Development and Feasibility Testing of an Integrated PTSD and Adherence Intervention Cognitive Processing Therapy-Lifesteps (CPT-L) to Improve HIV Outcomes
Phase: NA
Conditions: PTSD, Hiv
Sponsor: Medical University of South Carolina

Grant Title: Development and Feasibility Testing of an Integrated PTSD and Adherence 
Intervention Cognitive Processing Therapy-Lifesteps (CPT-L) to Improve HIV Outcomes 
 
Grant Number: NCT05275842 
 
Title of Document: CPT-L Protocol 
 
Date of Document: 07/13/2023 

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PROTOCOL TITLE: 
 
Development and Feasibility Testing of an Integrated PTSD and Adherence Intervention 
Cognitive Processing Therapy-Lifesteps (CPT-L) to Improve HIV Outcomes 
 
 
PRINCIPAL INVESTIGATOR: 
 
Cristina M. López, Ph.D. 
Associate Professor 
College of Nursing 
 
 
 

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1.0 
Objectives / Specific Aims 
The specific aims of this protocol are to: 
 
Aim 1. (Months 03-12). To theater test and deliver the un-adapted CPT protocol and one session 
adherence intervention (Lifesteps) with 12 trauma-exposed PLWH presenting for HIV treatment at the 
MUSC Ryan White Clinic and collect qualitative feedback for modifications to ensure feasible 
administration and relevant incorporation of HIV-related messages and/or content specific to HIV-related 
PTSD. Specific activities are to: 
A. Test methods and measurement protocol of the beta version of the research protocol. 
B. Utilize feedback provided through exit interviews, topical experts, and advisory panel discussion 
to shape any refinement of the integrated CPT and one session adherence protocol. 
C. Incorporate qualitative feedback into the CPT-L manual.  
 
Aim 2. (Months 13-30). To assess feasibility of the modified CPT protocol (CPT-L) compared to Lifesteps 
in 60 PLWH with comorbid PTSD over 3 months (baseline, post intervention, 3 month follow-up) in a pilot 
RCT to assess key variables for subsequent efficacy testing (attendance, ART adherence, HIV symptom 
distress, CD4 count, viral load, PTSD symptoms, avoidant coping). Specific feasibility benchmarks are: 
A. Achieve a recruitment rate of 4+ patients per month and retention rate of 80% or higher. 
B. Obtain variability estimates of outcomes (less than 10% missing data) and initial indicators of 
treatment effects for the following hypotheses in the subsequent efficacy trial: 
a. Participants who receive the CPT-L protocol will have improved HIV symptom distress, 
ART adherence, clinic attendance, and viral load at post intervention and 3-month follow 
up vs. control. 
b. Participants who receive the CPT-L protocol will report lower PTSD at post intervention 
and 3-month follow up versus those in the Lifesteps Control. 
C. Assess qualitative feedback from exit interviews for high satisfaction, successful saturation of 
themes, and action plan development, in conjunction with Advisory Board, to refine the 
intervention for an R01. 
 
Exploratory Aims. 1) We will assess between-group differences in other problems that commonly occur 
among PLWH and PTSD (substance misuse, depression). 2) Avoidant coping will be examined as a 
potential mechanism of action for the relationship between CPT-L and improved adherence. 
 
2.0 
Background 
The prevalence of trauma exposure, and post-traumatic stress disorder (PTSD) in particular, among 
individuals living with HIV (30-74%)6,7 is higher than the general population (7-10%).8 Individuals with co-
occurring PTSD and HIV are at high-risk for negative HIV-related outcomes, including low adherence to 
antiretroviral therapy (ART)9,10, faster disease progression11,12, more hospitalizations13,14, and almost 
twice the rate of death15, as well as increased mental health problems.16 In addition to PTSD resulting 
from traumatic events, such as sexual and physical assault/abuse, negative reinforcement conceptual 
models suggest that the avoidant behavior (a hallmark symptom of PTSD) tied to HIV status-related 
PTSD can also contribute to poor ART adherence and to less success of viral suppression (e.g., by 
avoiding cues, such as ART medications, that serve as reminders of the HIV status).  Despite the high 
rates of persons living with HIV/AIDS (PLWH) who report PTSD – and the poorer HIV patient outcomes 
among this population versus those without co-occurring PTSD– evaluation of the impact of evidence-
based treatment for PTSD among populations living with HIV on HIV outcomes has been highly 
neglected in clinical research. In other words, no research to date has examined the critical question of 
whether HIV outcomes can be improved among the large number of PLWH with co-morbid PTSD and 
related consequences (e.g., substance misuse) by treating PTSD symptoms. To address this 
tremendous void in the field, we propose to adapt and examine the acceptability and feasibility of an 
evidence-based PTSD treatment that has reduced other HIV transmission behavior (e.g., sexual risk), 
Cognitive Processing Therapy (CPT), at an HIV clinic as a strategy to improve HIV outcomes in this 
population. We propose to do so in South Carolina (ranked 8th state in the country in 2019 for HIV/AIDS 
incidence; 11th for prevalence), where PLWH may also encounter additional HIV-related intersectional 
stigma, itself linked to increased avoidant coping and ART non-adherence.  

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The multi-disciplinary investigative team housed at the Medical University of South Carolina (MUSC) has 
leveraged: a) its long-standing relationship with the MUSC Ryan White clinic; b) pilot data collected by PI 
Dr. Cristina López; c) consultant expertise in the HIV-PTSD link (Dr. S. Safren) and CPT (Dr. P. Resick);  
and d) an advisory panel made up of stakeholders and consumers (PLWH) to develop the proposed 
study, which aims to tailor CPT for PLWH with PTSD through integration of an adherence intervention, to 
demonstrate the acceptability and engagement of PLWH in CPT-L (CPT-Lifesteps), and to assess 
preliminary efficacy of CPT-L in improved adherence to ART, decreased viral loads, and retention in HIV 
care. 
 
PREMISE: Although research has demonstrated a clear connection between PTSD and problematic HIV 
outcomes, the applicability, feasibility, and efficacy of evidence-based treatment for PTSD on HIV 
outcomes among people living with HIV (PLWH) has not been examined. Cognitive Processing Therapy 
(CPT) is an evidence-based PTSD treatment that effectively reduces avoidant coping, which similarly 
has been linked with ART non-adherence among PLWH. Thus, we will demonstrate how the proposed 
framework of an adapted CPT protocol (CPT-Lifesteps or CPT-L) offers great promise as an intervention 
to improve HIV outcomes related to quality of life, adherence, and subsequent viral suppression in PLWH 
by targeting PTSD and avoidant coping. 
  
The proposed research plan is directly in line with several recently emphasized priorities of NIMH 
(NOT-MH-20-013, Notice of Special Interest: Mental Health Comorbidities in HIV Prevention and 
Treatment; and PA-20-141: Formative and Pilot Intervention Research for Prevention and Treatment 
of HIV/AIDS), the U=U campaign, and the national initiative Ending the HIV Epidemic (EHE) through 
targeting comorbid conditions. 
 
PTSD is prevalent among PLWH and negatively impacts HIV outcomes. PLWH report higher levels of 
traumatic events (e.g., child maltreatment, sexual assault, physical assault) than the general population, 
with trauma exposure ranging from 40-90%.17,18 Higher rates of traumatic events/exposure correspond 
with higher rates of Posttraumatic Stress Disorder (PTSD) in this population, ranging between 30-
74%.19,20 Beyond PTSD resulting from more conventional definitions of traumatic events (e.g., 
victimization, disasters), up to 64% of PLWH endorse PTSD symptoms directly related to HIV diagnosis 
or other issues related to the disease.19,21 PTSD is associated with other negative consequences, 
particularly substance use disorders (SUD) and depression. Lifetime prevalence of PTSD among people 
with SUDs is 50% compared to 7% in the general population22,23, and comorbid PTSD and SUD display a 
worse course of illness, physical health and overall functioning, and increased risk of suicide than 
individuals with only PTSD or SUD.24,25 Addressing PTSD can significantly reduce SUD among various 
populations26, although this has not been examined among PLWH. 
 
The connection of PTSD (HIV- and non-HIV-related traumas) with problematic HIV outcomes has been 
well-documented. PLWH with PTSD have been shown to have faster HIV progression18,27 twice the rate 
of death,28 lower ART adherence29-34, poorer retention in HIV care35, and increased viral load36,37 
compared to PLWH without co-occurring PTSD. Additionally, HIV-related stigma (community, 
anticipated, and internalized) is prevalent among PLWH38 and associated with problematic HIV outcomes 
(e.g., poor medication and visit adherence39,40).  
  
Trauma-focused treatment can be enhanced to address discrimination related to stigmatized identities 
(e.g., HIV-related intersectional stigma) associated with poorer outcomes in PTSD and ART adherence. 
HIV-related stigma is shame or disgrace affiliated with HIV and associated with negative health 
outcomes for PLWH.55 Fear of being judged by others predicted decreased ART adherence among 
PLWH56,57 and internalized HIV-stigma predicted poor ART adherence.58 Although individual treatment 
may not decrease society's harmful tendency to stigmatize PLWH [[and minoritized subgroups]], trauma-
focused treatment may combat internalized stigma and misperceptions or over-anticipation of perceived 
stigma, thus preventing additional psychological distress and non-adherence linked with stigma.63 
  
Despite high rates of PLWH with co-occurring PTSD, the link between PTSD on HIV health related 
outcomes, and the negative reinforcement conceptual model (e.g., avoidant coping) that provides a 
theoretical framework for this link, research evaluating evidence-based PTSD treatment among 
seropositive populations on HIV outcomes is scarce. Gold standard, evidence-based treatments for 
PTSD, including Cognitive Processing Therapy (CPT)64, have strong evidence for reducing avoidance 

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symptoms, as well as traumatic stress, substance use, and depression among civilian and military adults 
with complex trauma histories.65,66 CPT reduces trauma-related self-blame and guilt67,68, two factors 
intimately tied to avoidant coping. Most importantly, reductions in avoidance symptoms (in the context of 
traumatic stress symptoms) have been linked to increases in (non-HIV) medical regimen engagement, 
including medication adherence.69 Mental health treatment studies in adults with Type 2 diabetes 
(another chronic disease with self-management and adherence barriers) have demonstrated that 
interventions leading to mental health symptom reduction showed simultaneous improvements in 
medication adherence, HbA1C scores, and self-care behaviors.70,71 Although CPT has been enhanced to 
target alcohol use and high risk sexual behavior to prevent HIV among American Indian women72, CPT, 
nor other gold-standard, empirically supported individual treatments (e.g., Prolonged Exposure/PE)73,74, 
have been adapted for PLWH or evaluated as an efficacious approach to reduce problematic HIV 
outcomes. Thus, there is critical need to examine evidence-based treatments for PTSD among PLWH 
and co-occurring PTSD to improve HIV outcomes. CPT may be particularly beneficial for PLWH due to 
the focus on unhelpful cognitions, or “stuck points,” in the form of assimilation (beliefs related to self-
blame) and overaccommodation (extreme beliefs related to self and world).64 The flexibility of CPT to 
focus on unhelpful thoughts and thinking patterns would allow patients to address trauma- and HIV-
related intersectional stigma cognitions in treatment. In line with the Undetectable=Untransmittable (U=U) 
initiative to end HIV-related stigma, this proposal has broad implications not only from a public health 
standpoint, but also for the self esteem of individuals by reducing HIV-related stigma [[and other 
intersecting stigmatized identities]]. Themes addressed in CPT (i.e., safety, intimacy, trust, esteem, 
power, and control), although originally created from theory on sexual assault, may have relevant overlap 
to unique issues in disclosing HIV status, and with managing and coping with HIV in interpersonal and 
intrapersonal domains. [[Given that 28-52% of PLWH are estimated to experience cognitive impairment 
(CI)75,76, CPT is particularly well-matched for application with this population, as CPT has been delivered 
successfully with veterans who have experienced traumatic brain injury (TBI), resulting in cognitive and 
affective symptoms similar to PLWH with CI77,78]]. CPT dismantling studies have also demonstrated 
improved engagement and PTSD outcomes among complex and traditionally hard-to-reach 
populations,79-81 and can potentially decrease substance use in addition to PTSD symptoms,82 further 
supporting the intervention for complex mental health treatment needs of PLWH. Taken together, an 
empirically supported adaptation of CPT for PLWH (i.e., CPT-L) may improve HIV treatment outcomes 
for PLWH with comorbid PTSD. This study will address vital gaps by conducting the first pilot RCT to use 
an adapted evidence-based PTSD treatment, integrated with an evidence-based adherence session, 
(Lifesteps)83, to improve HIV outcomes among PLWH with co-occurring PTSD in a geographic 
jurisdiction identified in Phase 1 of the national End the Epidemic plan. To accomplish this goal, across 3 
time-points, we will rigorously measure: trauma history, PTSD symptoms and diagnosis, viral load, CD4 
count, stigma, ART adherence, clinic attendance, substance misuse, depression, and avoidant coping.  
 
