X  No   
 
Do you or does anyone on the research team who is determined by you to be responsible for the 
design, conduct or reporting of this research have any patent (sole right to make, use or sell an 
invention)  or  copyright  (exclusive  rights  
to  an  original  work)  
interests  related  
to  
this  research 
protocol? 
  Yes 
  
X  No   
  
  
 
If yes to either question above, list names of the investigator or responsible person: 
 
 
 
The  Yale  University  Principal  Investigator,  all  Yale  University  co-investigators,  and  all  Yale 
University individuals who are responsible for the design, conduct or reporting of research must 
have a current financial disclosure form on file with the University’s Conflict of Interest Office. 
Yale New Haven Hospital personnel who are listed as co-investigators on a protocol with a Yale 
University Principal Investigator must also have a current financial disclosure form on file with 
the  University’s  Conflict  of  
Interest  Office. If  
this  has  not  been  done,  
the  
individual(s)  should 
follow this link to the COI Office Website to complete the form:  http://www.yale.edu/coi/   
 
NOTE: The requirement for maintaining a current disclosure form on file with the University’s 
Conflict of  
Interest Office  extends primarily to Yale University and  Yale-New Haven Hospital 
personnel.  Whether  or  not  they  are  required  to  maintain  a disclosure  form  with  the 
University’s Conflict of Interest Office, all investigators and individuals deemed otherwise 
responsible by the PI who are listed on the protocol are required to disclose to the PI any 
interests that are specific to this protocol. 
 
SECTION II: GENERAL INFORMATION 
 
1. Performing Organizations:  Identify the hospital, in-patient or outpatient facility, school or 
other agency that will serve as the location of the research.  Choose all that apply: 
  
a. Internal Location[s] of the Study: 
 Magnetic Resonance Research Center    
 Yale University PET Center 
     (MR-TAC)     
  
  
  
 
 YCCI/Church Street Research Unit (CSRU) 
 Yale Cancer Center/Clinical Trials Office (CTO)     YCCI/Hospital Research Unit (HRU) 
 Yale Cancer Center/Smilow  
  
 
 YCCI/Keck Laboratories 
 Yale-New Haven Hospital   
  
 
 Yale-New Haven Hospital—Saint Raphael Campus 
 Cancer Data Repository/Tumor Registry 
 Specify Other Yale Location: 270 Congress Ave, New Haven; and 330 Main Street, 3rd Floor, Hartford, CT 
06106  
  
 
 
 
 
b. External Location[s]: 
 APT Foundation, Inc.    
  
 
 Haskins Laboratories 
 Connecticut Mental Health Center  
 
 John B. Pierce Laboratory, Inc. 
 Clinical Neuroscience Research Unit (CNRU) Veterans Affairs Hospital, West Haven   

Page 4 of 56 
 
 Other Locations, Specify:   
  
 
 International Research Site  
(Specify location(s)): 
 
 
c. Additional Required Documents (check all that apply): 
 N/A 
*YCCI-Scientific and Safety Committee (YCCI-SSC)    
Approval Date:  
*Pediatric Protocol Review Committee (PPRC)  
  
Approval Date:  
*YCC Protocol Review Committee (YRC-PRC)  
  
Approval Date:  
 
*Dept. of Veterans Affairs, West Haven VA HSS  
  
Approval Date:  
*Radioactive Drug Research Committee (RDRC)  
  
Approval Date:  
 YNHH-Radiation Safety Committee (YNHH-RSC)    
Approval Date:  
 Magnetic Resonance Research Center PRC (MRRC-PRC)  Approval Date:  
 YSM/YNHH Cancer Data Repository (CaDR)   
  
Approval Date:  
 Dept. of Lab Medicine request for services or specimens form 
 Imaging  on  YNHH  Diagnostic  Radiology  equipment  request  form  (YDRCTO  request)  found 
at  http://radiology.yale.edu/research/ClinTrials.aspx) 
*Approval from these committees is required before final HIC approval is granted. See instructions 
for documents required for initial submission and approval of the protocol. Allow sufficient time for 
these requests. Check with the oversight body for their time requirements. 
 
2. Probable Duration of Project: State the expected duration of the project, including all follow-
up and data analysis activities. Aug.1, 2016 – July 31, 2018 
 
3. Research Type/Phase: (Check all that apply) 
a. Study Type 
    Single Center Study 
    Multi-Center Study 
Does the Yale PI serve as the PI of the multi-site study? Yes  
No 
 
   Coordinating Center/Data Management 
   Other:  
 
 
b. Study Phase 
 N/A 
     Pilot  
 Phase I 
 Phase II 
 Phase III 
 Phase IV 
     Other (Specify)  
 
 
4. Area  of  Research:  
(Check  all  
that  apply) Note  
that  
these  are  overlapping  definitions and 
more than one category may apply to your research protocol. Definitions for the following can 
be found  in the instructions section 4c: 
 Clinical Research: Patient-Oriented  
    
 
 Clinical Research: Outcomes and  
 Clinical Research: Epidemiologic and Behavioral   
                  Health Services 
 Translational Research #1 (“Bench-to-Bedside”) 
     
 Interdisciplinary Research 
 Translational Research #2 (“Bedside-to-Community”)  
 Community-Based Research 
 
 

Page 5 of 56 
 
5.   Is this study a clinical trial? Yes  
No 
 
NOTE the current ICMJE (International Committee of Medical Journal Editors) definition of a 
clinical trial: “any research study that prospectively assigns human participants or groups of humans 
to one or more health-related interventions to evaluate the effects on health outcomes.” Health-related 
interventions  include  any  intervention  used  to  modify a  biomedical  or  health-related  outcome  (for 
example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process-
of-care  changes).  Health  outcomes  
include  any  biomedical  or  health-related  measures  obtained  
in 
patients or participants, including pharmacokinetic measures and adverse events” 
   
If yes, where is it registered? 
    
 
Clinical Trials.gov registry 
   
    
 
Other (Specify)  
 
The proposed study includes a randomized, pilot feasibility trial that may require registration at 
ClinicalTrials.gov.  If funded, the Principal Investigator agrees to register the proposed study as 
required.
 
 All
 currently
 funded
 studies
 by
 the
 Principal
 Investigator
 are
 currently
 registered
 at
 this
 
site and are identified within the respective publications. 
 
Registration of clinical trials at their initiation is required by the FDA, NIH and by the ICMJE. 
 
If this study is registered on clinicaltrials.gov, there is new language in the consent form and compound 
authorization that should be used. 
For more information on registering clinical trials, including whether your trial must be registered, 
see the YCCI webpage, http://ycci.yale.edu/researchers/ors/registerstudy.aspx or  contact YCCI at 
203.785.3482) 
 
6. Does the Clinical Trials Agreement (CTA) require compliance with ICH GCP (E6)?  
Yes 
 No
     n/a 
 
 
7. Will this study have a billable service? A billable service is defined as any service rendered to 
a study subject that, if he/she was not on a study, would normally generate a bill from either Yale-
New Haven Hospital or Yale Medical Group to the patient or the patient’s insurer. The service 
may  or  may  not  be  performed  by  the  research  staff  on  your  study,  but  may  be  provided  by 
professionals within either Yale-New Haven Hospital or Yale Medical Group (examples include 
x-rays, MRIs, CT scans, specimens sent to central labs, or specimens sent to pathology). Notes: 1. 
There  
is  no  distinction  made  whether  
the  service  
is  paid  
for  by  
the  subject  or  
their  
insurance 
(Standard of Care) or by the study’s funding mechanism (Research Sponsored). 2. This generally 
includes new services or orders placed in EPIC for research subjects.
  
 
Yes 
 No
 
 If  answered,  “yes”,  this  study  will  need  to  be  set  up  in  OnCore,  Yale’s  clinical  research 
management  system,  for  Epic  to  appropriately  route  research  related  charges.  Please  contact 
oncore.support@yale.edu 

Page 6 of 56 
 
8. Are there any procedures involved in this protocol that will be performed at YNHH or one of 
its affiliated entities?  Yes ___ No _X__  If Yes, please answer questions a through c and note 
instructions below.  If No, proceed to Section III. 
a. Does your YNHH privilege delineation currently include the specific procedure that you will 
perform? 
b. Will  you  be  using  any  new  equipment  or  equipment  
that  you  have  not  used  
in  
the  past  
for 
this procedure? 
  
c. Will a novel approach using existing equipment be applied? 
  
If  you  answered  “no”  
to  question 8a,  or  "yes"  
to  question  8b  or  c, please  contact  
the  YNHH 
Department of Physician Services (688-2615) for prior approval before commencing with  your 
research protocol
. 
 
Please note that if this protocol includes Yale-New Haven Hospital patients, including patients at 
the HRU, the Principal Investigator and any co-investigators who are physicians or  mid-level 
practitioners (includes PAs, APRNs, psychologists and speech pathologists) who may have direct 
patient  contact  with  patients  on  YNHH  premises  must  have  medical  staff  appointment  and 
appropriate clinical privileges at YNHH. If you are uncertain whether the study personnel meet 
the criteria, please telephone the Physician Services Department at 203-688-2615. By signing this 
protocol as a PI, you attest that you and any co-investigator who may have patient contact has 
a medical staff appointment and appropriate clinical privileges at YNHH.
 
 
 
SECTION III: FUNDING,
 RESEARCH TEAM AND TRAINING 
 
1. Funding Source: Indicate all of the funding source(s) for this study. Check all boxes that apply. 
Provide information regarding the external funding source.  This information should include 
identification of the agency/sponsor, the funding mechanism (grant or contract), and whether 
the  award  
is  pending  or  has  been  awarded.  Provide  
the  M/C#  and  Agency  name  
(if  grant-
funded).  
  If  
the  funding  source  associated  with  a  protocol  
is  “pending”  at  
the  
time  of  
the 
protocol submission to the HIC (as is the case for most NIH submissions), the PI should note 
“Pending” in the appropriate section of the protocol application, provide the M/C# and Agency 
name  (if  grant-funded)  and  further  note  that  University  (departmental)  funds  support  the 
research (until such time that an award is made).   
 
 

Page 7 of 56 
 
2. Research Team:  List all members of the research team. Indicate under the affiliation column whether 
the investigators or study personnel are part of the Yale faculty or staff, or part of the faculty or staff 
from a collaborating institution, or are not formally affiliated with any institution. ALL members of the 
research  team  MUST  complete  Human  Subject  Protection  Training  (HSPT)  and  Health 
Insurance Portability and Accountability Act (HIPAA) Training before they may be listed on the 
protocol.  See NOTE below. 
 
NOTE: The HIC will remove from the protocol any personnel who have not completed required training. A 
personnel protocol amendment will need to be submitted when training is completed. 

Page 8 of 56 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
   
    
 
 
 
 
 
 

Page 10 of 56 
 
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested.  
 
The  aim  of  this  study  is  to  examine  the  effect  of  mHealth  tools  on  antiretroviral  (ART) 
adherence  and  persistence  among  HIV-infected  individuals  with  co-occurring  cocaine  use 
disorders (CUDs). The specific aims are:  
(1) To conduct qualitative assessments using focus groups of  people living with HIV (PLH) 
who  use  cocaine  and  healthcare  providers  
that  will  assess  
the  acceptability,  
feasibility, 
facilitators and barriers of implementing mHealth interventions; and will aid in developing 
the final design and content of both automated and clinician feedback in preparation for 
designing a pilot feasibility study.  
(2) To conduct a 12-week pilot feasibility RCT among PLH with co-occurring CUDs that will 
examine the impact of mHealth tools (cellular-enabled smart pill boxes and cell phones) 
and feedback (no feedback vs. automated feedback vs. automated + clinician feedback vs. 
vs.  automated  +  
text-reminder  
from  a  social  network)  on  primary  
(ART  adherence  and 
persistence) and secondary outcomes (HIV viral suppression, cocaine use, retention in HIV 
care). 
 
The hypotheses include: 
 
(1) Patients with automated feedback + clinician feedback will have higher ART adherence 
and persistence than patients with only automated feedback and patients with no feedback. 
(2) Patients with automated feedback + clinician feedback will have improved HIV outcomes 
including lower changes in log10 HIV-1 RNA levels, higher CD4 counts and higher rates 
of retention in care, compared to patients with only automated feedback and patients with 
no feedback. 
(3) Patients with automated  
feedback  +  clinician  
feedback  will have decreased  cocaine  use 
compared to patients with only automated feedback and patients with no feedback. 
(4) Patients with automated feedback + text-reminder from a social network will have higher 
ART adherence and persistence than patients with only automated feedback and patients 
with no feedback. 
(5) Patients  with  automated  feedback  +  text-reminder  from  a  social  network  will  have 
improved HIV outcomes including lower changes in log10 HIV-1 RNA levels, higher CD4 
counts  and  higher  
rates  of  
retention  
in  care, compared  
to  patients  with  only  automated 
feedback and patients with no feedback. 
(6) Patients  with  automated  feedback  +  text-reminder  from  a  social  network  will  have 
decreased  cocaine  use  compared  
to  patients  with  only  automated  
feedback  and  patients 
with no feedback. 
(7) There  is  statistically  significant  difference  between  a  patient’s  ART  adherence  and 
persistence and HIV outcomes when their designated social network member lives inside 
vs outside patient’s activity space. 
 
 
 
2. Background: 
Describe the background information that led to the plan for this project. Provide 
references to support the expectation of obtaining useful scientific data. 
 

Page 11 of 56 
 
Antiretroviral therapy (ART) is extremely effective at reducing morbidity and mortality, and 
reducing  HIV  
transmission  among  people  
living  with  HIV  
(PLH).
1,2 Clinical  effectiveness, 
however,  is  largely  dependent  on  patients’  ART  adherence  and  persistence.3-9 ART non-
adherence and non-persistence substantially reduce viral suppression (VS)10 and increase HIV 
transmission  risk  
to  others.
11-15 Substance  use  disorders  (SUDs)  further  contribute  
to  poor 
health  outcomes,  primarily  by  reducing  ART  adherence  and  persistence.16-20 Cocaine  use 
disorders (CUDs), in particular, result in a number of poor HIV treatment outcomes, including 
decreased retention in care, poor ART adherence and persistence, low VS, and accelerated HIV 
progression.21-28 Considering the high prevalence of CUDs among PLH29-34 and the absence of 
effective  medication-assisted  therapies  (MAT)  for  treating  CUDs,  innovative  strategies  of 
improving ART adherence in this group are urgently needed. 
Opioid agonist treatments for opioid dependent PLH is an effective evidence-based adherence 
strategy;
35,36 however, for PLH with CUDs, currently the only effective adherence intervention 
is  directly  administered  antiretroviral  therapy  (DAART)
36 which  is  expensive  and  labor-
intensive.  Recent  international  guidelines  suggest  that  the  next  generation  of  adherence 
interventions will need to be scaled back both in terms of cost and personnel.
36 Mobile health 
(mHealth)  technologies  such  as  cell  phones can  provide  innovative,  efficacious  and  cost-
effective  strategies  
to  
improve  ART  adherence  and  optimize  HIV  
treatment  outcomes.
37,38 
They  already  show  great  promise  in  resource-limited  settings  due  to  their  low  costs  and 
ubiquitous  nature,38-41 making  
their  use  
in  underserved  communities  such  as  PLH  with  co-
occurring  CUDs,  particularly  appealing.  mHealth  tools  can  not  only  monitor  medication 
adherence in real-time (such as cellular-enabled smart pill boxes),
42,43 but can also be used to 
promote  adherence  in  temporal  proximity  to  actual  medication  intake  through  the  use  of 
automated reminders, feedback and interactive communication.
44-48 Already, text messaging 
using cell phones has been shown to increase treatment adherence and retention in care among 
patients  with  various  chronic  conditions  such  as  diabetes,49-53  
tuberculosis,
54-56 malaria,57-59 
asthma,
47,60 and HIV,
46,61,62 but has never been developed or tested in PLH with CUDs – a 
highly prevalent group of PLH with problematic ART adherence and persistence.  
 
mHealth interventions can be valuable for PLH since they make it possible to have a tightly 
woven network of coordinated care by providing real-time data about dosing reminders,
63,64 
medication intake,44,46 and solicitation of care.
62 The inclusion of tailored automated feedback 
has been especially successful at promoting positive health outcomes for other conditions,65-67 
yet has not been compared to personalized clinician feedback. Despite their immense potential, 
the acceptability, feasibility and effectiveness of mHealth tools have not yet been developed 
and tested among PLH with co-occurring CUDs. Moreover, mHealth interventions have not 
optimized the integration of feedback to determine what type of feedback improves outcomes. 
Thus,  this study will  provide  crucial  preliminary  information  necessary  to  determine 
acceptability, study design and implementation procedures for conducting the most optimal 
RCT using a quadruple (patient-mHealth-clinician-social network) relationship for improving 
ART adherence and persistence in PLH with CUDs. 
 
