Testing the Effectiveness of an Evidence-based Transdiagnostic Cognitive Behavioral Therapy Approach for Improving HIV Treatment Outcomes Among Violence-affected and Virally Unsuppressed Women in South Africa
Phase: NA
Conditions: HIV/AIDS, Violence
Sponsor: Boston University

 
1
 
 
Research Protocol 
 
Testing the effectiveness of an evidence-based transdiagnostic cognitive 
behavioral therapy approach for improving HIV treatment outcomes among 
violence-affected and virally unsuppressed women in South Africa 
June 30, 2025 
 
Version 1.8 
 
 
NCT04242992 
 
Statistical Analysis Plan- pages 30-33 
 
 
Wits Protocol No. : M200353 
BU Protocol No: H-39746 
Hopkins Protocol No: 12546 
Columbia Protocol No: IRB-AAAS9661 
 
 
 

 
2
CONTENTS 
 
SUMMARY .........................................................................................................................................4 
INVESTIGATORS .................................................................................................................................6 
BACKGROUND, RATIONALE, AND OBJECTIVES ....................................................................................7 
a. Background ........................................................................................................................................... 7 
b. Rationale............................................................................................................................................... 8 
c. Objectives ........................................................................................................................................... 10 
OVERVIEW OF STUDY DESIGN .......................................................................................................... 11 
STUDY SITES AND POPULATION ........................................................................................................ 11 
a. Study Sites .......................................................................................................................................... 11 
b. Inclusion and Exclusion Criteria ......................................................................................................... 11 
STUDY PROCEDURES ........................................................................................................................ 14 
a. 
Overview ......................................................................................................................................... 14 
b. 
Clinic Engagement .......................................................................................................................... 14 
c. 
Recruitment .................................................................................................................................... 15 
d. 
Screening and Screening Consent .................................................................................................. 15 
e. 
Full Consent .................................................................................................................................... 16 
f. 
Male Partners ................................................................................................................................. 17 
g. 
Baseline Assessment ...................................................................................................................... 18 
h. 
Randomization ............................................................................................................................... 19 
i. 
Study Arms: Common Elements Treatment Approach (CETA) ..................................................... 19 
j. 
CETA training and supervision ....................................................................................................... 21 
k. 
CETA Delivery ................................................................................................................................. 22 
l. 
CETA for male partners .................................................................................................................. 22 
m. 
Study Arms: Active control (Texting+Safety) ............................................................................ 23 
n. 
Training and Tracking ..................................................................................................................... 24 
o. 
Safety for both arms ....................................................................................................................... 24 
p. 
Follow-up and Retention ............................................................................................................... 26 
DATA SOURCES AND MANAGEMENT ................................................................................................ 27 
a. 
Baseline and follow up data........................................................................................................... 27 
b. 
Primary outcome data ................................................................................................................... 27 
c. 
Secondary outcome data ............................................................................................................... 27 
d. 
Data Sources ................................................................................................................................... 28 
e. 
Data Entry and Storage .................................................................................................................. 29 
DATA ANALYSIS ............................................................................................................................... 30 
a. 
Primary Outcome ........................................................................................................................... 30 
b. 
Secondary Outcomes ..................................................................................................................... 30 
c. 
Sample Size ..................................................................................................................................... 31 
d. 
Primary Analysis ............................................................................................................................. 32 
e. 
Moderator Analysis ........................................................................................................................ 32 
f. 
Mediator Analysis........................................................................................................................... 32 
a. 
Cost Effectiveness Analysis and Budget Impact Analysis.............................................................. 33 

 
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g. 
Dissemination of Findings .............................................................................................................. 33 
h. 
Costs and Payments ....................................................................................................................... 34 
DATA SAFETY AND MONITORING PLAN ............................................................................................ 34 
a. 
Roles and Responsibilities .............................................................................................................. 34 
b. 
Trial Safety ...................................................................................................................................... 35 
c. 
Assessment of Safety and Data Safety Monitoring Plan (DSMP) ................................................. 35 
ETHICAL CONSIDERATIONS ............................................................................................................... 38 
a. 
Human Subjects Involvement, Characteristics, and Design .......................................................... 38 
b. 
Characteristics of the subject population ...................................................................................... 39 
c. 
Referral of individuals with exclusion criteria ............................................................................... 40 
d. 
Vulnerable populations .................................................................................................................. 40 
e. 
Collaborating sites and data .......................................................................................................... 40 
f. 
Potential Risks ................................................................................................................................ 41 
g. 
Emotional distress protocol ........................................................................................................... 41 
h. 
Disclosure of HIV status, violence/abuse, or other confidential information ............................. 42 
i. 
Violations of Confidentiality .......................................................................................................... 43 
j. 
Violence Reports ............................................................................................................................ 43 
k. 
Suicidal intent ................................................................................................................................. 43 
l. 
Violence associated with being in the study ................................................................................. 44 
ADEQUACY OF PROTECTION AGAINST RISKS ..................................................................................... 44 
a. 
Protection Against Risk .................................................................................................................. 44 
b. 
Safety .............................................................................................................................................. 44 
c. 
Disclosure of HIV, violence/abuse, or other confidential information ........................................ 45 
d. 
Interpersonal Violence Disclosures ............................................................................................... 46 
e. 
Suicidal intent ................................................................................................................................. 46 
f. 
Violence associated with being in the study ................................................................................. 46 
POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO HUMAN SUBJECTS AND OTHERS................... 46 
a. 
Clients ............................................................................................................................................. 46 
b. 
Policy ............................................................................................................................................... 47 
IMPORTANCE OF THE KNOWELDGE TO BE GAINED ........................................................................... 47 
 
APPENDICES 
I. Study instruments 
 
Screening Form 
II. Informed Consent Forms 
 
Short consent for screening 
 
Full consent 
 
Consent form for male partners 
III. Information sheet for male partners 

 
4
SUMMARY 
There are just under one million people with HIV in South Africa who have initiated antiretroviral 
therapy (ART) but remain unsuppressed. South Africa has been making progress towards UNAIDS 90-90-
90 targets but currently only 47% of those infected are suppressed. In South Africa, one major barrier to 
consistent treatment is intimate partner violence (IPV); nearly 50% of women have experienced IPV. The 
Common Elements Treatment Approach (CETA) is an evidence-based intervention intended to provide 
coping skills to women who have experienced IPV, and is comprised of cognitive-behavioral therapy 
elements. It is a transdiagnostic tool that can flexibly address a range of mental health problems (e.g. 
depression, anxiety) and represents the current best practice in global mental health as a more cost-
effective, scalable and sustainable model. CETA is one of the most promising interventions to impact HIV 
outcomes through addressing the indirect effects of IPV on adherence and continuity of care. 
We will conduct a randomized controlled trial of HIV-infected women, with or without their partners, 
who have experienced IPV and have an unsuppressed viral load or have defaulted on treatment to test 
the effect of CETA, in increasing retention and viral suppression, and reducing violence. The study has 
four  aims:  
• 
Aim 1: Among HIV-infected women on ART who have experienced IPV and have an 
unsuppressed viral load, have missed or late visits or who have defaulted on treatment, we will 
assess the effectiveness of CETA vs. active control at increasing the proportion retained and 
virally suppressed by 12 months and at decreasing the severity and incidence of IPV and other 
mental and behavioral health problems using an individually randomized trial;  
• 
Aim 2: To identify mediators and moderators of CETA’s effect on the primary outcome 
(retention and viral suppression);  
• 
Aim 3: To assess the cost and cost-effectiveness of CETA vs. active control at increasing the 
proportion who are retained and virally suppressed by 12 months. Female patients will be 
recruited from the Themba Lethu HIV Clinic in Johannesburg, South Africa.  
• 
Aim 4: To explore the experiences and perceptions of receiving CETA from the perspective of 
CETA participants post-intervention, including knowledge and skills obtained, acceptability, and 
reporting on and discussing trauma and violence, as well as perceptions and experiences of 
CETA providers and healthcare providers at CETA sites.  
 
The study team will work with the clinic staff to refer eligible patients for the study. Patients who agree 
to be referred to a member of our study team will be given a brief screening consent. Study staff will 
obtain full informed consent from those who meet inclusion criteria. For those that agree to participate, 
study staff will then randomize patients to CETA or control using computer generated randomization 
assignment.  
All subjects will be followed for 24 months to ensure data for primary and secondary outcomes is 
complete. Follow-up HIV data will be passive using routinely collected medical records from the clinics. 
HIV outcomes will be assessed at 3-, 12- and 24-months post-baseline. Questionnaires on violence, 
substance use, and mental health will be administered at baseline, and at 3 months (following CETA 
end) and 12 months post-baseline. These include: Severity of Violence Against Women Scale, Center for 
Epidemiological Studies-Depression Scale, Harvard Trauma Questionnaire, and Alcohol, Smoking, and 
Substance Involvement Screening Test. The primary outcome will be retention and viral suppression 
(<50 copies/mL) by 12 months after randomization. Secondary outcomes will include: 1) Viral 

 
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suppression at 3 and 24 months; 2) Attrition at 12 and 24 months; 3) IPV, mental/behavioral health, 
alcohol and other substance use at 3 and 12 months; and 4) Cost and cost-effectiveness of the 
intervention.  
Our primary aim is to analyze the impact of CETA in the full study population; however, we have 
calculated our sample size to ensure our ability to detect differences separately among women who 
include a partner in the CETA intervention and those who do not. We will include a sample of 400 
women, which will give us 80% power to detect an absolute 21% difference between arms. Our primary 
analysis will be a comparison of intervention and control by risk differences with 95% confidence 
intervals. We will analyze direct effects of CETA on continuous outcomes (e.g., mental health) with linear 
mixed models. We will evaluate the impact of potential moderators on retention and mental health 
outcomes using interaction terms. Micro costing methods will be used to cost all resources utilized and 
the cost effectiveness of CETA achieving the primary outcome will be evaluated.  
We will also qualitatively explore participant and health provider perceptions and experiences of CETA. 
For this qualitative component we will use a sample of up to 50 participants which will consist of 3 focus 
group discussion and 10 in-depth interviews from CETA participants who completed CETA sessions in 
2023, as well as up to 10 in-depth interviews with  CETA providers and healthcare providers from  
implementing sites. The findings from these qualitative interviews and discussions will be thematically 
analyzed. 
  
 

 
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INVESTIGATORS 
 
This evaluation will be conducted by investigators from Boston University (School of Public Health), Wits 
University (Health Economics and Epidemiology Research Office, Wits Health Consortium), Johns 
Hopkins University (School of Public Health) and Columbia University (School of Public Health) in close 
collaboration with the Department of Health of South Africa. Individual investigators are: 
 
Boston University (BU) 
 
Boston University Principal investigator 
Dr. Matthew Fox 
Professor 
Departments of Epidemiology and Global Health 
Boston University School of Public Health (BUSPH) 
United States 
 
Co-investigator 
Dr. Donald Thea 
Professor 
Department of Global Health 
Boston University School of Public Health (BUSPH) 
United States 
 
Co-investigator 
Dr. Lawrence Long 
Assistant Professor 
Department of Global Health 
Boston University School of Public Health (BUSPH) 
United States 
 
HE2RO (Wits Health Consortium, Wits University) 
HE2RO Principal Investigator 
Dr. Sophie Pascoe 
Principal Researcher 
Health Economics and Epidemiology Research Office (HE2RO) 
South Africa 
 
Additional co-investigators from HE2RO may be added prior to starting the evaluation. 
 
Johns Hopkins (JH) 
 
Johns Hopkins Principal investigator 
Dr. Laura Murray 
Senior Scientist 
Department of Mental Health 
Johns Hopkins Bloomberg School of Public Health (JHBSPH) 
United States 

 
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Columbia University (CU) 
 
Columbia University Principal investigator 
Dr. Jeremy Kane 
Assistant Professor 
Department of Epidemiology 
Columbia Mailman School of Public Health (CMSPH) 
United States 
 
BACKGROUND, RATIONALE, AND OBJECTIVES  
 
a. Background 
 
There are currently just under one million people with HIV in South Africa who have initiated 
antiretroviral therapy (ART) but remain unsuppressed and globally that number is far greater. South 
Africa has the largest HIV care and treatment program in the world, yet progress towards the UNAIDS 
90-90-90 targets—90% of infected patients knowing their status, 90% of those on ART and 90% of those 
virally suppressed—has stalled. Recent estimates suggest that just 47%(1) of all infected patients in 
South Africa are suppressed, significantly lower than the UNAIDS target of 72%. Our work has shown 
that the third 90 target, which encompasses both long-term retention in HIV care and adherence to 
treatment, is well below ideal (with nearly 1 million people unsuppressed on ART) and new strategies 
are needed to address barriers to remaining in care and virally suppressed. Unsuppressed patients can 
suffer from morbidity and mortality associated with HIV and can pass on the infection to uninfected 
partners. Therefore, if effective approaches could be found to keep patients on treatment, adhering and 
virally suppressed, the impact would be significant.   
Most interventions that have been tested to support patients who have struggled to remain adherent 
on ART have shown limited results(2). The majority focus on counselling patients on how to adhere to 
treatment but don’t address the many overt or indirect barriers patients face in consistently taking ART. 
In South Africa, intimate partner violence (IPV), experienced by up to 50% of women, is one major 
barrier to adherence(3,4). Addressing IPV is of critical importance by itself and could have large effects 
in supporting ART adherence.  
The Common Elements Treatment Approach (CETA)(5) is an evidence-based intervention comprised of 
cognitive-behavioral therapy (CBT) elements. It is unique from other CBT models in that it can flexibly 
address a range of commonly co-occurring mental and behavioral health problems prevalent among 
people living with HIV, including IPV, depression, traumatic stress, anxiety and substance use. It also 
deals with the key practicality issues in global mental health as it is a more cost effective, scalable and 
sustainable model that addresses disease comorbidities and is delivered by lay counselors. The group 
that has been assembled for this study have completed three clinical trials of CETA in low- and middle-
income countries (LMIC) among violence-affected populations. In Iraq and Thailand(5–7), CETA had large 
statistically significant effects on improving depression, posttraumatic stress, and anxiety (Cohen’s d 
range: 0.80 to 2.38 across outcomes). In Zambia among an adult sample in which 33% were HIV-
infected, CETA was both statistically and clinically superior to standard of care in reducing IPV (d=0.49) 
and hazardous alcohol use (d=0.43)(8) with high treatment engagement (>80%). Studies also show the 
CBT elements within CETA are effective for improving ART adherence(9–16). The group has also tested 
Telephone CETA (T-CETA) where CETA is delivered by phone or smartphone, with or without video and 

 
8
shown its success. CETA therefore has strong potential to improve HIV outcomes in violence-affected 
populations. 
b. Rationale 
 
South Africa has the largest HIV epidemic in the world, including one of the highest HIV prevalence 
estimates and the largest treatment program globally. An estimated 7 million people are living with HIV 
in South Africa and over 4 million are accessing antiretroviral therapy (ART)(17). The national ART 
program has made impressive gains in terms of reducing morbidity and increasing life expectancy(18–
22) but incidence remains high (0.79% per year among adults)(23) particularly among young women. 
Some of this is related to those transmitting HIV in the absence of treatment, while in other cases it is 
related to patients with elevated viral loads currently or previously on treatment.   
Poor HIV treatment outcomes reduce the impact of the massive investment in treatment. Poor 
retention and viral suppression leads to treatment failure, disease progression, transmission and 
sometimes death(24–33). If patients return to care after defaulting, they often require more expensive 
second-line drugs(34,35) as we have shown in South Africa(34,36). Successful treatment requires 
sustained lifetime adherence. Only with high rates of linkage, early initiation, adherence, retention and 
viral suppression will transmission decrease(24). 
Violence negatively affects treatment outcomes including adherence and retention in HIV care and is a 
major barrier to achieving the 90-90-90 goals. Violence is an endemic problem in South Africa, 
particularly IPV. A 2016 survey among 3,515 South African young adults found that lifetime reports of 
physical abuse was 56% with 18% reporting abuse in the past year(37). The link between IPV and 
negative HIV treatment outcomes has also been established worldwide(3,38) and in South Africa(4). 
Women with HIV who experience IPV are less likely to adhere to PMTCT regimens(39), PrEP(40) and 
ART(41). A 2015 review found that among HIV-positive women, IPV was associated with a 50% reduction 
in ART adherence (OR 0.48; 95% CI: 0.30-0.75) and a 36% reduction in viral suppression (OR 0.64, 95% 
CI: 0.46-0.90), though most of the data came from the U.S.(42). One recent study from South Africa 
found that among young adults, IPV was associated with a 5-fold decrease in ART adherence (OR 5.37; 
95%CI: 1.37 to 21.1), a 4-fold increase in depression (OR 4.25; 95% CI: 1.64 to 11.0), and a 4-fold 
increase in substance abuse (OR 4.11; 95% CI: 1.42 to 11.9)(43). These studies suggest that achieving 90-
90-90 would be strongly supported by addressing IPV. 