3.0 
Intervention to be studied  
Overview of Methods using the ADAPT-ITT framework. The proposed adaptation and pilot RCT follows a 
2 (treatment type) × 3 (time points) at the MUSC Ryan White Clinic, ideally situated in the Southeast (i.e., 
a geographic jurisdiction identified in Phase 1 of EHE; where new HIV contraction rates remain in the top 
10 in the US). The ADAPT-ITT model provides a framework for adapting HIV-related evidence-based 
interventions111 that is widely used in treatment studies with diverse populations.112-114 ADAPT-ITT 
consists of eight phases: (1) Assessment of needs of the target population, (2) Decisions around which 
empirically supported intervention to use or adapt, (3) Administration of novel methods (e.g., theater 
testing) to adapt the chosen intervention, (4) Production of a first draft of the adapted intervention, (5) 
Identification of topical experts, (6) Integration of content provided by topical experts for the second draft 
of the adapted intervention (7) Training staff to implement the adapted intervention, and (8) Testing the 
adapted intervention. This model has been successfully applied to the cultural adaptation of several HIV 
programs112, including the PI’s adaptation of an HIV prevention program for Latina adolescents103 
(Davidson et al, 2014), and provides an empirically supported framework to understand the needs of 
individuals with comorbid PTSD and HIV and identify the “cultural” components (e.g., [[HIV-related 
intersectional stigma]], chronic disease coping, medication adherence, disclosure stress) that may not be 
addressed by evidence-based PTSD models. This team has begun initial steps of the ADAPT-ITT 
framework to determine whether adoption of or adaptation to evidence-based treatment was necessary 
to address this critical gap in comorbid PTSD and PLWH. PI López and colleagues100 highlight the need 
to modify CPT to fully encompass unique needs in the intersectionality of trauma and HIV status. 

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Research informs Assessment of the problem (i.e., Step 1 of ADAPT-ITT) and indicates that exposure to 
traumatic events and PTSD are high among PLWH and associated with ART nonadherence.17,115,116 The 
Decision (Step 2) to use CPT versus other evidence-based treatments for PTSD was based on the 
potential for CPT to target reductions in symptoms linked to ART adherence including avoidance, 
hyperarousal, reexperiencing, and depression.65-68,117 CPT is not an exposure-based intervention, which 
may often include a stabilization phase to develop skills for distress tolerance before entering exposure 
faces of treatment. CPT was chosen because of the cognitive, rather than exposure-based, focus. 
Specifically, CPT addresses problematic cognitions allowing flexibility to target HIV-related stuck points 
in addition to trauma-specific stuck points, which is central because stigma may increase risk for PTSD 
and ART nonadherence. Aims will continue to Execute Step 3 of ADAPT-ITT (administration of 
unadapted CPT and unadapted Life-Steps adherence) in which theater testing is used to deliver the 
unadapted interventions sequentially to the new target population (i.e., PLWH with PTSD) and obtaining 
qualitative data from patients and project therapist on integrating adherence principles throughout the 
modified protocol. The proposal will include steps 3-8 to Adapt CPT and LifeSteps and Test the 
integrated version (CPT-Life Steps, or CPT-L) in a pilot RCT delivered 2x/week for 6 weeks (i.e., 12 
individuals, 90 minute sessions, with homework assigned). 
 
Interventions 
Experimental Condition  (Lifesteps + CPT + SOC): Life-Steps for Medication Adherence83 is a one-
session intervention using cognitive behavioral strategies, problem-solving, and motivational interviewing 
to promote adherence. The evidence-based session has been used as an adjunct in other integrated 
mental health treatments (5R01MH078571-05).69,128 Lifesteps content includes psychoeducation on 
benefits of ART adherence, modification of maladaptive cognitions about taking medications, review of 
barriers to being adherent, and problem-solving techniques for problematic areas with adherence. 
Adherence monitoring will be included in weekly check-ins during CPT sessions. Cognitive Processing 
Therapy (CPT) is an evidence-based PTSD treatment with demonstrated efficacy through several RCT 
designs and comparators, with vulnerable populations, and for a range of traumatic events (e.g., rape, 
domestic violence, child sexual abuse, military combat and ACEs). CPT129 is based on information 
processing theory and includes education and cognitive components to help patients challenge and 
modify unhelpful beliefs related to trauma and/or living with HIV. The patient creates a new 
understanding and conceptualization of the trauma and/or HIV status to reduce ongoing negative effects 
on current life. CPT begins with PTSD psychoeducation, thoughts, and emotions. The patient becomes 
more aware of the relationship between thoughts and emotions and begins to identify “automatic 
thoughts” that may maintain the PTSD and intersectional stigma. In CPT-L, the team anticipates 
incorporating continuous reminders of the benefits of being ART adherent and identifying potentially 
maladaptive thoughts about taking medication, thus building on skills implemented in the first session of 
Lifesteps. In CPT, the patient details in an impact statement how the traumatic event and/or HIV 
diagnosis has impacted beliefs about self, others, and the world. Next, the patient begins more formal 
processing of the trauma(s). A detailed account of the traumatic event(s) is used to break the pattern of 
avoiding thoughts and feelings associated with the trauma. The therapist uses Socratic questioning to 
question unhelpful thoughts (e.g., self-blaming thoughts) to modify maladaptive thinking (e.g., “I’m 
unlovable”). Upon developing skills to identify and address unhelpful thinking and internalized stigma, the 
patient modifies beliefs related to trauma and uses adaptive strategies to improve overall functioning and 
quality of life. CPT focuses on safety, trust, power, control, esteem, and intimacy, as these are domains 
affected by trauma, but also with HIV-related intersectional stigma. Currently, potential adaptations in 
CPT-L based on PI preliminary case study (López et al., 2019), CAB input, and consultant feedback are 
demonstrated in Table 1. Additional modifications are expected after Aim 1 (steps 3-6 of ADAPT-ITT). 
 
Table 1. Initial Modifications Identified for CPT-L 
Session(s) 
Intervention component 
Proposed revisions for CPT-L from Case studies 
Adherence – Life-Steps 
1 
Psychoeducational information 
Benefits of adherence to ART and evidence-based PTSD therapy 
1 
Consequences of a missing a dose 
No changes 
1 
Enhance motivation with motivational 
interviewing 
For ART adherence, CPT session adherence, and homework compliance 
1 
Rehearse Adherence-related Behaviors 
Modify non-adaptive cognitions for PTSD therapy session adherence also 
1 
Solve problems interfering with 
adherence to HAART 
Review potential barriers to session adherence as well 

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1 
Accessibility to providers and obtaining 
medication 
No changes 
PTSD Treatment – Cognitive Processing Therapy 
1 
Overview of PTSD and CPT 
Psychoeducation related to HIV and impact of HIV-related intersectional stigma 
2-3 
Finding Stuck Points 
Identifying stuck points related to HIV-related intersectional stigma 
4-5 
Processing the Index Event 
Distinguish trauma event processing from receiving news about HIV status 
(potentially additional session if two separate events); Processing stigma from 
learning of HIV status; Explore trauma related to intersecting identities, e.g., 
racism-related trauma, gender and sexual identity discrimination 
6-7 
Learning to Self-Challenge 
Examples for in session discussion (disclose problem solving with co-worker, 
challenging intersectional stigma, handling microaggressions related to 
intersecting identities) 
8-10 
Trauma Themes – Safety, Trust, and 
Power/Control  
Checklist related to Disclosure Safety; Regain ‘control’ of health by challenging 
intersectional stigma stuck points (e.g. impact of intersectional stigma on trauma 
themes). 
11-12 
12+ 
Esteem, Intimacy, and Facing the Future 
Challenging intersectional stigma-related non-adaptive cognitions, Duty to warn 
review for clinician 
Alternatives in Delivery 
Format 
change 
Variable Length  
Use “stressor sessions” to discuss stigma-related stuck points, including those 
related to intersecting identities and discrimination130 in CPT variable length 
format 
All 
Adherence self-monitoring 
In addition to risk assessment in CPT, CPT-L could include ART adherence 
monitoring 
XXXX 
XXXXX 
New component(s) from proposed theater testing and ADAPT-ITT process 
 
The Control Condition: Lifesteps + SOC. Participants assigned to Lifesteps (N=30) will receive the one 
session Lifesteps intervention in addition to the standard treatment that an individual with a trauma 
history and co-occurring HIV and PTSD symptoms would receive at a local HIV care clinic (varying levels 
of case management services and program referrals). [[Lifesteps developer and consultant Dr. Safren 
has successfully trained master’s level social work clinicians in the intervention. To protect from 
contamination, two HIV care case managers with master’s level social work degrees will be trained by 
Safren to deliver Lifesteps to participants in the control condition. Independent raters (as described 
above) will rate 20% of randomly selected recorded Lifesteps sessions to determine appropriate fidelity.]] 
Interventions delivered as SOC are comprehensive and can include (but not limited to) motivational 
interviewing, supportive counseling, general mental health interventions, crisis counseling, pharmacist 
consultation, and case management support. This may include referrals to other community agencies. As 
with Co-I Danielson’s previous SOC protocols, close monitoring of the treatment provided has been 
incorporated into the study design, and the services/techniques administered in each condition will be 
closely measured to ensure appropriate evaluation comparisons, including: a) audio-taping and random 
selection of sessions tapes for audit by 2 independent coders136 b) participants will complete the 
Services Assessment137 at each assessment point; c) Chart review across both conditions and; d) weekly 
service utilization text message/electronic assessment (see Measurement section).  
 
4.0 
Study Endpoints  
Study end points for both Aims I and II include: successful study completion, participant consent 
withdrawal, and PI termination due to failure to adhere to the protocol, loss of contact with the 
participant, and/or unexpected adverse events.  
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 
AIMS 1 and II Participant Eligibility Screening 
A total of seventy-two,18 years old and older HIV-infected adults currently enrolled at a local HIV care 
clinic (i.e., MUSC or Roper) and prescribed antiretroviral treatment will be recruited into this pilot study.  
Potentially eligible participants will be screened through: 
• Confirmation of participant’s HIV diagnosis, medication retroviral treatment, and 
attendance an MUSC Infectious Disease Clinic (e.g., Ryan White Clinic, ID Outreach, ID 
Reproductive clinic),  Roper Ryan White Clinic or other SC HIV care clinic through query 
the clinic’s EHR. 

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• 
Confirmation that the participant meets clinically significant threshold of DSM-V PTSD criteria as 
determined by a Clinician Administered PTSD Scale for DSM-5 (CAPS-5) through clinical 
interview. 
• 
Confirmation that the participant exhibits no significant cognitive impairment as assessed by the 
adapted virtual Montreal Cognitive Assessment Test (MoCA- Blind [MoCA without the visual 
element]; in the severe range) and/or through EHR clinic chart review 
• 
Confirmation of that the participant is medically stabilized and/or is not exhibiting active psychosis 
through EHR clinic chart review. 
 