Significance 
A. ART Access, Adherence and Persistence: Among the ~1.2 million PLH in the U.S., ART 
adherence and persistence is problematic for many, resulting in too few patients achieving VS. 
In the absence of VS, HIV transmission and mortality among PLH increase.
1,2,68 Virological 

Page 12 of 56 
 
failure,  either  
through  suboptimal  adherence  (not  
taking  ART  as  prescribed)
36,69,70 or  non-
persistence  (gaps  in  continuous  ART  treatment),18,71 results  in  development  of  resistance 
mutations, increased mortality72, and complicated care.
3-9,16-19,73 For PLH with co-occurring 
SUDs,  there  are  additional  negative  health  outcomes;  active  drug  use  is  associated  with 
clinicians  not  prescribing  or  delaying  prescribing  ART.
74 When  ART  
is  optimized,  
it  also 
improves outcomes  
for  other co-morbid conditions.17 A meta-analysis has documented that 
patients  with  SUDs  who  receive  adherence  support,  adhere to  ART  similarly  
to  non-drug 
users.75 Adherence support, however, must be provided using a strong theoretical model with 
documented effectiveness and in this case, be effective with SUDs. 
B. Negative Consequences of Cocaine Use on HIV Outcomes: Although SUDs are associated 
with negative health outcomes; CUDs are especially problematic for access and retention in 
HIV  care.76-78 Cocaine  use  is  associated  with  high  rates  of  psychiatric  disorders,  criminal 
activity, negative social interactions, and risky sex practices that place users at even more risk 
of HIV transmission.11-15,79 Moreover, compared to PLH with other SUDs, those with CUDs 
are less likely to be prescribed ART,
78,80 have problematic adherence,22-27 and don’t achieve 
VS,21,30 thus  resulting  in  accelerated  HIV  progression  and  opportunistic  conditions.
28,81,82 
These cumulative negative effects ultimately are responsible for AIDS-related death being 3-
fold higher in CUDs than among non-drug users.30  
C. Current  ART  Adherence  Strategies  in  PLH  and  SUDs: The  CDC  supports  only  10 
interventions to promote ART adherence. A systematic review
35 and international guidelines 
only support 3 ART adherence interventions for PLH and SUDs: 1) DAART, 2) medication-
assisted therapies (MAT) to treat addiction, and 3) integrated care.
16,83-85 Since CUDs are not 
amenable  
to  MAT,  behavioral  
interventions  remain  crucial.  Even  
in  patients  on  MAT  and 
receiving DAART, cocaine reduces adherence.
86 DAART is effective irrespective of cocaine 
use,19,87-89 but is rarely available and too expensive for most settings.90 While integrated care 
is  also  effective,
35,91-98 recent  
international  guidelines
36 suggest  
that  
the  next  generation  of 
adherence interventions must be scaled back in terms of cost and personnel and incorporate 
three crucial “C” elements: Convenience, Confidentiality and Cost-effectiveness. None of the 
available interventions specifically address the 4
th C: Cocaine Users. Current behavioral and 
structural  interventions  designed  to  reduce  cocaine  use  have  met  with  limited  success – 
interventions that support ART adherence even in the  presence  of ongoing cocaine use are 
crucial. A RCT of a family-based structural vs. psycho-educational intervention in cocaine-
using PLH found neither reduction in cocaine use nor improvement in ART adherence.99 One 
pilot  RCT  (N=56)  comparing  the  effects  of  extended,  multi-session  adherence counseling 
intervention versus a single video-based control group showed reduction in cocaine use and 
improvement in ART adherence over time, but without differences between groups.
100 The use 
of reminders linked to medication-taking, which has documented benefits,
101 was not included, 
but this still provides support for technology-based ART adherence improvements in HIV+ 
cocaine users.  
D. mHealth as an Innovative and Effective Tool: In healthcare management, the use of mHealth 
is viewed as an innovative tool in managing personal healthcare and promoting preventive and 
treatment  behaviors.
38,50,102,103 mHealth  satisfies  recommendations that  newer  adherence 
strategies be scaled back in terms of cost and personnel. mHealth interventions have already 
been shown to be efficacious in improving treatment adherence in patients with various chronic 
conditions  such  as  diabetes,
49-53  tuberculosis,
54-56 malaria,57-59 and  asthma
47,60 and  are 
positioned to provide efficacious and cost-effective ART adherence strategies to optimize HIV 

Page 13 of 56 
 
treatment  outcomes.
37,38 A  2014  meta-analysis  of  text  messaging  interventions  in  PLH 
summarized  that  reminders  and  feedback  in  the  form  of  text  messages  improved  ART 
adherence,  with  larger  adherence  and  VS  effects  seen  when  text  messages  were:  1)  less 
frequent,  2)  bidirectional,  3)  personalized  messages,  and  4)  matched  
to  dosing  schedule;
104 
none  of  
the  9  studies  
in  
the  meta-analysis  however,  sampled  PLH  with  SUDs.  New  WHO 
guidelines  now  strongly  
recommend  
texting  
to  promote  adherence  and  
retention.101  Mobile 
phones and devices offer multiple benefits to PLH; they are cost-effective, require minimal 
direct  supervision,  allow  flexible  reminders  and  content  and  can  be  disseminated 
ubiquitously.38,41,48,63 Three-fourths of PLH have positive perceptions regarding the use of cell 
phones to support their adherence behaviors.105. In our current NIH study (R01 HD075630) of 
PLH  with  SUDs - several  with  unstable  housing,  we  have  found  high  acceptability  and 
retention  among  48  patients  video-recording  
their  medication-taking  
to  measure  adherence. 
Use of mHealth tools in cocaine users remains limited to assessing drug craving and use, and 
only  in  patients  without  HIV.106-108 Despite  evidence  that  adding  mHealth  tools  to  brief 
interventions  may  be  feasible  and  cost-effective  
in  
improving  HIV  outcomes  
in  PLH  and 
SUDs, mHealth assessments or interventions have never specifically targeted PLH with co-
occurring  CUDs – a  remarkably  vulnerable  population  with  excessive  health  disparities. 
Developing  effective  adherence  tools  for  patients  with  CUDs  will  benefit  patients  and 
encourage clinicians to not withhold ART prescription, and thus promote health strategies to 
treat and retain patients on ART. 
 
Innovation: Significance  and  innovation  are  high  because  of  the  combination  of  several 
factors – (1) the focus on PLH with CUDs to promote ART adherence; (2) incorporation of 
qualitative  assessment  using  focus  groups  among  HIV+  cocaine  users  to  examine  their 
willingness to incorporate mHealth interventions and among healthcare providers in order to 
understand their interest in deploying mHealth ART interventions for patients with CUDs; , 
and among selected social network members to understand their interest in becoming ‘health-
buddy’ and providing long-term and sustainable support for healthcare; (3) the intervention to 
be developed and pilot-tested involves two mHealth-based reminders (via  cellular-enabled 
smart pill boxes and cell phones), and three types of feedback (automated electronic feedback 
based  on  adherence  from  smart  pill  boxes,  and  clinician  feedback  based  on  a  weekly 
smartphone-based survey 
and weekly text-reminder from a designated social network member) 
– each of which has separately shown to improve ART adherence, persistence and VS in PLH 
but not in drug users; . In addition, prior studies have used network-driven interventions for HIV 
prevention  but  not  for ART  adherence,  persistence,  and  VS  in  PLH  and  definitely  not  by 
combining mhealth tools with social relations (4) the comparison of automated electronic and 
personalized clinician and text-reminder from a social network member feedback as part of the 
intervention, especially since feedback and communication loops have been under-utilized in 
interventions in PLH with SUDs;
109,110 (5) extension of our established use of feedback using 
the  Information-Motivation-Behavioral  Skills  (IMB)  conceptual  framework  for  adherence 
using a computer interface (LifeWindows project),111 but now applied to mHealth to promote 
adherence; and (6) a multidisciplinary group of researchers experienced in addiction medicine, 
HIV, intervention development  particularly  adherence  interventions, behavioral  science, 
Geographic Information System (GIS), social network analysis (SNA) and mHealth who have 
already created CDC-recommended ART adherence interventions for drug users. Thus, this 

Page 14 of 56 
 
study is uniquely positioned to provide crucial information necessary to develop a mHealth 
tool-enabled intervention strategy for PLH and CUDs.  
 
 
3. Research  Plan: Summarize  
the  study  design  and  research  procedures using  non-technical 
language  that  can  be readily  understood  by  someone  outside  the  discipline. Be  sure  to 
distinguish  between  standard  of  care  vs.  research  procedures  when  applicable,  and 
include any flowcharts of visits specifying their individual times and lengths. Describe the 
setting in which the research will take place. 
 
There are two specific aims within this study. In the first specific aim, we will conduct four 
focus  groups  of  people  living  with  HIV  (PLH)  with  co-occurring  cocaine  use  disorders 
(CUDs), and two focus groups of healthcare providers to assess the acceptability, feasibility, 
facilitators and barriers of implementing mHealth interventions. In the second aim of the study, 
we will conduct a pilot feasibility RCT among PLH with co-occurring CUDs to examine the 
effect of mHealth tools  
(blister  pack and cell phones) and  
feedback loops (no feedback  vs. 
automated feedback vs. automated + clinician feedback vs. automated + text-reminder from a 
designated social network member) to assess improvement in antiretroviral (ART) adherence 
and persistence and other HIV health outcomes.  
 
Specific Aim 1: To conduct qualitative assessments using focus groups (FGs), among HIV+ 
cocaine  users  and  among  healthcare  providers,  
that  will  assess  
the  acceptability,  feasibility, 
facilitators and barriers of implementing mHealth interventions; and will aid in developing the 
final design and content of both automated and clinician feedback in preparation for designing 
a pilot feasibility study. 
 
An initial set of 4 focus groups (FGs) comprised of 6-8 persons with HIV+ cocaine users and lasting 
one hour each will be conducted. Recruitment, screening, enrollment and other procedures for these 
FGs are discussed below. A second set of  
two FGs will be conducted among healthcare  providers 
including physicians, nurses, clinic supervisors, and substance abuse counselors from HIV clinics.  
   
Eligibility Criteria for Focus Groups of HIV-infected Cocaine Users: 
• Age >18 years old 
• HIV+ 
• Current cocaine use (in the past 30 days) 
• Able to speak English or Spanish 
• Able to provide informed consent 
Eligibility Criteria for Focus Groups of Healthcare Providers: 
• Currently employed as community-based HIV physician, clinician, healthcare worker, 
clinic supervisor or substance abuse counselor  
• Speaks English or Spanish 
• Able to give informed consent  

Page 15 of 56 
 
 
I.A. Recruitment:  In order to recruit people for the first four FGs of people with HIV+ cocaine 
users, IRB-approved flyers containing a toll-free number will be posted in a number of clinical 
and community venues including HIV and drug treatment clinics, our mobile medical unit, and 
community  support  groups.  Due  to  our  continued  presence  in  New  Haven  through  the 
implementation of several treatment programs and clinical trials, we are confident of being able to 
recruit  participants  for  the  FGs.  For  the  FGs  with  healthcare  providers,  IRB-approved  flyers 
containing a toll-free number will be posted in the offices of all five HIV clinics in the Ryan White 
Consortium. Providers from all sites have been successfully recruited and participated in previous 
FGs. We will also recruit through announcements in the electronic newsletter “Did You Know?” 
– an  electronic  newsletter  managed  by  Karina  Danvers,  Director  of  the  New  England  AIDS 
Education and Training Center - Local Performance Site - that is disseminated regularly to New 
Haven-area  clinics. Letters of support from the Ryan White Consortium  and  
the New England 
AIDS Education and Training Center are attached to this application. 
 
I.B. Screening:    All  flyers  and  recruitment  information  will  have  our  toll-free  number.  
Interested individuals who call will be asked a number of questions including (a) age, (b) gender, 
(c) race/ethnicity, (d) HIV status, and (e) cocaine use in the past 30 days. Individuals who meet 
the eligibility criteria will be invited to learn more about the qualitative interviews. At that point, 
we will ask for a name (preferably a PSEUDONYM) that they would like to use during the FGs.  
We will do this so that we can make nametags that will be used to identify speakers during the 
FGs.  Individuals who do not meet criteria will be thanked for their time and asked for permission 
to maintain their information in our database should the opportunity to participate in other studies 
arise. They  will  not,  however,  be  
told  why  
they  did  not  qualify  for  participation.  NO  specific 
screening  will  occur  
for  
the  community-based  clinicians  and  healthcare  providers  other  
than  a 
request to provide proof of identity to verify their designations. 
 
Enrollment:  Individuals who screen positive for the first set of FGs as described above will be 
told more about the details of the study, including that the FGs will be conducted in a confidential 
setting.  During these FGs, they will be told that they do not need to provide their real name and 
that the information will be recorded but will also be confidential.  No names or other identifiers 
will be recorded.  They will be told that we will provide certain rules that include raising their hand 
to  speak,  being  
identified  by  a  pseudonym  
if  wanted,  
that  others  within  
the  group  should  be 
considerate of others, and reminded that the FG will be recorded. They will be given a TIME and 
LOCATION of the FGs and asked to show up 15 minutes beforehand to review a fact sheet and 
the focus group guides and provide verbal consent.  Verbal consent will be used to AVOID the use 
of real names and minimize risk of breaches of confidentiality. These interviews will not be video 
recorded, and they can use a pseudonym if they do not want to use their actual names for the focus 
group interviews.  
 
I.C. Procedure: Before the FGs begin, the participants will be verbally consented and be asked 
to review the IRB-approved information sheet that will include a description of the study, risks, 
benefits, privacy, and alternatives. By using the verbal consent process, we will protect the identity 
of the participants; no additional personal information will be collected at any point.  They will be 
reminded  
that  
they  can  use  
fake  names  during  
the  
interview.  
  Each  participant  will  be  given  a 
nametag to use their fake name to identify each speaker in the FG and will be given a pen and 

Page 16 of 56 
 
paper. The facilitator (Dr. Shan-Estelle Brown under the supervision of Dr. Altice) will begin the 
FG with a brief introduction including a description of the purpose of the FG; review rules of the 
group (e.g. turn off cell phones, protect each other’s confidentiality, respect other’s opinions, and 
speak one at a time); ensure there are no questions; and remind participants that they will be audio-
recorded. FG guides will detail the conduct during and after the interview, including not using names, 
not discussing specific illegal activities, and maintaining the confidentiality of focus group participants. 
Drafts of guides for both sets of FGs are attached to this application. A note-taker will also be in the 
room to record non-verbal communication during the FGs. After informed consent, Dr. Brown will 
audio-record the sessions.  
 
Procedure for participants affected by technical problem with the pillbox: Due to a technical error 
with the pillbox, real time adherence data of 8 participants were not collected from July 19, 
2018, and they also were not able to receive the interactive text reminders to take medication. 
This has caused us to lose up to a month
's adherence data from the boxes. The following actions 
will be taken to resolve and move forward with the study: 
 
• We will extend participation by one month (4 weeks) to the end date so that the 8 
participants end up receiving all 12 weeks of intervention. Since participants will be at 
different stages (because of rolling recruitment), we will accordingly adjust the timeline 
for each participant. Hence, 8 participants will be participating in the study for about one 
month longer than the original time-line of the study. 
 