 
9
 
Figure 1 - Conceptual Model 
HIV positive women who experience IPV are at high risk for mental health and substance use problems 
that also negatively impact HIV outcomes (Figure 1 Conceptual Model). IPV occurs at high rates among 
HIV-positive women(44–47) and has been found to directly impact HIV outcomes(48) (CD4 counts and 
viral loads). IPV may also impact HIV outcomes indirectly, mediated through comorbid mental health 
problems and substance use.(46,49,50). Co-occurrence or comorbidity of IPV, substance use and mental 
health symptoms is the “norm” and puts individuals at even greater risk for poor HIV outcomes(51,52). 
We hypothesize that by reducing mental health problems, violence and substance use, we will be able 
to create more healthy behavior changes including increased adherence. 
There is a lack of effective, evidence-based interventions that address multiple, comorbid underlying 
barriers to HIV care and treatment. Several reviews suggest behavioral interventions directly targeting 
adherence alone, such as medication reminders, counseling support and contingency management, can 
improve ART adherence, although the effects are rarely durable(13,16,53–55). Other studies have 
focused on treating one co-occurring mental health or social problem (e.g., depression, traumatic stress) 
that correlates with poor ART adherence and retention. Although these approaches have shown 
promise at both treating mental health problems and initially increasing ART adherence, maintenance of 
adherence over time shows mixed results(12,56–60). A review of violence and HIV interventions found 
that treating IPV within an HIV clinic is acceptable and feasible, however, most approaches(61) (e.g. 
education, safety planning) were not effective in reducing IPV nor improving HIV outcomes. To date, 
interventions have been siloed (to treat one disorder only), and are prescribed interventions that do not 
account for the normal comorbid presentation of individuals such as IPV, substance use and mental 
health(48,62,63)., Approaches that address the multitude of comorbid underlying problems unique to 
each client are urgently needed to combat negative HIV outcomes. 
There is currently limited evidence on effective ways to intervene on IPV to improve HIV treatment 
outcomes. The Common Elements Treatment Approach (CETA)(5,64) is a Cognitive Behavioral Therapy 
(CBT) approach pioneered by our research team (Johns Hopkins PI Murray) and has been shown to be 
effective at reducing IPV as well as other comorbid problems related to HIV outcomes, including 
traumatic stress, depression, anxiety and substance use (see preliminary studies(5–8,65)). CETA consists 
of the same individual CBT elements found to reduce depression and traumatic stress, as well as to 

 
10 
increase adherence in HIV affected populations. Uniquely, CETA is a multi-problem, flexible approach 
that allows for the elements to be individualized to the client and targets both the distal (violence) and 
proximal (mental health, substance use) causes of poor HIV treatment outcomes within a single 
approach. CETA can be delivered by lay providers, and usually consists of 6-12, 1-hour sessions. Based 
on the problem presentation, CETA providers decide which elements, order and dose (of each element) 
will best address the reported problems. 
Evidence-based cognitive-behavioral therapy for HIV-infected women experiencing IPV addresses key 
sequelae associated with experiencing IPV, including mental health problems, substance use, and skills 
deficits. Addressing violence and comorbid underlying problems rather than simply trying to incentivize 
retention and viral suppression, has stronger potential to impact HIV treatment outcomes. 
c. Objectives 
 
We will test CETA’s effectiveness at increasing viral suppression and reducing violence in a community-
based randomized trial of 400 HIV-infected women who have recently experienced IPV, with CETA 
delivered to them alone or with their male partners (with at least 75 women with partners). Our aims 
are: 
 
• 
Aim 1: Among HIV-infected women on ART who have experienced IPV and have an 
unsuppressed viral load or have missed or late visits, we will assess the effectiveness of CETA vs. 
active control at increasing the proportion retained and virally suppressed by 12 months and at 
decreasing the incidence and severity of IPV and other mental and behavioral health problems 
using an individually randomized trial. Hypothesis: CETA will improve retention and viral 
suppression and reduce IPV, mental, and behavioral health problems vs. active control.   
 
• 
Aim 2: To identify mediators and moderators of CETA’s effect on the primary outcome 
(retention and viral suppression by 12 months). Our primary mediator will be IPV and primary 
moderator will be partner involvement. Hypothesis: Reduction in IPV after CETA will mediate 
improvement in retention and viral suppression among women who receive CETA; partner 
involvement in CETA will increase the effect size. 
 
• 
Aim 3: To assess the cost and cost-effectiveness of CETA vs. active control at increasing the 
proportion of unsuppressed women who have experienced IPV who are retained and virally 
suppressed by 12 months. Hypothesis: CETA will involve additional costs vs. standard of care but 
with better retention and viral suppression at 12 months, making it cost effective. 
 
• 
Aim 4: To explore the experience of receiving CETA from the perspective of CETA participants 
post-intervention, including knowledge and skills obtained, acceptability of reporting on and 
discussing violence, as well as perceptions of the impact of CETA 24 months or more post-
intervention. Hypothesis: The qualitative exploration will provide an in-depth understanding on 
the real experiences, perceptions and acceptability of CETA and durability of the intervention.  
 

 
11 
OVERVIEW OF STUDY DESIGN 
In order to achieve all three aims, we will conduct an individually randomized trial of the effectiveness of 
CETA for improving viral suppression and retention in HIV care among virally unsuppressed women 
experiencing IPV. Recruitment will be from an HIV clinic and we will enroll women who: 1) have 
experienced IPV within the last 12 months; 2) have initiated HIV treatment; and 3) have a last 
unsuppressed viral load or who have defaulted on treatment or missed or were late for visits in the last 
year. Women will be encouraged to invite a partner to be part of the CETA intervention. The woman will 
be the unit of analysis. The primary outcome is a composite measure of retention in care and viral 
suppression by 12 months. Because it is critical to know if any effects of CETA on retention and 
suppression are sustained, we will continue to follow women for a total of 24 months, approximately 21 
months after CETA is complete, to identify long term effects. We will also assess whether having a 
partner involved in CETA is a moderator of CETA’s effects and examine possible mediators of CETA’s 
impact on HIV outcomes, including IPV, mental health and substance use. Potential mediators and 
moderators will be measured with a battery of instruments and administered using a tablet-based 
questionnaire. This study is an effectiveness trial in that recruitment and care will be conducted within 
care systems already in place. 
To achieve the 4th aim, we will conduct 3 focus group discussions (with 6-10 participants per group) and 
10 in-depth interviews with study participants (this may include those who have been part of the FGD) 
post-intervention who completed the intervention in 2023. We will also conduct 5 in-depth interviews 
with the clinic healthcare providers (adherence counselors) and 5 in-depth interviews with CETA 
providers. The maximum total sample size for this objective will be 50 participants. All participants will 
be purposively selected. 
STUDY SITES AND POPULATION 
 
a. Study Sites 
 
The study will be conducted in Johannesburg, South Africa at one or more large HIV public sector sites. 
One such site will be the Themba Lethu HIV clinic, a comprehensive care management and treatment 
site in Gauteng Province. Themba Lethu is a large HIV testing, care, and treatment site located at the 
Helen Joseph Hospital. Themba Lethu is one of the largest HIV clinics in South Africa as it has initiated > 
30,000 adult patients on ART. If a sufficient number of women are not eligible to enroll in the study at 
TLC, then other suitable HIV clinics in Gauteng will be identified and included in the study. 
b. Inclusion and Exclusion Criteria  
 
Study participants will be adult women who are HIV positive, have initiated HIV treatment, have an 
unsuppressed viral load or who have defaulted from treatment since their last viral load, and have 
experienced intimate partner violence (IPV). Participants will be recruited by study staff after a warm 
hand-off referral from clinic staff. We will also enroll their male partners if the woman chooses to 
include them. The minimum age of research subjects will be 18. All subjects will be recruited from HIV 
clinics.  
Patient inclusion criteria will be: 
• Adult HIV positive women >= 18 years old 

 
12 
• Initiated HIV treatment  
• Most recent viral load >50 copies/mL, have defaulted from treatment or had a missed or late (>14 
days) visit in the last year 
• Has experienced IPV in the past 12 months 
• Has their own phone and can receive text messages 
• Literate and able to speak and read one of: English, Zulu, SeSotho 
• If including a partner, the woman has disclosed HIV status to the partner that will be invited to 
participate 
 
Exclusion criteria will be: 
 
• Unwilling to complete the informed consent process 
• Currently psychotic or on unstable psychiatric regimen  
• Suicide attempt/ideation with intent and plan, and/or self-harm in the past month 
• Enrolled in any other HIV treatment intervention study 
 
For Men, the inclusion/exclusions criteria will be 
 
Male inclusion criteria will be: 
• Adult >= 18 years old 
• Invited by partner to be in the study 
• Partner has disclosed their HIV status 
• Has their own phone and can receive text messages 
• Literate and able to speak and read one of: English, Zulu, SeSotho 
 
Exclusion criteria will be: 
 
• Unwilling to complete the informed consent process 
• Currently psychotic or on unstable psychiatric regimen  
• Suicide attempt/ideation with intent and plan, and/or self-harm in the past month 
 
Note that having one’s own phone means not sharing it with anyone else, including their partner. If a 
couple is participating, each partner would have to have their own phone that is not shared between 
them to be enrolled in the study. 
 
Inclusion and Exclusion Criteria for Qualitative Study Phase 
 
Inclusion criteria for participants - CETA users 
- 
Has participated in the CETA study in 2023 and was randomized into the treatment arm  
- 
Have received at least 5 completed CETA sessions and completed their CETA sessions in 2023 
-             Willing to complete the informed consent process 
 
Exclusion criteria for participants - CETA users 
- 
Unwilling to complete the informed consent process 
- 
Currently psychotic or on unstable psychiatric regimen  
- 
Suicide attempt/ideation with intent and plan, and/or self-harm in the past month 

 
13 
 
Inclusion criteria for healthcare providers  
- 
Healthcare providers (Adherence counselors at Ithembalethu clinic and Zola Clinic) during CETA 
study (November 2021 – August 2023) and actively participated in the patient referral to CETA study 
-            Willing to complete the informed consent process 
   
Exclusion criteria for healthcare providers  
- 
Unwilling to complete the informed consent process  
- 
Did not actively participate in CETA study referral during implementation 
 
Inclusion criteria for CETA providers 
- 
 Willing to consent to be part of the CETA qualitative phase 
- 
Has been actively providing CETA sessions to study participants since study implementation and 
in 2023  
 
Exclusion criteria for CETA providers 
- 
Unwilling to complete informed consent process 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
14 
 
STUDY PROCEDURES 
a. Overview 
 
Figure 2 below show the study flow. Below we describe each aspect of the study in detail. 
 
b. Clinic Engagement 
 
Before any data collection begins all local approval processes required by the Department of Health will 
be followed; meetings with clinic staff will take place in order to explain the procedures of the study, the 
risk and benefits, the confidentiality of results, to establish distress protocols and the referral processes 
that should be followed at the clinic, identify space to conduct the study, and to allow for any questions. 
Study participants will be enrolled from subjects referred from the HIV clinic by clinic staff. Study staff 
will work with clinic staff to ensure they refer to us patients they believe meet the screening criteria of 
HIV-positive, on ART and having an unsuppressed viral load or evidence of defaulting from treatment or 
missed/late visits but not necessarily around experiences of violence.  
FIGURE 2: 
Study Flow 
Focus group discussions and In-
depth interviews  

 
15 
c. Recruitment 
 
Recruitment will be from HIV clinics. Initial recruitment will be done by clinic staff (nurses and doctors) 
who will refer women to study staff whom they believe to be eligible by virtue of being on ART and 
virally unsuppressed, defaulted from treatment or had missed/late visits. They will describe the study as 
testing an approach to help those struggling with treatment adherence. Specifically, we will ask clinic 
staff to refer adult women who have initiated ART and are virally unsuppressed (viral load > 50) or have 
defaulted from treatment or had a missed or late visit in the last year to a member of our study team. 
This would be typical knowledge clinic staff has on women. Recruitment materials will not be provided 
as this may result in increased risk if there is a paper laying around the clinic with criteria. Clinic staff will 
not ask any questions of these women about experiences of violence beyond what they might otherwise 
do as part of usual clinical care. During our previous research, this has worked well.  
Study staff will speak with any woman who expresses a willingness to learn more about the study. 
Therefore, potential participants will have no initial contact with study staff unless they express an 
interest in hearing more about the study. Study staff will be highly trained and will receive specific 
training in human subject’s research and good clinical practice.  All referrals happen in person and 
introductions will occur at standard of care visits. 
d. 
Recruitment process for Focus group discussion and In-depth interviews  
Recruitment of participants for the qualitative phase of the study, will be done in the post intervention 
period. All those participants who were enrolled into the CETA study and randomized to the CETA 
treatment arm between 1 January and 31 July 2023 will be contacted via SMS using the contact details 
they provided, and asked if they are interested in participating in a follow-on discussion to the 
intervention.   Those study participants who can be reached and express an interest in participating will 
then receive a phone call from the study team member who will explain the additional consent process. 
The full informed consent process will be completed in person before the FGDs and IDIs.  
The recruitment process will adopt a purposive sampling method, as we are only selecting participants 
from the treatment arm who completed the intervention in 2023, making the sampling population much 
smaller, so this method will allow us, to maximize on the available population size to gain in-depth 
insights from the participants. For the recruitment of healthcare providers and CETA providers, they will 
be contacted and informed about this phase of the study and then asked if they will be interested in 
participating, informed consent will be conducted before the interview. 
e. Screening and Screening Consent 
Patients who agree to be referred to a member of our study team will receive a brief consent form only 
for screening to determine eligibility. This conversation will take place in a private location and include 
only the study staff and the patient. Potential participants will be counseled that they can refuse to 
participate in the study and still receive HIV care at the treatment site with no risk to the quality of care 
they receive.  The short consent form will explain what questions participants will be asked, including 
questions related to IPV, as part of the screening process. All those consenting to be screened will be 
assigned a unique Screening ID (generated a priori by a study team member) and administered a 
screening questionnaire to confirm the inclusion/exclusion criteria. This will include the Severity of 
Violence Against Women Scale (SVAWS) physical/sexual violence subscale to assess IPV exposure, which 
previously been used among women who experienced IPV in South Africa. This is a self-administered 
tablet-based form. Results of the screening will be documented on a tablet-based screening form 

 
16 
immediately. For those meeting all inclusion criteria, study staff will obtain full informed consent 
(described next). Consent will cover all remaining study activities (full assessments, randomization, 
intervention, data collection, etc.). All women who are screened for this study will be given resources for 
hotline and other local programs/experts in IPV, regardless of the type of abuse they may report 
(including verbal). Consent documentation will be done either using a paper form or via electronic 
consent by having the participant sign the document in REDCap. If an electronic signature is used, it will 
be on a PDF version of the IRB approved and stamped consent form. This will be done via a tablet in 
person (as would be done for a paper consent) and the participants will have access to the consent form 
as the consent process is taking place. Even if participants sign the consent electronically, they can also 
have a paper copy of the information sheet. As such, no electronic version of the e-consent will be made 
available to the participants. 
None of the screening data contains identifiable information. We will store paper files in locked filing 
cabinets. We will store electronic files in computer systems with password protection and encryption. 
For those who screen in and choose to participate, screening data will be linked to enrollment data 
through a study ID. For patients who screen out or who screen in and choose not to participate, only 
their screening data will be stored in order to allow us to later describe reasons for being excluded from 
the study. As with all other data, the data will be kept for 7 years post closure and then destroyed. No 
contact information will be kept for future research. Data access will be limited to the study team. 
 
f. Full Consent 
 
The full consent process, including signed informed consent, will be administered by a trained study 
staff member. The study staff will emphasize the voluntary nature of the study. The full consent form, 
for those who are eligible and interested in being in the study, will describe the nature and goals of the 
study and assure subjects their information will be kept confidential. We will explain to subjects the 
possible treatment options in the study and that they will not get to decide which group they will be in, 
but rather that we will decide by chance and they will have a 50-50 chance of being in either group. We 
will explain that if they are randomized to the intervention arm (CETA) their care will be different from 
the active control (text+safety) arm and the options they have to not participate. It will also be explained 
that they will be free to withdraw from the study at any time with no risk to the healthcare they receive 
at the clinic. The consent process will take place in a private space and women will be given adequate 
time to decide whether they want to participate and will be allowed to leave the clinic and return at a 
later time to complete the consent process if they choose to. Consent documentation will be done 
either using a paper form or via electronic consent by having the participant sign the document in 
REDCap. If an electronic signature is used, it will be on a PDF version of the IRB approved and stamped 
consent form. This will be done via a tablet in person (as would be done for a paper consent) and the 
participants will have access to the consent form as the consent process is taking place. Even if 
participants sign the consent electronically, they can also have a paper copy of the information sheet. As 
such, no electronic version of the e-consent will be made available to the participants. 
For safety reasons, we will inform women that they do not need to take a copy of the consent form if 
they do not wish to do so in order to minimize disclosure of information since the woman’s consent 
form includes experience with violence.  
The consent form will include permission to access their clinic records. The consent form will also state 
that the subject agrees to complete a baseline questionnaire for our study and that the questionnaire 
responses can also be linked to the subject’s treatment records. Participants will be assured that data 

 
17 
collected for our study will be kept strictly confidential and will never be reported to clinic staff or 
anyone outside the study team. We will also make clear to women the potential risks to being in the 
study, including the potential for increased risk of violence if associated with being part of a study. It will 
also be explained to the participant that they are also able to include their/a current male partner to 
participate in the study with them if they are randomized to the intervention arm and why this might be 
beneficial. Details of partner inclusion in the study are described next. Because inclusion in the study 
requires being able to send appointment reminders and questions to assess the safety of participants, 
contact details including a cell phone number that the participant can access safely to receive study 
messages and reminders will be collected and checked. After explaining the study, the study staff 
member will allow time for questions. They can take as long as they like and can return at another time 
to complete the process. 
g. Qualitative component consent 
  
For the FGDs and in-depth interviews with both recipients of care and providers, a separate information 
sheet and consent form will be administered by a study interviewer. We will make it clear to the study 
participant that this qualitative exploration activity is voluntary and that, if they decide to not participate 
in the FGDs and/or IDIs, it will not influence anything in the study or their follow up assessments or any 
aspect of their healthcare, and will not affect their work at the healthcare facilities as healthcare 
providers.  
h. Male Partners 
 
The violence literature encourages intervention with both males and females to effectively address IPV. 
After a detailed explanation of the intervention, women who consent will be asked if they are willing to 
include a current male partner in the intervention if they are randomized to the CETA arm. They will be 
informed that this is not a requirement to be in the study and that they can participate whether or not 
they want to include their current male partner. We will explain that if the woman is randomized to 
CETA and a male partner is included, both partners will be invited to participate in CETA separately; they 
would not be counselled together. In our team’s experience in Zambia, there were many males 
interested in participation and who enrolled and remained in CETA treatment throughout. Our 
qualitative findings indicated that women wanted their partners to join them in treatment and were 
generally invested in trying to improve the relationship (rather than exit it). We will explain to the 
woman participant that we will not disclose to the male partner that the woman has reported IPV.  
Women who wish to include a partner will be given an information sheet to give to their partner 
describing the study and inviting them to participate. The information sheet will invite the male to 
participate in a program that can help improve health and interpersonal relationships and will note that 
there will be tea/biscuits at the visit. This information sheet that will be given to the male partner will 
not mention IPV. Those men who are willing to know more about the study and potentially participate 
will be asked to either attend information sessions at the clinic on a specified time and date or to ring a 
free study number where they will be given more information about the study. Alternatively, they could 
complete their contact details and sign the form indicating that they give consent for the study team to 
contact them. They can then either return the form themselves to a secure designated collection point 
at the clinic or return it with their partner. Appointments will be made with all those men who indicate 
they are interested in the program to come to the clinic or meet at alternative secure locations to 
complete the consent process. The consent will focus on our primary outcome of adherence, and CETA 
work with the males will focus on increasing healthy behaviors and skill building to support their 

 
18 
partner.  We feel that in order to help ensure the safety of the women participants, it is important not to 
state that they were asked to join specifically because of violence.   
Included male partners will be consented and participate in CETA, but we will not collect any study 
outcome data on them; only demographic and intervention data. We are not capturing outcome data on 
men because no men will be included in the control group to conduct a comparative analysis and our 
previous trial already established CETA effectiveness for reducing men’s hazardous alcohol use and IPV 
perpetration. In addition, members of the study team previously showed that CETA can reduce women’s 
experience of IPV by reducing men’s hazardous alcohol use and aggression. However, we also 
acknowledge that in real-world HIV care settings, recruitment of couples will not always be possible, 
that there are many women who experience IPV outside of a long-term relationship, and that impacts of 
IPV can persist even after the relationship has ended. To enhance generalizability, we will include 
women who will have a male partner participate and women who will participate without a male 
partner. The consent process for men will take place in a private space and they will be given adequate 
time to decide whether they want to participate and will be allowed to leave the clinic and return at a 
later time to complete the consent process if they choose to. Consent documentation will be done 
either using a paper form or via electronic consent by having the participant sign the document in 
REDCap. If an electronic signature is used, it will be on a PDF version of the IRB approved and stamped 
consent form. This will be done via a tablet in person (as would be done for a paper consent) and the 
participants will have access to the consent form as the consent process is taking place. Even if 
participants sign the consent electronically, they can also have a paper copy of the information sheet. As 
such, no electronic version of the e-consent will be made available to the participants. 
We will include only one partner per woman and the partner must be a current partner. To help support 
the safety of women who enroll a partner in the study, we will take two steps. First, after each session 
that a male partner attends, we will send an additional safety check in text to the female partner to 
ensure her safety. Second, if a female in the study reports that her male partner’s participation in the 
study has led to increased risk to her, we will terminate participation of the male partner. We will 
however refer the male partner for support counselling outside of the study. 
i. Baseline Assessment 
Women who consent to be in the trial will complete a baseline assessment (about 30-45 minutes) using 
a self-administered tablet-based questionnaire (as with the SVAWS screener). This approach has been 
shown to be feasible and acceptable in studies conducted with this population as the majority reads 
written English (though it will be done in English, SeSotho and Zulu, the main languages at the clinic). 
The system allows responders to navigate and answer sensitive questions privately and discreetly, with 
the blinded assessor available to respond to questions.  
This baseline assessment will be completed immediately after consenting when possible.  If not possible 
due to extended time at the clinic or if a woman wishes to consider consent, an appointment will be 
made as soon as possible to complete the baseline assessment.  It will take place in a private location in 
the clinic and can be done while participants wait for their medications after they have seen a clinic 
provider given that typical wait times can be up to two hours. Food will be offered to participants during 
the assessment, as is customary when completing a research survey particularly in low-resource 
settings.  