AIMS I and II: Inclusion criteria  
The primary selection criteria for participants in both Aims of the study will be that the participants meet 
ALL of the following criteria: 
1. Individuals that are 18 years and older  
2. Linked with and/or eligible for treatment at MUSC, Roper Ryan White Clinic or other SC HIV care 
clinic.  
3. Participant meets clinically significant threshold of DSM-V PTSD criteria as determined by a 
Clinician Administered PTSD Scale for DSM-5 (CAPS-5) clinical interview.  
4. No changes in psychotropic medication within 4 weeks of study enrollment.  
5. Able to speak, read, and write English. 
6. Meet at least one of the following HIV care criteria: 
a. Diagnosed with HIV in the last 3 months; 
b. Detectable viral load in the last 12 months; 
c. Failed to show up for or missed 1 or more HIV care appointments in the past 12 months; 
d. Last HIV care visit was more than 6 months ago; 
e. Self-reporting less than 90% ART adherence in the past 4 weeks. 
7. A score of at least 10 on the adapted Montreal Cognitive Assessment test without visual elements 
(MoCA-Blind) 
 
AIMS I and II: Exclusion Criteria: 
Specific study exclusion criteria include the following: 
1. Evidence of significant cognitive impairment as assessed by the adapted Montreal Cognitive 
Assessment Test (MoCA-Blind; in the severe range). 
2. Evidence of developmental delays, or pervasive developmental disorder, or active suicidal or 
homicidal ideations. 
3. Evidence of psychotic symptoms (e.g., active hallucinations, delusions, impaired thought 
processes). 
 
Rationale for Exclusion Criteria: The proposed intervention(s) would likely not be sufficient for these 
individuals, who may either have a diminished capacity to benefit from cognitive-behavioral therapy. 
 
Statement on the Inclusion of Women: Participants in the proposed project will be recruited from a local 
HIV Care Clinic in South Carolina. We anticipate 72 participants for enrollment in the study. Based on the 
demographic composition of patients engaged in services at the Ryan White Wellness Center, we expect 
to recruit a sample that is 25% female, 74% male, and 1% transgender. 
 
Statement on the Inclusion of Minorities: The proposed research will include minority and non-minority 
participants, with no restrictions with regard to ethnic or racial background. Analysis of referral patterns 
for MUSC Ryan White clinic for the proposed study indicates that 64% of the population study will identify 
as African American, 4% as Hispanic, and 6% as Other and 50% will include men who have sex with 
men. Based on these referral rates, we expect that approximately 65% of participants included in the 
proposed study will be minorities. Study recruitment materials will encourage participants from all racial 
and ethnic backgrounds to volunteer. 
 

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Participant Compensation 
Aim 1: Upon enrollment, participants will be reimbursed with a $50 gift card for completing baseline 
assessments via REDCap and master’s level administered PTSD Diagnostic Interview (see Table 2). 
Participants will receive $50 for completion of post-intervention assessments and $25 for completion of a 
20-minute exit interview after completion of CPT sessions. Participants will also receive $5 per photo 
they submit of their prescription bottle and refill (i.e., self-reported adherence; totaling $15 per 
participant). Participants will be paid up to $140 for participation in Aim I of the study. 
 
Aim 2: Upon enrollment, all participants will be reimbursed with a $50 gift card for completing baseline 
assessments at the PTSD Diagnostic Interview. Participants assigned to the intervention group will 
receive $40 for attending the first session, then $60 for post-intervention assessments and 20-minute exit 
interview after completion of CPT-L sessions (i.e., post intervention ~6 weeks after study enrollment); 
and a $75 gift card for 3 month follow up surveys collected online or in person (CAPS can be conducted 
via telehealth by project coordinator). Participants enrolled in the control group will receive $50 for 
completing the first set of assessments, PTSD Diagnostic Interview, and for enrolling in the study, and 
then $40 for completing the Lifesteps session. Then, they will receive $60 for post-intervention 
assessments and 20-minute exit interview after completion of CPT-L sessions (i.e., post intervention ~6 
weeks after study enrollment); and a $75 gift card for 3 month follow up surveys. Participants will also 
receive up to $15 for self-reported adherence photos. Thus, participants can be paid up to $240 for 
participation in Aim 2. 
 
6.0 
Number of Subjects 
In total, seventy-two (72) HIV-infected adults will participate in this study. 12 individuals will participate in 
study Aim I and 60 individuals in study Aim II. 
 
7.0 
Setting 
All research activities will take place in-person on-campus at MUSC (College of Nursing (CON), MUSC 
Ryan White Clinic and the National Crime Victims Center (NCVC) and/or remotely with the use of MUSC 
secure and HIPAA compliant Information technologies (REDCap for data collection and management, 
and e-Consent).  
 
8.0 
Recruitment Methods 
AIMS I and II 
Participants under each study aims will be recruited through an MUSC Ryan White/Infectious Disease 
clinic and across the MUSC Enterprise as well as through the Roper Ryan White Wellness Center and 
other HIV care clinics in South Carolina. Recruitment will occur through several avenues:  
• 
Infectious Disease (ID) clinicians and staff in the HIV care clinic at MUSC will share an IRB study 
approved flyer with their patients with trauma backgrounds. The flyer will direct interested and 
potential eligible participants to contact the study team for more information. Staff at Roper Ryan 
White Wellness Center will provide minimal information about the project (ex. Title, 
exclusion/inclusion criteria) and relay interested contact information to the research team.  
• 
Study Staff and investigators will work together to pre-screen potential participants and 
investigators will determine eligibility. The study team will review existing Infectious Disease 
Division patient databases or EHR to identify patients who meet inclusion criteria. EMR review 
will be used for pre-screening purposes, but data will not be extracted/recorded from the medical 
record unless the subject signs an informed consent form. 
• 
Patients that are identified through the trauma screening questions (Primary Care PTSD 
Screener for DSM-5 2) included in the Ryan White clinic intake procedures will be handed a study 
flyer directing interested and potential eligible participants to contact the study team for more 
information. Patients can fill out an electronic version of the trauma screener though RedCap. 
• 
Study Flyers will be posted in the general patient waiting room areas of HIV care clinics directing 
interested and potential eligible participants to contact the study team for more information. 

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Advertisements will be used throughout the South Carolina area providers that take care of the 
HIV population as well as social media advertisements with community partners. 
• 
Infectious Disease providers and staff will distribute eligibility survey to potential participants via 
e-mail as a way to identify potential eligible participants 
• 
We will be utilizing a cold-call method as part of our recruitment plan. We will be submitting a 
Research Data Request to obtain a recruitment report of MUSC patients who potentially meet 
eligibility criteria. The study team will not cold-contact any patients who have opt-ed out of 
receiving contact about research or who have met the maximum number of contact attempts at 
the time of recruitment. The study team will reach out to potentially eligible participants via e-mail, 
text, or mailed letter. 
 
Interested patients will be contacted by the Study Coordinator or PI and provided with more information 
about the study. If interested, participants will then complete informed e-consent. After consent, 
participants will have their EHR chart reviewed and complete a structured diagnostic clinical interview to 
assess clinical threshold of DSM-V PTSD (CAPS) to confirm eligibility prior to enrollment. 
 
9.0 
Consent Process 
Prior to consent, the adapted MoCA-Blind (without visual elements) will be administered to the potential 
participant as part of the pre-eligibility process; and no PHI will be gathered during it’s administration. 
Research activities will not be conducted without documentation of the adult participant’s written informed 
consent. The informed consent process with take place either in-person at an MUSC Ryan White/Infectious 
Disease facility in the privacy of a clinic room or remotely via MUSC IRB approved REDCap e-Consent 
with the participant at a location of their choosing. As this study uses e-CRFs, all study participants will 
have their consented documented using MUSC IRB approved REDCap e-consent. 
 
Informed consent will be conducted by members of the study team that:  
1. are independent of the participant’s clinical treatment team;  
2. have received UM CITI training in both the Conduct of Human Subject Research and Good Clinical 
Practice; 
3. are designated to perform this process on the PI Delegation of Responsibility log; and, 
4. are IRB approved study personnel.  
 
Additionally, these individuals will attend a 1-day training given by the PI on how to provide information 
about the study and on how to obtain consent for participation in the study (i.e., informed consent), and 
will role play with the PI until competency is demonstrated in this area. This is so that each person collecting 
informed consent is familiar with all study aspects and potential questions and issues that may arise among 
this target population. Training for the assessor (i.e., master's level project coordinator) on the clinical 
diagnostic interview (CAPS) will include fidelity monitoring until reliability is achieved 4.  
 
During the consent meeting (both in-person and remotely), potential and pre-screened eligible 
participants will already have spoken with the researchers and been introduced to the opportunity to 
participate in the study. Additionally, they will have had as much time as requested to read the consent 
document prior to scheduling the meeting per their individual preference. During the meeting or call, the 
researcher will review the consent document in its entirety and be available to further answer any and all 
questions that the participant may have prior to the individual adding their respective signature to the 
form and submitting the e-consent. Participants will be asked to demonstrate an understanding of the 
demands of the study by being asked to provide a summary of the main study procedures. The informed 
consent document will be reviewed with individuals that initially exhibit less than full comprehension until 
an understanding is gained. Individuals that do not gain an understanding or demonstrate cognitive 
impairment will be excluded from study participation.  
 
Upon submitting the e-consent, a REDCap trigger will immediately notify the researcher, who will then 
provide their countersignature to the eCRF while they are physically present with the participant or 
remotely available on the phone to the participant during this entire process. All e-consents will be 
maintained in the REDCap study e-consent database for regulatory purposes and compliance 

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monitoring. All participants will be electronically sent a copy of the fully executed e-consent form to their 
email address. Hard copies will be printed out and/or mailed to participants upon request. In the case of 
in-person consenting, research staff will set-up a meeting with the participant at a time per their 
preference at a community yet private location and follow the same consenting procedures. 
 
10.0 Study Design / Methods 
Theater testing (Aim 1) is a pretesting methodology to assess consumer response to a product118 and 
has been successfully implemented to assess participants’ reactions to HIV-related interventions.111-113 
Using this approach, members of the target population participate in original versions of the evidence-
based intervention (e.g., unadapted CPT) and provide feedback to guide intervention refinement, to 
enhance relevance and efficacy for the new target population.111 As part of theater-testing, participants 
will each complete a brief qualitative interview of open-ended questions with follow-up probes at the end 
of every session to elicit (1) impressions about the un-adapted content (e.g., helpfulness, relevance, 
language and word choice, homework content), (2) perceptions about the need to adapt content and (3) 
potential adaptations participants would like incorporated (e.g., different role plays, modified examples). 
Interview responses will be recorded and coded by two independent coders. Following theater testing 
with 12 cases (≥18 yrs. old, PLWH with PTSD; step 3 of ADAPT-ITT), which was determined based upon 
saturation rates from previous similar studies, the team will analyze and integrate qualitative findings 
using content analyses, where a three-step inductive approach will identify and describe major themes 
that emerge from the interviews to derive categories from the data.119 Recommendations from the CAB 
will be incorporated and brought to the study team, to discuss and finalize what recommendations will be 
applied and incorporated to develop an adapted protocol (CPT-L; Step 4, Produce a manual). In Step 5, 
Topical experts (e.g., HIV stigma researchers, Adherence interventionists/experts) and CAB members 
will review the adapted protocol, providing feedback through individual qualitative interviews to determine 
if content is relevant and if data from theater testing has been adequately incorporated. The research 
team will Integrate expert feedback into refinement of the protocol (Step 6 of ADAPT-ITT). Consultants 
Safren (Life-Steps developer) and Resick (CPT developer) will review CPT-L to ensure adherence-based 
interventions have been incorporated and stigma-related examples adhere to CPT. 
 
In Aim 2, steps 7-8 of ADAPT-ITT will be completed. The project therapist is trained in evidence-based 
PTSD treatment, including CPT, thus Training in the integrated CPT-L protocol (step 7) will be relevant 
for adherence and stigma adaptations. For Testing the adapted intervention (step 8), we will randomize 
60 adults aged 18+ who meet DSM 5 criteria for PTSD and present for treatment at MUSC, Roper Ryan 
White Clinic, or other HIV care clinic, to either CPT-L + standard of care (SOC) or Lifesteps only + SOC. 
Participants must have experienced at least one traumatic event and report current clinically significant 
PTSD symptoms (via CAPS clinical interview89). Participants randomized to experimental condition 
(CPT-L; N=30) will be assigned to the project therapist (trained and supervised in CPT-L). Participants 
randomized to control condition will receive the unadapted Lifesteps session as well as SOC (measured 
via chart review), which includes supportive services typically received by PLWH identified as suffering 
from PTSD. Assessments will be conducted at pre- and post-treatment, and 3-month post study-entry. 
Outcomes for efficacy testing in the subsequent R01 will be collected, including viral load, ART 
adherence, clinic attendance, PTSD diagnosis and symptoms, avoidant coping, substance use, and 
depression. 
 