Transcription and Analysis of Data: The audio files from all of the FGs will be sent to a licensed 
HIPAA-compliant professional transcription service using secure and encrypted transfer systems. After transcription, 
audio recordings of the FG discussions will be first locked in double protected cabinets and destroyed after verification 
of the information.  After transcription of all FGs, content analysis – a technique designed to uncover 
meaningful  patterns  and  
themes.  Transcribed  
text  will  be  coded  
into  
themes  using  an  
iterative 
process. The text will first be reviewed in a preliminary review, then in an in-depth fashion to 
categorize words, phrases, and sentences into codes based on the identified facilitators and barriers 
to mHealth adoption. A directed content analysis approach
112 to analyzing FG data will be used. 
Content  analysis is  a  well-established  method  for  analyzing  qualitative  data  and  is  widely 
employed  across  
the  social,  behavioral,  and  biomedical  sciences.
113,114  
 Subsequently
,  
it  will  be 
analyzed using NVivo to identify new themes related to (1) access to mobile technologies; (2) barriers 
and  
facilitators  
to  adoption  of  mHealth  
tools;  and  
(3)  
types  of  acceptable  
feedback  during  mHealth 
interventions. Information gleaned from the FGs will be used to design the nature – such as frequency, 
duration, scheduling time -   and exact content of the feedback loops incorporated in the pilot feasibility 
study. All transcription data will be stored anonymously
 and backed up on the Yale server.  All audio 
files will be destroyed using procedures set in place by Yale University after they have been transcribed 
and listened to. 

Page 17 of 56 
 
Specific Aim 2: To conduct a 12-week pilot feasibility RCT among a sample of PLH with CUDs 
that  will  examine  the  impact  of  mHealth  tools  (cellular-enabled  smart  pill  boxes  and  cell 
phones) and feedback (no feedback vs. automated feedback vs. automated + clinician feedback 
vs. automated feedback + text-reminder from a designated social network member) on primary 
(ART adherence and persistence) and secondary outcomes (HIV VS, cocaine use, retention in 
HIV care and in trial). 
 
All 90 participants for the pilot RCT study will be recruited from New Haven-area community 
HIV  clinics,  the  Ryan  White  Consortium,  and  substance  abuse  treatment  (SAT)  centers.  As 
indicated  in  the  gender  and  minority  inclusion  statement,  women  and  minorities  will  be 
represented in all sites of recruitment. The minimum age is 18 years of age, thus children 18-21 
years old will be eligible for participation.  
 
2.A. Recruitment Procedures: Similar to the recruitment procedure for the FGs IRB-approved 
flyers containing a toll-free number will be posted in numerous venues such as community SAT 
centers and HIV care clinics. Centers that have collaborated with us before and have been prime 
sites of recruitment include the Nathan Hale Clinic, Haelen Center, Hill Health Center, Central 
Medical Unit, Fair Haven Clinic, most of which are included in the Ryan White consortium. Due 
to  our  continued  presence  in  New  Haven  through  the  implementation  of  several  treatment 
programs and clinical trials, we are confident of being able to recruit participants for the pilot RCT. 
If enrollment is insufficient, we will post an announcement in “Did You Know?” – an electronic 
newsletter  managed  by  Karina  Danvers,  Director  of  the  New  England  AIDS  Education  and 
Training  Center - Local  Performance  Site - that  
is  disseminated  regularly  
to  New  Haven-area 
clinics. This will help us reach all the local area HIV clinics that can refer potential participants to 
our study.  
 
In addition to the above-mentioned recruitment sources, we will also be able to recruit from the 
Community  Health  Care  Van  
(CHCV).  The  CHCV,  a  36-foot  van  
is  equipped  with  
two  exam 
rooms,  a  counseling/phlebotomy  room  and  a  waiting  area.  The  staff  has  developed  strategic 
liaisons  with  patients  and  providers  throughout  the  community  and  is  capable  of  connecting 
researchers with potential HIV-infected patients with co-occurring substance abuse issues. 
 
2.B. Screening Procedure: The initial screening eligibility criteria will include the following:  
(1) HIV+, (2) self-reported cocaine use in the past 6 months, and (4) speaks English or Spanish. If 
an  
individual  meets  
the  
initial  screening  criteria,  
they  will  be  
invited  
to  meet  with  a  research 
assistant (RA) to determine if they fulfill all the necessary eligibility criteria to be included in the 
study. 
 
Eligibility Criteria: 
 
Inclusion Criteria 
 
       Exclusion Criteria 

Page 18 of 56 
 
• Age ≥ 18 years  
• Clinic-confirmed HIV diagnosis  
• Currently prescribed or eligible for ART 
• Currently has insurance 
• Self-reported cocaine use  ever 
• Willing and able to use a cell phone and 
blister pack for the 12-week intervention  
• Unable to provide informed consent  
• Verbally  or  physically  threatening  to 
research staff 
• Unable to communicate in either English or 
Spanish 
 
2.C. Informed  Consent  and  Enrollment  Procedures: All  participants  must  be  able  
to  provide 
informed consent to be enrolled in the study. The RA will obtain 
informed consent 
and then 
explain 
the purposes, protocol, expectations, and possible risks and benefits of the study.  
 
2.D. Randomization:  Although a specific randomization process is not required for pilot RCTs, 
we want to ensure that crucial covariates that might influence our outcomes are controlled for a 
priori,  especially  given  
the  modest  sample  size  proposed  
in  
this  pilot.  Since  
it  has  been  well-
documented that individuals with underlying mental illness experience worse outcomes, we will 
minimally stratify based on the presence or absence of neurocognitive impairment. Randomization 
will  be  1:1:1:1 to  patients  receiving  either  no  feedback,  automated  feedback  or  automated  + 
clinician feedback, and automated feedback + text-reminder from a social network. 
 
2.E. Study Procedures:    
 
1. Baseline  
Interview: After  
the  
informed  consent  procedure,  participants  will  be  asked  
to 
sign a medical release of information (ROI) to allow research staff to confirm self-reports 
of  HIV  status,  medication  prescription  and  healthcare  utilization  and  to  be  able  to 
communicate  with  the  participants’  clinical  providers.  The  RA  will  then  conduct  the 
baseline  
interview  consisting  of  various  self-reported  measures  
including  demographic 
information, health care status, medical history, standardized measures for drug use and 
mental  
illness,  and  
Information  Motivation  Behavioral  
(IMB)  constructs  
for  adherence. 
Participants will also undergo phlebotomy.  
 
2. Intervention: After randomization, the RA will provide each subject with the following in 
order  to  commence  the  intervention  part  of  the  pilot  feasibility  study: a  monthly 
prescription  blister pack and  a  cell  phone (specifically,  an  Android  smartphone). 
Participants can  choose to use their own phones  
if they already  have  an  Android-based 
smartphone. The RA will teach the participants how to use blister pack and the smartphone 
(including using the voicemail and text messaging features).  
 
- RAs will contact the medical providers for prescriptions, which will be sent to the local 
pharmacy (see section on Smart Pill Box Refills below). The local pharmacy will create 
medication blister packs.  Participants will receive text feedback from the study + text-
reminder from social network. 

Page 19 of 56 
 
- We will use a text messaging system (Telerivet) to send text reminders to take pills at the 
dosage time. Information about dosage times will be collected by RA’s during the 
baseline interview time. 
-  
- We will collect adherence data by counting pills in the blister-pack, a traditional and widely 
used  method  in  the  medication  adherence  literature.  However,  instead of  manually 
counting  
the  pills,  
the  participants  will  
take  a  picture  of  
their  blister-pack  and  
text  
that 
picture to our study phone number. The participants will send this picture once a week for 
the intervention period (12 weeks) and the follow-up period (4 weeks). After downloading 
the pictures from the study phone, we will use image analysis techniques to count the pill(s) 
in  each  bin.  We  will  send  automated  reminders  for  
taking  medication  and  
texting  
the 
picture.  
 
During the intervention period (12 weeks), a text messaging system (Telerivet) will text all 
participants once a week on their smartphones to take a brief survey using an app on their 
smartphones. CommCare is  a  cloud-based  mobile  messaging  platform  that  allows  a 
research team to set up an SMS gateway phone. This gateway phone allows the research 
team to conduct bulk messaging to participants via the telerivet app on one smart phone 
that has a sufficient data plan. The telerivet app on the gateway phone is directly linked to 
a Telerivet account that is accessed and managed via the web. The phone number of the 
participant is loaded into the Telerivet account at baseline, and the Telerivet system is then 
able to send them automatic reminders on their chosen day via the gateway phone. 
 
This survey app will be designed on the open-source CommCare platform. The day and 
time  of  the  weekly reminder will  vary  according  to  each  subject’s  convenience  and 
preference. The interview questions will utilize a multiple-choice format and participants 
will be able to use their  smart phone screen to answer the questions. The questions will 
assess the following: (1) cocaine use in the past seven days, (2) triggers of cocaine use, (3) 
protected and unprotected sexual intercourse following cocaine use, (4) ART adherence in 
the past 7 days, and (5) reasons for non-adherence (options for non-adherence will be given 
with  numbers  associated  with  
them  
for  ease  of  answering  
(e.g.  Press “1 if you forgot”, 
Press “2 if you ran out of medicine”, etc.; as well as an “other” option). For participants 
in Groups A and B, the survey response will only be recorded; however, for participants in 
Group C, the survey app responses will be assessed each week by the RA who in turn will 
communicate the results to a clinical nurse. The clinical nurse will be funded through this 
study;  he/she  will  be  responsible  for  providing  personalized  feedback  to  all  Group  C 
participants. The clinic nurse will contact the subject with appropriate feedback about their 
health  behavior  and  suggestions  
for  sustained  adherence.  The  specifics  of  
this  clinician 
feedback will be established from the FG findings (Aim 1). Thus, the purpose of the weekly 
survey app is two-fold – to assess self-reported ART adherence and to inform the clinician 
feedback. The participants in Group D will be in an intervention called, ‘TRIDENT’ (Text 
Reminder In DEsignated NeTwork). The following protocol is developed for this arm: i) 
Telerivet  will  send  a  weekly  notification  to  the  cell  phone  of  their  designated  social 
network member as a prompt to send intervention text-reminder to the participant. ii) The 
social  network  designee  will  be asked to send the intervention text message within one 

Page 20 of 56 
 
hour,  for  example, ‘take  your  medications’,  to  the  participants.  No  fixed  text  or 
personalized text messages from the social network designee have not been developed for 
the intervention. Instead, the actual content of the text between the patient and the designee 
will be recorded as the intervention data.  
 
After the 12-week intervention, all participants will be followed for a 4-week period and 
primary and secondary outcomes will also be recorded during the post-intervention follow-
up period. 
 
 
 
 
 
3. Monthly  Research  Interviews: Monthly  interviews  will  take  place  for  the 16-week 
duration of the study (12-week intervention and 4-week follow-up) for all participants. 
The  
interviews  will  
include  health  care  utilization,  phlebotomy,  self-reports  of  drug 
use, and mental illness. All phlebotomy information obtained after community release 
will be obtained through Quest Diagnostics, a national reference laboratory. We have 
a prearranged system for phlebotomy, reporting of results and storing specimens at -
70C  that  has  been  in  place  for  the  past  decade.    None  of  the  assays  used  are 
experimental and will be drawn as 
part of clinical care at standardized times as outlined.  
Tests will include HIV-1 RNA testing (Amplicor 1.5, range 50 to 750,000 copies/mL) 
and CD4 lymphocyte count using flow cytometry at baseline, end of intervention (12 
weeks)  and  end  of  follow-up  period  (16  weeks). HIV  genotypic  mutations  will  be 
assessed at baseline and at 16 weeks (if VL>500 copies/mL).  
 
4. Monthly  Text-Message  Data  Collection: At  weeks  4,  8,  and  12,  
the  
following  
two  
types  of 
research  data  will  be  collected  from  
the  participants.  A  
total  of  4  
text  messages  (one  
text 
message per week) sent by the designated social network member to the participant will be 
downloaded. The text messages will be downloaded by a RA from the participant’s cell phone. 
In order to pull participant text message/ SMS data off of the project phones, the research team 
will  use  a  software  called SMS  Backup  and  Restore. With  consent,  this  software  will  be 
installed only on the phones of participants in the fourth arm. The SMS Backup and Restore 
application  allows  us to  connect  
the text  message/SMS  data  on  
the  participant  phones  
to  a 
secure Dropbox account. Our technical consultant will create these secure Dropbox accounts 
for every participant phone in the 4
th arm and link them to each of the participant’s phones.  
These Dropbox accounts will be protected with a unique password; the only individuals with 
access to the password and the accounts will be the project staff. During the monthly interviews 
with  participants,  the  Research  Assistants  will  navigate  to  the SMS  Backup  and  Restore 
application on the participants’ phones and backup the local SMS data to the Dropbox accounts. 
This is a two-step functionality within the SMS Backup and Restore application. The RAs will 
first click on “Backup” and then will be prompted to choose a location to sync the data to. The 
RAs will choose to backup the SMS data to the secure Dropbox that will already be linked to 
the phone. For more details, see the sections on “Risk, Minimizing Risk, and Data and Safety 
Monitoring Plan”.  
 

Page 23 of 56 
 
 
NOTE: Is this research proposal designed to enroll children who are wards of the state as potential 
subjects?  Yes  
 No (If yes, see Instructions section VII #4 for further requirements) 
7. Inclusion/Exclusion Criteria: What  are  
the  criteria  used  
to  determine  subject  
inclusion  or    
exclusion? 
 
Aim 1 (Focus Groups): An initial set of 4 focus groups (FGs) comprised of 6-8 persons with HIV+ 
cocaine users and lasting one hour each will be conducted. Recruitment, screening, enrollment and other 
procedures  
for  
these  FGs  are  discussed  below.  A  second  set  of  
two  FGs  will  be  conducted  among 
healthcare  providers  including  physicians,  nurses,  clinic  supervisors,  and  substance  abuse 
counselors from HIV clinics.  
   
 
 
Aim  2 (Pilot  Feasibility  Study): The  initial  screening  eligibility  criteria  will  include  the 
following: (1) HIV+, (2) self-reported cocaine use in the past 6 months, and (4) speaks English 
or Spanish. If an individual meets the initial screening criteria, they will be invited to meet with 
a research assistant (RA) to determine if they fulfill all the necessary eligibility criteria to be 
included in the study. 
 
Eligibility Criteria: 
 
Inclusion Criteria 
 
       Exclusion Criteria 
Eligibility Criteria for Focus Groups of HIV-infected Cocaine Users: 
• Age >18 years old 
• HIV+ 
• Current cocaine use (in the past 30 days) 
• Able to speak English or Spanish 
• Able to provide informed consent 
Eligibility Criteria for Focus Groups of Healthcare Providers: 
• Currently employed as community-based HIV physician, clinician, healthcare worker, 
clinic supervisor or substance abuse counselor  
• Speaks English or Spanish 
• Able to give informed consent  

Page 24 of 56 
 
• Age ≥ 18 years  
• Clinic-confirmed HIV diagnosis  
• Currently prescribed or eligible for ART 
• Currently has insurance 
• Self-reported cocaine use ever in lifetime 
• Willing and able to use a cell phone and 
blister pack for the 12-week intervention 
• Unable to provide informed consent  
• Verbally or  physically  threatening  to 
research staff 
• Unable to communicate in either English or 
Spanish 
 
8. How will eligibility be determined, and by whom?  
 
Aim 1 (Focus Groups): Individuals interested in participating in the FGs will be able to call 
the toll-free number listed in the flyers, during which they will be asked a number of screening 
questions by the study RA, including a) age, b) gender, c) HIV status, and d) cocaine use in the 
past 30 days. If initially eligible, they will be provided with more study details and invited to 
participate in the FGs. No specific screening will occur for the community-based clinicians and 
healthcare providers other than a request to provide proof of identity to verify their designations. 
Prior to the FG, informed consent will be obtained verbally by the RA who will explain the 
purpose, protocol, expectations and possible risks and benefits of the study. Verbal consent will 
be used to avoid the use of real names in the FGs and ensure confidentiality. Participants will 
be provided an informed consent form that will be approved through local authorities and the 
Yale University School of Medicine Institutional Review Boards (IRB). The consent form will 
outline the agreement to participate in this study. All patients will be reminded that their refusal 
to participate in no way will negatively affect their relationship with any of the participating 
agencies or clinics, substance abuse treatment or hospital facilities, their ability to continue in 
drug treatment, or their ability to obtain medical services from area clinics in the future. 
 
