Integrated Prevention of HIV Risk and Intimate Partner Violence Among Adolescents in South Africa
Phase: NA
Conditions: Sexual Behavior, Intimate Partner Violence
Sponsor: Brown University

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COVER PAGE PROTOCOL DETAILS  
 
Protocol Title: Integrated Prevention of HIV Risk and Intimate Partner Violence among Adolescents in South Africa 
NCT03179982  
 
 
 
Investigator Details: Principal Investigators: Dr. Catherine Mathews (Multi-Principal Investigator, South African Medical 
Research Council) Health Systems Research Unit Dr. Caroline Kuo (Multi-Principal Investigator, Brown University School 
of Public Health) Brown University School of Public Health Co Investigators: Dr. Abigail Harrison (co-Investigator, 
Brown University School of Public Health) Brown University School of Public Health Dr. Lindsay Orchowski (co-
Investigator, Rhode Island Hospital) Rhode Island Hospital, Outpatient Psychiatry Expert Consultants: Dr. Alan 
Berkowitz (anonymous data only, no human subjects contact) Dr. Naeemah Abrahams Gender and Health Research Unit 
Medical Research Council Funding.  
 
 
 
This study has been reviewed by the U.S. National Institute of Mental Health (NIMH) under a R34 mechanism (Grant 
#R34 MH 113484) from 2017-2020. The protocol was approved on April 25, 2017 
 
 

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Contents 
PROTOCOL DETAILS .............................................................................................................................................................................. 3 
RESEARCH PROPOSAL EXECUTIVE SUMMARY ........................................................................................................................................ 5 
Aims................................................................................................................................................................................................. 5 
Expected Outcomes .......................................................................................................................................................................... 5 
Intended Feedback ............................................................................................................................................................................ 5 
PROTOCOL NARRATIVE ......................................................................................................................................................................... 6 
A. 
STUDY OBJECTIVE .................................................................................................................................................................. 6 
B. 
STUDY AIMS, SIGNIFICANCE, INNOVATION............................................................................................................................. 6 
C. 
PROPOSED INTERVENTION OVERVIEW ................................................................................................................................. 10 
D. 
INVESTIGATIVE TEAM .......................................................................................................................................................... 14 
E. 
METHODS.............................................................................................................................................................................. 15 
SPECIFIC AIM 1: DEVELOPMENT PHASE – HIV PREVENTION INTEGRATION AND ADOLESCENT FOCUS GROUPS .................... 16 
SPECIFIC AIM 2: ACCEPTABILITY PHASE – TEST ACCEPTABILITY OF SAFE SOUTH AFRICA IN OPEN PILOT TRIAL ................ 18 
SPECIFIC AIM 3: FEASIBILITY PHASE – ASSESS FEASIBILITY OF SAFE SOUTH AFRICA IN TRIAL RCT ...................................... 21 
F. 
OTHER ETHICAL CONSIDERATIONS ..................................................................................................................................... 25 
G. 
MANAGEMENT DETAILS ......................................................................................................................................................... 31 
H.        REFERENCES ........................................................................................................................................................................ 34 
 
 
 
 

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PROTOCOL DETAILS 
Protocol Title:  Integrated Prevention of HIV Risk and Intimate Partner Violence among Adolescents in South 
Africa 
 
SAMRC Unit: Health Systems Unit 
 
Investigator Details: 
Principal Investigators:   
Dr. Catherine Mathews (Multi-Principal Investigator, South African Medical Research Council) 
Health Systems Research Unit 
Francie van Zijl Drive 
7505 Tygerberg, South Africa 
Phone: +27 21 9380247 
Email: Cathy.Mathews@mrc.ac.za 
 
Dr. Caroline Kuo (Multi-Principal Investigator, Brown University School of Public Health) 
Brown University School of Public Health 
121 South Main Street 
Box G-S121-4th Floor 
Providence, RI  02912 
USA 
Phone: +1 (401) 863-5453 
Fax: +1 (401) 863-6647 
Email: Caroline_Kuo@Brown.edu  
 
Co Investigators:  
Dr. Abigail Harrison (co-Investigator, Brown University School of Public Health) 
Brown University School of Public Health 
121 South Main Street 
Box G-S121-2nd Floor 
Providence, RI  02912 
USA 
Phone: +1 (401) 863-6183 
Fax: +1 (401) 863-6647 
Email: Abigail_Harrison@Brown.edu 
 
Dr. Lindsay Orchowski (co-Investigator, Rhode Island Hospital) 
Rhode Island Hospital, Outpatient Psychiatry 
 
146 West River Street, Suite 11B 
Providence, RI  02904 
USA 
Phone: +1 (401) 444-7021 
Fax: +1 (401) 444-7109 
Email: Lindsay_Orchowski@Brown.edu 
 
Expert Consultants:  
Dr. Alan Berkowitz (anonymous data only, no human subjects contact) 
PO Box 318 
Mount Shasta, CA 96067-0318  
Phone: 530 784-0416 
Email: alan@fltg.net 

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Dr. Naeemah Abrahams 
Gender and Health Research Unit  
Medical Research Council 
PO Box 19070 
7505 Tygerberg, South Africa 
Phone: +27 021 9380823 
Fax: +27 021 9380310 
Email: nabraham@mrc.ac.za 
 
Scientific Key words: human immunodeficiency virus (HIV); intimate partner violence (IPV); prevention; 
perpetration; adolescents; gender 
 
Funding. This study has been reviewed by the U.S. National Institute of Mental Health (NIMH) under a R34 
mechanism (Grant #R34 MH 113484) from 2017-2020.  
 