Randomization Procedures. For Aim 2, we will use an adaptive randomization procedure (urn 
randomization) to balance confounding variables among participants in each condition.127 Factors on 
which the adaptive randomization procedure will operate are viral load and self-identified gender. 
Computerized urn randomization will use an adaptation of Microsoft Access application gRand (used by 
Co-I Danielson). Efforts will be made to keep the project coordinator (PC) blind to condition, therefore, PI 
López will randomize participants. Participants will be randomized following consent and baseline 
assessment (to determine severity of symptoms for the urn) to one of two conditions: (1) CPT-L + 
Standard of Care (SOC) or (2) Lifesteps + SOC. Within 7 days of interview and PI’s randomization, the 
PI will contact the participant to inform him/her of condition. Case managers will do phone check-ins 
between sessions to encourage attendance and provide referrals and information to individuals in both 
CPT-L and Lifesteps groups. Individuals in the Lifesteps condition will receive the one-session 
adherence intervention in addition to any other standard treatment that a PLWH with PTSD symptoms 
would typically receive at a HIV care clinic. SOC treatment will vary in type, duration, and frequency (e.g., 

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spiritual counseling, crisis hotline phone call, resource help for case manager,), but will be measured 
carefully across both conditions through coding of chart review and weekly electronic dairy assessment 
of service utilization (methods used successfully by Co-I Danielson in prior RCTs85) to account for 
Treatment dosage. Baseline, post-intervention and follow-up assessments will be collected by the PC. In 
the CPT-L condition, the PI, assigned case manager, and project therapist will make contact within 7 
days of randomization. Participants in the control condition will be contacted by one of the Lifesteps-
trained HIV care case managers.  
 
Figure 2. Participant Flow Diagram 
 
 
 
 
 
Assessments and Data Collection Procedures. The PC (blind to condition) will conduct the initial eligibility 
(baseline) diagnostic assessments and all study assessments. The CAPS will be audio-taped and study 
personnel will listen to a randomly selected 20% to ensure reliability of CAPS diagnosis over the course 
of the study. The PC will administer the battery in the HIV care clinic or remotely by phone to the 
participant, based on participant preference. All timepoints will be collected on all participants, even if 
they drop out of treatment. Pilot trials indicate that major assessments take between 1.5 – 2 hours to 
complete. Individuals will be given $50 for completing the baseline interview, $40 for attending the first 
session, then $60 for post-intervention assessments and 20-minute exit interview after completion of 
CPT-L sessions (i.e., post intervention ~6 weeks after study enrollment); and a $75 gift card for 3 month 
follow up surveys. Several questionnaires were drawn from the PROMIS common data elements and 
NIH sponsored repositories to promote data sharing (e.g., PROMIS depression and BRICS Social 
Determinants of Health). Participants will complete a brief electronic diary on a weekly basis to assess 
use of resources/additional supports. Research has demonstrated the validity of this approach, including 
capturing “real-time” data beyond what can be captured with retrospective reports.139 Surveys (<1 minute 
each) will be electronically collected once a week for the 6 weeks of the intervention period starting one 
week after randomization (i.e., 6 electronic survey entries), leading up to the 3-month follow up. With 
input from the CAB, we have established procedures to auto-send an email or SMS text (participant 
choice) on a set schedule. SMS text messaging is possible via Twilio, embedded within our REDCap 
system, which allows participants to complete a survey directly from their phone, without having to 
access a webpage.139 Participants will be asked permission for the study team to access electronic 
medical records to collect CD4 count and viral load at the time of enrollment. As an attending physician 
in the clinic, Co-I Eckard is familiar with these electronic records and will oversee the data pull. CD4 T-
cell counts and HIV viral load will be measured as standard clinical practice using standard clinical 
assays (HIV viral load less than 200 considered virologic suppression. Relevant data from the clinic’s 
electronic medical record (e.g., CD4 count, no-shows) will be collected at intervals and study completion 
(i.e., 6 months after participation) to document retention in HIV clinical care using the industry standard140 
of 2 appointments with a provider with prescribing privileges per year, no longer than 6 months apart. PI 
López has planned for adequate staff training and coverage based on experience. The PI will assist in 
training research staff on consent, diagnostic interview, assessment measures, and medical chart data 
retrieval (with Co-I Eckard and Co-I Danielson for service utilization data) and will conduct weekly 
meetings, quarterly reviews, and booster trainings to ensure standardized procedures. See Table 2 for 
research instruments. 
 
 
Table 2. Research Instruments 
Assessment 
Res. 
BL 
Post 
3 
mon* 
weekly 
Description 
Demographics 
questionnaire 
P 
x 
 
 
 
Data collected from participant after consent 
BRICS NINR Social 
Determinants of Health 
P 
x 
 
 
 
18-items assess financial resource strain, physical activity, social 
connectivity/isolation, safety, family income. 
MOS Social Support 
Survey 
P 
x 
 
 
 
19-items assessing different types of support (emotional/informational, 
tangible, affectionate, and positive social interaction 

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[[Montreal Cognitive 
Assessment Test 
(MoCA)]] 
P 
 
 
 
 
[[A brief 10-item screening tool developed to detect cognitive impairment 
that measures 8 cognitive domains, takes 5-10 minutes to administer 
(Nesdarrine et al., 2005), and has been tested in PLWH (e.g., Janssen et 
al., 2015; Koski et al., 2011).]] MoCA-Blind (without requiring visual 
elements) will be conducted prior to consent as part of the pre-eligibility 
process. 
HIV, Trauma, PTSD, and Related 
Outcomes from Clinical Interview 
and Self-Report 
  
  
  
  
ART adherence (self-
report) 
P 
x 
x 
x 
 
ACTG trial adherence measure self-report of medication within the last 4 
days and self-efficacy. 
Saberi Method 
Adherence 
P 
x 
 
 
X 
(week 
4 and 
week 
8) 
Another method for ART adherence through collecting self-rated 
adherence (SRA), Pill count based adherence (PCA), and Proportion of 
days covered (PDC). PCA and PDC will be collected by the participant 
sending a text photograph of pharmacy refill and remainder of pills to a 
MUSC approved study cell phone. SRA, PCA, and PDC will be collected 
at Baseline, Week 4, and Week 8.  
HIV Quality of Life 
(WHOQOL-BREF) 
P 
x 
x 
x 
 
A 26-item measure categorized into four domains (i.e., physical health, 
psychological well-being, social relationships, and environment); 
measures effects of disease and health interventions on an individual’s 
perception of quality of life and assesses changes in quality of life across 
treatment. 
HIV stigma measure 
P 
x 
x 
x 
 
Developed by Berger et al. (2001)141, revised by Bunn et al. (2007)142; 
multiple dimensions of stigma 
[[Everyday 
Discrimination Scale]] 
P 
x 
x 
x 
 
[[Developed by Williams et al (1997), 10-item self report measure is a 
common approach to measuring intersectional stigma (Turan et al. 2019) 
by asking parallel questions related to different identities.]] 
CAPS PTSD 
Diagnostic Interview 
PC 
x 
x 
x 
 
A 30-item structured clinical interview to derive PTSD diagnoses, but also 
provides PTSD intensity scores. Considered the gold standard in PTSD 
assessment and corresponds to DSM-5 criteria for PTSD. Interview items 
focus on symptom presence, onset and duration of symptoms, subjective 
distress, impact of symptoms on social and occupational functioning and 
improvement in symptoms 
Life Events Checklist  
(LEC-5) 
P 
x 
 
x 
 
Assesses exposure to 16 events known to potentially result in PTSD and 
includes one additional item assessing any other extraordinarily stressful 
event not captured in the first 16 items. 
PTSD Checklist (PCL) 
P 
x 
x 
x 
x 
Corresponds to current DSM-5 PTSD criteria; 20-items scored on a 0-4 
Likert scale for each symptom corresponding to “Not at all” to 
“Extremely”. Psychometric data demonstrates good internal consistency 
(α =.96) and test-retest reliability (r = .84).  
Emotion Regulation 
Questionnaire (ERQ) 
P 
x 
x 
x 
 
Consists of 10 items capturing two emotion regulation strategies, 
cognitive reappraisal and emotion suppression on a 7-point Likert scale 
("1" strongly disagree, "4" neutral, and "7" strongly agree). 
Substance use: 
AUDIT; DAST 
P 
x 
x 
x 
 
Each self report consists of 10 items; excellent reliability and convergent 
validity. 
PROMIS Depression 
A-6 items 
P 
x 
x 
x 
 
Assesses negative mood (e.g., sadness, guilt), views of self (self-
criticism), social cognition (loneliness), decreased positive affect and 
decreased engagement (loss of interest, meaning). 
Patient Health 
Questionnaire (PHQ-9) 
P 
x 
x 
x 
 
Validated for use to monitor the severity of depression and response to 
treatment; scores major depressive episode criteria as "0" (not at all) to 
"3" (nearly every day).  
Participant Treatment 
Engagement 
  
  
  
  
Treatment Expectancy 
Scale 
P 
 
 
 
x 
(first wk.) 
6-item scale assesses patient expectancy for the intervention to improve 
their lifestyle/functioning. 
Credibility Expectancy 
Quest. 
P 
x 
 
 
 
Assesses how much participant believes that the intervention will reduce 
their mental health symptoms.  
Engagement in 
Session 
CM 
 
 
 
x 
Research clinician rates on a 1 to 5 scale on total patient engagement, 
cooperation. 
Services Tracking 
Form 
P 
x 
x 
x 
x 
6 items (McLellan et al., 1992)137; records type and amount of services 
engaged in for PTSD symptoms, including mode (group, individual 
couples, family, self-help, medication) and # of hours in each service. 
Support Electronic 
Survey 
P 
x 
x 
x 
 
Captures more ecologically valid data than retrospective recall at three 
data assessment points (0, post intervention, 3 month follow up), support 
services will be collected via REDCap survey from baseline until 3 month 
follow up across both conditions.  
Electronic Medical Record Data 
  
  
  
  
CD4 count 
PC 
x 
x 
x 
 
We will use clinic lab test (standard clinical assays) results for our data. 
HIV care appointment 
adherence† 
PC 
x 
 
x 
 
Electronic medical record data coding at end of study for clinic 
appointment attendance with a provider with prescribing privileges 
Viral load 
PC 
x 
x 
x 
 
We will use standard clinical assays (collected for clinical purposes). An 
HIV viral load less than 200 will be considered consistent with virologic 
suppression. 

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Services Chart Review 
PC 
x 
x 
x 
 
PC will use the same Services Tracking Form to capture data on service 
utilization entered by case managers of SOC and CPT-L participants in 
the electronic medical record. 
Treatment Assessment 
  
  
  
  
Clinician Survey on 
PTSD 
PC 
x 
x 
x 
 
Assesses therapist experience and attitudes (completed by the project 
therapist before training, after training, and at 3-month intervals 
throughout the trial) 
Therapist Fidelity 
Checklist 
CM 
 
 
 
x 
Checklist used by Drs. Resick and Safren in CPT and Lifesteps protocol 
studies. 
Reactions to Treatment 
  
  
  
  
Client Satisfaction  
Questionnaire-8 
P 
 
x 
 
 
Likert scale with 8 items that has been standardized to investigate client 
satisfaction. 
Acceptability 
P 
 
x 
 
 
At the first assessment following treatment graduation or discontinuation, 
participants will complete a survey (1 = strongly disagree to 4 = strongly 
agree) on their satisfaction (with intervention, therapist, frequency, length 
of sessions, with amount of confidentiality and respect received); ratings 
of usefulness of each session; perceived barriers, general experience 
with the study, likelihood of recommending the study to other patients, 
and suggestions for improving treatment. 
Working Alliance 
Inventory-Short 
Revised (WAI-SR) 
P 
 
x 
 
x  
(wk 3; mid 
treatment) 
Assesses three key aspects of the therapeutic alliance: (a) agreement on 
tasks of therapy, (b) agreement on goals of therapy and (c) development 
of an affective bond. 
Exit Interview 
PC 
 
x 
 
 
Conducted with PC to avoid potential impression management bias. 
"what are advantages/ disadvantages of getting referred to PTSD 
treatment, do family members support you, barriers to participation, are 
there steps in place to help with participation, what were previous barriers 
to PTSD treatment; would you recommend this to others; how can this 
intervention better fit your needs, etc." 
Summative Exit 
Interview 
AP 
 
x 
 
 
A research team member will guide CAB members to understand their 
reactions to the training and treatment models, perceived fit and 
usefulness within HIV care clinic treatment settings, identified 
implementation barriers/facilitators, and recommendations to improve 
larger scale trial procedures  
Note. Res = Respondent; P = Participant; CM = Case Manager; PC = Project Coordinator; AP = Advisory Panel; BL = Baseline 
* Collected in Aim 2 participants 
† Adherence will be collected up to 6 months after participant completion 
 
Impact and Future Directions. Evaluating evidence-based trauma treatments to target specific needs of 
hard-to-engage populations will significantly impact public health by improving patient outcomes, 
engagement, and medication adherence across pathologies and health promotion efforts. This study will 
provide valuable data for PLWH by establishing the protocol for increasing ART adherence and retention 
in care through an adapted PTSD treatment, CPT-L. 
 