Aim 2 (Pilot Feasibility Study): Individuals interested in participating in the pilot study will 
be able to  
call the toll-free number listed in the flyers, during which they will be asked a number 
of screening questions. Eligible participants will be asked if they would like to participate and 
will  be  referred  to  a  study  RA  to  definitively  assess  them  for  eligibility.  Referral  will  be 
conducted by asking the subject to sign a release of medical and drug treatment information 
form.  After explaining the details of the study, informed consent will be obtained either by the 
RA or the PI. These persons will explain the purposes, protocol, expectations, and possible risks 
and benefits of the study. Participants will be provided an informed consent form that will be 
approved through the Yale University School of Medicine Institutional Review Board (IRB). 
The informed consent form will outline the agreement to participate in this research study. All 
patients will be reminded that their refusal to participate in no way will negatively affect their 
relationship with Yale University and local alcohol drug treatment or hospital facilities, their 
ability to continue in drug treatment, or their ability to obtain medical services from area clinics 
in the future.  
 
 
9. Risks: Describe  the  reasonably  foreseeable  risks,  including  risks  to  subject  privacy, 
discomforts, or inconveniences associated with subjects participating in the research.  

Page 25 of 56 
 
 
Risks Associated with Focus Groups: During the FG sessions with PLH who use cocaine, topics 
such  as  cocaine  use  and  substance  use  treatment  will  be  discussed.  These  topics  may  make 
participants feel uncomfortable. 
 Participants may choose not to answer all or any part of a question 
during  
the  sessions.  There  are  minimal  risks  expected  from  participating  
in  
the  study  such  as 
feeling uncomfortable in certain topics being discussed.  If anyone feels uncomfortable, they may 
choose not to answer any part or all of a question. Participant names will not be used or recorded 
in the focus groups.  Instead, FG participants will be asked to use a pseudonym/nickname. Yale 
IRB-approved fliers will be used to help with recruitment for focus groups and the drug treatment 
counselors will also assist in recruitment of participants. When recruiting participants from venues, 
the participants will be briefly told about the FG and if they want to learn more about it, recruiters 
will hand out a contact information card to call into the study site. 
 No information will be collected 
from them at this time so they may choose to not to call into the site or if they do call in and want 
to  come  
in  
for  consenting,  
information  
is  still  not  collected  and  
they  may  decline  
to  come  
in.  
During the consent process, they will be read the consent form verbatim and will be asked if they 
would like to participate in the study or not.  They will also be able to decline or take more time 
to think about it. 
 If they verbally consent, another appointment will be scheduled for the participant 
to come in and participate in the focus group.  They may choose to withdraw from the study at any 
point and decide not to come in for the focus group session. During the  FGs, participants may 
choose  not  
to  answer  a  question  or  part  of  a  question  and  are  
free  
to  give  as  
little  or  as  much 
information as they feel comfortable doing. No study-related unanticipated problems or adverse 
events are expected to occur in this part of the study. Real names will not be used during the FGs 
and answers to questions will not be linked to a participant’s real name. Transcripts will be linked 
only to pseudonyms or nicknames. Hard copies of data collected will be stored in a locked cabinet.  
Electronic  copies  can  be  accessed  by  providing  a  user  identification  and  password. For  FGs 
involving community healthcare providers and clinicians, similar attention to confidentiality will 
be given. 
 
Risks Associated with Pilot Feasibility Study 
 
1. 
Risks  Associated  with  Standardized  Assessments:  The  standardized  assessments 
administered  during  baseline  and  monthly  research  interviews  will  include:  (1)  demographic 
information, including age, race, and gender; (2) health care status, including past medical history, 
current  medications,  (3)  standardized  screening  for  mental  illness  using  the  Center  for 
Epidemiologic  Studies  Depression  Scale  (CES-D);121 (4)  standardized  measures  of  drug  use, 
including  determination  of  DSM-V  criteria  
for  cocaine  use  disorder;122 (5)  Addiction Severity 
Index (ASI)-Lite  
to  assess  cocaine  use,  polysubstance  use and  severity;
123,124 (6)  LifeWindows 
questionnaire  
to  measure  
the  
Information-Motivation-Behavioral  constructs  of  adherence;111,125 
(7) ART adherence using blister pack , 
Visual Analog Scale (VAS) 
and brief adherence scale;
126,127 
(8)  change  
in  cocaine  use  using  
the  Timeline  Follow-Back  
(TLFB);
128 (9)  AUDIT-C  
to  assess 
alcohol  use;
129 (10)  health  literacy;
130 (11)  social  support;
131 (12)  trust  in  physicians;
132  (13) 
acceptance  of  smart  pill  box  and  smartphones;
133 and  
(14)  perceived  source  credibility
134,  
(15) 
neighborhood delineation using the Activity Space; and (16) mapping and interpreting social or 
personal  networks  using  a  egocentric  social  network  analysis  questionnaire. It  
is  possible  
that 
participants may feel uncomfortable answering these questions; in this case, they will be able to 
refuse answering any questions that they do not wish to answer.  

Page 26 of 56 
 
 
2. 
Risks Associated with Interviews:  During the baseline and monthly research interviews, 
topics such as cocaine use and substance use treatment will be discussed. These topics may make 
participants feel uncomfortable. 
 Participants may choose not to answer all or any part of a question 
during the interviews. There are minimal risks expected from participating in the study such as 
feeling uncomfortable in certain topics being discussed.  If anyone feels uncomfortable, they may 
choose  not  
to  answer  any  part  or  all  of  a  question.  Participant  and  designated  social  network 
member’s names  will  not  be  used  or  recorded  
in  
the  
interview  data;  
instead  participant  study 
numbers will be used.  Yale IRB-approved flyers will be used to help with recruitment for the RCT 
and the drug treatment counselors will also assist in recruitment of participants. When recruiting 
participants from venues, participants will be briefly told about the study and if they want to learn 
more about it, recruiters will hand out a contact information card to call into the study site.  No 
information will be collected from them at this time so they may choose to not to call into the site 
or if they do call in and want to come in for consenting, information is still not collected and they 
may  decline  
to  come  
in.  
  Prior  
to  obtaining  
informed  consent, the  participant  will  be  
read  
the 
consent form verbatim and will be asked if they would like to participate in the study or not.  They 
will also be able to decline or take more time to think about it.  If they agree, they will be asked to 
sign the consent form. They may choose to withdraw from the study at any point. 
 
3. 
Risks  Associated  with  Loss  of  Confidentiality:  As  with  all  
research,  
there  
is  a  
risk  
that 
involves potential breaches of confidentiality. We intend to do everything possible to reduce this 
risk and this is one of the process measures we propose to measure. All study assessments will be 
administered  
in  a  private  setting  
that  will  minimizes  breaches  
in  confidentiality.  Patients  with 
substance use disorders, including cocaine, are a vulnerable population. Thus, our research to date 
has  
insured  strict  confidentiality  safeguards.  
  
  We  will  
further  
increase  
the  protection  of  
these 
participants by obtaining a Certificate of Confidentiality. 
 
Participants’ confidentiality will be well protected at our research offices in New Haven.  Studies 
that are currently underway at these sites include trials for the treatment of opioid, alcohol and 
CUDs.  Additionally, there are studies that involve both HIV+ and HIV- patients, those that have 
been involved and uninvolved with the criminal justice system as well as those with and without 
mental  illness.  
  Thus,  the  entry  into  our  research  offices  will  not  
identify  our  participants  as 
belonging to one or another class of citizens.  While within our research offices, we implement a 
number  of  additional  safeguards.  First,  participants  will  be  
interviewed  
in  a  private  
room  
in  a 
research setting where participants for a number of research projects are conducted with HIV+ and 
HIV-,  HCV+  and  HCV- and  drug  using  and  non-drug  using  participants.  Potential  sites  for 
breaches of confidentiality include during the study interviews at our research storefront. 
 Our New 
Haven study site is handicap accessible and has two possible entrances that may be used for entry 
and exit from the building.  The research environment ensures that confidentiality is protected in 
that  each  person  enters  
individually  
through  
the  
front  door,  goes  
immediately  
to  
the  computer 
workstation, and  
then  
to  
the  
interview  
room.  
  Appointments  are  staggered  
to  avoid  participant 
encounters in the hallway.  Participants have the option of leaving through a different doorway 
from  the  one  they  entered.    All  information  is  stored  in  password-protected,  PGP  encrypted 
computers  with  double-password  protection  for  opening  specified  files.    All  confidential 
information (study instruments, pharmacy records, etc.) will be recorded with study participant 
number only and maintained in locked cabinets within our offices at the Yale University AIDS 

Page 27 of 56 
 
Program and  will only be available to be opened by the Data Manager, Project Director or the 
Principal  Investigator.  Electronic  databases  will  be  maintained  through  password-protected 
computers and files and maintained at the Yale University AIDS Program. 
 
To help us protect participant privacy, we have obtained a Certificate of Confidentiality from the 
National Institutes of Health on May 22, 2017. The researchers can use this Certificate to legally 
refuse to disclose information that may identify participants in any federal, state, or local civil, 
criminal, administrative, legislative, or other proceedings, for example, if there is a court 
subpoena. The researchers will use the Certificate to resist any demands for information that 
would identify participants, except as explained below. 
 
The Certificate of Confidentiality will not be used to prevent disclosure to state or local 
authorities of events associated with child abuse and neglect, or harm to self or others. 
 
 
4. 
Risks Associated  with  Phlebotomy:  As  part  of  routine  care,  patients  will  undergo 
phlebotomy.  Patients  may  experience  discomfort  or  bleeding  at  the  site.  Since  no  additional 
laboratory results are being obtained other than those that would be used for routine clinical care, 
this poses no additional risk to the subject. 
 
 
10. Minimizing  Risks: Describe  the  manner  in  which  the  above-mentioned  risks  will  be 
minimized. 
 
Aim 1 (Focus Groups): There are minimal risks expected from participating in the FGs such as 
feeling  uncomfortable  with  certain  topics  being  discussed.  As  mentioned  previously, all 
participants  
recruited  
for  FGs  will  be  
reminded  
that  
their  
refusal  
to  participate  
in  no  way  will 
negatively  affect  
their  relationship  with  any  of  
the  participating  agencies  or  clinics,  substance 
abuse treatment or hospital facilities, their ability to continue in drug treatment, or their ability to 
obtain medical services from area clinics in the future. If participants do feel uncomfortable about 
certain questions asked during the FGs, they will be able to choose not to answer the question that 
makes them uncomfortable. FGs will be conducted in private rooms to ensure the confidentiality 
of the participants. All focus group and survey data will be stored in secure locations. To address 
the possibility of individuals coercing others to participate, all participants will be asked to confirm 
that they are coming forward out of their own free will and will be given the option not to continue 
with the study at any point. Individuals, who may go on to recruit others, will also be instructed 
not to coerce members of their network into coming forward to participate in the study. Of note, 
no one in the FGs will be asked for their name or any specific Identifier since this is a one-time 
assessment and we do not need to contact the subject for follow-up interviews.  At the FGs, they 
can either provide their real name or make up a name.  During the FGs, rules will be established 
at the outset and all participants will be told that the meeting is confidential and that any personal 
information shared would not be shared with others.  We will explain that confidentiality is key, 
so as to allow everyone to feel comfortable in sharing their opinions. 
 
Aim 2 (Pilot Feasibility Study): Standardized interviews will take place in a confidential setting 
in our research office in New Haven. Our research staff has completed IRB and HIPAA training 

Page 28 of 56 
 
and  we  have  put  
in  place  
rigorous  procedures  
for  protecting  data  at  
the  Yale  University  AIDS 
Program  
that  have  
resulted from  years of conducting research  with vulnerable populations. All 
confidential information (study instruments, pharmacy records, etc.) will be recorded with study 
participant  numbers  only  and  maintained  in  locked  cabinets  within  our  offices  at  the Yale 
University AIDS Program and will only be available to be opened by the Data Manager, Project 
Director  or  the  Principal  Investigator.    All  clinical  information  will  be  stored  in  locked  file 
cabinets.  Electronic databases will be maintained through password-protected computers and files 
and maintained at the Yale University AIDS Program. The adherence data obtained through text 
messaging will be saved in the research team’s server associated with Yale University. Similarly, 
the smartphone survey data will be saved on a central secure server owned by Dimagi, Inc. and 
will  be  accessible  only  to  the  study  researchers. Additionally,  for  text  message/SMS  data 
download: a two-step process (secure Dropbox and unique password to access available only to 
the  research  team)  leveraging  the SMS  Backup  and  Restore application  will  ensure  that  the 
participant SMS data is never downloaded locally to a non-University machine and will also ensure 
that it is never stored on a non-vetted third party server.  
 
The project staff will remove all SMS messages from this file that are sent from phone numbers 
that  do  not  match  with  someone  (social  network  designee)  who  has  consented  to  have  their 
information shared with the research team.  In addition, all the text messages will be "shredded" 
using PGP Desktop Shred which removes all traces of the file on the computer. 
 
11. Data and Safety Monitoring Plan: Include an appropriate Data and Safety Monitoring Plan 
(DSMP) based on the investigator’s risk assessment stated below. (Note: the HIC will make 
the final determination of the risk to subjects.) For more information, see the Instructions, page 
24. 
 
The  anticipated  risks  associated  with  this  study  are  deemed  overall  to  be  low.  Since  the 
intervention  does  not  utilize  any  pharmacology  therapy,  there  is  no  scope  for  unintended 
medication side-effects. The assessment of risk does not, however, preclude the potential for 
anticipated and/or unanticipated adverse events, serious or otherwise, since it is not possible to 
predict  with  certainty  
the  absolute  
risk  
in  any  given  
individual  or  
in  advance  of  
first-hand 
experience with the proposed study methods.  The proposed RCT is a single-site investigation.  
As  such,  
it  does  not  require  an  
independent  Data  and  Safety  Monitoring  Board  (DSMB), 
however it is essential to have a Data and Safety Monitoring Plan (DSMP).  
 
Some  of  the  factors  we  intend  to  monitor  closely  include:    1)  Are  the  treatment  groups 
comparable at baseline; 2) Are the accrual rates meeting initial projections and is the trial on 
its scheduled  timeline;  3)  Are  the  data  of  sufficient  quality;  4)  Are  the  treatment  groups 
different with respect to efficacy data; 5) Is there an indication to discontinue the trial due to 
predefined criteria; and 6) Should the protocol be modified in response to any unanticipated 
outcome or change in temporal event? 
 