 
19 
j. Randomization 
At the clinic, study staff will have a randomization code within the tablet system used for data collection. 
Following completion of the baseline assessment, the computer will generate the next randomization 
group. Randomization will be blocked to ensure that roughly equal numbers end up in each arm. The 
computer will also generate the randomization assignment for the Randomization ID assigned to the 
patient (and subsequently linked with their Screening ID). Randomization IDs and assignments will be 
generated a priori by a U.S.-based study team member and linked into the computer system. We will 
inform the participant of their assignment immediately after the baseline assessment. Those 
participants who are assigned to CETA will then be asked whether they want to invite a partner and if so, 
will be given the information sheet and forms to be completed and returned by their partner. Because 
randomization will occur only after the baseline assessment, some subjects may drop out before 
randomization, which will be tracked.  
k. Study Arms: Common Elements Treatment Approach (CETA) 
 
CETA, developed by Dr. Murray (Johns Hopkins PI), is a modular, multi-problem, flexible psychotherapy 
approach that trains a lay provider in nine evidence-based CBT elements so they can treat a variety of 
common problems, including violence, substance use, depression, anxiety, risky behaviors (sexual, non-
adherence), and other trauma-related symptoms. It is well known that individuals often present with 
comorbid problems – yet treatments are often focal or single-problem focused – for example an 
intervention that only addresses depression. CETA follows the past decade of the mental/behavioral 
health research in both high and low-income settings suggesting that focal treatments, while useful in 
some contexts, are wrought with challenges of scalability, sustainability, cost, and minimal ability to 
address the multi-faceted needs of most populations. CETA is not a new treatment, but a more cost-
effective, scalable, and sustainable approach to delivering evidence-based CBT principles (Table 2) in 
low-resource settings. As it is comprised of evidence-based, widely used CBT elements, CETA teaches 
decision rules on which elements to provide based on research evidence generated worldwide, including 
South Africa, but permits flexibility, allowing for the ability to address comorbidity and individualized 
treatment(48). CETA is unique in that: a) it is built specifically for lower-income settings and use by lay 
providers, b) it addresses multiple problems linked to poor HIV outcomes, c) it has been well-studied 
through rigorous trials in LMIC (6,7), d) it is the only common elements treatment showing strong 
effectiveness for violence in a sub-Saharan African trial, and e) it is comprised of the same CBT elements 
that positively impact adherence and retention in both HIC and LMIC(56–58,66–69). In summary, unlike 
other single-problem-focused HIV CBT interventions, CETA targets multiple proximal causes (e.g. 
depression, trauma, anxiety, AND substance use) of non-adherence and attrition as well as the distal 
causes (i.e. IPV) (Figure 1)    

 
20 
 
* MI = motivational interviewing 
 
CETA is a multi-problem, flexible approach that allows for the elements to be individualized to the client. 
CETA treatment is typically between 6 to 12 sessions. Sessions are on a weekly basis for approximately 
60 minutes and may consist of the following elements: Encouraging Participation/Introduction (i.e. 
learning about the symptoms and program), Cognitive Coping/Restructuring, Gradual Exposure for 
trauma, Behavioral Activation, Substance Use Reduction, Problem Solving, Relaxation and Safety. The 
elements implemented as well as their dosing is dependent on the client’s clinical presentation. CETA is 
flexible in what elements are used, their order, and the dose (the number of sessions an element is 
done).  
 
CETA has been shown to be effective in reducing mental health symptoms in three different randomized 
trials in LMIC. A recent study by us utilizing CETA in Zambia showed its effectiveness in reducing reports 
of IPV from both males (with respect to IPV perpetration) and females (with respect to experiencing IPV) 
in a relationship. Because CETA addresses multiple problems depending on individual presentation, it 
has the ability to target several correlates of IPV including traumatic stress responses, communication 
patterns, behavioral problems like aggression, safety planning, and substance use – all from either a 
perpetrator or survivor angle. IPV will be addressed in multiple additional ways including: 1) Clients will 
Table 2: Common Elements Treatment Approach (CETA) 
Component 
Content 
Target 
Engagement 
Discuss how program helps, 
identify obstacles to engagement 
Promote client buy in 
Safety 
Assess client risk or harm to 
self/others, IPV, abuse; initiate 
safety planning as needed. 
Assess/address client safety 
Empirically-supported cognitive behavioral elements 
Psychoeducation/Introduction 
Program information, normalize 
symptoms and problems 
Psychoeducation; Reduce stigma 
Substance Use Reduction 
CBT and MI merged to set goals 
and reduce substance use; 
identification and strategies for 
“drivers” of substance use 
Reduce substance use, increase 
social support  
Behavioral Activation 
Identify and Engage in 
pleasurable activities 
Reduce depressive symptoms; 
Activate action to engage in 
helpful programs (e.g., HIV care) 
Cognitive coping/restructuring 
Identify and connect thoughts, 
feelings and behaviors; replace 
unhelpful thoughts with helpful 
ones in order to feel better and 
behavior in a more healthy, 
productive way 
Reduce depressive, anxious and 
trauma-related symptoms, reduce 
self-blame and stigma, reduce 
negative thoughts on HIV care; 
reduce aggressive/violent 
behavior, reduce risk-taking, 
improve retention and adherence 
Relaxation 
e.g., breathing, imagery,  
Reduce anxiety and stress-related 
symptoms 
Exposure 
Talk about trauma memories or 
face fears using gradual 
desensitization 
Reduce trauma and anxiety 
symptoms 
Problem Solving 
Teach a process of steps to solve 
problems and make healthy 
decisions. 
Promote health decision making, 
Skills training for problem solving; 
improve relationships and 
communication 

 
21 
participate in safety planning, which includes assessing the severity of the safety concern and 
developing a plan to prevent IPV when possible as well as a plan to implement when a partner becomes 
violent. These plans will be created in the first session and updated as needed throughout treatment. 2) 
Individuals and their partners will be receiving treatment that may address underlying problems related 
to their perpetration of violence (e.g. substance misuse, unhelpful thinking, trauma symptoms, etc.). We 
will include women who choose to have a male partner participate and women who choose to 
participate without a male partner. 
 
To address HIV adherence and retention, the content of some of the skills is adjusted. For example, an 
unhelpful thought we would work on might be “I will never be able to be consistent with taking my 
medication.”  With the problem-solving element, we may specifically work on how to better manage 
consistently taking medication.  
 
At the beginning of each individual session (for both females and males), the Client Monitoring Form 
(CMF) will be administered. The CMF is administered at the beginning of every CETA session to track 
symptomology and make clinical decisions. This is a short list of questions that ask about current 
symptoms and problems, and help an approach like CETA tailor its element choice to the participants’ 
needs, while also tracking progress. This is a clinical tool to help providers and supervisors deliver CETA. 
Following the end of the study we may also conduct de-identified analysis with the CMF data to explore 
trajectories of symptom change over the course of CETA treatment.  
 
CETA can (and in this study will) also be delivered by telephone or smartphone, with or without video 
and is referred to as Telephone CETA or T-CETA.  A T-CETA manual has been developed that includes key 
ideas and techniques specific to virtual administration of CETA elements, including confidentiality, 
privacy, and ensuring proper connection. This manual has been utilized with success across many 
project locations, including Zambia, Ukraine, Moldova, Myanmar, Lebanon, Syria, and Mexico.  T-CETA 
reduces the burden of travel for the patient making it easier to engage with the full CETA program. T-
CETA requires ensuring that participants have a safe and private space to engage in CETA over the 
telephone and then following all the procedures of in person CETA but adapted to the telephone 
modality. 
 
d. CETA training and supervision  
 
CETA leverages lay providers and/or community health workers, usually without any formal mental 
health or counseling training. In South Africa’s National Adherence Guidelines, lay counsellors and CHWs 
are responsible for mental health screening. In the field of global mental health, this is a widely accepted 
practice (i.e., task shifting) which is supported by the WHO as well as numerous rigorous trials and a 
Cochrane review proving they can deliver cognitive behavioral and similar psychotherapeutic treatments 
with fidelity and effectiveness. 
Training will follow the widely accepted apprenticeship model utilized in global mental health of 10 days 
of in person training, followed by local supervision groups, led by a local supervisor. This model notes 

 
22 
the literature showing that one-off trainings are ineffective, and providers require on-the-job training 
with supervision and feedback. First, providers (study staff members) are taught to use the evidence-
based CBT elements in varying combinations of elements, order and dose to address multiple areas such 
as violence, substance use, mental or behavioral health problems, and skills deficits that affect HIV care 
(e.g., healthy decision making, adherence). Within the providers, 2-4 are chosen as local supervisors and 
receive additional training on how to supervise. Following the 10 day in–person training, groups of 5-6 
providers meet each week with one of the local CETA supervisors for approximately 2 hours to review 
cases, present problems, and decide which treatment elements should be used for each individual. Each 
local supervisor has weekly calls with CETA trainers for supervision, trouble shooting and further 
capacity building. 
Counselors will also receive an additional 2-day training by a Master CETA Trainer on administering CETA 
elements via telephone (i.e., T-CETA). This training includes a review of the adaptations as well as live 
practice of the element adaptations.  
e. CETA Delivery 
 
Patients randomized to CETA will meet weekly with a lay provider or community health worker member 
of the study staff for about an hour once each week, approximately 6-12 times depending on 
presentation and symptom level. This can be done at a location of the person’s choosing or by 
telephone if they choose, including the clinic but can also be a private space in the community to make 
it more convenient and comfortable for the participant. This treatment arm will include SMS reminders 
of their HIV care appointments, similar to the active control group (described below).  
f. CETA for male partners 
The rationale for including male partners is two-fold: a) extensive violence literature suggests 
interventions should focus on both the female and male counterparts to effectively combat IPV, and b) 
our previous trial showed that CETA can reduce women’s experience of IPV by reducing men’s 
hazardous alcohol use and aggression.  
Female participants will be asked if they would like their male partner included or not. If they would like 
their male partner included, the female participant will be given an information sheet to bring home to 
their partner that invites the male to participate in a program to improve health and interpersonal 
relationships/family life. There will be no mention that any IPV was disclosed by their partner in order to 
protect the female partner. The letter will indicate that someone will call the male within a week to see 
if he is interested in the program, and if so, will set up a time for him to come to the clinic or meet at an 
agreed upon place.  
Male partners who consent to receive CETA will complete some short assessments designed to help 
individualize the CETA treatment. Male partners only involvement is to attend individual CETA sessions 
CETA is provided to each male separately and will be tailored towards general skill building to support 
their partner. We will not collect outcome data from the men, however, we will track whether or not 
the men successfully complete CETA treatment. The providers of CETA for men will be the same 
providers as for the women, and proceed through the same Apprenticeship model of training and 
ongoing supervision. There will be no disclosure about reports of IPV from their partners and CETA will 
be tailored to meet the needs of the male. We are not capturing outcome data on men because no men 
will be included in the control group to conduct a comparative analysis and our previous trial already 

 
23 
established CETA effectiveness for reducing men’s hazardous alcohol use and IPV perpetration. Male 
participants also may not have HIV so they wouldn’t be eligible for our primary outcome anyway. 
For this study, the female participant will be given an information sheet to bring home to their partner 
that invites the male to participate in a program to improve health and interpersonal 
relationships/family life. The letter will invite these men to either attend information sessions at the 
clinic on a specified time and date or to ring a free study number where they will be given more 
information about the study. Alternatively, they can complete their contact details and return the form 
themselves to a secure designated collection point at the clinic or with their partner. Appointments will 
be made with all those men who indicate they are interested in the program to come to the clinic or 
meet at alternative secure locations to complete the consent process. 
To help support the safety of women who enroll a partner in the study, we will take two steps. First, 
after each session that a male partner attends, we will send an additional safety check in text to the 
female partner to ensure her safety. Second, if a female in the study reports that her male partner’s 
participation in the study has led to increased risk to her, we will terminate participation of the male 
partner. We will however refer the male partner for support counselling outside of the study. 
CETA fidelity and competency 
A fidelity monitoring system for CETA has been well established through the Hopkins teams’ clinical 
trials, where session information is documented by the CETA provider, the local CETA supervisor, and 
the CETA trainer (all members of the study team). Since audio-taping is not a feasible long-term 
monitoring technique in LMICs, we developed a process of triangulation across the counselor, supervisor 
and trainer to document and monitor fidelity, allowing for flexibility in “fit” and cultural modifications. 
Counselors and supervisors are trained to objectively document what they did in each session relating to 
specific steps outlined in each CETA element. Counselors document and report this to local supervisors, 
who document the case details in a database. This database is reviewed weekly by the trainer who gives 
feedback and coaching on each case until competency is reached. Each element in the CETA manual is 
executed through detailed “steps” – many of which are direct quotes. This design was deliberate and 
lends CETA to have fidelity tracked easier than many psychotherapeutic manuals. If counselors miss 
steps (i.e. low fidelity), they are expected to complete or re-do the element steps to prevent significant 
severe “drift” from the outlined intervention. Our fidelity includes what CETA elements are chosen, 
when they are delivered, completion of steps within each element, and the frequency in which each 
element is delivered.  
g. Study Arms: Active control (Texting + Safety)  
 
Reviews of mHealth have concluded there have been few efficacy studies for retention and viral 
suppression and results have been mixed (some showing positive effects on adherence, some no 
effects). Despite this, mHealth interventions have been recommended as a cost-effective improvement 
upon standard of care for HIV retention in sub-Saharan Africa and therefore make an appropriate active 
attention control. 
Our comparison arm will be an active control receiving usual care for IPV, which, in South Africa means 
no formal intervention. However, we will send text messages monthly to our control group participants 
to remind them of HIV care appointments(70). The widespread use of mobile phones in LMICs has led to 
numerous studies investigating how text-messaging can promote adherence and retention(71–76). 