 
12.0 Data Management  
Sample size, Statistical Power and Analysis 
Sample size justification. As the study is designed to demonstrate feasibility, sample size was 
determined based on pragmatic considerations, rather than formal power analysis.143 The study plans to 
enroll 60 PLWH randomized to CPT-L or Lifesteps.144 This sample size is adequate to assess feasibility 
outcomes (enrollment, attrition, retention, adherence to protocol and fidelity). The sample size recruited 
during our recruitment period (18 months) will allow the team to specifically justify that we can approach 
a reasonable sample for a larger RCT in an expanded recruitment period. Further, with a target retention 
rate of ≥90%, an enrolled sample of 60 participants produces a 95% confidence interval from 82% to 
98% and an adherence rate of 80% will produce a 95% confidence interval between 70% and 90%. The 
study will produce both within and between treatment group estimates of visit attendance (yes/no), ART 
adherence (85% of doses taken), and proportion of detectible viral load (yes/no). Further, if mean HIV 
Symptom Severity, CD4 cell counts, PCL and CAPS-5 scores will be assessed post-intervention and a 
sample of 30 participants in each group will provide adequate power to determine estimated a 
confidence interval with a difference of ½ a standard deviation (0.51 SD) of the between group mean 
estimate. If the difference in proportion of participants with detectible viral load is 10% in the CPT group 
and 20% in the SOC Lifesteps group at the close of treatment (10% difference), the sample of 30 
participants in each study group will provide an 18% confidence interval on either side of the estimated 
difference. 
 

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Data Analysis Aim 1. All therapy sessions and exit interviews will be audio-recorded and analyzed using 
NVivo12 software by PI Moreland for unique and essential elements to improve the protocol (or CPT 
intervention). Qualitative data analysis is inductive, iterative, and eclectic.145 Qualitative content analysis, 
specifically latent and manifest content analysis146, will be used to identify and describe major themes 
and sub-themes that emerge.121,147 This is a dynamic type of analysis oriented toward recognizing, 
coding and categorizing patterns from text data.121,147 Manifest content analysis involves the visible, 
obvious components of what the transcript says; latent content analysis involves an interpretation of the 
underlying meaning of the text. Methods are utilized to explore participants’ unique perspectives via 
identification of themes/patterns that naturally emerge from the data and systematic classification of 
these themes. [[In qualitative analyses, independent coders will immerse together with their analyses to 
confirm themes and resolve any divergent analyses through a reconciliation and refinement process.]] 
Co-I Moreland has utilized this qualitative approach in 8 federally funded studies, where she has 
published106, 148-152 and presented peer-reviewed findings utilizing qualitative data. PI Moreland will 
review emerging themes with the study team, CAB members, stakeholder, and topical experts to 
incorporate data from qualitative interviews into each step of the refinement process.153 Consultants 
Resick and Safren will ensure fidelity to manual for any suggested changes to CPT-L. Data collected will 
provide the pathway to improve the protocol and ensure feasibility and acceptability. Contingency Plan. 
Completion of Aim 1 will allow refinements of the integrated protocol of CPT-L for Aim 2. PI López has 
assembled a team with extensive expertise in recruiting high-risk and difficult to engage participants in 
both PTSD and PLWH (Co-Is Danielson, Moreland, Eckard; Consultant Safren) and in feasibility testing 
for clinical interventions (Consultant Safren, Resick, Co-I Danielson). Low acceptability in Aim 1 will 
prompt meetings with the CAB to make modifications before implementing Aim 2. Any unanticipated 
challenges to feasibility will be addressed by the qualitative analyses and the approach will be refined. 
Exit interviews will provide suggestions to improve the protocol. Data will be examined to find whether 
specific factors explain differential effects among participants.   
 
Data Analysis Aim 2. Descriptive analyses will characterize the entire sample and two conditions as 
appropriate using measures of central tendency or frequency distributions and proportions. Feasibility will 
be determined by patient willingness to be screened, proportion of participants meeting PTSD criteria, 
and flow of participants through the study. Feasibility of assessments will be examined through self-
report and medical record abstraction. While CPT has been evaluated in other populations, acceptability 
within PLWH is important for feasibility data. Intervention feasibility will be monitored through 
randomization, session attendance and quality assurance data collection on intervention fidelity and 
supervision. Exit interviews will be analyzed using the same techniques for qualitative analyses 
described for Aim 1. Study feasibility will be determined by ability to adequately randomize and retain 
study participants throughout study intervention and follow-up, determined through ability to successfully 
randomize 4+ patients per month and retain 90% of randomized patients throughout the study. In 
addition to retention, a low rate of missing primary outcome data (≤10% missing) will demonstrate ability 
to integrate the intervention with standard clinical care components and medical health records. Protocol 
adherence will be monitored weekly and reported as the proportion of weekly PCL checklists completed, 
and distribution of clinician rated treatment engagement and cooperation levels. Acceptable protocol 
adherence will be determined by completion of ≥80% of assigned weekly PCL checklists across 
participants. 
 
 
In addition to feasibility, efficacy and adherence outcomes will aid in development of the subsequent 
R01. Parameter and variability estimates of efficacy outcomes will be derived from appropriate statistical 
models. Specifically, HIV symptom distress (physical and mental), CD4 cell counts, viral load, clinic 
attendance and ART adherence will be measured at pre- and post-intervention and 3-month follow-up. 
Proportion of participants with Clinic attendance (yes/no), ART adherence (yes/no), and detectible viral 
load at the end of treatment and follow up will be compared between study groups using a modified 
Poisson regression approach with a robust sandwich variance estimator.154 Initial analytic models for 
binary outcomes will include the primary treatment effect, study visit and interaction of study visit and 
treatment as well as variables used to balance the randomization procedure. Adjusted models will 
explore the additional baseline covariates significantly associated with outcomes. The proportion 
successful in each treatment group at each visit, the relative risk of success and associated 95% 
confidence interval will be reported. We anticipate that treatment will decrease CD4 cell counts and HIV 

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symptom severity more so in the CPT-L group compared to Lifesteps at the follow up clinic visit. 
Treatment group differences will be assessed using generalized linear models adjusted for baseline cell 
counts/symptom scores. Normality of model residuals will be assessed using Q-Q plots and data 
transformations will be performed as needed. The CAPS-5 and PCL will examine PTSD severity at 
baseline, post-intervention and 3-month follow-up. The PCL will be assessed weekly during study 
intervention and follow-up. Rates of change from baseline to post-intervention and follow up will be 
estimated with generalized linear mixed effects regression models. Linear slope trends over time and 
associated standard errors will be calculated for each treatment assignment using a single model for all 
data. Estimated CAPS, PCL, and HIV symptom severity scores and associated standard error estimates 
will be calculated for each study group at each study visit and effect size estimates (Cohen’s d, partial 
eta2) will be tabulated and reported. As PCL scores are measured weekly, non-linear mixed effects 
models will be fit to not any cubic or quadratic trends that occur during study treatment and estimates of 
when treatment efficacy begins to show changes in effect size will be assessed and reported.  
 
Exploratory investigations of substance use/misuse will be collected using the AUDIT and DAST.  
Changes in the proportion of participants reporting substance use between groups following study 
treatment and follow-up will be compared using modified Poisson regression models adjusted for 
baseline use and study treatment.  Continuous AUDIT and DAST scores will be assessed in those who 
report use and compared between groups using generalized linear mixed effects models. Depression will 
be assessed at the same time points using the PROMIS Emotional Distress-Depression short form. Both 
raw and prorated T-scores will be assessed at each timepoint and treatment group comparisons will be 
made using generalized linear mixed effect models, adjusted for baseline PROMIS scores and study 
visit.  Exploratory models will be adjusted variables used to balance the randomization procedure and 
those correlated with study outcomes. Secondary analysis of additional  measures (QOL, HIV Stigma, 
Intersectional Stigma, ERQ) will be assessed between study groups using appropriate statistical 
methods.  Analyses will be conducted using SAS version 9.4 (SAS Institute, Cary, NC, USA). 
 
Exploratory Investigation into Moderators and Mediators. Baseline measures of sex and gender identity 
as well as history of viral suppression will be assessed as treatment moderators of feasibility, HIV and 
PTSD outcomes. Moderation will be assessed utilizing addition of interactions into models described 
above.  Although not specifically powered to detect statistically significant interactions, interaction and 
stratified effect sizes will be presented. Effect sizes will inform relevant hypothesis for future R01 study 
development. We hypothesize that changes in PTSD-related avoidant coping following the intervention 
will mediate the relationship between treatment and HIV outcomes at follow up (CD4 Cell Counts, HIV 
Symptom Severity, ART adherence). Mediation models will estimate indirect and direct effects as well as 
the proportion mediated using the PROCESS macro.155 Bootstrap resamples (1000 resamples) will 
provide point estimates and confidence intervals of the mediating effect of changes in avoidant coping on 
the relationship between treatment with CPT-L and HIV related outcomes. Feasibility for the subsequent 
R01 is needed to demonstrate that data can be successfully collected to analyze proposed efficacy and 
mechanism testing hypotheses (see Form F for Proposed RCT analyses).  
 
Data Capture and Management. This study will use Research Electronic Data Capture (REDCap) for 
data capture and management. REDCap is a software toolset and workflow methodology for the 
electronic collection and management of research and clinical trials data. REDCap provides secure, 
web-based, flexible applications, including real-time validation rules with automated data type and 
range checks at the time of data entry. Exports are made available for several statistical packages 
including SPSS, SAS, SATA, R and Microsoft Excel. The study-specific REDCap database will be 
designed and developed by MUSC research team.  The provision of REDCap is made available through 
the South Carolina Clinical & Translational Research (SCTR) Institute at MUSC with NIH Grant awards 
UL1RR029882 and UL1TR000062. The recruitment report will be stored in REDCap but will be separate 
from the research database. Only IRB approved study personnel will have access to the recruitment 
report. The study team will lose access to the recruitment project at the conclusion of enrollment. The 
recruitment REDcap will contain both identifiers and health information in the same project. 
 
Regulatory Binders. The MUSC PI will prepare and maintain an electronic regulatory file to include the 
IRB-approved protocol, IRB correspondence, approved study advertising, and other required study-
related regulatory documents.   

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Deidentification of the research record, data sharing, and retention. At the end of all study activities and 
upon study closure, the electronic study record will be stripped of any and all personal identifiers. 
Deidentified data will be maintained per MUSC Records Retention Policy for a period of 6 years for Federal 
studies before destruction. 
 
13.0 Provisions to Monitor the Data to Ensure the Safety of Subjects  
 
DATA SAFETY MONITORING PLAN 
The Principal Investigator (Dr. López), with support from Co-Investigators, will be responsible for 
monitoring the safety and efficacy of this trial, executing the Data and Safety Monitoring (DSM) plan, and 
complying with the reporting requirements. Data are randomly inspected weekly and inspected thoroughly 
on a quarterly basis. Dr. López will provide a summary of the DSM reports to NIH/NIMH on an annual 
basis as part of the progress report. All DSM reports will include a brief description of the trial, baseline 
sociodemographic characteristics, retention rates and disposition of study participants, quality assurance 
issues, regulatory issues, AEs and SAEs, as well as any actions or changes with respect to the protocol. 
The DSM report to NIH will also include, when available, the results of any efficacy data analysis 
conducted. 
 