Listed below are a number of items that potentially could be an adverse event for participation 
in this study: 
a. Subjects  whose  cocaine  use  
imposes  
risk  
to  
themselves: We  will  continue  
to  enroll  
the 
subject in their randomized arm of the study according to protocol; however, we will refer 

Page 29 of 56 
 
them  to  more  intensive  counseling.  For  participants  who  become  unstable  with  their 
cocaine use, they will be offered transfer to  an  
inpatient drug treatment  program where 
more structure can be provided to meet their drug treatment goals.   
b. Plan for subjects who develop serious psychiatric/medical symptoms during the follow-up 
phase: If the subjects develop serious DSM-V psychiatric symptoms or medical symptoms 
they will have many opportunities to report their symptoms with not only the clinicians but 
also the RA who will be available 7 days a week by telephone. If serious symptoms are 
reported, the participants will be evaluated by the PI of the study, Dr. Altice who is board-
certified  
in  Internal  Medicine,  Infectious  Diseases  and  Internal  Medicine. If  Dr. Altice 
determines  that  the  subjects’  medical  or  psychiatric  symptoms  cannot  be  treated  as 
outpatients, they will be admitted to the local hospital Emergency Room. Furthermore, the 
subjects’  chronic  medical  primary  care  providers  will  be  notified  immediately  of  any 
changes in their psychiatric or medical condition to continue with follow-up. 
c. Notification to HIV physicians due to lack of ART adherence or persistence: During the 
RCT,  if  participants  are  found  to  be  non-adherent  or  non-persistent  to  their  ART 
medication,  where  a  risk  of  HIV  virus  can  mutate  to  become  resistant  to  the  current 
regiment, their physician will be notified.
135  When an individual is enrolled in the study, 
he/she  will be asked to provide us with the  name of their physician and  sign a medical 
release of information (ROI) allowing us permission to communicate with the physician as 
need. A letter will be faxed to the physician’s office stating that the participant is enrolled 
in an ART adherence study; this initial communication will also request notification of any 
medication changes. Additional communication with the provider will include phlebotomy 
results and information if the participant is found to be non-compliant to their ART regimen 
(missed 2 weeks or more of medications). 
d. Halting Rules for the Study:  A DSMP, similar to a DSMB, may institute a number of pre-
planned rules for halting the study or modifying the study design. For pilot studies of this 
size, when there is not expected to be a difference in efficacy anticipated, there will be no 
halting  rules  aside  from  adverse  events.  For  
the  purposes  of  
this  study,  a  pre-planned 
interim analysis is planned when 50% of the subjects are accrued and have completed 6 
weeks of the study. This time point is  based  upon efficacy outcomes when the primary 
measure of interest can be assessed.  
e. Confidentiality of research data:  Breaches of confidentiality regarding research data are 
more difficult to detect.  For that reason, we have in place a number of safeguards including 
double-locked  doors,  
locked  file  cabinets,  confidential  and  dedicated  fax  machine  and 
double password-protected computers. In accordance with federal and university policy, 
all  research  personnel  are  compliant  with  HIPAA  training.  If  any  breach  of  data 
confidentiality were detected, we would use similarly detailed procedures for report to the 
PI and IRB simultaneously. 
 
 
12. Statistical Considerations: Describe the statistical analyses that support the study design.  
 
Aim 1 (Focus Groups): The audio files from all of the FGs will be sent to a licensed HIPAA-
compliant  professional  
transcription  
service  using  
secure  and  encrypted  
transfer  
systems.  After 
transcription,  audio  recordings  of  
the  FG  discussions  will  be first  
locked  
in  double  protected 
cabinets and destroyed after verification of the information.  After transcription of all FGs, content 

Page 30 of 56 
 
analysis – a technique designed to uncover meaningful patterns and themes. Transcribed text will 
be coded into themes using an iterative process. The text will first be reviewed in a preliminary 
review, then in an in-depth fashion to categorize words, phrases, and sentences into codes based 
on  the  identified  facilitators  and  barriers  to  mHealth  adoption.  A  directed  content  analysis 
approach
112 to analyzing FG data will be used to identify patterns and themes in the data based on 
the categories of interest, to extend the IMB model to the mHealth context. Content analysis is a 
well-established method for analyzing qualitative data and is widely employed across the social, 
behavioral, and biomedical sciences.113,114  Subsequently
, it will be analyzed using NVivo to identify 
new  
themes  
related  
to  
(1)  access  
to  mobile  
technologies;  
(2)  barriers  and  
facilitators  
to  adoption  of 
mHealth tools; and (3) types of acceptable feedback during mHealth interventions. Information gleaned 
from the FGs will be used to design the nature – such as frequency, duration, scheduling time -   and 
exact content of the feedback loops incorporated in the pilot feasibility
 study
. All transcription data will 
be stored  anonymously  and  backed  up  on  
the  Yale  server.  
  All  audio  
files  will  be  destroyed  using 
procedures set in place by Yale University after they have been transcribed and listened to.   
 
Aim 2 (Pilot Feasibility Study): The primary outcomes will be ART adherence and persistence, 
measured as a composite score ranging from 0 to 100%, and as number of continuous days taking 
ART without a 7-day (or 3-day) gap18,71 respectively. Outcome analyses will be conducted for (a) 
adherence and persistence behavior, (b) drug outcomes (cocaine use), (c) HIV treatment outcomes 
(VL<20  copies/mL;  change  in  CD4+  T  lymphocytes),  and  (d)    ART-related  Information, 
Motivation, and Behavioral Skills constructs. The general framework for discerning differences 
between study conditions on main outcome variables will be to perform 3 (intervention condition) 
x 3 (repeated follow-up  assessments) mixed design  analysis entering pre-intervention scores as 
covariates and additional theoretically and empirically relevant covariates (such as baseline mental 
status etc.). For variables that are approximately normally distributed, we will use multivariate 
analyses of covariance (MANCOVA), with significant multivariate tests followed by subsequent 
analyses  of  co-variance  (ANCOVA).  Variables  that  violate  distributional  assumptions  of 
normality will be analyzed using generalized linear model (GLM) procedures, which enable the 
use of non-Gaussian error models. Based on a review of the literature, GLM is the most appropriate 
approach for variables with strong positive skew, e.g., adherence.  
 
To examine the mediating and moderating effects of activity space and social network facilitators 
and  barriers  on  primary  
(ART  adherence  and  persistence)  and  secondary  outcomes  
(HIV  viral 
suppression, cocaine use, retention in HIV care), the following steps are going to be followed:  
a. A range of variables associated to activity space and social networks (both risk and support) 
will  be  calculated  using  a  combination  of  GIS,  SNA,  and  spatial  statistics  methods.  The 
variables will be the covariates. 
b. The  outcome  variables  are: primary  (ART  adherence  and  persistence)  and  secondary 
outcomes (HIV viral suppression, cocaine use, retention in HIV care). 
c. We will first use descriptive statistics, bivariate correlation, and t-tests to understand the 
distribution  and  association  of  all  
the  covariates  calculated  
in  step#a  with  
the  outcome 
variables (step#b).  
d. After running tests of multicolinearity, only uncorrelated covariates at p ≤ 0.05 (considered 
statistically  significant)  will  be  included  in  the  subsequent  mediation  and  moderation 
analysis.  

Page 31 of 56 
 
e. Using  
the  framework  of  structural  equation  modeling,  we  will  
identify  
the  moderating 
and/or mediating effects of spatial (activity space and neighborhood levels) and non-spatial 
data (individual and interpersonal) covariates on the primary and secondary outcomes.  
A  comparative  analysis  will  be  conducted  to  contrast  the  model  performance  (R2,  AIC,  and 
RMSE) of two mediation/moderation models with the primary (ART adherence) and a secondary 
(HIV viral suppression) outcome:1) with social network metrics and b) with spatial-social network 
metrics (calculated in step#a). 

Page 32 of 56 
 
 

Page 34 of 56 
 

Page 35 of 56 
 
SECTION VII: RECRUITMENT/
CONSENT AND ASSENT PROCEDURES  
1. Targeted Enrollment: Give the number of subjects: 
a. targeted for enrollment at Yale for this protocol___  
Aim 1 (Focus Groups): 42 (30 PLH cocaine users; 12 healthcare providers) 
Aim 2 (Pilot Feasibility Study): 90 PLH with co-occurring CUD 
 
b.    If this is a multi-site study, give the total number of subjects targeted across all sites___  
 
2. Indicate recruitment methods below.  Attach copies of any recruitment materials that will be used. 
 

Page 36 of 56 
 
 Flyers    
  
  
 
 Internet/Web Postings    
 
 Radio 
 Posters    
  
  
 
 Mass E-mail Solicitation    
 
 Telephone 
 Letter    
  
  
  
 Departmental/Center Website   
 Television 
 Medical Record Review 
  
 
 Departmental/Center Research Boards 
 Newspaper 
 Departmental/Center Newsletters 
 Web-Based Clinical Trial Registries  
 
  YCCI Recruitment database   
 Clinicaltrials.gov Registry (do not send materials to HIC) 
 Other (describe): 
 
Upon funding of this study, flyers will be created. 
 
3.  Recruitment Procedures:  
a. Describe how potential subjects will be identified. 
b. Describe how potential subjects are contacted.  
c. Who is recruiting potential subjects?  
 
Aim 1 (Focus Groups): In order to recruit people the FGs of HIV+ cocaine users, IRB-approved 
flyers containing a toll-free number will be posted in a number of clinical and community venues 
including HIV and drug treatment clinics, our mobile medical unit, and community support groups. 
Due to our continued presence in New Haven through the implementation of several treatment 
programs and clinical trials, we are confident of being able to recruit participants for the FGs. For 
the  FGs  with  healthcare  providers,  IRB-approved  flyers  containing  a  
toll-free  number  will  be 
posted in the offices of all five HIV clinics in the Ryan White Consortium. Providers from all sites 
have been successfully recruited and participated in previous FGs. We will also recruit through 
announcements in the electronic newsletter “Did You Know?” – an electronic newsletter managed 
by Karina Danvers, Director of the New England AIDS Education and Training Center - Local 
Performance Site - that is disseminated regularly to New Haven-area clinics. 
 
Aim 2 (Pilot Feasibility Study): Similar to the recruitment procedure for the FGs, IRB-approved 
flyers containing a toll-free number will be posted in numerous venues such as community SAT 
centers and HIV care clinics. Centers that have collaborated with us before and have been prime 
sites of recruitment include the Nathan Hale Clinic, Haelen Center, Hill Health Center, Central 
Medical Unit, Fair Haven Clinic, most of which are included in the Ryan White consortium. Due 
to  our  continued  presence  in  New  Haven  through  the  implementation  of  several  treatment 
programs and clinical trials, we are confident of being able to recruit participants for the pilot RCT. 
If enrollment is insufficient, we will post an announcement in “Did You Know?” – an electronic 
newsletter  managed  by  Karina  Danvers,  Director  of  the  New  England  AIDS  Education  and 
Training  Center - Local  Performance  Site - that  
is  disseminated  regularly  
to  New  Haven-area 
clinics. This will help us reach all the local area HIV clinics that can refer potential participants to 
our study.  
 
In addition to the above-mentioned recruitment sources, we will also be able to recruit from the 
Community  Health  Care  Van  
(CHCV).  The  CHCV,  a  36-foot  van  
is  equipped  with  
two  exam 
rooms,  a  counseling/phlebotomy  room  and  a  waiting  area.  Partial  support  from  NIDA  (R01-
DA10186) has enabled the CHCV project to expand service delivery and to reach a number of 
goals  which  improve  the  health  care  of  out-of-treatment  drug  users.  The  program  currently 
operates five days (and some evenings) a week in five underserved neighborhoods in New Haven. 
The  CHCV  
is  staffed  by  a  full-time  clinical  coordinator,  a  drug  
treatment  coordinator,  a  case 

Page 37 of 56 
 
manager, HIV counselors, social workers, mental health workers, clinicians from several hospitals 
and  community  health  care  centers  and  a  dedicated  driver/outreach  worker.  The  staff  has 
developed strategic liaisons with patients and providers throughout the community and is capable 
of connecting researchers with potential HIV-infected patients with co-occurring substance abuse 
issues. 
 
For the fourth arm, we will be asking the participants to provide us with three names of people in 
their social network, who has a phone and are willing to send them weekly text reminder to take 
their medication. Out of the three people, one person will be chosen by the RA to be the social 
designee. The RA will be contacting all three social designees via phone and upon verbal consent, 
the social designee will be provided information about the study and their role, and reminded to 
send text messages to the participants on the weekly basis. 
 
  
 
4. Screening Procedures 
a. Will email or telephone correspondence 
be used to screen potential subjects for eligibility 
prior to the potential subject coming to the research office?  Yes  
 No 
b.  If yes, identify below all health information to be collected as part of screening and check 
off any of the following HIPAA identifiers to be collected and retained by the research 
team during this screening process.  
 
HEALTH INFORMATION TO BE COLLECTED: 
 
 
 

Page 38 of 56 
 

Page 39 of 56 
 
 
9. Process of Consent/Assent: Describe the setting and conditions under which consent/assent will be 
obtained,  including  parental  permission  or  surrogate  permission  and  the  steps  taken  to  ensure 
subjects’ independent decision-making.  
 
Aim 1 (Focus Groups): Yale IRB-approved fliers will be used to help with recruitment for FGs 
with cocaine-using individuals and the drug treatment counselors will also assist in recruitment of 
participants. For  
the  FGs  with  healthcare  providers,  
IRB-approved  
flyers  containing  a  
toll-free 
number will be posted in the offices of all five HIV clinics in the Ryan White Consortium. When 
recruiting participants from venues, the participants will be briefly told about the FG and if they 
want to learn more about it, recruiters will hand out a contact information card to call into the study 
site.  No information will be collected from them at this time so they may choose to not to call into 
the site or if they do call in and want to come in for consenting, information is still not collected 
and they may decline to come in.  During the consent process, they will be read the consent form 
verbatim and will be asked if they would like to participate in the study or not.  They will also be 
able to decline or take more time to think about it.  If they verbally consent, another appointment 
will be scheduled for the participant to come in and participate in the focus group.   
 
Aim 2 (Pilot Feasibility Study): Yale IRB-approved fliers will be used to help with recruitment 
for the RCT and the drug treatment counselors will also assist in recruitment of participants. When 
recruiting participants from venues, participants will be briefly told about the study and if they 
want to learn more about it, recruiters will hand out a contact information card to call into the study 
site.  No information will be collected from them at this time so they may choose to not to call into 
the site or if they do call in and want to come in for consenting, information is still not collected 
and they may decline to come in.  Participants will be provided an informed consent form that will 
be approved through the Yale University School of Medicine Institutional Review Board (IRB). 
The participant will be read the consent form verbatim and will be asked if they would like to 
participate in the study or not.  The consent form will outline the agreement to participate in this 
research study. Participants will indicate consent by signing and dating the informed consent form. 
All  patients  will  be  reminded  that  their  refusal  to  participate  will  not  negatively  affect  their 
relationship with Yale University, local SAT or hospital facilities, their ability to continue in drug 
treatment, or their ability to obtain medical services from area clinics in the future. They will also 
be able to decline or take more time to think about it.  If they agree, they will be asked to sign the 
consent form. They may choose to withdraw from the study at any point. 
 
In  addition,  
the  
following  process  of  consent  
is  going  
to  be  
followed  
for  
the  designated  social 
network member for the fourth arm intervention (TRIDENT): a) after randomized to the 4th arm, 
the RAs and/or the Project Coordinator will ask the participant to call his/her designated social 
network member, b) the participant will explain the study details from an information sheet to the 
designee. At this stage the RAs and/or the Project Coordinator will also help in explaining the role 

Page 40 of 56 
 
of  
the  designee  
in  
the  
intervention,  c)  We  will  obtain  a  verbal  consent  from  
the  designees  as 
minimal  risk  
is  
involved.  The  risk is  minimal  for  designees  because:  a)  
the  designees  are  not 
answering any questions, b) they are not completing any surveys at the study sites, c) they will use 
their own phone to send text messages to the participant, d) the data from the messages will be 
downloaded from the patient’s phone and not from the designee’s phone, and e) after obtaining 
the verbal consent, the designee will be given an unique ID and their name or phone number will 
not be used.  
 
 
10. Evaluation  of  Subject(s)  Capacity  to  Provide  Informed  Consent/Assent: Indicate  how  the 
personnel obtaining consent will assess the potential subject’s ability and capacity to consent to the 
research being proposed.  
 
The  study  
interviewers  are  
trained  
in  
interviewing  and  will  assess  
the  subject’s  understanding 
through verbal responses and non-verbal cues. Interviewers will ask open ended questions while 
introducing the details of the study to the subject such as “Can you tell me what you understood 
from our discussion?” or “What should you do if you want to stop participating in this study?” and 
will  use  IRB  approved  consent  forms  during  informed  consent  procedure.  If  the  interviewer 
determines that the subject does not fully comprehend the study purpose and his or her role as a 
participant, the subject will not be consented and will not be eligible for the study. 
 
11. Documentation  of  Consent/Assent: Specify  the  documents  that  will  be  used  during  the 
consent/assent process. Copies of all documents should be appended to the protocol, in the same 
format that they will be given to subjects.  
 