 
24 
Despite mixed results, it remains a suggested, low-cost method that may help improve retention and 
adherence, and thus viral suppression. Nearly everyone in our clinic population has a phone. Sometimes 
a phone is shared within a family or friends. This text messaging activity will also be provided in the 
CETA arm. 
In previous CETA studies, the team has utilized text messaging with HIV women experiencing IPV. Text 
messages will be discussed with the individual and can be “in code” and will not include HIV or IPV 
specific information. This allows for women to have check-ins as needed without the increased risk. 
Study staff will receive training on simple example messages (e.g. “Please remember to come to the 
clinic this Wednesday for your appointment. We will be happy to see you as this is important.”), but 
actual texts can be personalized. Texts may be anonymized to avoid stigma by leaving out references to 
the clinic (e.g. “We are looking forward to seeing you Wednesday.”). Messages can also be more covert 
such as “Remember to walk Wednesday”. If participants are sharing a phone, we will always be talking 
to participants about phrasing texts in certain ways to assure safety and confidentiality. Study staff will 
SMS patients in both arms for appointment reminders. Text message appointment reminders will not be 
interactive. These follow typical procedures at the clinic around HIV care and treatment and are just a 
reminder message of the appointment day and time.  
h. Training and Tracking  
 
Study staff will receive training on simple example messages (e.g. “Please remember to come to the 
clinic this Wednesday for your appointment. We will be happy to see you as this is important.”), but 
actual texts can be personalized. Texts may be anonymized to avoid stigma by leaving out references to 
the clinic (e.g. “We are looking forward to seeing you Wednesday.”). Messages can also be more covert 
such as “Remember to walk Wednesday”. Personalization and anonymization of messages will be 
discussed and agreed with the participant at the recruitment/baseline visit. Study staff will SMS patients 
in both arms for appointment reminders.  
i. 
Safety for both arms  
Ethically, due to the population being violence affected, we will need to maintain a safety net for 
everyone in the study. We will individually meet with each woman to assess the IPV situation and 
severity, and give community resources to those in the active control arm. At this “zero” session, we will 
explain that we are going to check in weekly on their safety – including suicide and violence and we will 
ask how best to do this to assure safety and confidentiality. For example, women may suggest a number 
of a neighbor or family member, or we will agree on a “code” text that they could explain to others 
should their phone be shared or lost. We will request multiple ways to contact the women, including 
ability to message others in case we do not hear from them. Research on suicide and violence indicate 
that it is much more dangerous NOT to ask someone, than to ask. This in no way has been translated to 
increased risk, but instead is received as someone looking after them or caring for them. A text does not 
“force” an individual to do anything that would increase risk.  
Before participation in the study begins, we will be meeting with each individual woman to assess her 
IPV situation and severity and develop a safety plan for identified concerns. Therefore, all women would 
have a plan that they could put into action. Those in the active control arm will be given community 
resources including a 24/7 hotline they could call. Those in the CETA condition will be asked weekly 
about the IPV situation and will continue to receive modifications to a detailed safety plan as needed, as 

 
25 
well as have access to the CETA provider via SMS and the 24/7 hotline. South Africa has numerous such 
hotlines and programs to support victims of rape and violence. These include: 
1. The Tears Foundation which have a 24/7 hotline for anyone experiencing Gender-Based 
Violence or Domestic Abuse, which is accessible 24/7 and in all 9 provinces in South Africa 
(https://www.tears.co.za/gbv-domestic-abuse/) 
2. People Opposing Women Abuse (POWA) offer counselling (face to face) and legal support as 
well as some short-term sheltering (https://www.powa.co.za/POWA/get-help/) 
3. Child Line offer counselling support to abused and abandoned children and their families – for 
any woman who has concerns for their children. They offer a 24/7 line 
(https://childlinegauteng.co.za/) 
4. LifeLine South Africa have a dedicated 24/7 counselling line for victims of IPV/domestic 
violence/gender abuse (http://lifelinesa.co.za/) 
5. SheConquers SA also has support hotlines for women experiencing violence 
(http://sheconquerssa.co.za/emergency-connect/) 
To maintain a safety net during the study, we will send three suicide questions and one IPV safety 
question via SMS weekly during the intervention period (3 months). These questions are:  
1) “Are you thinking of killing yourself?” 
2) “Do you have a plan to kill yourself?” 
3) “Do you have the means to kill yourself?” 
4) “Are you at risk of serious injury or death from interpersonal violence?” 
We note that the last question will not be sent to male partners, only to women. We can also provide 
cell phones to those enrolled (regardless of arm) if they do not have their own, though as this is an 
inclusion criteria, this would only likely happen if a woman lost her phone during the course of the 
study. Questions can also be modified, working with the study participant to ensure that the question is 
disguised.  
Texts on IPV may be altered to avoid risk if there is concern that a partner or other perpetrator of 
violence might pick up this message (for example we may say “Please type Yes if there is any issues you 
need help with”). These same questions are asked weekly for all study participants (not just those 
receiving CETA). If all the responses are no, the study staff will do nothing. If any of the responses are 
yes, the study staff, who will be trained in safety planning, will telephone the participant to ask 
additional safety questions to assess risk. If the study staff member determines there is minimal risk, a 
telephone safety contract will be completed. This involves asking the participant to “promise” to keep 
themselves safe and alive for the next 7 days. If the study staff member decides the participant needs 
further evaluation or requires assistance, they will phone a CETA supervisor who will call the participant 
and complete safety planning. CETA supervisors are more trained in safety assessment and planning and 
will assess, and if needed, plan to meet the participant to assure safety. A supervisor will either speak 
directly with the client or even travel to their home should there be imminent danger. Johns Hopkins PI, 
Dr. Murray, wrote a seminal paper on integrating safety planning within LMIC programs regardless of 
location or availability of professionals – and has successfully delivered this in multiple programs and 
trials(77). If there is no response we would text again and if still no response we could call. If a patient 
has previously shown signs of distress, we would attempt a home visit where safe and possible, 
otherwise the patient will be considered lost to follow up. As the clinic already has protocols for 
supporting admission to the hospital or referral for services for distressed patients and they already 

 
26 
have strong links to the hospital providers, we will work with the clinic staff to ensure distressed 
participants get the care they need. 
We will be ensuring that study participants have their own phones to enhance safety. The sharing of 
phones and potential for others to read messages will be discussed when we agree how to send 
messages to participants. Male participants will require a phone that receive texts as they will follow the 
same protocol as the women participants for safety concerns (i.e. suicidal thoughts, homicidal thoughts 
and victimization of IPV).   
For women who choose T-CETA we will work with them during the initial in person session to determine 
ways to keep them safe. We will discuss the risks associated with T-CETA to ensure they have a clear 
understanding of the potential for their conversations to be overheard and the risk for violence should 
an abusive partner hear the conversation. This session will include planning to ensure they have a safe 
and private place to be when in T-CETA sessions, having the option for the participant to contact the 
team using a free “call me” text message to inform the counsellor they are ready and in a safe place if 
they choose and ways that any communications between the counselor and the participant can be 
coded to ensure privacy. For example, rather than asking, "are you in a safe and private space for 
today's session?" the counselor might use an initial coded question tailored to that participant 
associated with several possible benign responses, determined in advance, to indicate "YES" I am alone, 
it's ok to continue, or "NO" I can't talk, with an exit strategy planned as well. The safety plan will also 
include a pre-determined plan to decide what will happen if the counsellor hears voices in the 
background, or the participant’s tone of voice changes, etc. These can include changing the topic of 
conversation or ending the conversation completely and then later rescheduling the session.  
We will end each T-CETA session with a plan for determining the success of the T-CETA approach and 
any plans to change to in person CETA. This can be done in coded form if the participant wants. 
j. 
Follow-up and Retention 
 
There will be four data collection points: baseline, and 3, 12, and 24 months post baseline. For a 
purposively selected sample of those participants (n=40) who completed the intervention in 2023 there 
will also be a qualitative data collection point around 24 months (+/- 3 months) post intervention.  
Electronic medical records will be obtained to assess our primary outcome. This data collection will be 
completed in-person. We will assess, violence, mental health and substance use at 3 data collection 
points: baseline, 3 months post-baseline (the approximate length of CETA treatment and again at 12 
months (Figure 2). Because our primary outcomes are retention based (retention and viral suppression) 
we have no plan to retain patients in the study beyond outreach to complete the CETA intervention. Any 
effort to do so would undermine the results of the trial. 
 
At 3 months post-baseline (end of the CETA intervention) and 12 months post-baseline, participants will 
again complete the following tablet-based instruments: SVAWS, CES-D, HTQ, and ASSIST. Although the 
3-month time-point could impact the primary retention-based outcome, we feel it is important given 
the dynamic nature of mental/behavioral problems, and any impact should be equal across arms. With 
the exception of contacting participants for post-baseline assessments , qualitative data collection and 
safety checks, research staff will not contact participants for the reasons stated above. This is essential 
for the trial given the intervention is designed to improve retention and viral suppression as well as 
reduce violence. Questionnaire data will also provide key patient-level data for evaluating costs and we 
will also collect resource utilization data (drugs, lab tests, supplies, staff cadre consulted etc.) 

 
27 
DATA SOURCES AND MANAGEMENT 
  
a. Baseline and follow up data  
At the baseline visit we will collect the following information: 
• 
Enrollment Information (e.g., clinic ID, enrollment date, etc.) 
• 
Contact information (e.g. phone number, address where they stay, who they share their household 
with) 
• 
Demographic information (e.g., date of birth, sex, socioeconomic data, etc.) 
• 
HIV-related information (only for women): (e.g., initiation date, ART regimen, pharmacy data, lab 
results, etc.) 
 
At the baseline and at 3 and 12 months, participants will complete the following tablet-based 
instruments: 
 
• 
Severity of Violence Against Women Scale (SVAWS): 46 items assessing frequency of recent IPV. 
Subscales include: a) threats of violence (19 items); b) physical violence (21 items); and c) sexual 
violence (6 items). It was previously used in a study of IPV among women with partners who have 
alcohol abuse in South Africa(78). 
• 
Center for Epidemiological Studies-Depression Scale (CES-D): 20 items assessing frequency of 
depression symptoms over the past week (never, 1-2 days, 3-4 days, 5-7 days)(79). 
• 
Harvard Trauma Questionnaire (HTQ): 17 items assessing lifetime traumatic events. 39 items 
assessing post-traumatic stress symptoms in past week (not at all, a little, quite a bit, extremely)(80). 
• 
Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST): A comprehensive 
assessment of substance use for a range of substance types(81) . 
 
b. Primary outcome data  
Follow-up data for the primary outcome for both arms will be passively gathered using routinely 
collected medical records from the clinics. This is important as any attempts at active follow up would 
impact our primary outcome, which is viral suppression and retention. As noted, we have successfully 
used this process at Themba Lethu in the past as data collection is strong and mostly electronic at this 
site. Themba Lethu has a direct data link with the National Health Laboratory Service which completes 
all the lab work. Thus, if a viral load is done, no data entry is required for the result to be in the 
electronic data record at the site. We will not implement any other data collection or follow-up 
procedures during the study. We will extract the data on all clinic visits and viral loads at 3-, 12- and 24- 
months post baseline. 
c. Secondary outcome data 
 
The tablet-based questionnaire assessments (described above) will be repeated at 3 months post-
baseline (end of the CETA intervention) and at 12 months post-baseline for both arms. Although the 3 
month time-point could impact the primary retention-based outcome, we feel it is important given the 
dynamic nature of mental/behavioral problems, and any impact should be equal across arms. With the 
exception of contacting participants for post-baseline assessments and safety checks, study staff will not 

 
28 
contact participants. Questionnaire data will also provide key patient-level data for evaluating costs and 
we will also collect resource utilization data (drugs, lab tests, supplies, staff cadre consulted etc.). For 
patients in the control arm for whom we identify significant mental health issues, we will refer for care. 
For the qualitative component, focus group discussions and in-depth interviews will provide an in-depth 
understanding and insight on perceptions, experiences, feasibility, acceptance and durability of the CETA 
intervention.   
d. Data Sources 
 
The study will require individual research material from several different sources: 1) routinely collected 
clinic records stored in electronic format (with paper files as backup only if necessary), 2) study 
questionnaire and resource utilization data, and 3) intervention data and 4) qualitative data from FGDs 
and IDIs. All data collected by the study will be identified using a Study ID number only. A password 
protected linking file that links Study ID numbers to patient identifiers (client names, clinic ID numbers, 
etc.) will be held separately in a secure location. This linking file will be used to 1) allow follow-up clinic 
record data to be matched to baseline data, and 2) allow the research team members assigned to the 
case to engage participants in the intervention.  
i. Clinic records 
 
No clinic record data will be needed beyond what is routinely collected for patient management. The 
clinics have agreed to make available for analysis its clinic records in an electronic format that we have 
been working with for over a decade. We will obtain permission from participants to access these 
records during informed consent. We will use the following data from medical records at baseline and 
up to 24 months post-baseline to assess primary and secondary outcomes:  
• 
All visit dates and scheduled visit dates, reasons 
• 
All confirmation HIV tests, CD4, viral load results and dates 
• 
Date of ART initiation and ART regimen 
• 
Pharmacy refill records  
• 
Resource utilization: drugs, lab tests, supplies, etc. 
 
ii. Study questionnaires 
 
After subjects’ consent for the study they will be screened for eligibility. The screening questionnaire will 
contain questions related to mental health, experiences with intimate partner violence and experiences 
with HIV care and ART initiation. If eligible, and the participant agrees to the second informed consent, 
participants will be administered a baseline questionnaire. The study instrument, called the Client 
Monitoring Form (CMF), will be administered to clients using a tablet which allows the responder 
control to navigate and ability to answer sensitive questions privately and discreetly. The assessment 
asks questions about symptoms related to common mental and behavioral health problems. It will be 
kept in a password protected database with identifiers removed. Data collected will be electronically 
transferred from the field devices into the study database at HE2RO offices daily. Data on the devices will 
then be permanently deleted. Data will be securely transferred to BU and JHU weekly.  
iii. 
 Intervention records 
 

 
29 
Intervention data will be maintained for all participants in password protected databases. The data will 
include no identifying information about the client, only his/her study ID number. These data will 
include: 
• 
Dates, times and SMS messages sent for both arms 
• 
Attendance at CETA sessions (both in person and T-CETA) 
• 
Weekly checks of symptom severity (e.g., substance use, mental health) 
• 
Clinical notes recorded after each session by the peer educator 
• 
Responses to the weekly safety questions and any additional notes on safety 
 
iv. Focus Group Discussion and In-depth Interviews  
 
For the CETA user insights, FGD’s and IDI’s will include CETA treatment arm study participants from Zola 
CHC, who completed the intervention in 2023. Participants need to have participated in at least 5 CETA 
sessions.   
 
For insights from CETA providers and facility healthcare providers from both study sites (Themba Lethu 
clinic and Zola CHC). We will also conduct IDI’s, with CETA providers, who need to have conducted CETA 
sessions for the duration of the study, and with healthcare providers who were part of the CETA study’s 
referral of participants and know about the CETA study.   
 
The FGD’s and in-depth interviews with the CETA participants, will include questions around experiences 
with CETA, their perceptions on the varying dynamics of reporting violence and trauma as well as any 
cultural nuances associated dealing with and reporting of violence and mental health. The in-depth 
interviews with the CETA providers, will include questions around their experiences in delivering CETA, 
as well as their perceptions on the feasibility and acceptability of CETA.   
 
Before starting the FGDs and the IDIs, the study team will go through the appropriate information sheet, 
the participant will then be taken through the consenting process in which permission to record the 
discussions and take notes will also be solicited. Written participants’ consent will be requested first 
prior to recording any interviews and discussions. The recorded transcripts from these discussions will 
be saved electronically in a password protected database without any identifiers, including names and 
or/contact numbers. 
 
All the IDIs and FGDs will take place in-person, at the spaces provided by the community health facilities 
that we previously used for the trial, as this is much more convenient for the participants to travel to. 
The informed consent process will be done individually with each participant before starting the FGDs, 
so when the individuals are gathered in a group for the FGD, they will have all completed the consent 
process individually in-person. Similarly, for IDIs, the informed consent process will be completed and 
determined with the individual participant before the IDI discussion starts. 
 
e. Data Entry and Storage 
 
We anticipate entering all clinical and questionnaire data into electronic databases on site, so that paper 
forms do not need to be removed from the study clinics. In some cases (e.g. if there are power failures 
or other difficulties with using computers on site), it may be necessary to enter data onto paper study 
forms and then enter them into a database at the local office. These forms will be stored in a locked 
cabinet at the study sites, with access limited to the study team. Electronic data files will be stored on 

 
30 
secure, protected drives at the Health Economics and Epidemiology Research Office (HE2RO) in 
Johannesburg, with access limited to relevant study staff. In order to support data safety and 
compliance with South African privacy laws, only de-identified data (with the exception of the signed 
consent forms) will be sent to and stored at the three US sites.  
 
All subjects will be assigned a seven-digit, sequential identification number. The study ID number will be 
used to identify individual subjects in the study databases and for all data analysis. For each subject in 
the study, electronic clinic record number, date of birth, contact information and name will be collected 
to allow linking of fields extracted from multiple data sources (questionnaires, registers, records, lab 
reports, etc.) and for longitudinal follow up. Data will be collected using an electronic data entry system 
(described below). The data will only be collected in an electronic database (i.e. no paper forms will be 
used) and the form collecting identifying information is separate to and will be stored in a separate 
database from the remaining questions. An electronic linking file will be created to link this information 
to a patient ID number. The linking file (i.e. the database containing the study ID and identifying 
information) will be stored separately from all other data. It will be kept on a secure server at the study 
office and stored securely, separately from the study data sets, with access limited to the South African 
study team. The linking file will be kept until all data collection is complete and the final analytic dataset 
has been created. We will also link data from women with any data from their participating male 
partner through their study IDs. We will keep a linking file in South Africa that allows us to connect the 
two and therefore link information on completion of CETA by the male partner and study data for the 
female partner. All data including the linking files will be stored securely for 7 years post closure and 
then destroyed. All data collection files will be coded using study ID numbers and not contain subject 
identifiers. All data will be stored and transferred securely in accordance with HE2RO and BU policy on 
data classification and storage.  
 
REDCap or a similar software program requiring secure log-in and access by invitation will be used to 
create an electronic database to manage any quantitative study data not entered directly into tablets. 
The database will be used by field staff to double enter data where necessary. Data files will be reviewed 
by the study team on a monthly basis and queries returned to the site-level staff for response. On a 
regular basis, the data will be converted to SAS, STATA or SPSS for final cleaning and data analysis. All 
analytic databases will be password protected with access restricted to the members of the study team.  
 
DATA ANALYSIS 
 
a. Primary Outcome  
Our primary outcome is the proportion of participants who are retained and suppressed by 12 months 
post randomization(34,82). Viral load testing is routinely done at the clinic at 6- and 12-months post ART 
initiation and every 12 months thereafter. Due to the variability in when viral load testing is done, we 
will define the primary outcome to be suppression (i.e. a viral load <50 copies/mL) any time up to 18 
months. As our primary outcome includes retention, we are not able to contact patients who miss 
routine viral loads as this would affect attrition. Instead we will use routine clinic data collection (as we 
have done in the past (83–86)) to determine outcomes. Missing viral loads will be a negative outcome.  
b. Secondary Outcomes 
 
• 
Viral suppression at 3 and 24 months: CETA may have some effects on suppression and retention 
over the first year on treatment mediated through the increased contact with patients that CETA 

 
31 
entails. It is not clear for how long after the CETA intervention effects will be sustained. Thus, we will 
look at suppression at 24 months, long after CETA is complete. As our population should be 
monitored for suppression more frequently than every 12 months, we will also examine suppression 
within 3 months.  
• 
Attrition at 12 and 24 months - Attrition (the opposite of retention) will be defined as being more 
than 90 days late for a study visit.  
• 
IPV, mental/behavioral health, alcohol and other substance use: We will measure the effectiveness 
of CETA in reducing IPV and stress-related problems commonly associated with IPV and HIV, mental 
health (trauma, depression, anxiety), and alcohol and substance use. We will also assess whether a 
change in these factors mediates the effectiveness of CETA on the primary outcome.   
• 
Cost and cost-effectiveness: We will estimate the incremental cost-effectiveness of CETA versus 
active control in achieving the primary study outcome, retained in care and virally suppressed by 12 
months, from the provider perspective. If found to be effective, a budget impact analysis will be 
conducted to estimate the affordability of routine implementation of the intervention at scale.  
• 
Perceptions and acceptability of CETA: Using qualitative focus group discussions and in-depth 
interviews with both study participants in the treatment arm, CETA providers and healthcare 
providers. we will also explore the perceptions, acceptability and durability of the intervention, both 
as a recipient of care and provider and also the feasibility of delivering this intervention which will 
help inform recommendations for further implementation and scale up of the intervention, which 
will help inform recommendations for further implementation and scale up of the intervention.  
 
c. Sample Size  
 
Based on the ENHANCE study(85), we estimate that only 40% of those who are unsuppressed will be 
retained in care and virally suppressed 12 months post-baseline in the control arm. We believe a 20% 
increase in the percent suppressed and retained between the CETA and control arms would be clinically 
meaningful. Our primary aim is to analyze the impact of CETA in the full population; however, we have 
calculated our sample size to ensure our ability to detect differences separately among women who 
include a partner. With 80% power and 2-sided α=0.05, using a chi-squared test for independent 
proportions our sample size required is 91 per arm (182 total). To have power to detect mediators and 
moderators (Aim 2), we will increase the sample size to 400 total with a minimum of 75 women in the 
CETA arm who include partners (max of 100), which will give us 80% power to detect an absolute 21% 
difference between arms in women with partners. To get 75 women who include partners in the CETA 
arm we will have to randomize about 150 women willing to include a partner if randomized to CETA. We 
will also include at least 75 partners of women, up to 100. 
Themba Lethu clinic alone has about 4000 female patients, while other clinics have similar numbers of 
patients. Of these, about 1000 had an unsuppressed viral load in the past year. We anticipate that 50% 
of those we screen will be eligible for the study and of those 50% will enroll. We therefore estimate we 
will need to screen approximately 1600 patients over 18 months, requiring us to screen about 20 
patients and enroll approximately 5 patients per week over the enrollment period. 
Given we are randomizing 400 women and including up to 100 men, the total sample size for the IRB will 
be 500. 