SECTION A. Monitoring Entity. 
Considering the study rationale, population, intervention and control procedures, and the risk: benefit 
profile as outlined, the overall risk level for participation in this study is viewed to be classified as: 
Minimum Risk. 
 
DSM Plan Administration 
A Data Safety and Monitoring Board (DSMB) will be assembled. The DSMB will act in an advisory 
capacity to the PI to monitor participant safety, to evaluate the progress of the study, and to review 
procedures for maintaining the confidentiality of data, the quality of data collection, and data 
management and analyses. Frequency of meetings of the DSMB will be determined by recruitment 
milestones (e.g., after 25% of participants have been recruited, etc.), and will follow each SAE report, but 
meetings will occur no less than once per year. The purpose of these meetings will be to review study 
progress, data quality, and participant safety.  
 
The DSMB will be made up of professionals with appropriate expertise, who are willing to participate, and 
who do not have any conflicts of interest. The DSMB will include: 1) one expert in the area of PTSD 
treatment, 2) one expert in the area of adherence intervention, 3) a statistician with expertise in feasibility 
measurement, and 4) two members with expertise in the area of HIV care. DSMB membership will be 
reviewed and approved by the MUSC IRB and NIH. Should there be any questions regarding the 
independence of the DSMB, it will be addressed and corrected, if necessary, at that time. 
 
Conflict of Interest for DSMB 
DSMB members will have no direct involvement with the study investigators or intervention (e.g., 
no portion of their effort will be covered by the study). Each DSMB member will sign a Conflict of 
Interest statement which includes current affiliations (if any) with pharmaceutical and biotechnology 
companies (e.g., stockholder, consultant), and any other relationship that could be perceived as a conflict 
of interest related to the study and/or associated with commercial interests pertinent to study objectives. 
Data will be presented in a blinded manner during the open sessions of the DSMB. At DSMB meetings, 
data and discussion are confidential. Participant identities will not be known to the DSMB members. 
 
DSMB Responsibilities 
The responsibilities of the DSM for this study are as follows: 
• 
Review the research protocol, informed consent documents, and plans for data safety and 
monitoring; 
• 
Evaluate the progress of the pilot trial, including periodic assessments of data quality and 

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timeliness, recruitment, participant risk versus benefit, performance of the trial site, and other factors 
that can affect study outcome; 
• 
Consider factors external to the study when relevant information becomes available, such as 
scientific or therapeutic developments that may have an impact on the safety of the participants or 
the ethics of the study; 
• 
Review study performance, make recommendations and assist in the resolution of problems reported 
by the Principal Investigator; 
• 
Protect the safety of the study participants; 
• 
Make recommendations to the Principal Investigator concerning continuation, termination, or other 
modifications of the trial based on the observed beneficial or adverse effects of the treatment under 
study; 
• 
Review interim analyses (The interim data analyses will only include safety related results; analyses in 
regards to study outcome will not be performed. The interim AE reports will provide typology, 
frequency data and outcomes of all reported and documented AE in the electronic study database); 
• 
Ensure the confidentiality of the study data and the results of monitoring; 
• 
Assist the PI by commenting on any problems with study conduct, enrollment, sample size, and/or 
data collection; 
• 
The DSMB will have the authority to temporarily or permanently discontinue the study if it perceives 
that harm is occurring due to the intervention. The DSMB statistician will evaluate the confidentiality 
and integrity of the database and the procedures for recording and storing confidential files. The 
DSMB will also review the elements of the plan to manage emergencies.  
   
SECTION B. Procedures for Safety, Risk and Confidentiality 
1) Monitoring Study Safety 
From the initial screening of the participant by inclusion and exclusion criteria to the informed consent 
process to the provision of participant study instruction to staff training in Good Clinical Practices (GCP) 
and regulations pertaining to the Conduct of Human Participant Research to weekly contact with 
participants to internal monthly quality control audits and protocol fidelity monitoring to the real-time review 
of AE by the DSM to the oversight of MUSC’s IRB, procedures for monitoring study safety are consistently 
afforded throughout study. Specific procedures include: 
• 
Participants will be screened for inclusion and exclusion per the protocol; the PI or project coordinator 
(PC) shall verify 100% of participants’ eligibility prior to study enrollment through review of inclusion 
and exclusion criteria with potential participants.  
• 
Participants will be fully informed as to all known risks and the possibility of risk from study 
participation in the informed consent process. These risks are minimal. 
• 
Participants will be instructed to notify the researchers of any/all suspected or experienced adverse 
events whether they believe them to be related or not to the intervention. 
• 
The PI or PC will track all reported participant AEs through to resolution. Please see Section C. 1 – 4. 
• 
All investigators and research staff will maintain active CITI training. 
• 
The PI or PC will maintain weekly contact with all participants to elicit information about AE’s and to 
monitor participant study progress, compliance and safety. 
• 
The PI or PC will review participants study logs for fidelity compliance with the CPT-L and Lifesteps 
Protocols. 
• 
The PI or PC will conduct a monthly internal quality control audit of all participant records to ensure 
compliance with MUSC IRB regulations; the PI and PC will work together to correct any errors. 
• 
The PI and/or designee will observe and evaluate ten (10%) percent of eligibility screening visits, 
informed consents and study instructions performed by IRB approved study personnel and provide 
feedback and/or retraining of study personnel if fidelity to both applicable federal regulations and the 
protocol is not observed. 
• 
The DSMB Biostatistician shall generate semi-annual AE reports for the PI and DSMB to review. 
• 
Investigator performance and compliance will be provided for through MUSC IRB and ORI study 
oversight. 
 

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2)  Minimizing Research-Associated Risk 
Diligent study safety monitoring will be conducted by the PI and the study’s DSM team throughout the 
conduct of this study in compliance with the following required elements of MUSC IRB’s continuing review 
process: 
1. Tracking and follow-up of participant accrual (inc. withdrawn consents) will minimize risk by identifying, 
disclosing, and mitigating any potentially unknown risk(s) of harm to study participants. These risks 
are minimal. 
2. Timely and appropriate reporting of informed consent process deficiencies, protocol deviations, 
privacy breaches, conflicts of interest, and/or changes in personnel. 
3. Ongoing soliciting, monitoring and appropriate reporting of adverse event activities. 
4. Timely and appropriate IRB submission of safety-related documents such as audit reports, sponsor 
progress reports, ISM reports, and other materials or communications that might impact the safe 
conduct of this study. 
5. Active cooperation with the IRB, ACO, sponsor, and other applicable entities in the event of a random 
or for-cause internal or external audit. 
 
Institution-Wide Assurances 
This protocol will be conducted fully in keeping with the signed MUSC IRB Principal Investigator 
Statement of Assurance and Department Chair’s Statement of Assurance, when submitted to the IRB as 
a required component of the MUSC IRB Human Research Review Application. Assurances include the 
following safety-related agreements. 
 
3) Protecting Confidentiality of Participant data 
Participant Screening and Enrollment. All data from participants screened for the study will be entered 
into a REDCap electronic study database. Screened patients who do not meet study eligibility will have 
specific screening data entered into this database. The collected data will be helpful in examining the 
patient population and feasibility of enrollment criteria and will include reason for exclusion. PHI will be 
immediately stripped from this database for screen failures or for those participants who do not consent or 
are enrolled into the study. For participant enrolled into the study, dates will be shifted and other Personal 
Health Information (PHI) will be removed upon completion of the study. All data obtained from this study 
will be used for research purposes only and will comply with Federal HIPAA regulations. Master 
Screening and Enrollment Logs will be maintained electronically and will only be accessible to be used by 
the PIs or PC in preparation of reports on accrual and attrition for the DSMB. 
 
Electronic Case Report Forms. All proposed study specific case report forms (source documents) for 
data collection will be designed by the PI and transferred by the PI or PC into electronic Case Report 
Forms (eCRFs) for use in the study’s REDCap database. These study specific eCRFs source documents 
(study logs for correspondence, compensation and other forms such as pre-eligibility screens) will be 
coded by the participant’s unique study ID# for all data collected including study instruments and will be 
maintained in the participant’s unique electronic research record. 
 
Regulatory Binders. The MUSC PI and/or designee will prepare and maintain an electronic regulatory 
file to include the IRB-approved protocol, IRB correspondence, approved study advertising, and other 
required study-related regulatory documents.   
 
Data Processing. This study will use Research Electronic Data Capture (REDCap) for data capture 
and management. REDCap is a software toolset and workflow methodology for the electronic 
collection and management of research and clinical trials data. REDCap provides secure, web-based, 
flexible applications, including real-time validation rules with automated data type and range checks at 
the time of data entry. Exports are made available for several statistical packages including SPSS, 
SAS, SATA, R and Microsoft Excel. The study-specific REDCap electronic database will be designed 
and developed by the PI or PC in concert with the biostatistician.  The provision of REDCap is made 
available through the South Carolina Clinical & Translational Research (SCTR) Institute at MUSC 
with NIH Grant awards UL1RR029882 and UL1TR000062.  

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Data Security. Ensuring data security, compliance with 45 CFR 46 and maintaining the integrity of PHI is 
a top priority. MUSC has Standard Operating Procedures (SOP) to ensure a high level of data security 
while coordinating electronic and paper data management activities for clinical research trials. The 
REDCap study database will be hosted in the Biomedical Informatics secure data center at MUSC, a 
secure environment for data systems and servers on campus, and includes firewall, redundancy, failover 
capability, backups and extensive security checks. The secure data center has strict access control; only 
authorized core personnel may access the facility un-escorted. Only authorized users are allowed to 
connect to the network, and the security of the network is actively monitored.  Power and environmental 
controls have several layers of backups, from interruptible power supplies to alternate and redundant 
feeds to the local utility company. The REDCap system administrator contributes to the maintenance of 
institutional disaster recovery and business continuity plans.  Load balancers and a highly fault tolerant 
SAN infrastructure contribute to high availability.  
 
The REDCap system itself has several additional layers of protection including password protection. 
Access to the data and its security is managed institutionally by sponsored login IDs through a 
Shibboleth login with an MUSC issued NetID and features a user account management filter that controls 
who can access the data and to what degree. All personnel must pass an employment background 
check before being issued an ID. Password complexity, history and expiration standards are 
implemented at the institutional level. Access to individual REDCap projects and their data is managed 
by the owner of the project. All transactions are securely delivered to the application using Secure 
Sockets Layer (SSL – SHA-1 with RSA Encryption; 2048-bits). It is then transmitted internally (behind the 
firewall) to the database server. All transactions are logged at the server layer (httpd logging), application 
layers (REDCap logs activity to a database table), and the database layer, using both query and binary 
logging. This feature provides audit trails for all changes, queries, data exports and reports. MUSC 
Information security policies are available at: https://mainweb-v.musc.edu/security/policy/  
 
Data Entry. Only MUSC IRB approved study personnel that are authorized to have access to the 
REDCap study database will be granted password access. Study personnel using computers that are 
connected to the Internet will directly enter data into the remotely housed database. As such, no 
electronic study data will be stored on hard drives and/or any portable electronic devices. Additionally, all 
personnel with access to the database will have current University of Miami CITI training in the Conduct of 
Human Subject Protections, and HIPAA and Information Security trainings that are completed annually. 
Each participant will be assigned a unique study identifier, all PHIs will be masked, and data exports will 
be limited to the PIs, the PC, or the project biostatistician for generating reports and the conduct of 
statistical data analysis. 
 
Data Monitoring. Ongoing quality control procedures will be implemented for data collection, storage 
and processing. The PI or PC will conduct monthly monitoring of the study database and generate a 
report for review at team meetings. Standing agenda items for these meetings will include participant 
recruitment and retention, AE’s, protocol deviations, data integrity and overall study conduct. The PI and 
PC will work to resolve and validate discrepant data. Discrepancies that warrant clarification will be sent 
to appropriate parties for review and resolution. All data entry and changes made in the study database 
by authorized study personnel will be automatically logged by REDCap, and provide a transparent visible 
audit trail for reviewers. 
 