Aim 1 (Focus Groups): No signed consent forms will be required for the focus group participants 
since  signatures  would  be  the  only  identifiers.  An  IRB-approved  consent  form  will  be  read 
verbatim and assent will be given verbally. Additionally, a copy of the consent form will be given 
to the participants. 
 
Aim 2 (Pilot Feasibility Study): A compound consent and authorization form will be used 
(attached in this application).  
 
No signed consent forms will be required for the designated social network members, involved in 
the 4
th arm of Aim 2, since their health and personal identifiers are not used in the study. An IRB-
approved information sheet will be read verbatim and assent will be given verbally. A unique ID 
will be provided for the designee and their names will not be used. 
 
 
12. Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for research 
involving non-English speaking subjects. If enrollment of these subjects is anticipated, translated 
copies of all consent materials must be submitted for approval prior to use.  
 
All  consent  forms,  information  sheets  and  study  documents  will  be  available  in  English  and 
Spanish. Our team consists of individuals who are bi-lingual/bi-cultural in Spanish and English. 
 

Page 41 of 56 
 
 
12(a) As a limited alternative to the above requirement, will you use the short form* for consenting 
process  if  you  unexpectedly  encounter  a  non-English  speaking  individual  interested  in  study 
participation and the translation of the long form is not possible prior to intended enrollment?  
YES ☐  NO ☒ 
 
Note* If more than 2 study participants are enrolled using a short form translated into the same 
language, then the full consent form should be translated into that language for use the next time 
a subject speaking that language is to be enrolled. 
 
Several  translated  short  form  templates  are  found  on  our  website 
at:  http://www.yale.edu/hrpp/forms-templates/biomedical.html. If 
the translation of the short form 
is not available on our website, then the translated short form needs to be submitted to the IRB 
office for approval via amendment prior to enrolling the subject. Please review the guidance and 
presentation on use of the short form available on the HRPP website. 
 
If  using  a  short  
form  without  a  translated  HIPAA  Research  Authorization  Form,  please 
request a HIPAA waiver in the section above.  
 

Page 42 of 56 
 

Page 43 of 56 
 
SECTION VIII: PROTECTION OF RESEARCH SUBJECTS 
 
    Confidentiality & Security of Data: 
a.    What protected health information (medical information along with the HIPAA identifiers) 
about subjects will be collected and used for the research?    
        
Private  identifiable  data  about  study  participants  including  their  names,  age,  sex,  ethnicity, 
addresses, phone numbers and other contact information, photos, dates of birth will be collected. 
Names  and  phone numbers  will  be  collected  from  social  designee for  the  fourth  arm. All 
confidential information (study instruments etc.) will be recorded with study participant number 
only, maintained in locked cabinets within our offices at the Yale University AIDS Program and 
will  only  be available  to  be  opened  by  the  Data  Manager,  Project  Manager  or  the  Principal 
Investigator.  
 
b. How will the research data be collected, recorded and stored?  
 
Aim  1  (Focus  Groups): FG  guides  will  be  prepared  
that  detail  
the  conduct  during  and  after  
the 
interview,  
including  not  using  names,  not  discussing  specific  
illegal  activities,  and  maintaining  
the 
confidentiality
 of focus group participants. Materials will consist of interviews with the participants that 
have been described previously
 that will be audio-recorded and then transcribed. The audio files from 
all  of  the  FGs  will  be  sent  to  a  licensed  professional  transcription  service  using  secure  and 
encrypted transfer systems. 
 
Aim 2 (Pilot Feasibility Study): The research materials of interest in this study include structured 
questionnaire data (primarily using standardized and validated measures), laboratory data obtained 
at Quest Diagnostics laboratories, chart review, and biological measures obtained at research sites 
including urinary toxicology screens, data obtained through participants sending pictures of blister 
packs, and survey data obtained through the smartphone app-based survey. All such materials and 
questionnaire data (excluding laboratory data) will be specifically obtained for research purposes.  
 
Data Sources: 
 
1. Structured Interviews: Structured interviews will include: (1) demographics; (2) health status, 
including past medical history and current medications; (3) depressive symptoms using the CES-
D;136 (4)  standardized  measures  of  drug  use,  
including  determination  of  DSM-V  criteria122 for 
severity  of  cocaine  use; (5)  Addiction  Severity  Index  (ASI)-Lite  to  assess  cocaine  use, 
polysubstance use and severity on HIV outcomes;137 (6) ART adherence using the Smart Pill Box 
, Visual Analog Scale (VAS) and brief adherence scale;
126,127 (8) change in cocaine use using the 
Timeline Follow-Back (TLFB);128 (9) AUDIT-C to assess alcohol use;129 (10) health literacy;
130 
(11)  social  support;
131 (12)  
trust  
in  physicians;
132 (13)  acceptance  of  smartphones;
133 and  (14) 
perceived source credibility134, , (15) neighborhood effects using the Activity Space questionnaire, 
and (16) egocentric social network inventory to understand support and risk networks.  
 

Page 44 of 56 
 
2. Photos  of  blister  pack:  We  will  be  asking  participants  
to  
text  
the  
image  of  
the  medication 
blister pack every week. This method will be used to count the pills they have taken in the week, 
and hence, adherence will be determined using this source. 
 
3. Smart phone app survey: During the intervention period, a smartphone app built on the open-
source CommCare platform (powered by Dimagi, Inc.) will be used to collect weekly data from  
participants. The weekly survey data will be stored on HIPAA-compliant CommCare servers and  
transferred to Yale-secured and encrypted computers periodically. As per Yale HIPAA Privacy 
rules,  Business  Associates  Agreements  (BAA)  will be  established  between  vendors  such  as 
Dimagi, Inc., which will store the Protected Health Information (PHI) of the participants. 
 
4. Laboratory  Measurements:  We  have  a  prearranged  system  for  phlebotomy,  reporting  of 
results  and  storing  of  specimens  at -70C through  Quest  Diagnostics.  Because  tests  are  not 
experiment, all results (HIV VL, CD4 and genotypic  analyses)  will be sent to the participants’ 
providers, including HIV-1 RNA testing (Amplicor 1.5, range 20 to 750,000 copies/mL) and CD4 
lymphocyte count at baseline, and end of intervention (12 weeks) . HIV genotypic mutations will 
be assessed at baseline and at 16 weeks (if VL>500 copies/mL).  
33 
5. Chart Review: During consenting procedures, a medical release of information (ROI) will be 
obtained to allow research  
staff  
to  
review  medical  
records  at  drug  and  alcohol  
treatment,  
local 
hospitals, pharmacies and HIV care sites. Medical records will be retrieved to confirm self-reports 
of healthcare utilization, HIV status, documented medical history and prescribed medications. The 
ROI  will  allow  us  
to  communicate  with  medical,  psychiatric  and  drug  
treatment  providers  
to 
inform them that their patient will be in an adherence study, to alert research staff of any changes 
in ART medication, and in case of the participant becoming acutely ill. 
 
6.Text messages/SMS download: A total of 4 text messages (one text message per week) sent 
by the designated social network member to the participant will be downloaded. The text messages 
will be downloaded by a RA from the participant’s cell phone after receiving consent from the 
participants All phones are will be password protected and encrypted. 
 
Storage of Data: All information will be stored in password-protected computers with double-
password protection for opening specified files. The computers in our research facility have been 
encrypted in accordance to HIPAA guidelines. NetIDs of all research personnel will be provided 
to the IRB and to the IT Services for verification for encryption. If new members are added to 
the research team, and if personal computers were to be used for accessing PHI, all such 
machines will need to be Yale encrypted and verified by the IT service office. For the duration of 
the pilot study, medication adherence data obtained through the use of smart pill boxes will be 
stored in a secure, encrypted cloud system owned by TowerView Health® Corp. This data will be 
erased once it has been transferred securely to our research computers. Similarly, CommCare 
survey data will be saved on a central server owned by Dimagi, Inc. until it has been securely 
transferred to our computers. In addition, data collected from the Activity Space, and Social 
Network Questionnaire will be saved on Microsoft’s cloud computing platform called University 
of Connecticut’s (UConn) instance of Microsoft Azure, which is also compliant with UConn’s 
and similar to Yale’s HIPAA policy. UConn’s UITS offers the use of a HIPAA approved 

Page 45 of 56 
 
instance of Microsoft Azure as a service. A BAA from UConn will be provided to Yale IRB. We 
are using UConn’s Azure service for the following reasons: 
- Dr. Ghosh, a Co-PI/collaborator of this study, and her team from UConn have built an 
android based survey app using PowerApps, which is connected to UConn’s Azure 
platform.  
- The data that will be collected using this survey will be stored on UConn’s Azure SQL 
database  
- Only Dr. Ghosh has access to that database and uses her UConn’s administrator netID to 
login.  
. Text  download/  SMS  
from  participants  
(fourth  arm)  will  
initially  be  stored  
in  a  secure Yale 
Dropbox which will protected by unique password available only to the project staff.All research 
data  will  be  stored  in  the  double-locked  research  offices  within  the  Clinical  and  Community 
Research Program within the Yale University AIDS Program. Client level data will be stored with 
the  research  study  number  and  without  any  unique  
identifiers.  
  All  
identifiers  
that  
link  study 
number to study subject will be housed in PGP encrypted, password-protected computers available 
only  to  the  Data  Manager/Statistician,  Project  Director  and  the  Principal  Investigator.  All 
computers used for study purposes have been PGP encrypted to meet all HIPAA requirements. 
During  the  20  years  of  Dr.  Altice’s  research  experience,  there  has  never  been  a  breach  in 
confidential data.  The data will be stored in the manner noted above for at least seven years after 
completion of the study. All confidential information (study instruments, pharmacy record, etc.) 
will be recorded with the study participant number only and maintained in locked cabinets within 
our offices at the Yale University AIDS Program and will only be available to be opened by the 
Data Manager, Project Director or the Principal Investigator. These data will be analyzed so that 
the  findings  can  contribute  to  scientific  literature that  could  be  used  to  develop  effective 
interventions for HIV+ cocaine users. 
 All files will be stored in locked cabinets in a locked facility. 
 
c.    How will the digital data be stored? 
 CD  
 DVD  
 Flash Drive   Portable Hard    
       Drive  
 Secured Server   Laptop Computer   Desktop Computer   Other 
 
d.    What methods and procedures will be used to safeguard the confidentiality and security of     
the identifiable study data and the storage media indicated above during and after the subject’s 
participation in the study? 
 
All  information  will  be  stored  in  password-protected  computers  with  double-password 
protection  for  opening  specified  files.  The  computers  in  our  research  facility  have  been 
encrypted in accordance to HIPAA guidelines. For new personnel added to the team or use of 
personal  computers  will  be  encrypted  by  the  ITS.  For  the  duration  of  the  pilot  study, 
medication adherence data obtained through the use of smart pill boxes will be stored in a 
secure, encrypted cloud system owned by TowerView Health® Corp. This data will be erased 
once it has been transferred securely to our research computers. Similarly, the smart phone 
app survey data will be saved on a central server owned by HIPPA-compliant CommCare and 
UConn Microsoft Azure Cloud until it has been securely transferred to our computers. All 
research  data  will  be  stored  
in  
the  double-locked  research offices  within  
the  Clinical  and 
Community Research Program within the Yale University AIDS Program. Client level data 
will  be  stored  with  the  research  study  number  and  without  any  unique  identifiers.    All 
identifiers that link study number to study subject will be housed in PGP encrypted, password-

Page 46 of 56 
 
protected computers available only to the Data Manager/Statistician, Project Director and the 
Principal Investigator. 
Do all portable devices contain encryption software? 
 Yes   
 No 
         If no, see http://hipaa.yale.edu/guidance/policy.html 
  
e. What will be done with the data when the research is completed? Are there plans to destroy 
the identifiable data? If yes, describe how, by whom and when identifiers will be destroyed. 
If no, describe how the data and/or identifiers will be secured. 
 
The data will be stored in the manner noted above for at least seven years after completion 
of  the  study.  All  confidential  information  (study  instruments,  pharmacy  record,  etc.) , 
collected  
in  paper  format,  willbe  recorded  with  
the  study  participant  number  only  and 
maintained in locked cabinets within our offices at the Yale University AIDS Program and 
will only be available to be opened by the Data Manager, Project Director or the Principal 
Investigator. Data collected from online platforms such as CommCare and saved in soft 
copy  
format  will  be  
stored  
in  
the  Yale  
shared  
folder  
(J  drive).  Only  
the  Data  Manager, 
Project Director, the PI, and Co-Is, with valid Yale NetIDs and special permission from 
the  Yale  administrator,  will  have  access  to  this  data. With  the  guidance  of  the  Yale 
University  Information  Technology  Services  and  HIPAA  departments,  data  will  be 
destroyed  to  ensure  proper  methodology  is  used  when  shredding  files  and  deleting 
computer files. In addition, all the text messages will be "shredded" using PGP Desktop 
Shred which removes all traces of the file on the computer. 
 
f.   Who will have access to the protected health information (such as the research sponsor, the  
investigator, the research staff, all research monitors, FDA, Yale Cancer Center Data and Safety 
Monitoring Committee (DSMC), SSC, etc.)? (please distinguish between PHI and de-identified 
data)  
 
The Principal Investigator, Co-Investigator, and research staff will have access to the data. 
 
Dr. Yerina Ranjit, Assistant Professor in the Department of Communication at the University of 
Missouri Columbia, will also have access to the data. University of Missouri, Columbia is a site 
that will be relying on Yale IRB review for the limited engagement of Dr. Ranjit for obtaining 
identifiable data. 
 
g.   If appropriate, has a Certificate of Confidentiality been obtained? 
 
Yes, the Certificate of Confidentiality from National Institute on Drug Abuse (NIDA) has been 
obtained on May 22, 2017. 
 
h.   Are any of the study procedures likely to  yield information subject to mandatory reporting   
requirements? (e.g. HIV testing – reporting of communicable diseases; parent interview -incidents 
of child abuse, elderly abuse, etc.). Please verify to whom such instances will need to be reported.  
 
Attempts to harm oneself or someone else will be reported to the proper authorities.  
 

Page 47 of 56 
 

Page 48 of 56 
 
 
 
References: 
 
1. 
Hammond  R,  Harry  TC.  Efficacy  of  antiretroviral  therapy  in  Africa:  effect  on 
immunological and virological outcome measures -- a meta-analysis. Int J STD AIDS. May 
2008;19(5):291-296. 
2. 
Bartlett  JA,  Fath  MJ,  Demasi  R,  et  al.  An  updated systematic  overview  of  triple 
combination  therapy  in  antiretroviral-naive  HIV-infected  adults. Aids. Oct  24 
2006;20(16):2051-2064. 
3. 
Attia S, Egger M, Muller M, Zwahlen M, Low N. Sexual transmission of HIV according 
to viral load and antiretroviral therapy: Systematic review and meta-analysis. AIDS. Jul 17 
2009;23(11):1397-1404. 
4. 
Phillips AN, Sabin C, Pillay D, Lundgren JD. HIV in the UK 1980-2006: reconstruction 
using a model of HIV infection and the effect of antiretroviral therapy. HIV medicine. Nov 
2007;8(8):536-546. 
5. 
Marks  G,  Crepaz  N,  Janssen  RS.  Estimating  sexual  
transmission  of  HIV  
from  persons 
aware  and  unaware  that  they  are  infected  with  the  virus  in  the  USA. AIDS. Jun  26 
2006;20(10):1447-1450. 
6. 
Velasco-Hernandez  JX,  Gershengorn  HB,  Blower  SM.  Could  widespread  use  of 
combination antiretroviral therapy eradicate HIV epidemics? Lancet Infectious Diseases. 
2002;2(8):487-493. 