 
32 
The IPV literature strongly suggests that more needs to be done with perpetrators of violence (not just 
survivors), and we know from studies like ours in Zambia that helping male partners led to many positive 
changes on outcomes, and from the perspective of the women.  However, for this study, we wanted the 
choice to be the womans’ – for ethical and safety reasons. Therefore, we could not confirm the ultimate 
number of male participants we would have.  
Sample Size – Qualitative Study Component  
For the FGDs and IDIs we will purposively select participants from the main study. We will recruit a total 
of 40 participants from the treatment arm who completed the trial in 2023. There will be 3 FGDs, with 6-
10 participants in each FGD, and 10 IDIs with study participants. We will also recruit 5 CETA providers 
and 5 healthcare providers who supported referral to CETA from Themba Lethu Clinic and Zola clinic 
(adherence counselors), for in-depth interviews. 
d. Primary Analysis 
 
All primary analyses will be by intention-to-treat. The unit of analysis will be the woman. Our primary 
analysis will be a comparison of risk differences with 95% confidence intervals. If we identify differences 
(RD) in baseline covariates we will conduct an adjusted linear regression to get an adjusted RD.  
We will analyze direct effects of CETA on continuous secondary outcomes (e.g., IPV [via SVAWS], mental 
health [via CES-D and HTQ], and substance use [via ASSIST score]) using linear mixed models. Fixed 
effects will include treatment arm, time, and arm X time interactions. Random effects will include 
participant ID to account for repeat measures. We will calculate robust standard errors. The models will 
estimate the difference in mean symptom change from baseline to each post-assessment between the 
treatment groups. The difference in mean change will be standardized to calculate Cohen’s d effect size. 
e. Moderator Analysis 
 
In addition to main effects for the primary and secondary outcomes, we will evaluate the impact of 
potential moderators (e.g., lack of viral suppression, partner involvement, age, ethnicity, HIV knowledge 
and attitudes, education, physical health, duration on treatment, presence of side effects, regimen) on 
suppression and retention and mental health outcomes. An interaction between the moderator and 
treatment arm will be included in models described above. The interaction term will serve as the 
coefficient of interest in assessing whether treatment effects varied by levels of the moderator. For the 
effect of CETA by inclusion of partners we will compare women who included a partner in the CETA arm 
to those who said they would have included a partner in the control arm. Risk differences will be used to 
assess effect sizes within moderator levels. 
f. Mediator Analysis  
 
We will assess the role of potential mediating variables (IPV, mental health, substance use) on the 
impact of treatment on our primary outcome to tease out the direct and indirect effects of CETA. 
Several of the proposed mediators (e.g., interpersonal violence) may reasonably be expected to interact 
with the treatment arm to impact our primary outcomes. Invalid estimates may occur if this interaction 
is not considered in the mediator analysis. To allow for the possibility of exposure-mediator interactions, 
we will use a counterfactual approach and follow methods described by VanderWeele and 
Vansteelandt(87,88) and Valeri and VanderWeele(89). These methods are appropriate for both 

 
33 
continuous and binary mediators and outcomes and allow for estimating valid controlled direct effects 
as well as natural direct and indirect effects.   
g. Cost Effectiveness Analysis and Budget Impact Analysis 
Costs will be estimated from the provider perspective over the 12-month study period. Micro costing 
methods will be used to cost all resources utilized for the care and treatment of the patient during this 
period, including drugs dispensed, laboratory tests performed, and consultations with clinical staff. This 
resource utilization will be estimated based on routine patient medical records in addition to study 
specific patient records. The cost will then be estimated by multiplying the resource usage with the 
relevant unit costs. In addition to the resources utilized directly by the patient we will estimate costs of 
infrastructure and shared services including equipment, space, utilities, general supplies and non-clinical 
staff. These costs will be allocated to the patient using an appropriate allocation factor. Trial specific 
costs which would not be incurred in routine implementation will be excluded (i.e. screening, informed 
consent). Unit costs and shared indirect costs will be collected from various sources including national 
drug tender price lists, state price lists for laboratory and diagnostic tests, national public sector salary 
banding, site level financial and management reports and our prior HIV costing studies.   
Based on the primary outcome, the difference in the cost of producing a patient retained and 
suppressed by 12 months between arms (total costs of all patients in an arm divided by number 
achieving primary outcome) as well as the incremental cost effectiveness ratio (ICER) between the study 
arms (difference in costs divided by difference in effectiveness) will be evaluated. Because cost data are 
often skewed, and the costs per successful outcome and ICER are ratios of random variables, 
bootstrapping methods will be used to produce confidence intervals around the cost differences. 
If the intervention is found to be effective, we will conduct a budget impact analysis (BIA) to understand 
the affordability of the intervention based on various possible scale up strategies. This will consider how 
the intervention may replace (or not) any existing interventions, whether it is likely to change health 
care utilization and likely intervention uptake. The BIA will take the payer’s perspective using a short-
term time horizon. 
h. 
Qualitative Data Analysis  
We will conduct a thematic analysis using NVivo, or similar software such as MAXQDA 2022 (which has 
artificial intelligence features) to code and analyze findings from the focus group discussions and in-
depth interviews. We will develop a codebook, which will be based on key themes coming from the data 
and the key concepts of the research questions. The codebook and themes will be reviewed and 
discussed by the coders, ranked in order of relevance and importance to the main objectives before 
finalizing. Qualitative data will also be triangulated with data from questions related to implementation 
completed by participants at the 3-month and 12-month follow-up. Qualitative data will be reported 
based on the key themes and concepts that are identified including any recommendations for 
adaptation of the intervention that arise from this work.  
i. Dissemination of Findings 
 
We seek to disseminate our results as widely as possible including through presentation to key 
stakeholders, presentation at national and international conferences and through publication in peer 
reviewed journals. We will also ensure that the study is registered in clinicaltrials.gov before the study 
begins and then we will ensure that the study results are updated in clinicaltrials.gov as required by NIH 

 
34 
policy. Further, Boston University has an internal policy in place to ensure that clinicaltrials.gov 
registration and updating is completed which includes a dedicated person who monitors all submissions 
to the system to ensure that timely updating is completed. Finally, we will ensure that informed consent 
documents for the trial include a specific statement noting that results will be posted to 
clinicaltrials.gov. 
h. Costs and Payments 
 
Study subjects will not incur any costs from study participation in the study though they may incur 
transportation costs for CETA study visits. Participants will not incur costs for text messaging or airtime 
as the program will pay for all messages that are sent to the participant, for messages that are responses 
to the safety questions and for talk time for CETA sessions done by telephone/video. Participants will be 
reimbursed 150 rand per study visit. For CETA visits, because adherence to the protocol and retention in 
care are our outcomes, payment for study visits would have an influence on the outcome and make it 
impossible for the intervention to be used in practice. Instead for CETA visits we will be reimbursed 50 
rand per visit for the cost of transportation if the sessions are completed by telephone, sufficient talk 
time will be provided for the T-CETA sessions. 
 
i. 
k. Qualitative Participants – Costs and Payments  
 
Participants, CETA users and CETA providers will be reimbursed R350 rand per study visit, for an FGD 
and IDI to reimburse them for their time and travel costs.   
 
DATA SAFETY AND MONITORING PLAN 
 
a. Roles and Responsibilities 
 
The PIs, with the assistance of co-investigators, will assume principal responsibilities for monitoring the 
consent, data collection, data security and safety of the participating staff from the service institutions. 
As databases are completed, they will be checked for completeness by a member of the study team to 
ensure missing or illogical data are corrected when possible. Bi-monthly updates on study enrollment 
numbers and randomization allocation will be sent by the site study team to the MPIs for monitoring 
progress. Data completeness and quality will also be reviewed on a monthly basis by Drs. Kane and Fox. 
Calls with the local study team (at least every two weeks, often weekly) will be conducted by Dr. Fox and 
Dr. Murray, and the CETA intervention will include weekly supervision by the local PI. 
We will convene a 3 member DSMB including a violence in LMIC specialist, a statistician, a HIV expert, 
and ethical specialist. They will assist the study in monitoring adverse events and the random allocation 
of participants to study arms. The DSMB will meet at least once yearly via phone conference calls for the 
enrollment phase of the project and through the completion of all active passive follow up, which 
includes the first three months of the intervention period. Once the enrollment and active intervention 
period is completed (3 months after the last enrolled client), the DSMB will continue to receive quarterly 
updates until all one year follow ups are completed but will not meet. Rather, at that point they will 
discuss the quarterly reports by email and sign off on a yearly report. The DSMB will cease to meet once 
all one year follow ups are completed for all participants in the study. The DSMB met this milestone and 
signed off on the last report March 2025 with the completion of all one-year follow-ups for participants. 
The addition of this qualitative component will not involve any review by the DSMB or body outside of 
the PI and study team. 

 
35 
At the initial meeting the DSMB will review and approve all study protocols before study initiation to 
ensure participant safety. Protocols will include formal procedures for reporting and tracking all adverse 
events; tracking progress in the study; and identifying any need for premature termination of the 
protocol. Also, during this initial meeting, the DSMB will provide feedback to the PIs concerning 
enrollment, attrition, and adverse events. At subsequent meetings the DSMB will be provided with 
summary study progress reports and adverse events. We will not require the DSMB to conduct interim 
analyses of data prior to end of study because the intervention is not considered harmful, and to avoid 
erroneous conclusions by doing multiple analyses during the study. The RCT will be registered in 
clinicaltrials.gov prior to data collection. 
b. Trial Safety 
 
Some risk is due to the assessment measures inherent in any mental health care with questions asking 
about thoughts, feelings, and personal difficulties that may be private (e.g., alcohol, substance use, 
trauma-related or depressive symptoms). Risks also include possible embarrassment, distress, or 
inconvenience related to questions regarding personal information and mental health problems. 
Assessment measures of mental health symptoms include items regarding suicidal or homicidal ideation, 
and disclosure of traumatic events inclusive of abuse. By US and local ethics standards, reports of 
suicidal and/or homicidal ideation also ethically require follow-up by the counselors and investigators, 
and could potentially result in the need to violate confidentiality in order to protect the participants and 
their families. Thus, this represents a potential limit to confidentiality. For this and other reasons, 
possible breaches of confidentiality also pose a potential risk in the proposed study. Our team has 
published specifically on developing safety protocols in low-resource settings and has implemented 
these in previous work. Still, each of these risks is carefully considered below. 
c. Assessment of Safety and Data Safety Monitoring Plan (DSMP) 
 
Adverse Events. The PIs will be responsible for oversight of potential adverse events. An adverse event 
(AE) is any untoward medical occurrence in a subject during participation in the study. We anticipate 
two potential types of AEs that could be directly related to study participation. These include distress 
experienced with regard to research participation and breach of confidentiality and privacy. With regard 
to both matters, we have protocols in place that include conferring with the PIs or a project mental 
health provider and appropriate safeguards to reduce risk of breach of confidentiality and privacy (see 
Human Subjects plan). We anticipate that AEs related to suicidal ideation and/or intent, homicidal 
ideation and/or intent, clinical worsening necessitating a higher level of care, and neglect/abuse may 
come to the attention of study staff during the consenting and during provision of care. We note that 
given the study population, it is anticipated that some women will continue to experience violence and 
suicidal ideation. Further given the population includes women who are not virally suppressed on the 
HIV treatment, some deaths may occur due to HIV. 
Participants will be asked if they believe there has been any increase in partner violence due to the 
study. If a participant believes an increase in IPV is a direct result of study participation, we would report 
this to the DSMB, and immediately move into the safety protocol regardless of condition.  If there is an 
increase in the level of severity of IPV against a participant such as a rise to severe physical harm or 
severe danger (hospitalized, broken bones…etc.), we would report these to the DSMB. We will report 
increases in severity of physical harm to the DSMB even if they are not considered to be related to study 
participation. During the intervention period, the DSMB examined all events at least quarterly during 
enrollment and completion of one year of follow up for all participants. If there was concern, they 
examined the violence data from all participants in the study on a weekly basis. All DSMB activities for 

 
36 
the main portion of the study were completed and signed off by March 2025. The addition of the 
qualitative component will not involve any further DSMB monitoring. Rather, the PI and study team will 
monitor this portion for adverse events and other reportable information. 
Definitions 
Serious Adverse Event (SAE) is any adverse event that: 
(1) results in death; 
(2) is life-threatening; 
(3) results in inpatient hospitalization or prolongation of existing hospitalization; 
(4) results in a persistent or significant disability/incapacity; 
(5) results in a congenital anomaly/birth defect; or 
(6) based upon appropriate medical judgment, may jeopardize the subject's health and may require 
medical or surgical intervention to prevent one of the other outcomes listed in this definition 
(examples of such events include allergic bronchospasm requiring intensive treatment in the 
emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse).  
 
Life-threatening means that the event places the subject at immediate risk of death from the event as it 
occurred.  
Unanticipated Problem is defined as an event, experience or outcome that meets all three of the 
following criteria:  
• 
is unexpected; AND 
• 
is related or possibly related to participation in the research; AND 
• 
suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized.  
 
Possibly related means there is a reasonable possibility that the incident, experience, or outcome may 
have been caused by the procedures involved in the research 
Unexpected means the nature, severity, or frequency of the event is not consistent with either: 
• 
the known or foreseeable risk of adverse events associated with the procedures involved in the 
research that are described in (a) the protocol–related documents, such as the IRB-approved 
research protocol, any applicable investigator brochure, and the current IRB-approved informed 
consent document, and (b) other relevant sources of information, such as product labeling and 
package inserts; or 
• 
the expected natural progression of any underlying disease, disorder, or condition of the 
subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the 
adverse event. 
 
AEs will be classified by severity (mild, moderate, or severe) depending on the intensity of the event on 
the patient. An AE will be “mild” if it does not have a major impact on the patient, “moderate” if it 
causes some inconvenience, and “severe” if it causes a substantial disruption to the patient’s well-being. 
A severe AE is distinct from a serious adverse event (SAE), which is any AE that is medical and results in 
death, a life-threatening event, inpatient hospitalization, disability, congenital anomaly or birth defect, 

 
37 
and/or an important medical event based upon appropriate medical judgment. AE’s and SAE’s will also 
be classified according to the likelihood that they are related to the study intervention (CETA or Control). 
 
Safety Review 
Both the risks listed below and unknown risks will be monitored as follows:  
1. The risks that will be monitored in this study are 1) intimate partner violence episodes; and 2) 
new onset suicidal or homicidal ideation. 
2. These will be assessed by study staff and elevated to study supervisors who will have been 
trained in clinical matters such as identifying levels of distress, local referral options and 
processes, and clinical interviewing on sensitive topics and when detected. Should they detect a 
level of urgency and immediacy, the event will be elevated to the local clinical psychologist and, 
if required, will do an evaluation of the severity, seriousness, relatedness and expectedness of 
the event. The clinical psychologist’s assessment will determine the immediate need for 
intervention and referral to a higher level of care. 
3. If the event is considered to be serious, related and unexpected, the clinical psychologist will 
inform the MPIs of the event within 48 hours.  
4. The aggregate SAEs will be reviewed by the MPI’s in real time and passed on to the DSMB 
quarterly. The DSMB will assess the frequency (by study arm), severity and relatedness of the 
SAEs on a quarterly basis to determine if the study intervention is posing an increased risk. If 
there is concern, they will examine the violence data from all participants in the study on a 
weekly basis. 
5. As this is not a blinded study, there will be no need to provide guidance to the DSMB for when/if 
to unblind the study.  
6. The qualitative portion of the study will be monitored by the PI and study team, not the DSMB. 
 
Reporting Plans 
 
The Principal Investigator at BMC/BU Medical Campus will report Unanticipated Problems, safety 
monitors’ reports, and Adverse Events to the BMC/BU Medical Center IRB in accordance with IRB 
policies. The local PI will report all such events to the Wits HREC in accordance with their policies and on 
request: 
• 
Unanticipated Problems occurring involving a fatal or life-threatening event will be reported to the 
IRB within 2 days of the investigator learning of the event. 
• 
Unanticipated Problems occurring not involving a fatal or life-threatening event will be reported 
to the IRB within 7 days of the investigator learning of the event. 
• 
Reports from safety monitors with recommended changes will be reported to the IRB within 7 
days of the investigator receiving the report.  
• 
Adverse Events (including Serious Adverse Events) will be reported in summary at the time of 
continuing review, along with a statement that the pattern of adverse events, in total, does not 
suggest that the research places subjects or others at a greater risk of harm than was previously 
known. 
• 
Reports from safety monitors with no recommended changes will be reported to the IRB at the 
time of continuing review.  
 