Data Resource Sharing: 
1. DATA FORMAT: Data will be delivered in quantitative format using SPSS software. 
2. DATA COLLECTION: Data will be collected via print questionnaires entered into redcap data collection 
portals within 72 hours of collection. The unit of analysis will be the individual respondent.  
3. ASSURANCES: Assurances, consent form, etc. will be obtained and be compliant with and reviewed 
by MUSC IRB. 
4. VARIABLE CREATION: All variable creation computation syntax will be in SPSS format and 
delivered in txt file for reproduction by any interested party. All weighting computations will be 

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delivered in txt file. All imputation will be outlined and syntax delivered in txt file. A variable definition 
list / codebook and computational syntax document will be delivered. 
PI CONTACT: Information will be included. 
 
SECTION C. Procedures for Identifying, Reviewing and Reporting Adverse Events 
1)  Identifying. Potential minimum risks identified for participants are outlined in the Protection of Human 
Subjects and will also be outlined in the IRB-approved informed consent document. Additional 
unknown risks may occur and, if so, will be identified through diligent monitoring by the PIs or PC 
throughout the conduct of this study. During the informed consent process, participants will be 
advised of the potential minimum risks of participation as identified in the IRB-approved informed 
consent document and reminded throughout the study that the researchers should be promptly 
informed about any concerns regarding potential side effects, adverse events, or clinical 
deterioration. Participants will also be instructed to notify the PI, PC, and/or designee of any 
suspected adverse events immediately if possible. Throughout the course of study enrollment, the 
researchers will maintain weekly telephone and/or face-to-face contact with the study participants to 
elicit information about experienced AE and to monitor participant progress. The PI or PC will 
maintain an electronic record of all reported adverse events and notify the DSMB of all reportable 
events as they occur. The DSM team will have real-time access to the study database to review and 
monitor all reported serious adverse events (SAE) that were reported as related to the intervention. 
The PI or PC will generate and provide de-identified monthly administrative human subject safety 
reports for the DSM team to review participant progress, accrual and attrition rates, and monitor the 
frequency of all reported side effects and AE. Additionally, the biostatistician will generate and 
provide de-identified cumulative administrative human participant semi-annual safety reports for the 
DSMB to review. 
 
2) Reviewing. Adverse events will be assessed and graded by the members of the SMC according to 
the following MUSC’s IRB Adverse Event Reporting Policy  
http://academicdepartments.musc.edu/research/ori/irb/HRPP/HRPP Guide Section 4.7 
• 
Expected/Anticipated—Identified in nature, severity, or frequency in the current protocol, 
informed consent, investigator brochure, or with other current risk information. 
• 
Unexpected/Unanticipated—Not identified in nature, severity, or frequency in the current 
protocol, informed consent, investigator brochure, or with other current risk information. 
• 
More Prevalent—Occurs more frequently than anticipated or at a higher prevalence than 
expected. 
• 
Serious—Results in death, is life threatening, requires inpatient hospitalization or prolongs 
existing hospitalization, results in persistent or significant disability/incapacity, cancer, overdose, 
or causes a congenital anomaly/birth defect. The relationship of adverse events to study 
participation will be determined by the SMC according to the MUSC IRB Adverse Event Reporting 
Policy: 
• 
Unrelated—There is not a reasonable possibility that the adverse event may have been caused 
by the drug, device or intervention. 
• 
Possibly Related—The adverse event may have been caused by the drug, device, or intervention, 
however there is insufficient information to determine the likelihood of this possibility. 
• 
Related—There is a reasonable possibility that the adverse event may have been caused by the 
drug, device or intervention. 
 
3)  Reporting. All reportable AE, SAE and unanticipated problems experienced by participants will be 
reported to the NIH and MUSC IRB in compliance with their Adverse Event Reporting Policy 
requirements, using the IRB's password protected on-line secure server adverse event reporting 
system. Within 24 hours after a reportable AE, SAE or unanticipated problem has been reported by 
the participant, it will be graded by the PI or PC and submitted by the PI to MUSC IRB. After IRB 
review and acknowledgement, the PIs or PC will forward a copy of the reportable AE, SAE or 
unanticipated problem and IRB acknowledgement letter to the NIH Program Officer through MUSC’s 

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OSRP within 24 hours. In addition, all cumulative reportable AE, SAE and unanticipated problems 
included in the DSMB reports will be submitted to the NIH in the PI’s Annual Progress Reports. 
 
4) Definitions of Potential Reportable Adverse Events. In accordance with MUSC IRB Adverse Event 
Reporting Policy, an AE is reportable if it meets all of the following criteria: 1) is unexpected 2) is 
related and/or possibly related, and 3) is serious and/or suggests that the research places subjects or 
others at a greater risk of physical or psychological harm than was previously known or recognized. 
Additionally, per MUSC’s policy all participant deaths, protocol deviations, complaints about the 
research, and breaches of confidentiality are reportable events. In this study we will use the FDA 
definition of serious adverse events (SAEs). SAEs will be systematically assessed at each clinic visit. 
Any SAE, whether or not related to study intervention, will be reported to the IRB and NIH. The initial 
SAE report will be followed by submission of a completed SAE report to both institutions. In the event 
that a client either withdraws from the study or the investigator decides to discontinue a patient due to 
SAE, the client will be monitored by the investigators via ongoing status assessment until 1) a 
resolution is reached i.e., the problem requiring hospitalization has resolved or stabilized with no 
further changes expected 2) the SAE is determined to be clearly unrelated to the study intervention, or 
3) the SAE results in death. Outcome of SAEs will be periodically reported to NIH. A summary of the 
SAEs that occurred during the previous year will be included in the annual progress report to NIH. 
During screening, study applicants will undergo a baseline assessment to determine their eligibility 
and safety of their participation in this study. History of suicidal ideation or suicide attempts, and other 
suicidal risk factors, including suicidal ideation, intent, and plan will be carefully assessed and 
monitored through the study. The PI, who is a licensed clinical psychologist, will be contacted 
immediately regarding clients who are at risk to commit suicide to aid in safety assessment (as 
described in Human Subjects plan) and will be offered additional treatment (e.g., hospitalization) as 
needed and appropriate. As noted above, all adverse effects of the interventions, assessment 
procedures, or any aspect of the study will be documented and reported within 24 hours to the 
University IRB and the Project Officer(s). 
 
SECTION D. Assessment of External Factors 
The PI will conduct a semiannual assessment of external factors through a review of literature related to 
new developments in the areas of HIV adherence, PTSD symptom management (including avoidant 
coping and stigma), symptom reporting and other approaches that may have an impact on the safety of 
participants or on the ethics of the study. To determine whether any changes are necessitated to the 
study protocol, DSMB will review any identified literature or product safety data that may pose as a 
potential impact to the risk benefit ratio study and/or safety of study participants. 
 
SECTION E. Interim Analysis 
This study aims to test the feasibility and acceptability of an integrated, evidence-based protocol for 
PTSD and adherence for PLWH within a HIV care clinic. To our knowledge, there are no similar studies 
specifically designed for this patient population and purpose. As such, the biostatistician will generate 
semi-annual qualitative interim analysis reports on a) adverse events; and b) data obtained during phone 
call and returned end-of-study surveys to understand issues related to the uptake, usability, and adoption 
of this intervention among this population. We will evaluate the screening and enrollment procedures, 
barriers to participation and retention, including, safety, adherence, acceptability, problems encountered, if 
any, and feedback from the participants and the case managers. This information gained from this 
structured process will be used to both guide the refinement of the current protocol and to inform the 
design of a larger efficacy trial. Interim analysis of outcome variables (e.g., PTSD symptoms, ART 
adherence, viral load) was not considered to avoid inexact inferences and increased chance of error due 
to few data points, as well as potential for bias if interim results were known to the investigators. 
Therefore, there are no planned stopping rules for this study.  
 
14.0 Withdrawal of Subjects 
Participants may voluntarily elect to withdraw their consent at any time for any or no given reason while 
enrolled in the study. The PI may withdraw participants from the study at any time if they decide it is in 

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the participant’s best interest, if they do not follow the investigator’s instructions, and/or if they fail to 
maintain to contact with the researchers or attend study visits. Withdrawals of participants may also 
occur if there is a protocol violation or early study closure. All data gathered from withdrawn participants 
will be used in the analysis plan under an Intention-to-Treat (ITT) model. 
 
15.0 Risks to Subjects and Risk Management 
We do not anticipate any elevated risk level associated with the comparison of the intervention treatment 
as compared to the current standard of care. However, there are known inherent risks associated with 
the conduct of human subject research as well as with the provision of mental health services to this 
target population. These risks, as well as mitigation strategies, are identified and outlined below, 
respectively. 
 
Loss of privacy: PHI from participants will be gathered and stored electronically on secure and encrypted 
servers and there are risks associated for the loss of privacy and confidentiality. We will minimize the 
potential for loss of confidentiality through the physical separation of participant names from their 
research record according to the process described below. Clinical interviews will take place in a private 
setting. Audio recordings of interviews will be uploaded for transcription within 48 hours to an outside 
agency with which MUSC has established a Business Associates Agreement (BAA). Once uploaded, all 
audio recordings will be deleted from the portable storage device. 
 
All information obtained from participants will be confidentially maintained. Participants will be reminded 
on a weekly basis that content of treatment will not be reported to providers and will be anonymous. 
Research staff will receive training from the Principal Investigator on the importance of privacy and 
confidentiality and will have a supervision meeting with the Principal Investigator to ensure strict 
compliance with the Human Subjects Protection plan. With regard to data management, safety, and 
storage, all data will be collected, managed and maintained through MUSC REDCap survey 
 
Participant will be assigned a unique study ID code. Only participants’ study identification codes will be 
on collected measures and e-CRFs. The REDCap database that links the name of the participant and 
their study ID will be maintained as a separate REDCap project from the research REDCap database. 
The secure servers that will house the data files are located at MUSC on SSL (Secure Sockets Layer) 
128-bit encrypted servers behind firewalls. Respondent confidentiality will be masked in all data files by 
the use of uniquely assigned study identification numbers rather than personal information. All other 
electronic records, including digital audio recordings of sessions, are de-identified in collection and will be 
maintained in password protected locations also on the secure server. The only document linking 
participants with identification numbers will be retained in an encrypted file on MUSC REDCap secure 
server with access limited to the Principal Investigator, Program Coordinator and Nurse Interventionist. 
Data presented at professional meetings or published in journals or books will not allow identification of 
individual participants. These procedures are expected to minimize any potential risk of loss of privacy 
from participating in this study.  Audio files of participation in the intervention or exit interviews will be used 
solely for research purposes. Exit interviews will be conducted either in-person in the privacy of a clinic 
room at MUSC Ryan White, or remotely via telephone at a time location and setting of the participants 
choosing. Participants will be informed when the interview recording has begun and ended and will be will 
receive initial instruction not to use the names of individuals or reveal any personally identifiable 
information. Audio interview files will be temporarily on a portable recording device, prior to being uploaded 
within 24hrs to the deidentified research database and later transcribed by a vendor that has executed a 
BAA with MUSC. Audio files will only be identified by numeric codes of sessions recorded and will be 
destroyed from the recording device after upload to REDCap. Only the project therapist, raters, and 
investigators will hear the content of the audio recordings.  
 
The only exceptions to confidentiality include situations involving participant’s self-disclosure of potential 
abuse/neglect or risk of harm to self or others or report of nonconsensual sexual activity. These cases will 
be contacted by Dr. López, a licensed clinical psychologist (SC # 1227) who has substantial experience 
successfully handling crises. In addition, the MUSC Institute of Psychiatry clinics have standard protocols 

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for handling these high-risk situations. If a Research therapist or team member is told that there is any 
risk of harm to the participant or others, s/he will immediately contact Dr. López. Dr. López will assess 
safety and provide instructions to the project team member to address any risks (according to the research 
protocol developed over years of experience at MUSC). Dr. López will conduct a comprehensive risk 
assessment with the participant. If there is any indication of a potential for harm, Dr. López will take 
appropriate action (e.g., contacting the police or ensuring the participant is taken to the emergency room). 
The therapist will have a cell phone number where Dr. López will be available at all times.  
 