Page 49 of 56 
 
7. 
Montaner  JS,  Hogg  R,  Wood  E,  et  al.  The  case  for  expanding  access  
to  highly  active 
antiretroviral  therapy  to  curb  the  growth  of  the  HIV  epidemic. LANCET. 
2006;368(9534):531-536. 
8. 
Lima  VD,  Johnston  K,  Hogg  RS,  et  al.  Expanded  access  
to  highly  active  antiretroviral 
therapy: A potentially powerful strategy to curb the growth of the HIV epidemic. Journal 
of Infectious Diseases. 2008;198(1):59-67. 
9. 
Cohen  MS,  Chen  YQ,  McCauley  M,  et  al.  Prevention  of  HIV-1  Infection  with  Early 
Antiretroviral Therapy. New England Journal of Medicine. 2011;365(6):493-505. 
10. 
Gardner  EM,  McLees  MP,  Steiner  JF,  Del  Rio  C,  Burman  WJ.  The  spectrum  of 
engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV 
infection. Clin Infect Dis. Mar 15 2011;52(6):793-800. 
11. 
Logan  TK,  Leukefeld  C.  Sexual  and  drug  use  behaviors  among  female  crack  users:  A 
multi-site sample. Drug Alcohol Depend. Mar 1 2000;58(3):237-245. 
12. 
Wechsberg WM, Golin C, El-Bassel N, Hopkins J, Zule W. Current interventions to reduce 
sexual  risk  behaviors  and  crack  cocaine  use  among  HIV-infected  individuals. Curr 
HIV/AIDS Rep. Dec 2012;9(4):385-393. 
13. 
Edlin BR, Irwin KL, Faruque S, et al. Intersecting epidemics--crack cocaine use and HIV 
infection among inner-city  young adults. Multicenter Crack Cocaine and  HIV  
Infection 
Study Team. N Engl J Med. Nov 24 1994;331(21):1422-1427. 
14. 
Wilson  T,  DeHovitz JA.  STDs,  HIV,  and  crack  cocaine:  A  
review. AIDS  Patient  Care 
STDS. Apr 1997;11(2):62-66. 
15. 
Marx R, Aral SO, Rolfs RT, Sterk CE, Kahn JG. Crack, sex, and STD. Sexually transmitted 
diseases. Apr-Jun 1991;18(2):92-101. 
16. 
Azar M, Springer SA, Meyer JP, Altice FL. A systematic review of the impact of alcohol 
use disorders on HIV treatment outcomes, adherence to antiretroviral therapy and health 
care utilization. Drug Alcohol Depend. 2011;112(3):15. 
17. 
Altice  FL,  Kamarulzaman  A,  Soriano  VV,  Schechter  M,  Friedland  GH.  Treatment  of 
medical,  psychiatric,  and  
substance-use comorbidities in people infected  with HIV who 
use drugs. The Lancet. 2010;376(9738):367-387. 
18. 
Bae JW, Guyer W, Grimm K, Altice FL. Medication persistence in the treatment of HIV 
infection: A review of the literature and implications for future clinical care and research. 
AIDS. Jan 28 2011;25(3):279-290. 
19. 
Ing EC, Bae JW, Maru DS, Altice FL. Medication Persistence of HIV-infected Drug Users 
on Directly Administered Antiretroviral Therapy. AIDS Behav. Nov 22 2011. 
20.  Anand P, Springer SA, Copenhaver MM, Altice FL. Neurocognitive impairment and HIV 
risk factors: a reciprocal relationship. AIDS Behav. Dec 2010;14(6):1213-1226. 
21. 
Lucas GM, Cheever LW, Chaisson RE, Moore RD. Detrimental effects of continued illicit 
drug  use  on  the  treatment  of  HIV-1  infection. J  Acquir  Immune  Defic  Syndr. Jul  1 
2001;27(3):251-259. 
22. 
Sharpe TT, Lee LM, Nakashima AK, Elam-Evans LD, Fleming PL. Crack cocaine use and 
adherence  to  antiretroviral  treatment  among  HIV-infected  black  women. Journal  of 
community health. Apr 2004;29(2):117-127. 
23. 
Ingersoll K. The impact of psychiatric symptoms, drug use, and medication regimen on 
non-adherence to HIV treatment. AIDS Care. Feb 2004;16(2):199-211. 

Page 50 of 56 
 
24.  
Moss AR, Hahn JA, Perry S, et al. Adherence to highly active antiretroviral therapy in the 
homeless  population  in  San  Francisco:  a  prospective  study. Clin  Infect  Dis. Oct  15 
2004;39(8):1190-1198. 
25. 
Tucker JS, Burnam MA, Sherbourne CD, Kung FY, Gifford AL. Substance use and mental 
health correlates of nonadherence to antiretroviral medications in a sample of patients with 
human  immunodeficiency  virus  infection. The  American  journal  of  medicine. May 
2003;114(7):573-580. 
26. 
Arnsten JH, Demas PA, Grant RW, et al. Impact of active drug use on antiretroviral therapy 
adherence  and  viral  suppression  in  HIV-infected  drug  users. J  Gen  Intern  Med. May 
2002;17(5):377-381. 
27. 
Crisp BR, Williams M, Timpson S, Ross MW.  Medication compliance  and satisfaction 
with treatment for HIV disease in a sample of African-American crack cocaine smokers. 
AIDS Behav. Jun 2004;8(2):199-206. 
28. 
Webber MP, Schoenbaum EE, Gourevitch MN, Buono D, Klein RS. A prospective study 
of HIV disease progression in female and male drug users. AIDS. Feb 4 1999;13(2):257-
262. 
29. 
Chander G, Himelhoch S, Moore RD. Substance abuse and psychiatric disorders in HIV-
positive  patients:  Epidemiology  and  impact  on  antiretroviral  therapy. Drugs. 
2006;66(6):769-789. 
30. 
Cook  JA,  Burke-Miller  JK,  Cohen  MH,  et  al.  Crack  cocaine, disease  progression,  and 
mortality  in  a  multicenter  cohort  of  HIV-1  positive  women. AIDS. Jul  11 
2008;22(11):1355-1363. 
31. 
Kuo I, Golin CE, Wang J, et al. Substance use patterns and factors associated with changes 
over  
time  
in  a  cohort  of  heterosexual  women  at  
risk  
for  HIV  acquisition  
in  
the  United 
States. Drug Alcohol Depend. Jun 1 2014;139:93-99. 
32. 
Keen L, 2nd, Khan M, Clifford L, Harrell PT, Latimer WW. Injection and non-injection 
drug use and infectious disease in Baltimore City: differences by race. Addict Behav. Sep 
2014;39(9):1325-1328. 
33. 
Tiwari  S,  Nair  MP,  Saxena  SK.  Latest  trends  in  drugs  of  abuse - HIV  infection  and 
neuroAIDS. Future virology. Feb 2013;8(2):121-127. 
34. 
Mimiaga  MJ,  Reisner  SL,  Grasso  C,  et  al.  Substance  use  among  HIV-infected patients 
engaged in primary care in the United States: findings from the Centers for AIDS Research 
Network  of  Integrated  Clinical  Systems  cohort. Am  J  Public  Health. Aug 
2013;103(8):1457-1467. 
35. 
Binford  MC,  Kahana  SY,  Altice  FL.  A  systematic  review  of  antiretroviral  adherence 
interventions  for  HIV-infected  people  who  use  drugs. Curr  HIV/AIDS  Rep. Dec 
2012;9(4):287-312. 
36. 
Thompson MA, Mugavero MJ, Amico KR, et al. Guidelines for improving entry into and 
retention  in  care  and  antiretroviral  adherence  for  persons  with  HIV:  evidence-based 
recommendations  
from  an  
International  Association  of  Physicians  
in  AIDS  Care  panel. 
Ann Intern Med. Jun 05 2012;156(11):817-833, W-284, W-285, W-286, W-287, W-288, 
W-289, W-290, W-291, W-292, W-293, W-294. 
37. 
Boyer E, Smelson D, Fletcher R, Ziedonis D, Picard R. Wireless technologies, ubiquitous 
computing and mobile health: Application to drug abuse treatment and compliance with 
HIV therapies. Journal of Medical Toxicology. 2010;6(2):212-216. 

Page 51 of 56 
 
38. 
Lester RT, Gelmon L, Plummer FA. Cell phones: Tightening the communication gap in 
resource-limited antiretroviral programmes? AIDS. 11 2006;20(17):2242-2244. 
39. 
Atun R, Sittampalam S. A review of the characteristics and benefits of SMS in delivering 
healthcare. Berkshire, UK: Vodafone;2006. 
40. 
Karanja S, Mbuagbaw L, Ritvo P, et al. A workshop report on HIV mHealth synergy and 
strategy meeting to review emerging evidence-based mHealth interventions and develop a 
framework  for  scale-up  of  these  interventions. The  Pan  African  medical journal. 
2011;10:37. 
41. 
Leach-Lemens  C.  Using  mobile  phones  in  HIV  care  and  prevention. HIV  &  AIDS 
Treatment in Practice. 2009;137:7. 
42. 
Fairley CK, Levy R, Rayner CR, et al. Randomized trial of an adherence programme for 
clients with HIV. Int J STD AIDS. December 1, 2003 2003;14(12):805-809. 
43. 
Simoni J, Wiebe J, Sauceda J, et al. A Preliminary RCT of CBT-AD for Adherence and 
Depression  Among  HIV-Positive  Latinos  on  
the  U.S.-Mexico  Border:  The  Nuevo  Día 
Study. AIDS and Behavior. 2013/10/01 2013;17(8):2816-2829. 
44. 
Hardy H, Kumar V, Doros G, et al. Randomized controlled trial of a personalized cellular 
phone reminder system to enhance adherence to antiretroviral therapy. AIDS Patient Care 
STDS. Mar 2011;25(3):153-161. 
45. 
Zurovac  D,  Sudoi  RK,  Akhwale  WS, et  al.  The  effect  of  mobile  phone  text-message 
reminders on Kenyan health workers
' adherence to malaria treatment guidelines: a cluster 
randomised trial. The Lancet. 2011;378(9793):795-803. 
46. 
Harris LT, Lehavot K, Huh D, et al. Two-way text messaging for health behavior change 
among  human  immunodeficiency  virus-positive  individuals. Telemed  J  E  Health. Dec 
2010;16(10):1024-1029. 
47. 
Ryan  D, Pinnock H,  Lee AJ, et al.  The  CYMPLA trial. Mobile phone-based  
structured 
intervention to achieve asthma control in patients with uncontrolled persistent asthma: A 
pragmatic randomised controlled trial. Prim Care Respir J. Dec 2009;18(4):343-345. 
48. 
Lester R, Karanja S. Mobile phones: exceptional tools for HIV/AIDS, health, and crisis 
management. The Lancet Infectious Diseases. 2008;8(12):738-739. 
49. 
Hanauer  DA,  Wentzell  K,  Laffel  N,  Laffel  LM.  Computerized  Automated  Reminder 
Diabetes  System  (CARDS):  E-mail  and  SMS  cell  phone  text  messaging  reminders  to 
support diabetes management. Diabetes Technol Ther. Feb 2009;11(2):99-106. 
50. 
Fjeldsoe BS, Marshall AL, Miller YD. Behavior change interventions delivered by mobile 
telephone  short-message  service. American  Journal  of  Preventive  Medicine. 02 
2009;36(2):165-173. 
51. 
Kim  HS,  Kim  NC,  Ahn  SH.  Impact  of  a  nurse  short  message  service  
intervention  for 
patients with diabetes. J Nurs Care Qual. Jul-Sep 2006;21(3):266-271. 
52. 
Upadhyay N, Kokalj Kokot M, Car J, Svab I. Mobile phone messaging - A telemedicine 
for people with diabetes mellitus. Cochrane Database of Systematic Reviews. 2007. 
53. 
Kim HS, Jeong HS. A nurse short message service by cellular phone in type-2 diabetic 
patients for six months. J Clin Nurs. Jun 2007;16(6):1082-1087. 
54. 
Fraser HS, Allen C, Bailey C, Douglas G, Shin S, Blaya J. Information systems for patient 
follow-up and chronic management of HIV and tuberculosis: a life-saving technology in 
resource-poor areas. J Med Internet Res. 2007;9(4):e29. 

Page 52 of 56 
 
55. 
Hoffman  JA,  Cunningham  JR,  Suleh  AJ,  et  al.  Mobile  direct  observation  
treatment  
for 
Tuberculosis patients: A technical feasibility pilot using mobile phones in Nairobi, Kenya. 
American Journal of Preventive Medicine. 2010;39(1):78-80. 
56. 
Person AK, Blain ML, Jiang H, Rasmussen PW, Stout JE. Text messaging for enhancement 
of testing and treatment for tuberculosis, human immunodeficiency virus, and syphilis: A 
survey  of  attitudes  toward  cellular  phones  and  healthcare. Telemed  J  E  Health. Apr 
2011;17(3):189-195. 
57. 
Asiimwe C, Gelvin D, Lee EJ, et al.  Use  of an innovative, affordable, and open-source 
short  message  service–based  tool  to  monitor  Malaria  in  remote  areas  of  Uganda. The 
American Journal of Tropical Medicine and Hygiene. July 1, 2011 2011;85(1):26-33. 
58. 
Meankaew  P,  Kaewkungwal  J,  Khamsiriwatchara  A,  Khunthong  P,  Singhasivanon  P, 
Satimai  W.  Application  of mobile-technology  for  disease  and  
treatment  monitoring  of 
malaria in the "Better Border Healthcare Programme". Malaria journal. 2010;9:237. 
59. 
Moonen B, Cohen JM. Text messaging to improve adherence to malaria guidelines. The 
Lancet. 2011;378(9793):750-752. 
60. 
Prabhakaran  L,  Chee  WY,  Chua  KC,  Abisheganaden  J,  Wong  WM.  The  use  of  text 
messaging  to  improve  asthma  control:  A  pilot  study  using  the  mobile  phone  short 
messaging service (SMS). J Telemed Telecare. Jul 2010;16(5):286-290. 
61. 
Lester  RT,  Kariri  A. Mobilizing  cell  phones  to  improve  antiretroviral  adherence  and 
follow-up in Kenya: A randomized controlled trial in progress. WHO Essential Medicines 
Monitor. 2009;2:Article 1. 
62. 
Lester RT, Ritvo P, Mills EJ, et al. Effects of a mobile phone short message service on 
antiretroviral  
treatment  adherence  
in  Kenya  
(WelTel  Kenya1):  A  
randomised  
trial. The 
Lancet. 2010;376(9755):1838-1845. 
63.  Pop-Eleches  C,  Thirumurthy  H,  Habyarimana  JP,  et  al.  Mobile  phone  technologies 
improve adherence to antiretroviral treatment in a resource-limited setting: A randomized 
controlled trial of text message reminders. AIDS. Mar 27 2011;25(6):825-834. 
64. 
Puccio JA, Belzer M, Olson J, et al. The Use of Cell Phone Reminder Calls for Assisting 
HIV-Infected Adolescents and Young Adults to Adhere to Highly Active Antiretroviral 
Therapy: A Pilot Study. AIDS Patient Care & STDs. 2006;20(6):438-444. 
65. 
Haapala I, Barengo NC, Biggs S, Surakka L, Manninen P. Weight loss by mobile phone: a 
1-year effectiveness study. Public health nutrition. Dec 2009;12(12):2382-2391. 
66. 
Hurling  R,  Catt  M,  De Boni  M,  et  al.  Using  
Internet  and  Mobile  Phone  Technology  
to 
Deliver an Automated Physical Activity Program: Randomized Controlled Trial. Journal 
of Medical Internet Research. 2007;9(2):179-192. 
67. 
Quinn  CC,  Clough  SS,  Minor  JM,  Lender  D,  Okafor  MC,  Gruber-Baldini  A.  WellDoc 
mobile diabetes management randomized controlled trial: change in clinical and behavioral 
outcomes  and  patient  and  physician  satisfaction. Diabetes  Technol  Ther. Jun 
2008;10(3):160-168. 
68. 
Palella FJ, Jr., Delaney KM, Moorman AC, et al. Declining morbidity and mortality among 
patients with advanced human immunodeficiency virus infection. HIV Outpatient Study 
Investigators. N Engl J Med. Mar 26 1998;338(13):853-860. 
69. 
Simoni JM, Frick PA, Pantalone DW, Turner BJ. Antiretroviral adherence interventions: a 
review of current literature and ongoing studies. Top HIV Med. Nov-Dec 2003;11(6):185-
198. 