 
38 
The PIs will submit a report to the DSMB within 10 working days of events that meet the definition of an 
unanticipated problem involving risks to subjects or others. One exception may be if the SAE involved 
death and indicates that participants or others are at increased risk of harm, the PIs will be required to 
submit a report to the DSMB within 3 days. We will report to the DSMB any events that represent 
increased severity of violence whether or not the event is considered to be related to the study or not. 
Another exception will be if the details of the death are delayed as often happens in low-resource 
countries. However, all attempts will be made to report as soon as possible. Reports will be submitted 
electronically to the DSMB chair. The DSMB representative, when necessary in conjunction with the full 
DSMB, will review reports and decide whether the event meets the definition of an unanticipated 
problem increasing risks to subjects or others. Events that meet these criteria will be considered 
unanticipated problems involving risks to participants or others, will be reviewed by the convened 
DSMB. We will also notify all IRBs of any deaths. The Principal Investigator will report Severe Adverse 
Events not related to study participation and all Adverse Events to the DSMB on a yearly basis.  
In addition, participants will be asked if they believe there has been any increase in partner violence due 
to the study. If a participant believes an increase in IPV is a direct result of study participation, we would 
report this to the DSMB, and immediately move into the safety protocol regardless of condition.  If there 
is an increase in the level of severity of IPV against a participant such as a rise to severe physical harm or 
severe danger (hospitalized, broken bones…etc.), we would report these to the DSMB. We will report 
increases in severity of physical harm to the DSMB even if they are not considered to be related to study 
participation. The DSMB will examine all events at least quarterly and if there is concern, they will 
examine the violence data from all participants in the study on a weekly basis. 
We note that given the study population, we do expect experiences of violence (given the inclusion 
criteria) and some hospitalizations and deaths to occur related to HIV treatment. 
A Data Safety Monitoring Board charter document has been attached as an appendix describing the 
purposes and specific functions and processes of the DSMB.  
The qualitative portion of the study will be monitored by the PI. The DSMB will not be involved in this 
portion of the study. 
Stopping Rules 
The study has no stopping rules.  
 
ETHICAL CONSIDERATIONS  
 
a. Human Subjects Involvement, Characteristics, and Design 
 
The proposed research is a randomized controlled trial of a cognitive behavioral therapy approach 
(CETA) compared to an active control (mHealth) for women with unsuppressed viral loads or who have 
defaulted from HIV treatment in South Africa and for some of them, inclusion of their male partners in 
the intervention process. The study will involve enrolling and randomizing women at an HIV treatment 
clinic who are HIV positive women with an unsuppressed viral load, had missed or late visits in the last 
year or who have defaulted from treatment and who experienced IPV. They will be randomized into two 
groups, an intervention arm and a control arm. The study team will interact with these populations for 
the duration of the intervention and collect medical data through routine clinic records. Our plan to 
protect human subjects is detailed below. 

 
39 
The proposed study will fall under the purview of the local South African Institutional Review Board (The 
University of the Witwatersrand Human Research Ethics Committee), Boston University, Columbia 
University and Johns Hopkins University Institutional Review Boards. Every effort will be made to assure 
that the principles of ethical research—beneficence, justice, and respect for persons—are maintained. 
All study staff have obtained (or will obtain prior to the study in the case of new hires) their institution’s 
required certification to conduct ethical research. 
The University of the Witwatersrand Human Research Ethics Committee is a leader in evaluating and 
supervising the ethical conduct of research. They have worked with BU and HE2RO in previous research 
with similar populations and are familiar with the particular ethical considerations that arise when 
working with this population.   
b. Characteristics of the subject population 
 
Study participants will be adult women who are HIV positive, have initiated HIV treatment, have an 
unsuppressed viral load or have defaulted from treatment since their last viral load, and have 
experienced intimate partner violence (IPV). Participants will be recruited by study staff after referral 
from clinic staff. We will also enroll their male partners of women randomized to the intervention if they 
choose to include them. The minimum age of research subjects will be 18. All subjects will be recruited 
from HIV clinics.  
Patient (women) inclusion criteria will be: 
• Adult HIV positive women >= 18 years old 
• Initiated HIV treatment  
• Most recent viral load >50 copies/mL, they have defaulted from treatment or had a missed or late 
(>14 days) visit in the past year 
• Has experienced IPV in the past 12 months 
• Has their own phone and can receive text messages 
• Literate and able to speak and read one of: English, Zulu, SeSotho 
• If including a partner, the woman has disclosed HIV status to the partner that will be invited to 
participate 
 
Exclusion criteria will be: 
 
• Unwilling to complete the informed consent process 
• Currently psychotic or on unstable psychiatric regimen  
• Suicide attempt/ideation with intent and plan, and/or self-harm in the past month 
• Enrolled in any other HIV treatment intervention study 
 
Males partners will also be included, though we will not collect data from them for research purposes. 
The partners will be one per woman and will be a current partner as she defines it. 
For Men, the inclusion/exclusions criteria will be 
 
Male (partner) inclusion criteria will be: 
• Adult >= 18 years old 
• Invited by partner to be in the study 

 
40 
• Partner has disclosed HIV 
• Has their own phone and can receive text messages 
• Literate and able to speak and read one of: English, Zulu, Sesotho 
 
Exclusion criteria will be: 
 
• Unwilling to complete the informed consent process 
• Currently psychotic or on unstable psychiatric regimen  
• Suicide attempt/ideation with intent and plan, and/or self-harm in the past month 
 
c. Referral of individuals with exclusion criteria 
 
If serious mental illness or active suicidal intent is found, there are several options our team has utilized 
over the past 20 years in our work. HE2RO has a wealth of connections to medical doctors that are well 
versed in psychiatric symptoms, particularly in conjunction with HIV, and are available for consultation 
to better assess and determine a treatment plan. The hospital where the clinic we will recruit from is 
located, the Helen Joseph Hospital in Johannesburg, also has a psychiatric department which specializes 
in serious mental health problems and is available for individuals either outpatient or inpatient. As other 
study sites are added to the study, the referral process for psychiatric emergencies at each site will be 
established and followed. As part of the study we will also have a clinical psychologist based at the clinic 
to consult and oversee appropriate referral of such cases. In addition, Dr. Marnie Vujovic is a clinical 
psychologist with over ten years’ experience working as a consultant psychologist and as a Programme 
Manager on psychosocial-related research programs in South Africa. She is available to help out with 
referrals as needed (see letter of support).  
 
d. Vulnerable populations 
 
This study will be conducted among women who have experienced recent IPV. No children will be 
included in this study. While data from vulnerable populations such as pregnant women will be included 
in the study, we may not be aware of their pregnancy status. We do not anticipate the research will 
have any additional negative consequences for pregnant women, and in fact is likely to help. We believe 
it would be unethical to purposefully exclude them. 
e. Collaborating sites and data 
 
The research team will be from Departments of Global Health at Boston University, the Health 
Economics and Epidemiology Research Office (HE2RO) in Johannesburg, South Africa, Columbia and 
Johns Hopkins University. Participants will be recruited from HIV clinics identified in Gauteng province in 
South Africa. A wide range of study instruments will be administered using a tablet-based questionnaire. 
This tablet-based approach, which we have used in previous studies in South Africa, gives the responder 
the ability to answer sensitive questions privately and discreetly and data is immediately exported with 
only the study ID numbers. Data will also consist of detailed session notes on the interventions so that 
fidelity to the interventions can be monitored. Finally, we will also collect HIV care and treatment data, 
including data on viral suppression and retention in HIV care, all from normal clinic practice databases. 
All data files will be password-protected, with access limited to authorized study staff. Study subjects 
will be assigned a random study ID number upon enrollment, and data files will contain study ID 

 
41 
numbers only, without any other individual identifiers. Identifiers will be kept in a separate, password 
protected linking file (with access limited to study staff) that will be used to link the intervention data to 
clinical data with any paper versions needed for contacting study subjects kept in a locked cabinet. Only 
deidentified data will be sent to the US sites, with the exception of the signed consent forms. Routinely 
collected clinical data will be obtained in electronic format (with paper back up if needed) by study staff 
and linked to the Study ID numbers in order to link to other study documents, then all identifiers will be 
removed after the final analytic dataset is created. The electronic database will be password protected 
and will not include identifying information. 
f. Potential Risks 
 
We will not collect any biomedical samples for this study that would not be collected as part of routine 
care. All biomedical data for the study will be drawn from routinely collected medical records. The only 
other new data generated for the study will be responses to questionnaires.  
Psychological risks for participants posed by the research may be related to the sensitivity of some of 
the measures. Items include thoughts, feelings, and personal difficulties that may be private, such as 
acts of violence and/or symptomatology related to common mental health problems and/or substance 
use. Risks also include possible embarrassment, distress, or inconvenience related to questions 
regarding personal information and mental health problems. Assessment measures of mental health 
symptoms include items regarding suicidal or homicidal ideation, and disclosure of traumatic events 
inclusive of sexual and physical abuse commonly experienced by violence-affective populations. By US 
and local ethics standards, reports of suicidal and/or homicidal ideation also ethically require follow-up 
by the counselors and investigators, and could potentially result in the need to violate confidentiality in 
order to protect the participants. Thus, this represents a potential limit to confidentiality. For this and 
other reasons, possible breaches of confidentiality also pose a potential risk in the proposed study. 
There is a risk that the interventions (CETA; mHealth + safety) will not be efficacious for some individuals 
or that the interventions could lead to a worsening of symptoms. The Johns Hopkins PI (Dr. Murray) has 
published specifically on developing safety protocols in low-resource settings and has implemented 
these in her 15+ years of work in multiple low resource settings. Still, each of these risks is carefully 
considered below. 
g. Emotional distress protocol 
 
Some participants may experience emotional distress as a result of responding to the assessments or 
receiving feedback. We will take multiple measures to minimize this occurrence. First, study staff and 
counselors will be trained in responding to distress. Second, multiple levels of back-up support will be 
developed for our study staff. Dr. Murray will train supervisors as part of the CETA training who will 
receive thorough training in clinical matters such as identifying levels of distress, local referral options 
and processes, and clinical interviewing on sensitive topics. Our team will also be able to contact Dr. 
Vujovic (a clinical psychologist) who has worked closely with the clinical psychologists at the hospital 
where the clinic is based if required. Finally, in the event that an individual is experiencing significant 
distress, the local research team can consult with Dr. Murray. The instruments in this study have been 
used by the JHU team in several projects in LMIC, without undue distress occurring. All participants will 
also be told that they can refuse to answer any questions and still participate in the project.  
It is also possible that the participants could become distressed by participation in the interventions, 
CETA or mHealth + safety checks. Many therapeutic interventions like CETA deal with small degrees of 
stress within a session as part of the treatment.  Based on research and experience, the expected degree 

 
42 
of distress will be minimal and therapeutic rather than harmful. In cases where distress does occur, the 
participant would be with a trained counselor who is skilled at handling such situations. In addition, 
these counselors will have local supervisors, Dr. Vujovic, and supervision from Dr. Murray (MPI; Clinical 
Psychologist) as needed. In addressing safety, there can be some distress in planning for preventing 
suicide. Again, the research is strong that this is life-saving and therapeutic rather than harmful. 
For those participants selected to participate and enrolled in the qualitative phase of study who may 
become distressed during the FGDs and IDIs when they are asked to recall their experiences with CETA, 
we will follow the same distress protocol that is described above. Data collection for those sessions will 
pause or stop as needed and support provided. Dr. Vujovic will again be on hand to provide clinical 
support and guidance and clinic referral processes will be followed as needed.  
h. Disclosure of HIV status, violence/abuse, or other confidential information 
 
A potential risk of the study concerns the confidentiality of data about experiences of violence, mental 
health, HIV status and HIV treatment program enrollment. A high level of stigmatization continues to 
inhibit the disclosure of HIV status in the study population. Given that we are pulling from a clinic, 
participants will already be interacting with staff around their HIV status. IPV, mental health problems, 
and substance use may also be stigmatizing. When doing psychotherapy, disclosure of significant social 
problems such as violence, substance use, abuse and/or other related problems, may result in negative 
stigma being associated with the individual and/or family, and other such problems. It has been 
established that these social problems are common and exist in South Africa and attempts are currently 
underway to reduce the problems attached to admittance and discussion of such 
social/interpersonal/behavioral problems. Research shows that admitting and disclosing is the first step 
to healing, so even in assessment we will attempt to make participants comfortable with disclosing if 
they are experiencing IPV or other social or behavioral problems. We recognize that stigma may occur 
despite efforts and we will therefore do everything possible to maintain privacy for our participants. The 
counselors and study staff consenting will all be specifically trained in how to handle disclosures 
ethically, legally and sensitively. If there are questions, the counselor and supervisor may also work with 
the local supervisors, the clinical psychologist and Dr Vujovic, and/or Dr. Murray (who has extensive 
experience with sensitive disclosures).  We also note that given some participants may choose T-CETA, 
the risk of disclosure of being in the study may increase if the participant chooses not to take the call in 
a private space. 
The local teams will also be trained in how to handle disclosures, what resources are available in the 
community, and the JHU safety protocol. This protocol teaches specific steps if there is concern, 
including immediately calling a local supervisor, asking additional questions, and consulting with the 
supervisors and either Dr. Vujovic or Dr. Murray to make a plan. 
To ensure confidentiality and minimize the risk of accidental disclosure of sensitive information during 
the qualitative phase of this study, all individual interviews with participants will be conducted in a 
private area or room designated for this purpose at location that is convenient for the participant. For 
the focus group discussions, we will explain the importance of confidentiality and request that the 

 
43 
participants use a nickname or made-up name that is not their own and that they do not share what 
they have heard in the group session with anyone outside of the group. However, we cannot guarantee 
that they will not share the information and this will be made clear during the consent process. 
i. 
Violations of Confidentiality   
 
There is always the possibility of an accidental breach of confidentiality when conducting research. 
Further because data will be linked between women and any included partner, breach of confidentiality 
of one partner could reveal inclusion of the other partner. While this is acknowledged, we feel there is a 
very low likelihood of this occurring because of the precautions that will be taken to protect 
confidentiality and based on our experience conducting trials among HIV- and IPV-affected families. 
Disclosure of significant social problems such as intimate partner violence, may result in negative stigma 
being associated with the individual and/or family, fear of imprisonment of a family bread-winner who is 
a perpetrator, and other such problems. Domestic violence disclosure may result in unwanted 
intervention and consequences for the individual responsible. Our team has over a decade of experience 
specifically working with youth and families that experience abuse and violence and believe that the 
benefits of these issues coming out far outweighs the risks inherent in violence and abuse situations. We 
also believe we have established an effective method to reduce this risk.  
j. 
Violence Reports   
 
Previously undisclosed interpersonal violence (IPV) incidents may be revealed. In South Africa, violence 
is usually not reported to any officials. However, if there is physical harm being caused (i.e., not just 
verbal abuse), the victim will be given information about their rights, the South African laws and how 
and where to report if they are interested in this. This report may result in unwanted intervention and 
consequences for the individual responsible. We also recognize that given the gender-based hierarchies 
present in South African culture, this may have a detrimental effect on the participant. To address this 
potential risk, we will not report any disclosures – this will be the participant’s choice as is allowed under 
South African law. With disclosures, the potential benefit to the safety of the woman (and her family) is 
deemed as outweighing these potential negative consequences. Individuals who disclose experiences of 
violence will be randomized, and also be given a list of services that may be available. In addition, all 
active study participants will receive safety planning.   
k. Suicidal intent  
 
Participants may reveal severe depression and/or suicidal intent during the course of the study. 
Although this is not a direct risk with participation of this study, and thus a low likelihood, it is important 
to have a plan in place, particularly in a low-resource setting. All counselors will be trained specifically in 
how to assess for suicide risk, and the procedure to follow if there is intent. The protocol includes an 
immediate evaluation by a trained CETA supervisor to understand the seriousness of the suicidal 
ideation/intent and activation of a safety plan for the individual. The procedure to follow for study staff 
and CETA providers includes: a) immediately contacting a local supervisor, b) the supervisor will guide 
them through additional questions and help make a decision if the individual needs to be brought to see 
someone, or if a safety contract or safety “watch” may be completed, c) The clinical psychologist on hire 
(Dr. Vujovic) and the local PI Dr. Sophie Pascoe will be contacted immediately by the supervisor to help 
confirm if further assessment is needed and/or give recommendations, and d) Dr. Murray and Dr. Fox 
will be contacted within 24 hours and notified of the situation. Given our decades of work in LMIC (many 

 
44 
in sub-Saharan Africa), we have multiple medical contacts through HE2RO and could also refer to a 
psychiatrist at the Helen Joseph Hospital where the Themba Lethu clinic is located.  
l. 
Violence associated with being in the study 
 
In our experience to date, we have not observed an increase in violence or severity of violence towards 
women because of being in studies of CETA or other cognitive behavioral therapies, however, we do 
acknowledge that it is possible that such a situation could arise. This could occur if a partner who was 
abusive increased their level of abusiveness because the women chose to be in the study or if being in 
the study without telling the violent partner was unintentionally discovered. Accordingly, we have a plan 
for dealing with this should it arise. We will mitigate this risk (as described below) through a series of 
steps designed to minimize accidental disclosure of being in the study for women who do not want their 
participation revealed and through training of study staff to support women in employing CETA 
techniques as they are comfortable. 
ADEQUACY OF PROTECTION AGAINST RISKS 
 
a. Protection Against Risk 
 
Study staff and peer educators will be trained in responding to distress and multiple levels of back-up 
support have been developed. If any issue arises, study staff are encouraged to contact the clinical 
supervisor who will have received additional training in clinical matters such as identifying levels of 
distress, local referral options and processes, and clinical interviewing on sensitive topics.  The clinical 
supervisors have regular 24-hour access to CETA trainers and will alert them to any case with an issue. 
Dr. Vujovic is a local clinical psychologist that will also help with any issues.  Counselors and study staff 
will also have a safety protocol that will be developed in collaboration with our local partner which lays 
out the plan: a) immediately contacting their supervisor, b) the supervisor will guide them through 
additional questions and help make a decision if the woman needs to be referred somewhere, or if a 
safety contract may be completed, c) a CETA trainer will be contacted immediately by the supervisor to 
further assess and give recommendations, d) Dr. Vujovic will be called if needed, and d) MPIs Fox and 
Murray will be contacted within 24 hours and notified of the situation. This safety protocol has been 
used successfully by MPI Murray and her team in multiple LMIC for over 15 years. 
b. Safety 
 
Assessments and Intervention: All participants will be directly asked a set of questions each week during 
the active treatment phase (first 3 months after baseline) to assess suicide and homicide risk, and IPV. 
For CETA participants, this will be done during CETA sessions. For control participants, this will be via a 
mobile safety survey. The primary outcome of the proposed study is retention in HIV care and 
suppression by 12 months. Therefore, we want to minimize research contacts with participants as much 
as possible. We must balance that research aim, however, with the need to clinically monitor our study 
participants for safety. If a participant indicates any level of risk of harm to themselves, others or are 
being hurt by someone else, the study staff will immediately follow the locally developed safety protocol 
described above. In the active control, if the participant does not respond within 24 hours to the mobile 
safety survey, a staff member will call them and/or do a home visit when possible (though this has to be 
balanced against safety of staff) to assure response to safety questions. Study staff will be trained in 
how to recognize and respond to distress that may occur during the intervention and will call their 
supervisor if they are unsure of how to handle the situation. 