If a participant is deemed at risk for suicide and will not contract for safety, or has made a suicidal 
gesture or attempt, the participant will be assessed by the local emergency department for possible 
inpatient hospitalization. In circumstances where patients express suicidal ideation and are sincerely 
willing to contract for safety (i.e., will agree to keep her/himself safe), project therapists will do follow up 
phone calls to monitor safety until suicidal ideation has decreased.  Dr. López will ensure individuals 
disclosing suicidal ideation are well educated on how to access 24-hour emergency care. A detailed 
safety plan - detailing what to do and whom to speak with if ideation should escalate - will be discussed, 
including specifics on how to access 24-hour care for suicidality via dialing 9-1-1 and/or going to the 
closest emergency department when therapist is not available.  Thus, a 24-hour safety plan is in place, 
including access to medical care 24 hours per day.  If a participant is deemed at risk for suicide and the 
participant will not contract for safety, or has made a suicidal gesture or attempt, assessment and 
evaluation by a local emergency department for possible inpatient hospitalization will be recommended. 
Dr. López has the capacity and will coordinate to arrange for direct inpatient admission assessment at 
the MUSC inpatient units (MUSC Institute of Psychiatry) for individuals requiring such assessment (e.g., 
concerns about danger to self or others) and who elect to go to MUSC. Routine monitoring of adverse 
events will also occur through weekly meetings between the Principal Investigator and therapists 
 
Emotional distress: Some of the questions asked may be upsetting to participants or make them feel 
uncomfortable answering them. Participants will be instructed that if they do not wish to answer a 
question, they can skip it and go to the next question.  
 
Regarding instances of more significant distress, including suicidality (suicide-related thoughts, intent, 
plan, and means), participants will undergo a complete battery of psychological tests to determine their 
eligibility and safety of their participation in this study during the initial assessment. Special attention will 
be placed on history of suicidal ideation or suicide attempts. Participants who are at high risk of 
attempting suicide will not be recruited into the study (i.e., have made an attempt in the past 36 hours).  
They will be offered access to additional treatment (including additional appropriate mental health 
referrals) if warranted. 
 
For participants enrolled in the study, in any circumstances where an assessor or a therapist is concerned 
regarding suicidal ideation or attempt, Dr. López or Dr. Danielson will be contacted immediately. All 
research staff will have a cell phone number where Dr. Lopez will be available 24 hours 7 days a week. In 
rare instances where Dr. Lopez cannot be reached, Dr. Danielson will serve as a back-up. Dr. Lopez will 
ensure project therapist is well trained in assessing distress and suicidality (intent, plan, etc). In 
circumstances where participants in either condition express suicidal ideation and are sincerely willing to 
contract for safety (i.e., will agree to keep themselves safe), PI Dr. Lopez will form a safety contract with 
participant and continue to monitor and re-assess risk until risk has been reduced. If a participant is 
deemed at risk for suicide and will not contract for safety, or has made a suicidal gesture or attempt, the 
participant will be assessed by local emergency department for possible inpatient hospitalization. Dr. Lopez 
will help facilitate direct inpatient admission assessment at the inpatient units for individuals requiring such 
assessment (e.g., concerns about danger to self or others). The project coordinator also will ensure all 
participating individuals are well educated on how to access 24-hour emergency care (through 9-1-1 or 
going to the local Emergency Department).  
 
Physical fatigue: Completion of the questionnaire, measures and interviews may be tiring to some 
participants.  Participants will be given ample time to complete the questionnaire and may take breaks as 

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necessary throughout the process. Participants are also informed in the informed consent process that 
that may voluntarily stop their participation in the study at any time. 
 
Randomization: Participants are being assigned to the intervention and control group by chance. The 
intervention under investigation may prove to be less or more effective than currently available standard 
of care treatment (control).  
 
16.0 Potential Benefits to Subjects or Others 
This project will assess the feasibility of providing the CPT-L protocol for PTSD populations with co-
occurring HIV infections in an ID clinic. If support for feasibility is found in this project, we plan to conduct 
a larger-scale evaluation to assess the incremental dissemination, reach, and efficacy of the exercises and 
tools that will be developed under the current proposal. Taken together, if data from these studies suggest 
that the integrated intervention enhances engagement and patient outcomes, benefits to participants are 
potentially very high. The proposed approach is highly sustainable due to low costs of disseminating these 
resources, and therefore has the ability to reach a large population.  
 
The benefit to be gained to the adults participating in this project is that we are providing evidence-based 
treatment that they could not previously access. CPT is an evidence-based treatment for PTSD; thus, 
participants that have not been able to access trauma treatment are expected to experience a reduction in 
PTSD symptoms, though this cannot be guaranteed. Moreover, it is anticipated that participants will find 
the co-location of services as a means of better engagement, which may improve their intervention 
experience. Potential benefits to participants also include improved adaptive functioning (via increased 
emotional regulation skills/reduced avoidant coping) and increase in ART adherence (with the Lifesteps 
protocol), though these cannot be guaranteed. Participants will receive comprehensive psychosocial 
assessments at no charge. Potential benefits may also include personal validation that comes from being 
told their experiences are important and that the information gathered from the study will be used to learn 
how to help other people with similar histories. In addition, the successful validation of co-located PTSD 
treatment programs as an intervention for increasing adherence and viral suppression would be of 
significant benefit to society. 
 
IMPORTANCE OF KNOWLEDGE TO BE GAINED 
Persons who live with HIV experience (PLWH) higher levels of trauma during childhood and continue at 
increased risk during adulthood (40-90%5) relative to the general population. This is particularly 
unfortunate because trauma experience in this population is associated with increased mental health 
problems6, faster disease progression7, more hospitalizations 8, almost twice the rate of death 9 and, 
distressingly, and lower adherence to Anti-Retroviral Therapy (ART) 10. Effective treatment of 
posttraumatic stress disorder (PTSD) in PLWH with comorbid PTSD may reduce negative HIV-related 
outcomes and enhance ART adherence. Yet, despite the high occurrence and harmful effects of PTSD in 
HIV-infected individuals, there is relatively little research on the efficacy of treating PTSD in this difficult-
to-engage population. Providing trauma treatment to target the specific needs of PLWH living with 
comorbid PTSD may reduce avoidant coping in this typically treatment-resistant population and increase 
ART adherence. 
 
Despite the exacerbated consequences of trauma exposure related to HIV patient outcomes, improvement 
of patient access to trauma treatment for populations living with HIV has been neglected. By capitalizing 
on existing resources (i.e., MUSC Ryan White clinic), the current application proposes to integrate 
evidence-based trauma treatment (e.g., CPT) with an adherence intervention (Lifesteps) and implement 
into an ID/HIV care clinic and provide initial test of feasibility and safety for a high risk group with co-
occurring PTSD and self-management with HIV care. Data from this pilot RCT are critical to the 
development of a full-scale appropriately powered trial that would enable us to determine the efficacy of 
CPT-L intervention on increasing ART adherence and viral suppression, and to identify the best, most cost-
effective method for delivering these trauma treatment services with high fidelity to high risk and 
underserved populations. The tailoring of evidence-based trauma treatments to target specific needs of 
hard-to-engage populations (e.g., engagement, disclosure distress) can have a significant public health 

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impact by improving patient outcomes, engagement, and medication adherence across several 
pathologies and health promotion efforts. 
 
17.0 Sharing of Results with Subjects 
As this is a feasibility study, we do not intend to directly share study results with participants. We 
will however share our findings through Open Access journal publications in alignment with 
NIH/NIMH policy. These findings will be available to the general public, including previously 
enrolled study participants. 
 
 
 

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BIBLIOGRAPHY & REFERENCES CITED WITHIN THE 4.2.a. NARRATIVE STUDY DESCRIPTION 
 
1. Farmer, C. C., Mitchell, K. S., Parker-Guilbert, K., & Galovski, T. E. (2017). Fidelity to the cognitive 
processing therapy protocol: evaluation of critical elements. Behavior Therapy. 48(2), 195-206.  
2.  Resick, P. A., Monson, C. M., & Chard, K. M. (2010). Cognifive Processing Therapy: Veteran/military 
version. Washington, DC: Department of Veterans’ Affairs. 
3. Hedden SL, Woolson RF, Malcolm RJ. (2006). Randomization in substance abuse clinical trials. 
Subst Abuse Treat Prev Policy. 1:6. PMCID: PMC1436001. 
4. Eldridge SM, Chan CL, Campbell MJ, et al. (2016). CONSORT 2010 statement: extension to 
randomised pilot and feasibility trials. BMJ. 355:i5239.PMCID: PMC5076380. 
 
BIBLIOGRAPHY & REFERENCES CITED WITHIN THE PROTECTION OF HUMAN SUBJECTS 
 
1. Guest G, Namey E, McKenna K. How Many Focus Groups Are Enough? Building an Evidence Base 
for Nonprobability Sample Sizes. Field Methods. 2017;29:3-22. 
2. Prins A, Bovin MJ, Smolenski DJ, et al. The Primary Care PTSD Screen for DSM-5 (PC-PTSD-5): 
Development and Evaluation Within a Veteran Primary Care Sample. J Gen Intern Med. 
2016;31(10):1206-1211. PMCID: PMC5023594. 
3. Danielson CK Adams Z, McCart MR, Chapman JE, Sheidow AJ, Walker J, Smalling A, de Arellano 
MA.Safety and Efficacy of Exposure-Based Risk Reduction Through Fsmily Therapy for Co-
Occurring Substance Use Problems and PTSD Among Adolescents: A Randomized Clinical Trial. 
JAMA Psychiatry. 2020; 77(6): 1-14. PMCID: PMC7042939. 
4. Acierno R, Knapp R, Tuerk P, et al. A non-inferiority trial of Prolonged Exposure for posttraumatic 
stress disorder: In person versus home-based telehealth. Behav Res Ther. 2017;89:57-65. 
PMC5222772. 
5. Brezing C, Ferrara M, Freudenreich O. The syndemic illness of HIV and trauma: implications for a 
trauma-informed model of care. Psychosomatics. 2015;56(2):107-118. 
6. Leserman J, Pence BW, Whetten K, et al. Relation of lifetime trauma and depressive symptoms to 
mortality in HIV. Am J Psychiatry. 2007;164(11):1707-1713. 
7. Kimerling R, Armistead L, Forehand R. Victimization experiences and HIV infection in women: 
associations with serostatus, psychological symptoms, and health status. J Trauma Stress. 
1999;12(1):41-58. 
8. Mugavero MJ, Lin HY, Allison JJ, et al. Racial disparities in HIV virologic failure: do missed visits 
matter? J Acquir Immune Defic Syndr. 2009;50(1):100-108. PMCID: PMC2766510. 
9. Machtinger EL, Lavin SM, Hilliard S, et al. An expressive therapy group disclosure intervention for 
women living with HIV improves social support, self-efficacy, and the safety and quality of 
relationships: a qualitative analysis. J Assoc Nurses AIDS Care. 2015;26(2):187-198. 
10. Spies G, Afifi TO, Archibald SL, Fennema-Notestine C, Sareen J, Seedat S. Mental health outcomes 
in HIV and childhood maltreatment: a systematic review. Syst Rev. 2012;1:30. PMCID: 
PMC3441909. 
 
 BIBLIOGRAPHY & REFERENCES CITED WITHIN THE RECRUITMENT AND RETENTION PLAN 
 
1. Guest G, Namey E, McKenna K. How Many Focus Groups Are Enough? Building an Evidence Base 
for Nonprobability Sample Sizes. Field Methods. 2017;29:3-22. 
2. Prins A, Bovin MJ, Smolenski DJ, et al. The Primary Care PTSD Screen for DSM-5 (PC-PTSD-5): 
Development and Evaluation Within a Veteran Primary Care Sample. J Gen Intern Med. 
2016;31(10):1206-1211. PMCID: PMC5023594. 
3. Danielson CK et al. The Safety and Efficacy of Exposure-Based Treatment of Co-Occurring 
Substance Use Problems and PTSD Among Adolescents: A Randomized Controlled Trial of Risk 
Reduction through Family Therapy (RRFT). Manuscript submitted for publication. Under Review. 
 
BIBLIOGRAPHY & REFERENCES CITED WITHIN THE STATISTICAL DESIGN AND POWER 
 

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1.  Hayes, A. F. (2017). Introduction to mediation, moderation, and conditional process analysis: A 
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