Page 53 of 56 
 
70. 
Altice  FL,  Friedland  GH.  The  era  of  adherence  to  HIV  therapy. Ann  Intern  Med. 
1998;129(6):503-505. 
71. 
Ing EC, Bae JW, Maru DS, Altice FL. Medication persistence of HIV-infected drug users 
on directly administered antiretroviral therapy. AIDS Behav. Jan 2013;17(1):113-121. 
72. 
Lewden C. Time with CD4 cell count above 500 cells/mm³ allows HIV-infected men, but 
not women, to reach similar mortality rates to those of the general population: A seven-
year  analysis. 17th  Conference  on  Retroviruses  and  Opportunistic  Infections.  San 
Francisco, CA, USA2010. 
73. 
Mocroft  A,  Madge  S,  Johnson  AM,  et  al.  A  comparison  of  exposure  groups  in  the 
EuroSIDA  study:  starting  highly  active  antiretroviral  therapy  (HAART),  response  to 
HAART, and survival. J Acquir Immune Defic Syndr. Dec 1 1999;22(4):369-378. 
74. 
Westergaard RP, Ambrose BK, Mehta SH, Kirk GD. Provider and clinic-level correlates 
of deferring antiretroviral therapy for people who inject drugs: a survey of North American 
HIV providers. J Int AIDS Soc. 2012;15(1):10. 
75. 
Malta M, Magnanini MM, Strathdee SA, Bastos FI. Adherence to antiretroviral therapy 
among HIV-infected drug users: a meta-analysis. AIDS Behav. Aug 2010;14(4):731-747. 
76. 
Cunningham CO, Sohler NL, Berg KM, Shapiro S, Heller D. Type of substance use and 
access to HIV-related health care. AIDS Patient Care STDS. Jun 2006;20(6):399-407. 
77. 
Metsch LR, McCoy HV, McCoy CB, Miles CC, Edlin BR, Pereyra M. Use of health care 
services by women who use crack cocaine. Women & health. 1999;30(1):35-51. 
78. 
Metsch  LR,  Pereyra  M,  Brewer  TH.  Use  of  HIV  health  care  
in  HIV-seropositive  crack 
cocaine smokers and other active drug users. J Subst Abuse. 2001;13(1-2):155-167. 
79. 
Grella CE, Anglin MD, Wugalter SE. Patterns and predictors of cocaine and crack use by 
clients in standard and enhanced methadone maintenance treatment. Am J Drug Alcohol 
Abuse. Feb 1997;23(1):15-42. 
80. 
Sohler NL, Wong MD, Cunningham WE, Cabral H, Drainoni ML, Cunningham CO. Type 
and pattern of illicit drug use and access to health care services for HIV-infected people. 
AIDS Patient Care STDS. 2007;21 Suppl 1:S68-76. 
81.  Vlahov D, Galai N, Safaeian M, et al. Effectiveness of highly active antiretroviral therapy 
among injection drug users with late-stage human immunodeficiency virus infection. Am 
J Epidemiol. Jun 1 2005;161(11):999-1012. 
82. 
Lucas GM, Griswold M, Gebo KA, Keruly J, Chaisson RE, Moore RD. Illicit drug use and 
HIV-1 disease progression: a longitudinal study in the era of highly active antiretroviral 
therapy. Am J Epidemiol. Mar 1 2006;163(5):412-420. 
83. 
Springer SA, Chen S, Altice FL. Improved HIV and substance abuse treatment outcomes 
for  released  HIV-infected  prisoners:  the  impact  of  buprenorphine  treatment. J  Urban 
Health. Jul 2010;87(4):592-602. 
84. 
Springer SA, Qiu J, Saber-Tehrani AS, Altice FL. Retention on buprenorphine is associated 
with  high  levels  of  maximal viral  suppression  among  HIV-infected  opioid  dependent 
released prisoners. PLoS One. 2012;7(5):e38335. 
85. 
Altice FL, Mezger JA, Hodges J, et al. Developing a Directly Administered Antiretroviral 
Therapy Intervention for HIV-Infected Drug Users: Implications for Program Replication. 
Clinical Infectious Diseases. 2004;38:S376-S387. 
86. 
Brust JC, Litwin AH, Berg KM, Li X, Heo M, Arnsten JH. Directly observed antiretroviral 
therapy  
in  substance  abusers  
receiving  methadone  maintenance  
therapy  does  not  cause 
increased drug resistance. AIDS Res Hum Retroviruses. May 2011;27(5):535-541. 

Page 54 of 56 
 
87. 
Altice FL, Springer S, Buitrago M, Hunt DP, Friedland GH. Pilot study to enhance HIV 
care using needle exchange-based health services for out-of-treatment injecting drug users. 
J Urban Health. Sep 2003;80(3):416-427. 
88. 
Macalino  GE,  Mitty  JA,  Bazerman  LB,  Singh  K,  McKenzie  M,  Flanigan  T.  Modified 
directly observed therapy for the treatment of HIV-seropositive substance users: lessons 
learned from a pilot study. Clin Infect Dis. Jun 1 2004;38 Suppl 5:S393-397. 
89. 
Mitty  JA,  Macalino  GE,  Bazerman  LB,  et  al.  The  use  of  community-based  modified 
directly  observed  
therapy  for  
the  
treatment  of  HIV-infected  persons. J  Acquir  Immune 
Defic Syndr. Aug 15 2005;39(5):545-550. 
90. 
Smith-Rohrberg Maru D, Bruce RD, Walton M, et al. Initiation, adherence, and retention 
in a randomized controlled trial of Directly Administered Antiretroviral Therapy. AIDS & 
Behavior. 2008;12(1):284-293. 
91. 
Altice  FL,  Kamarulzaman  A,  Soriano  VV,  Schechter  M,  Friedland  GH.  Treatment  of 
medical,  psychiatric,  and  
substance-use comorbidities in people infected  with HIV who 
use drugs. Lancet. 2010;376(9738):59-79. 
92. 
Haddad  MS,  Zelenev  A,  Altice  FL.  Buprenorphine  Maintenance  Treatment  Retention 
Improves  Comprehensive  Preventive  Primary  Care  Outcomes  when  Integrated  into 
Federally-Qualified Health Centers J Subst Abuse Treat. 2014: In Press. 
93. 
Meyer JP, Althoff AL, Altice FL. Optimizing care for HIV-infected people who use drugs: 
evidence-based  approaches  to  overcoming  healthcare  disparities. Clin  Infect  Dis. Nov 
2013;57(9):1309-1317. 
94. 
Morozova O, Dvoryak S, Altice FL. Methadone treatment improves tuberculosis treatment 
among  hospitalized  opioid  dependent  patients  in  Ukraine. Int  J  Drug  Policy. 
2013;24(6):e91-98. 
95.  Schackman  BR,  Leff  JA,  Botsko  M,  et  al.  The  cost  of  integrated  HIV  care  and 
buprenorphine/naloxone  treatment:  results  of  a  cross-site  evaluation. J  Acquir  Immune 
Defic Syndr. 2011;56 Suppl 1:S76-82. 
96. 
Smith-Rohrberg  D,  Mezger  J,  Walton  M,  Bruce  RD,  Altice FL.  Impact  of  enhanced 
services on virologic outcomes in  a directly administered antiretroviral therapy trial for 
HIV-infected drug users. J Acquir Immune Defic Syndr. 2006;43 Suppl 1:S48-53. 
97. 
Sylla L, Bruce RD, Kamarulzaman A, Altice FL. Integration and co-location of HIV/AIDS, 
tuberculosis and drug treatment services. Int J Drug Policy. 2007;18(4):306-312. 
98. 
Weiss L,  Netherland J, Egan JE, et al.  
Integration of buprenorphine/naloxone treatment 
into HIV clinical care: lessons from the BHIVES collaborative. J Acquir Immune  Defic 
Syndr. 2011;56 Suppl 1:S68-75. 
99. 
Feaster  DJ,  Mitrani  VB,  Burns  MJ,  et  al.  A  randomized  controlled  trial  of  Structural 
Ecosystems  Therapy  for  HIV  medication  adherence  and  substance  abuse  relapse 
prevention. Drug Alcohol Depend. Oct 1 2010;111(3):227-234. 
100. Ingersoll KS, Farrell-Carnahan L, Cohen-Filipic J, et al. A pilot randomized clinical trial 
of  
two  medication  adherence  and  drug  use  
interventions  
for  HIV+  crack  cocaine  users. 
Drug Alcohol Depend. Jul 1 2011;116(1-3):177-187. 
101. World Health Organization (WHO). Consolidated guidelines on general HIV care and the 
use of antiretroviral drugs for treating and preventing HIV infection: recommendations for 
a  
public  
health  
approach.  
2013;  
Available: 
www.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf.  .  Accessed  April 
14, 2014. 

Page 55 of 56 
 
102. Lim MSC, Hocking JS, Hellard ME, Aitken CK. SMS STI: A review of the uses of mobile 
phone  text  messaging  in  sexual  health. International  Journal  of  STD  &  AIDS. 05 
2008;19(5):287-290. 
103. Katz DL, Nordwall B. Novel interactive cell-phone technology for health enhancement. 
Journal of diabetes science and technology. Jan 2008;2(1):147-153. 
104. Finitsis  DJ, Pellowski  JA,  Johnson  BT.  Text  message  
intervention  designs  
to  promote 
adherence to antiretroviral therapy (ART): a meta-analysis of randomized controlled trials. 
PLoS One. 2014;9(2):e88166. 
105. Curioso WH, Kurth AE. Access, use and perceptions regarding Internet, cell phones and 
PDAs  as  a  means  
for  health  promotion  
for  people  
living  with  HIV  
in  Peru. BMC  Med 
Inform Decis Mak. 2007;7:24. 
106. Freedman M, Lester K, McNamara C, Milby J, Schumacher J. Cell phones for ecological 
momentary assessment with cocaine-addicted homeless patients in treatment. Journal of 
substance abuse treatment. 2006;30(2):105-111. 
107. Epstein D, Preston K. Daily life hour by  hour,  with and without cocaine: an ecological 
momentary assessment study. Psychopharmacology. 2010;211(2):223-232. 
108. Epstein DH, Willner-Reid J, Vahabzadeh M, Mezghanni M, Lin JL, Preston KL. Real-time 
electronic diary reports of cue exposure and mood in the hours before cocaine and heroin 
craving and use. Arch Gen Psychiatry. Jan 2009;66(1):88-94. 
109. Raes V, De Jong CAJ, De Bacquer D, Broekaert E, De Maeseneer J. The Effect of Using 
Assessment  Instruments  on  Substance-abuse  Outpatients
'  Adherence  to  Treatment:  a 
Multi-centre Randomised Controlled Trial. Bmc Health Services Research. May 2011;11. 
110. Aharonovich  E,  Greenstein  E,  O
'Leary  A,  Johnston  B,  Seol  SG,  Hasin DS.  HealthCall: 
technology-based extension of motivational interviewing to reduce non-injection drug use 
in HIV primary care patients - a pilot study. AIDS Care. 2012;24(12):1461-1469. 
111. Fisher JD, Amico KR, Fisher WA, et al. Computer-based intervention in HIV clinical care 
setting  
improves  antiretroviral  adherence:  
the  LifeWindows  Project. AIDS  Behav. Nov 
2011;15(8):1635-1646. 
112. Boyatzis  RE. Transforming  Qualitative  Information:  Thematic  Analysis  and  Code 
Development: Sage Publications, Inc; 1998. 
113. Franzosi R. Content analysis. London ; Thousand, Oaks, Calif.: SAGE Publications; 2008. 
114. Hsieh HF, Shannon SE. Three approaches to qualitative content analysis. Qual Health Res. 
Nov 2005;15(9):1277-1288. 
115. Billingham S, Whitehead A, Julious S. An audit of sample sizes for pilot and feasibility 
trials being undertaken in the United Kingdom registered in the United Kingdom Clinical 
Research Network database. BMC medical research methodology. 2013;13(1):104. 
116. Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical 
Statistics. 2005;4(4):287-291. 
117. Birkett MA, Day SJ. Internal pilot studies for estimating sample size. Stat Med. Dec 15-30 
1994;13(23-24):2455-2463. 
118.  Browne RH. On the use of a pilot sample for sample size determination. Stat Med. Sep 15 
1995;14(17):1933-1940. 
119. Cocks K, Torgerson DJ. Sample size calculations for pilot randomized trials: a confidence 
interval approach. Journal of Clinical Epidemiology. 2013;66(2):197-201. 
120. Wittes J, Brittain E. The role of internal pilot studies in increasing the efficiency of clinical 
trials. Stat Med. Jan-Feb 1990;9(1-2):65-71; discussion 71-62. 

Page 56 of 56 
 
121. Radloff LS. The CES-D scale: A self report depression scale for research in the general 
population. . Applied Psychological Measurement. 1977;1:385-401. 
122. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 
5th ed. Arlington, VA: American Psychiatric Publishing; 2013. 
123. McLellan AT, Kushner H, Metzger D, et al. The Fifth Edition of the Addiction Severity 
Index. J Subst Abuse Treat. 1992;9(3):199-213. 
124. Rosen C, Henson B, Finney J, Moos R. Consistency of self-administered and interview-
based Addiction Severity Index composite scores. . Addiction. 2000;95(3):419-425. 
125. Amico KR, Toro-Alfonso J, Fisher JD. An empirical test of the information, motivation 
and  behavioral  skills  model  of  antiretroviral  therapy  adherence. AIDS  Care. Aug 
2005;17(6):661-673. 
126.  Amico KR, Fisher W, Cornman D, et al. Visual analog scale of ART adherence: association 
with  3-day  self-report  and  adherence  barriers. J  Acquir  Immune  Defic  Syndr  Hum 
Retrovirol. 2006;42(4):455-459. 
127. Wilson IB, Lee Y, Michaud J, Fowler FJ, Jr., Rogers WH. Validation of a New Three-Item 
Self-Report  Measure  for  Medication  Adherence. AIDS  Behav. Nov  2016;20(11):2700-
2708. 
128. Robinson SM, Sobell LC, Sobell MB, Leo GI. Reliability of the Timeline Followback for 
cocaine,  cannabis,  and  cigarette  use. Psychology of addictive behaviors : journal of the 
Society of Psychologists in Addictive Behaviors. Mar 2014;28(1):154-162. 
129. Bush  K,  Kivlahan  DR,  McDonell  MB,  Fihn  SD,  Bradley  KA.  The  AUDIT  alcohol 
consumption questions (AUDIT-C): an effective brief screening test for problem drinking. 
Ambulatory  Care  Quality  Improvement  Project  (ACQUIP).  Alcohol  Use  Disorders 
Identification Test. Arch Intern Med. Sep 14 1998;158(16):1789-1795. 
130. Chew  LD,  Bradley  KA,  Boyko  EJ.  Brief  questions  
to  
identify  patients  with  
inadequate 
health literacy. Family medicine. Sep 2004;36(8):588-594. 
131. Sherbourne CD, Stewart AL. The MOS Social Support Survey. Social Science Medicine. 
1991;32(6):705-714. 
132. Anderson LA, Dedrick RF. Development of the Trust in Physician Scale: A measure to 
assess  interpersonal  trust  in  patient-physician  relationships. Psychological  Reports. 
1990;67(3, Pt 2):1091-1100. 
133. Davis FD. Perceived usefulness, perceived ease of use, and user acceptance of information 
technology. MIS quarterly. 1989:319-340. 
134. Hass RG. Effects of source characteristics on cognitive responses on persuasion. Hillsdale, 
NJ:: Lawrence Erlbaum Associates; 1981. 
135. Braithwaite RS, Shechter S, Roberts MS, et al. Explaining variability in the relationship 
between  antiretroviral  adherence  and  HIV  mutation  accumulation. Journal  of 
Antimicrobial Chemotherapy. November 1, 2006 2006;58(5):1036-1043. 
136. Radloff LS. The CES-D scale: A self report depression scale for research in the general 
population. Applied Psychological Measurement. 1977;1(385-401). 
137. McLellan  AT,  Kushner  H,  Metzger  D,  et  al.  The  
fifth  edition  of  
the  addiction  severity 
index. Journal of substance abuse treatment. 1992;9(3):199-213.