 
45 
Texts on IPV and/or safety may be altered to avoid risk if a partner is not involved or has not discussed 
IPV (for example we may say “Please type Yes if there are any issues you need help with”). We will 
individually meet with each woman to assess the IPV situation and severity, and give community 
resources to those in the control condition. At this “zero” session, we will explain that we are going to 
check in weekly on their safety – including suicide and violence and asked how best to do this to assure 
safety and confidentiality. For example, women may suggest a number of a neighbor or family member, 
or we will agree on a “code” text that they could explain to others should their phone be shared or lost. 
In the event that a response via text or phone, or home visit, indicates that someone is thinking of killing 
themselves, or someone in the house was in danger from the violence, the safety protocol of CETA will 
be utilized with an experienced Supervisor. This is a protocol used in multiple trials by the JHU team 
effectively. In this protocol, a supervisor would be called immediately by the researcher, ask a number 
of questions, and either speak directly with the client or even travel to their home should there be 
imminent danger. 
The study team will review data collected to assure that no study findings warrant immediate 
intervention. Additionally, weekly research meetings and team calls will serve as another mechanism 
through which to monitor treatment of random treatment cases. Clinical interventions will be provided 
as clinically warranted on an ongoing basis. 
We will track and report any severe increases in IPV, or any increase that participants feel is directly 
related to the study. If a participant believes an increase in IPV is a result of study participation, we 
would report this to the DSMB, and immediately move into the safety protocol regardless of condition. 
If there is an increase in the level of severity of IPV against a participant, such as physical harm or severe 
danger (hospitalized, broken bones…etc.), we would report these to the DSMB. We will report increases 
in severity of physical harm to the DSMB even if they are not considered to be related to study 
participation. During the intervention period, the DSMB examined all events at least quarterly during 
enrollment and completion of one year of follow up for all participants. If there was concern, they 
examined the violence data from all participants in the study on a weekly basis. All DSMB activities for 
the main portion of the study were completed in March 2025. The addition of the qualitative 
component will not involve any further DSMB monitoring. Rather, the PI will monitor this portion for 
adverse events and other reportable information. 
c. Disclosure of HIV, violence/abuse, or other confidential information 
 
Subjects will be protected against the risk and repercussions of accidental disclosure of HIV status and 
other confidential information, in several ways. First, all study data will be de-identified. That is, it will 
contain only a unique study ID number. The link between the ID and the participant’s identifying 
information will be kept in a password protected database in a locked office in South Africa. We also 
note that given some participants may choose T-CETA, the risk of disclosure of being in the study may 
increase if they were overheard and as such we will work with participants to ensure they are in a safe 
and private location for any T-CETA sessions. To protect against other violations of confidentiality, study 
staff will be trained in expectations that they are not to disclose any information collected in the study 
to anyone outside the study team. All study staff will be trained in human subjects’ research and 
required to pass an ethics certification course and receive training in Good Clinical Practices. All 
participants will be encouraged to contact the local study coordinator, local investigators, or other staff 
to report any undesirable conduct associated with the study. These reports will be brought to the 
attention of the study coordinator, local PI and co-Is and the MPIs, and appropriate steps will be taken 
to solve the problems, including reporting to the ethical review boards.  

 
46 
d. Interpersonal Violence Disclosures 
 
Previously undisclosed IPV incidents may be revealed.  As is true for most countries, in South Africa, IPV 
is usually not required to be reported to any officials. Providers serving these populations are not 
mandated to report IPV unless requested by the client directly. All participants in the study will have 
reported varying levels of violence in the past year. As such study staff will follow the same safety 
protocol listed above and will support clients by providing assistance and access to referral sources that 
can help with reporting at the client’s request. All participants at the screening visit will receive a 
comprehensive list of available services for victims of violence and alcohol abuse problems. They will 
also be informed of their rights according to South African law. We will also explicitly ask at all of these 
check-ins if she would like us to help her report any current or past violence to the police, seek any 
other services, or receive help in having her and her children leave the home. In the event of severe 
psychiatric difficulties, the study team will aid in appropriate referral for services.   
e. Suicidal intent  
 
Although this is not a direct risk with participation of this study, it is important to have a plan in place, 
particularly in a low-resource setting. All study staff with patient contact will be trained specifically in 
how to assess for suicide risk, and the procedure to follow if there is intent. In the event that a 
participant indicates a positive response to a suicide question, the above safety plan will be followed. 
The protocol will include an immediate evaluation of risk by the study staff with consultation from the 
clinical supervisor and/or clinical psychologist and as needed direct evaluation by a CETA clinician, 
supervisor or the clinical psychologist depending on the seriousness of the suicidal ideation/intent. In all 
cases study staff will work to develop and activate a safety plan for the individual. This includes a range 
of activities from setting up a suicide contract that includes 24-hour supervision of the individual by a 
community member(s) until the crisis subsides to a full evaluation by a psychiatrist.  
f. Violence associated with being in the study 
 
As noted, we consider this risk to be small given our previous experience working with CETA in low-
income countries, however it is a possibility.  Accordingly, we have a plan for dealing with this should it 
arise. First, we will attempt to minimize the risk through fully informing all participants at enrollment 
and consent that this is a possibility and that we will work with them to anticipate ways that accidental 
disclosure could occur and plan to prevent this. Second, we will work with participants to ensure that 
the text messages that the team sends are acceptable to the participant, even if they do not in any way 
mention safety or violence. Third, all counselors will be trained specifically to be sensitive to this issue 
and to take steps to ensure they do not accidentally disclose information about study participation. 
Fourth, should an increase in violence occur, such as physical harm or severe danger (hospitalized, 
broken bones…etc.), we will consider this an expected risk to participation in the study and will follow all 
procedures for reporting expected adverse events to the DSMB as described in our Data and Safety and 
Monitoring Plan. 
POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO HUMAN SUBJECTS AND OTHERS 
 
a. Clients 
 
There may be no direct benefit to patients participating in the study. However, through participation in 
the research, client participants will receive assessments that may benefit them by providing 
information about some of their problems. Further, some will be provided treatment (CETA) that is likely 

 
47 
to be of benefit in addressing their violence and related mental/behavioral health problems that may be 
negatively affecting their HIV care and treatment. Risks to the client participants are not great in that 
they will receive CETA, which has been proven to be efficacious in addressing violence and related 
symptoms, as well as helping with maintenance and adherence. In addition, some individuals may 
choose to take advantage of a referral to someone they can talk with, and therefore benefit.  
b. Policy 
 
A core principle of this research is that key stakeholders, including policymakers such as the South 
African Department of Health and implementing partner organizations (e.g. Right to Care), will be 
involved in the study. Relevant members of these organizations will be invited to the workshops and 
relevant meetings, and included on relevant communications, to share the research data for scaling up 
and sustaining violence-related services. Their involvement will serve as a compass for the work of this 
study and allow real-time policy influence. If CETA proves effective in improving retention and viral 
suppression, the design of this project is such that South Africa will be positioned to scale-up and ideally 
sustain the intervention in country. In addition, if effective, this use of CETA to improve HIV care and 
treatment could be replicated and used in other areas of South Africa and in other countries globally.   
IMPORTANCE OF THE KNOWELDGE TO BE GAINED 
 
The knowledge to be generated by this study will allow HIV treatment programs to identify what 
strategies may improve HIV treatment outcomes and reduce experiences of violence for women with 
elevated viral loads. Research on this area is desperately needed given the strong connection between 
violence and poor HIV outcomes. This study will produce evidence on the effectiveness of an 
intervention to improve the HIV care cascade. Given the extensive evidence on cognitive behavioral 
therapy as a skill-based resiliency treatment for multiple problems, and the evidence that a common 
elements approach is feasible and more scalable, it is likely that CETA will prove to be an effective 
intervention for violence and mental health for this high-stress population even if it does not improve 
HIV treatment outcomes. The knowledge to be gained in understanding the effectiveness of this 
important approach outweighs the risks and could have a major impact on HIV services and policy.   
 
Contingency plan for qualitative phase in the case of termination of the NIH no-cost extension 
 
As of January 2025, this study had received approval and a notice of award of a no-cost extension (NCE) 
from the NIH with permission to complete additional work and analyses up to January 2026. Should 
further notice be received at any point before that date that work cannot continue under the NCE and 
that the project needs to be close out then the final qualitative phase of this study would be 
discontinued and we may potentially seek to secure funding from this phase elsewhere. Even if this 
phase is partially completed because the intervention period has already been completed no 
participants will be at risk of loss of treatment or abandonment. 
 
REFERENCES 
 
1.  
UNAIDS. UNAIDS Data 2018. Geneva, Switzerland; 2018.  
2.  
Bärnighausen T, Chaiyachati K, Chimbindi N, Peoples A, Haberer J, Newell M-L. Interventions to 
increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation 
studies. Lancet Infect Dis [Internet]. 2011 Dec [cited 2013 Apr 23];11(12):942–51. Available from: 
http://www.ncbi.nlm.nih.gov/pubmed/22030332 

 
48 
3.  
Andersson N, Cockcroft A, Shea B. Gender-based violence and HIV: relevance for HIV prevention 
in hyperendemic countries of southern Africa. AIDS [Internet]. 2008 Dec [cited 2019 Feb 
22];22(Suppl 4):S73–86. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19033757 
4.  
Karim QA, Bazter C. The dual burden of gender-based violence and HIV in adolescent girls and 
young women in South Africa. SAMJ [Internet]. 2016 [cited 2019 Feb 22];106:1151–2. Available 
from: http://dx.doi.org/10.1136/jech-2015-205860 
5.  
Murray LK, Dorsey S, Haroz E, Lee C, Alsiary MM, Haydary A, et al. A common elements 
treatment approach for adult mental health problems in low- and middle-income countries. Cogn 
Behav Pract. 2014;21:111–23.  
6.  
Bolton, P., Lee, C., Haroz, E.E., Murray, L.K., Dorsey, S., Robinson, C., Ugueto, A.M., & Bass J. A 
Transdiagnostic Community-Based Mental Health Treatment for Comorbid Disorders: 
Development and Outcomes of a Randomized Controlled Trial among Burmese Refugees in 
Thailand. PLoS Med.  
7.  
Weiss WM, Murray LK, Zangana GAS, Mahmooth Z, Kaysen D, Dorsey S, et al. Community-based 
mental health treatments for survivors of torture and militant attacks in Southern Iraq: a 
randomized control trial. BMC Psychiatry. 2015;15(1):249.  
8.  
Murray L, Kane J, Glass N, Skavenski van Wyk S, Melendez F, Paul R, et al. Effectiveness of the 
Common Elements Treatment Approach (CETA) in reducing intimate partner violence and 
hazardous alcohol use in Zambia (VATU): a randomised controlled trial. Under Rev.  
9.  
Bere T, Nyamayaro P, Magidson JF, Chibanda D, Chingono A, Munjoma R, et al. Cultural 
adaptation of a cognitive-behavioural intervention to improve adherence to antiretroviral 
therapy among people living with HIV/AIDS in Zimbabwe: Nzira Itsva. J Health Psychol. 2016;  
10.  
Safren SA, Perry NS, Blashill AJ, O’Cleirigh C, Mayer KH. The Cost and Intensity of Behavioral 
Interventions to Promote HIV Treatment for Prevention Among HIV-Positive Men Who Have Sex 
with Men. Arch Sex Behav. 2015;44(7):1833–41.  
11.  
Safren SA, Ph D, Cleirigh CO, Tan J, Raminani S, Laura C, et al. NIH Public Access. 2010;28(1):1–10.  
12.  
Safren SA, O’Cleirigh CM, Bullis JR, Otto MW, Stein MD, Pollack MH. Cognitive behavioral therapy 
for adherence and depression (CBT-AD) in HIV-infected injection drug users: a randomized 
controlled trial. J Consult Clin Psychol. 2012;80(3):404–15.  
13.  
Amico KR, Harman JJ, Johnson BT. Efficacy of antiretroviral therapy adherence interventions: a 
research synthesis of trials, 1996 to 2004. J Acquir Immune Defic Syndr JAIDS. 2006;41(3):285–97.  
14.  
Simoni JM, Amico KR, Pearson CR, Malow R. Strategies for promoting adherence to antiretroviral 
therapy: a review of the literature. Curr Infect Dis Rep [Internet]. 2008 Nov;10(6):515–21. 
Available from: http://www.ncbi.nlm.nih.gov/pubmed/18945394 
15.  
Simoni JM, Frick PA, Pantalone DW, Turner BJ. Antiretroviral adherence interventions: a review of 
current literature and ongoing studies. Top HIV Med [Internet]. [cited 2019 Mar 18];11(6):185–
98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14724327 
16.  
Simoni JM, Pearson CR, Pantalone DW, Marks G, Crepaz N. Efficacy of interventions in improving 
highly active antiretroviral therapy adherence and HIV-1 RNA viral load. A meta-analytic review 
of randomized controlled trials. J Acquir Immune Defic Syndr [Internet]. 2006 Dec 1 [cited 2013 
Mar 6];43 Suppl 1:S23-35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17133201 
17.  
Kaplan SR, Oosthuizen C, Stinson K, Little F, Euvrard J, Schomaker M, et al. Contemporary 
disengagement from antiretroviral therapy in Khayelitsha, South Africa: A cohort study. Newell 
M-L, editor. PLoS Med [Internet]. 2017 Nov 7 [cited 2018 Mar 12];14(11):e1002407. Available 
from: http://dx.plos.org/10.1371/journal.pmed.1002407 
18.  
Fox M, Shearer K, Maskew M, Macleod W, Majuba P, Macphail P, et al. Treatment outcomes 
after 7 years of public-sector HIV treatment. AIDS [Internet]. 2012 [cited 2013 May 
9];26(14):1823–8. Available from: 

 
49 
http://journals.lww.com/aidsonline/Abstract/2012/09100/Treatment_outcomes_after_7_years_
of_public_sector.13.aspx 
19.  
Johnson LF, Mossong J, Dorrington RE, Schomaker M, Hoffmann CJ, Keiser O, et al. Life 
expectancies of South African adults starting antiretroviral treatment: collaborative analysis of 
cohort studies. PLoS Med [Internet]. 2013 Jan [cited 2013 Aug 14];10(4):e1001418. Available 
from: 
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3621664&tool=pmcentrez&rendert
ype=abstract 
20.  
Boulle A, Van Cutsem G, Hilderbrand K, Cragg C, Abrahams M, Mathee S, et al. Seven-year 
experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. 
AIDS. 2010;24(4):563–72.  
21.  
Fatti G, Meintjes G, Shea J, Eley B, Grimwood A. Improved Survival and Antiretroviral Treatment 
Outcomes in Adults Receiving Community-Based Adherence Support: 5-Year Results From a 
Multicentre Cohort Study in South Africa. JAIDS. 2012;61(4):50–8.  
22.  
Bor J, Herbst AJ, Newell M-L, Bärnighausen T. Increases in adult life expectancy in rural South 
Africa: valuing the scale-up of HIV treatment. Science (80- ) [Internet]. 2013 Feb 22 [cited 2018 
Apr 21];339(6122):961–5. Available from: 
http://www.sciencemag.org/cgi/doi/10.1126/science.1230413 
23.  
Human Sciences Research Council. HIV Impact Assessment Summary: The Fifth South African 
National HIV Prevalence, Incidence, Behavior and Communication Survey, 2017. Pretoria, South 
Africa; 2018.  
24.  
Anglemyer A, Rutherford GW, Baggaley RC, Egger M, Siegfried N. Antiretroviral therapy for 
prevention of HIV transmission in HIV-discordant couples. Cochrane Database Syst Rev. 
2011;(8):CD009153.  
25.  
Garcia de Olalla P, Knobel H, Carmona A, Guelar A, Lopez-Colomes JL, Cayla JA. Impact of 
adherence and highly active antiretroviral therapy on survival in HIV-infected patients. J Acquir 
Immune Defic Syndr. 2002;30(1):105–10.  
26.  
Bangsberg, David R.ab; Perry, Sharonc; Charlebois, Edwin D.a; Clark, Richard A.c; Roberston, 
Marjoried; Zolopa, Andrew R.e; Moss A. Non-adherence to highly active antiretroviral therapy 
predicts progression to AIDS. AIDS. 2001;15:1181–3.  
27.  
Hogg RS, Heath K, Bangsberg D, Yip B, Press N, O’Shaughnessy M V, et al. Intermittent use of 
triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up. 
AIDS. 2002;16(7):1051–8.  
28.  
Nachega JB, Hislop M, Dowdy DW, Lo M, Omer SB, Regensberg L, et al. Adherence to highly 
active antiretroviral therapy assessed by pharmacy claims predicts survival in HIV-infected South 
African adults. J Acquir Immune Defic Syndr. 2006;43(1):78–84.  
29.  
Colson P, Ravaux I, Yahi N, Tourrès C, Gallais H, Tamalet C. Transmission of HIV-1 variants 
resistant to the three classes of antiretroviral agents: implications for HIV therapy in primary 
infection. AIDS [Internet]. 2002 Feb;16(3):507–9. Available from: 
http://www.ncbi.nlm.nih.gov/pubmed/11834974 
30.  
Yerly S, Kaiser L, Race E, Bru JP, Clavel F, Perrin L. Transmission of antiretroviral-drug-resistant 
HIV-1 variants. Lancet. 1999;354(9180):729–33.  
31.  
Siegrist C-A, Yerly S, Kaiser L, Wyler C-A, Perrin L. Mother to child transmission of zidovudine-
resistant HIV-1. Lancet. 1994;344(8939):1771–2.  
32.  
Barnabas, R; Bendavid, E; Bershteyn A. HIV Mortality by Care Cascase Stage and Implications for 
Universal ART eligibility. In: CROI. 2016.  
33.  
Lahuerta M, Ue F, Hoffman S, Elul B, Kulkarni SG, Wu Y, et al. The problem of late ART initiation in 
Sub-Saharan Africa: a transient aspect of scale-up or a long-term phenomenon? J Health Care 

 
50 
Poor Underserved. 2013;24(1):359–83.  
34.  
Fox MP, Larson B, Rosen S. Defining retention and attrition in pre-antiretroviral HIV care: 
proposals based on experience in Africa. Trop Med Int Heal [Internet]. 2012 Oct [cited 2014 Jul 
29];17(10):1235–44. Available from: 
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3726560&tool=pmcentrez&rendert
ype=abstract 
35.  
WHO. HIV drug resistance fact sheet. 2010.  
36.  
Long L, Brennan A, Fox MP, Ndibongo B, Jaffray I, Sanne I, et al. Treatment outcomes and cost-
effectiveness of shifting management of stable ART patients to nurses in South Africa: an 
observational cohort. PLoS Med [Internet]. 2011 Jul [cited 2013 Aug 27];8(7):e1001055. Available 
from: 
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3139666&tool=pmcentrez&rendert
ype=abstract 
37.  
Meinck F, Cluver LD, Boyes ME, Loening-Voysey H. Physical, emotional and sexual adolescent 
abuse victimisation in South Africa: prevalence, incidence, perpetrators and locations. J 
Epidemiol Community Heal [Internet]. 2016 [cited 2019 Feb 22];70:910–916. Available from: 
http://dx.doi.org/10.1136/jech-2015-205860 
38.  
Schafer KR, Brant J, Gupta S, Thorpe J, Winstead-Derlega C, Pinkerton R, et al. Intimate Partner 
Violence: A Predictor of Worse HIV Outcomes and Engagement in Care. AIDS Patient Care STDS 
[Internet]. 2012 [cited 2019 Feb 22];26:356–65. Available from: 
https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3366337&blobtype=pdf 
39.  
Hampanda KM, Edu KH. Intimate Partner Violence and HIV-Positive Women’s Non-Adherence to 
Antiretroviral Medication for the Purpose of Prevention of Mother-to-Child Transmission in 
Lusaka, Zambia. Soc Sci Med [Internet]. 2016 [cited 2019 Feb 22];153:123–30. Available from: 
https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC4788551&blobtype=pdf 
40.  
Roberts ST, Haberer J, Celum C, Mugo N, Ware NC, Cohen CR, et al. Intimate Partner Violence 
and Adherence to HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant 
Relationships: A Prospective Cohort Study. J Acquir Immune Defic Syndr [Internet]. 2016 [cited 
2019 Feb 22];73(3):313–22. Available from: http://nrs.harvard.edu/urn-
3:HUL.InstRepos:30370973 
41.  
Cluver L, Meinck F, Toska E, Orkin FM, Hodes R, Sherr L. Multitype violence exposures and 
adolescent antiretroviral nonadherence in South Africa. AIDS [Internet]. 2018 [cited 2019 Feb 
22];32:975–83. Available from: https://journals.lww.com/aidsonline 
42.  
Hatcher AM, Smout EM, Turan JM, Christofides N, Stöckl H. Intimate partner violence and 
engagement in HIV care and treatment among women. AIDS [Internet]. 2015 Oct 23 [cited 2019 
Feb 22];29(16):2183–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26353027 
43.  
Kidman R, Violari A. Dating violence against HIV-infected youth in South Africa. J Acquir Immune 
Defic Syndr [Internet]. 2017 Oct [cited 2019 Feb 22];77:64–71. Available from: 
http://insights.ovid.com/crossref?an=00126334-900000000-96823 
44.  
Machtinger EL, Wilson TC, Haberer JE, Weiss DS. Psychological trauma and PTSD in HIV-positive 
women: a meta-analysis. AIDS Behav [Internet]. 2012 Nov 17 [cited 2019 Mar 15];16(8):2091–
100. Available from: http://link.springer.com/10.1007/s10461-011-0127-4 
45.  
Zierler S, Cunningham WE, Andersen R, Shapiro MF, Nakazono T, Morton S, et al. Violence 
victimization after HIV infection in a US probability sample of adult patients in primary care. Am J 
Public Health [Internet]. 2000 Feb [cited 2019 Mar 15];90(2):208–15. Available from: 
http://www.ncbi.nlm.nih.gov/pubmed/10667181 
46.  
Campbell JC, Baty ML, Ghandour RM, Stockman JK, Francisco L, Wagman J. The intersection of 
intimate partner violence against women and HIV/AIDS: a review. Int J Inj Contr Saf Promot 

 
51 
[Internet]. 2008 Dec [cited 2019 Mar 15];15(4):221–31. Available from: 
http://www.tandfonline.com/doi/abs/10.1080/17457300802423224 
47.  
Groves AK, Reyes HLM, Moodley D, Maman S. HIV Positive Diagnosis During Pregnancy Increases 
Risk of IPV Postpartum Among Women with No History of IPV in Their Relationship. AIDS Behav 
[Internet]. 2018 Jun 24 [cited 2019 Mar 15];22(6):1750–7. Available from: 
http://link.springer.com/10.1007/s10461-017-1868-5 
48.  
Kane JC, Vinikoor MJ, Haroz EE, Al-Yasiri M, Bogdanov S, Mayeya J, et al. Mental health 
comorbidity in low-income and middle-income countries: a call for improved measurement and 
treatment. The Lancet Psychiatry [Internet]. 2018 Nov 1 [cited 2019 Mar 11];5(11):864–6. 
Available from: 
https://www.sciencedirect.com/science/article/pii/S2215036618303018?via%3Dihub 
49.  
Weiss NH, Peasant C, Sullivan TP. Intimate Partner Violence and HIV-Risk Behaviors: Evaluating 
Avoidant Coping as a Moderator. AIDS Behav [Internet]. 2017 Aug 24 [cited 2019 Mar 
15];21(8):2233–42. Available from: http://link.springer.com/10.1007/s10461-016-1588-2 
50.  
Rose R, House A, Theory LS, research  undefined, 2010  undefined. Intimate partner violence and 
its effects on the health of African American HIV-positive women. Psychol Trauma Theory, Res 
Pract Policy  [Internet]. 2010 [cited 2019 Mar 15];2(4):311–7. Available from: 
https://psycnet.apa.org/fulltext/2010-19216-001.html 
51.  
Kiene SM, Lule H, Sileo KM, Silmi KP, Wanyenze RK. Depression, alcohol use, and intimate partner 
violence among outpatients in rural Uganda: vulnerabilities for HIV, STIs and high risk sexual 
behavior. BMC Infect Dis [Internet]. 2017 Dec 19 [cited 2019 Mar 15];17(1):88. Available from: 
http://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-2162-2 
52.  
Sikkema KJ, Watt MH, Drabkin AS, Meade CS, Hansen NB, Pence BW. Mental health treatment to 
reduce HIV transmission risk behavior: a positive prevention model. AIDS Behav [Internet]. 2010 
Apr 15 [cited 2019 Mar 15];14(2):252–62. Available from: 
http://link.springer.com/10.1007/s10461-009-9650-y 
53.  
Simoni JM, Amico KR, Smith L, Nelson K. Antiretroviral adherence interventions: Translating 
research findings to the real world clinic. Vol. 7, Current HIV/AIDS Reports. 2010. p. 44–51.  
54.  
Barnighausen T, Chaiyachati K, Chimbindi N, Peoples A, Haberer J, Newell ML. Interventions to 
increase antiretroviral adherence in sub-Saharan Africa: a systematic review of evaluation 
studies. Lancet Infect Dis. 2011;11(12):942–51.  
55.  
Chaiyachati KH, Ogbuoji O, Price M, Suthar AB, Negussie EK, Bärnighausen T. Interventions to 
improve adherence to antiretroviral therapy: a rapid systematic review. AIDS. 2014 Mar;28 Suppl 
2:S187-204.  
56.  
Sikkema KJ, Mulawa MI, Robertson C, Watt MH, Ciya N, Stein DJ, et al. Improving AIDS Care After 
Trauma (ImpACT): Pilot Outcomes of a Coping intervention Among HIV-Infected Women with 
Sexual Trauma in South Africa. AIDS Behav [Internet]. 2018 Mar 21 [cited 2019 Mar 
15];22(3):1039–52. Available from: http://link.springer.com/10.1007/s10461-017-2013-1 
57.  
Abas M, Nyamayaro P, Bere T, Saruchera E, Mothobi N, Simms V, et al. Feasibility and 
Acceptability of a Task-Shifted Intervention to Enhance Adherence to HIV Medication and 
Improve Depression in People Living with HIV in Zimbabwe, a Low Income Country in Sub-
Saharan Africa. AIDS Behav [Internet]. 2018 Jan 6 [cited 2019 Mar 15];22(1):86–101. Available 
from: http://link.springer.com/10.1007/s10461-016-1659-4 
58.  
Safren SA, O’Cleirigh C, Tan JY, Raminani SR, Reilly LC, Otto MW, et al. A randomized controlled 
trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected 
individuals. Heal Psychol [Internet]. 2009 Jan [cited 2019 Mar 15];28(1):1–10. Available from: 
http://www.ncbi.nlm.nih.gov/pubmed/19210012 
59.  
Simoni JM, Wiebe JS, Sauceda JA, Huh D, Sanchez G, Longoria V, et al. A preliminary RCT of CBT-

 
52 
AD for adherence and depression among HIV-positive Latinos on the U.S.-Mexico border: the 
Nuevo Día study. AIDS Behav [Internet]. 2013 Oct 28 [cited 2019 Mar 15];17(8):2816–29. 
Available from: http://link.springer.com/10.1007/s10461-013-0538-5 
60.  
Chaiyachati KH, Ogbuoji O, Price M, Suthar AB, Negussie EK, Bärnighausen T. Interventions to 
improve adherence to antiretroviral therapy. AIDS [Internet]. 2014 Mar [cited 2019 Feb 
12];28:S187–204. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24849479 
61.  
Gibbs A, Jacobson J, Kerr Wilson A. A global comprehensive review of economic interventions to 
prevent intimate partner violence and HIV risk behaviours. Glob Heal Action  [Internet]. 2017 
[cited 2019 Feb 22];(10 supp 2). Available from: 
https://doi.org/10.1080/16549716.2017.1290427 
62.  
Straus H, Cerulli C, McNutt LA, Rhodes K V, Conner KR, Kemball RS, et al. Intimate partner 
violence and functional health status: associations with severity, danger, and self-advocacy 
behaviors. J Womens Health (Larchmt) [Internet]. 2009 May [cited 2019 Mar 28];18(5):625–31. 
Available from: http://www.liebertpub.com/doi/10.1089/jwh.2007.0521 
63.  
Demyttenaere K, Bruffaerts R, Posada-Villa J, Gasquet I, Kovess V, Lepine JP, et al. Prevalence, 
Severity, and Unmet Need for Treatment of Mental Disorders in the World Health Organization 
World Mental Health Surveys. JAMA [Internet]. 2004 Jun 2 [cited 2019 Mar 28];291(21):2581. 
Available from: http://www.ncbi.nlm.nih.gov/pubmed/15173149 
64.  
Kane JC, Skavenski S, Wyk V, Murray SM, Bolton P, Melendez F, et al. Testing the effectiveness of 
a transdiagnostic treatment approach in reducing violence and alcohol abuse among families in 
Zambia: study protocol of the Violence and Alcohol Treatment (VATU) trial. Glob Ment Heal 
[Internet]. 2017 [cited 2019 Feb 22];4:1–15. Available from: 
https://doi.org/10.1017/gmh.2017.10 
65.  
Murray LK, Hall BJ, Dorsey S, Ugueto AM, Puffer ES, Sim A, et al. An evaluation of a common 
elements treatment approach for youth in Somali refugee camps. Glob Ment Heal (Cambridge, 
England) [Internet]. 2018 Apr 25 [cited 2019 Mar 28];5:e16. Available from: 
https://www.cambridge.org/core/product/identifier/S2054425118000079/type/journal_article 
66.  
Pettifor A, Corneli A, Kamanga G, McKenna K, Rosenberg NE, Yu X, et al. HPTN 062: A Pilot 
Randomized Controlled Trial Exploring the Effect of a Motivational-Interviewing Intervention on 
Sexual Behavior among Individuals with Acute HIV Infection in Lilongwe, Malawi. Helleringer S, 
editor. PLoS One [Internet]. 2015 May 11 [cited 2019 Mar 15];10(5):e0124452. Available from: 
https://dx.plos.org/10.1371/journal.pone.0124452 
67.  
Sikkema KJ, Dennis AC, Watt MH, Choi KW, Yemeke TT, Joska JA. Improving mental health among 
people living with HIV: a review of intervention trials in low- and middle-income countries. Glob 
Ment Heal [Internet]. 2015 Sep 9 [cited 2019 Mar 15];2:e19. Available from: 
http://www.ncbi.nlm.nih.gov/pubmed/26435843 
68.  
Andersen LS, Magidson JF, O’Cleirigh C, Remmert JE, Kagee A, Leaver M, et al. A pilot study of a 
nurse-delivered cognitive behavioral therapy intervention (Ziphamandla) for adherence and 
depression in HIV in South Africa. J Health Psychol [Internet]. 2018 May 26 [cited 2019 Mar 
15];23(6):776–87. Available from: http://journals.sagepub.com/doi/10.1177/1359105316643375 
69.  
Crepaz N, Lyles CM, Wolitski RJ, Passin WF, Rama SM, Herbst JH, et al. Do prevention 
interventions reduce HIV risk behaviours among people living with HIV? A meta-analytic review 
of controlled trials. AIDS [Internet]. 2006 Jan 9 [cited 2019 Mar 15];20(2):143–57. Available from: 
https://insights.ovid.com/crossref?an=00002030-200601090-00002 
70.  
Finitsis DJ, Pellowski JA, Johnson BT. Text Message Intervention Designs to Promote Adherence 
to Antiretroviral Therapy (ART): A Meta-Analysis of Randomized Controlled Trials. Winston A, 
editor. PLoS One [Internet]. 2014 Feb 5 [cited 2017 Dec 4];9(2):e88166. Available from: 
http://www.ncbi.nlm.nih.gov/pubmed/24505411 

 
53 
71.  
Mbuagbaw L, Thabane L, Ongolo-Zogo P, Lester RT, Mills EJ, Smieja M, et al. The Cameroon 
Mobile Phone SMS (CAMPS) Trial: A Randomized Trial of Text Messaging versus Usual Care for 
Adherence to Antiretroviral Therapy. PLoS One. 2012;7(12):6–12.  
72.  
Lester RT, Ritvo P, Mills EJ, Kariri A, Karanja S, Chung MH, et al. Effects of a mobile phone short 
message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): A randomised 
trial. Lancet. 2010;376(9755):1838–45.  
73.  
Pop-Eleches C, Thirumurthy H, Habyarimana JP, Zivin JG, Goldstein MP, de Walque D, et al. 
Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited 
setting: a randomized controlled trial of text message reminders. AIDS [Internet]. 2011 Mar 27 
[cited 2013 Mar 10];25(6):825–34. Available from: 
http://www.ncbi.nlm.nih.gov/pubmed/21252632 
74.  
Burton J, Brook G, McSorley J, Murphy S. The utility of short message service (SMS) texts to 
remind patients at higher risk of STIs and HIV to reattend for testing: a controlled before and 
after study. Sex Transm Infect. 2014;90(1):11–3.  
75.  
Rana Y, Haberer J, Huang H, Kambugu A, Mukasa B, Thirumurthy H, et al. Short Message Service 
(SMS)-based intervention to improve treatment adherence among HIV-positive youth in Uganda: 
Focus group findings. PLoS One. 2015;10(4):1–14.  
76.  
Thirumurthy H, Lester RT. M-health for health behaviour change in resource-limited settings: 
Applications to HIV care and beyond. Bull World Health Organ. 2012;90(5):390–2.  
77.  
Murray, LK, Skavenski, S, Bass, J, Wilcox, HC, Bolton, P, Imasiku, M, Mayeya J. Implementing 
Evidence-Based Mental Health Care in Low-Resource Settings: A Focus on Safety Planning 
Procedures. J Cogn Psychother An Int Q. 2014;28(3):168–85.  
78.  
Marshall LL. Development of the severity of violence against women scales. J Fam Violence 
[Internet]. 1992 Jun [cited 2019 Mar 11];7(2):103–21. Available from: 
http://link.springer.com/10.1007/BF00978700 
79.  
Radloff LS. The CES-D Scale: A Self-Report Depression Scale for Research in the General 
Population. Appl Psychol Meas [Internet]. 1977 Jun 26 [cited 2019 Mar 11];1(3):385–401. 
Available from: http://journals.sagepub.com/doi/10.1177/014662167700100306 
80.  
Mollica RF, Caspi-Yavin Y, Bollini P, Truong T, Tor S, Lavelle J. The Harvard Trauma Questionnaire. 
Validating a cross-cultural instrument for measuring torture, trauma, and posttraumatic stress 
disorder in Indochinese refugees. J Nerv Ment Dis [Internet]. 1992 Feb [cited 2019 Mar 
11];180(2):111–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1737972 
81.  
Humeniuk R, Ali R, Babor TF, Farrell M, Formigoni ML, Jittiwutikarn J, et al. Validation of the 
alcohol, smoking and substance involvement screening test (ASSIST). Addiction. 2008 
Jun;103(6):1039–47.  
82.  
Mugavero MJ, Westfall AO, Zinski A, Davila J, Drainoni M-L, Gardner LI, et al. Measuring retention 
in HIV care: the elusive gold standard. J Acquir Immune Defic Syndr. 2012;61(5):574–80.  
83.  
Rosen S, Maskew M, Fox MP, Nyoni C, Mongwenyana C, Malete G, et al. Initiating Antiretroviral 
Therapy for HIV at a Patient’s First Clinic Visit: The RapIT Randomized Controlled Trial. PLoS Med. 
2016;13(5).  
84.  
Rosen S, Fox MP, Larson BA, Brennan AT, Maskew M, Tsikhutsu I, et al. Simplified clinical 
algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV 
(SLATE): protocol for a randomised evaluation. BMJ Open [Internet]. 2017 May 28 [cited 2017 
Aug 31];7(5):e016340. Available from: http://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-
2017-016340 
85.  
Fox MP, Pascoe SJS, Huber AN, Murphy J, Phokojoe M, Gorgens M, et al. Effectiveness of 
interventions for unstable patients on antiretroviral therapy in South Africa: results of a cluster-
randomised evaluation. Trop Med Int Heal [Internet]. 2018 Dec [cited 2019 Feb 12];23(12):1314–

 
54 
25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30281882 
86.  
Fox MP, Pascoe SJ, Huber AN, Murphy J, Phokojoe M, Gorgens M, et al. Assessing the impact of 
the National Department of Health’s National Adherence Guidelines for Chronic Diseases in 
South Africa using routinely collected data: a cluster-randomised evaluation. BMJ Open 
[Internet]. 2018 Jan 21 [cited 2018 Feb 5];8(1):e019680. Available from: 
http://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2017-019680 
87.  
Vanderweele TJ, Vansteelandt S. Conceptual issues concerning mediation, interventions and 
composition. Stat Interface. 2009;2:457–68.  
88.  
VanderWeele TJ, Vansteelandt S. Odds ratios for mediation analysis for a dichotomous outcome. 
Vol. 172, American Journal of Epidemiology. 2010. p. 1339–48.  
89.  
Valeri L, Vanderweele TJ. Mediation analysis allowing for exposure-mediator interactions and 
causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros. 
Psychol Methods. 2013 Jun;18(2):137–50.