 
 
 

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RESEARCH PROPOSAL EXECUTIVE SUMMARY 
Aims 
This study will investigate the acceptability and feasibility of Safe South Africa, an integrated intervention 
to prevent adolescent behavioral risk for human immunodeficiency virus (HIV) and perpetration of intimate 
partner violence (IPV). Safe South Africa is a theory-driven, developmentally-tailored and gender-specific 
intervention designed for male adolescents 15-17 years of age. The research will be conducted in South Africa, a 
country with the largest HIV epidemic and some of the highest rates of IPV perpetration in the world. Preventive 
interventions are urgently needed during adolescence when risk for human immunodeficiency virus (HIV) and 
intimate partner violence (IPV) increases exponentially. Yet, few behavioral interventions integrate HIV-IPV 
prevention and are tailored for the unique age and developmental needs of adolescents. We utilize the insights of 
adolescent development theory in our preventive intervention strategy by capitalizing on adolescents’ 
developmental propensities for maximum prevention gains. Adolescence presents an ideal age and developmental 
transition period for an integrated intervention targeting prevention of HIV behavioral risk reduction and 
perpetration of IPV including sexual violence. Developmental hallmarks of adolescence – including for example, 
the role of social norms in motivating behaviors, the importance of peers in shaping behavioral choices, and the 
desire for increased responsibility – can all be leveraged for prevention of sexual risk behavior driving acquisition 
of HIV infection and engagement in IPV. For example, we use social norms marketing insights to shift attitudes 
and motivations to engage in protective HIV behaviors and prevent IPV. We use positive peer pressure and tap 
into adolescents’ desire to be responsible future leaders to motivate adolescents to intervene as bystanders when 
their peers are involved in HIV risk behaviors or sexual assault and aggression. The motivation and 
implementation of these positive behaviors relating to prevention of HIV and IPV perpetration are occurring in a 
period when identity formation and life-long health patterns are being habituated; our intervention approach 
leverages the formation of identity and habits during adolescence to support long term prevention behaviors. An 
integrated approach for prevention of adolescent HIV and IPV perpetration has not yet been tested. We will 
investigate the acceptability and feasibility of Safe South Africa, an integrated HIV-IPV intervention to prevent 
adolescent HIV behavioral risk and perpetration of IPV among male adolescents 15-17 years of age through three 
study aims: (1) development aim  – create Safe South Africa, an integrated male adolescent preventive intervention 
for HIV risk behavior and IPV perpetration; (2) acceptability aim – evaluate social ecology of HIV and IPV risk 
with a survey of N=100 of adolescents, and test the acceptability of Safe South Africa through an open pilot trial 
with N=20 male adolescents; and (3) feasibility aim  – conduct a randomized controlled pilot trial with 1- and 6-
month follow-up in a sample of N=60 male adolescents to assess the feasibility and acceptability for a future fully 
powered randomized controlled trial to evaluate efficacy of the intervention.  
Expected Outcomes 
Findings will advance preventive intervention science for young people at elevated risk for HIV and IPV 
in a high impact setting. The expected outcomes of this study include findings on the acceptability and feasibility 
data that will inform a future fully-powered RCT to test efficacy of Safe South Africa for preventing acquisition 
of HIV and IPV perpetration. In Year 3, we will submit an R01 application for a fully powered clinical trial to 
test the efficacy of Safe South Africa. 
Intended Feedback 
Intended feedback and dissemination include peer review papers and conference presentations. In 
addition, we will develop research briefs for adolescents, school stakeholders, and policy makers.  
 
 
 

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PROTOCOL NARRATIVE 
A. STUDY OBJECTIVE 
The purpose of this study is to investigate the feasibility and acceptability of an integrated approach for 
preventing or reducing risk behavior related to acquisition of human immunodeficiency virus (HIV) and 
perpetration of intimate partner violence (IPV) among adolescents in South Africa. South Africa faces some of 
the highest global rates of HIV and IPV with sustained high incidence of HIV and alarming rates of IPV among 
adolescents. Developing preventive intervention science in this setting and population can advance our 
scientific understanding of how to intervene early in the life course, and to promote healthy long-term sexual 
and reproductive lives for adolescents, their future partners, and society.  
 
B. STUDY AIMS, SIGNIFICANCE, INNOVATION 
STUDY AIMS 
South African adolescents face exponentially greater risk for human immunodeficiency virus (HIV) and 
intimate partner violence (IPV), with sustained high HIV incidence and unacceptably high rates of IPV. South 
African adolescents are being infected at a rate of 1.5%,1 equivalent to 139,000 new infections each year or the 
largest share of new infections of any age group in the country.2 South Africa has the largest country population 
of individuals living with HIV3 and Southern African adolescents engage in high rates of sexual activity,4-7 
early sexual debut,4,6 and multiple partners.6,8 Similar to HIV, prevalence of IPV – defined as sexual, physical, 
and emotional violence– is also among the highest in the world. Half of African children experienced sexual, 
physical, emotional violence, bullying, or witnessed violence in the past year.9 In South Africa, IPV and non-
intimate sexual violence is alarmingly high; for example 1 in 3 men (31.9%) perpetrated rape in a population-
based survey of N=1,737 South African men 18-49 years.10 The majority (75%) perpetrated their first rape 
before age 20, with the average age of first rape at 17.11,12 This young age of sexual perpetration underscores the 
need for preventive interventions during adolescence. Preliminary data from our HIV prevention study with 
South African adolescents 13-15 years (in a community with 33.1% HIV prevalence13) indicated high rates of 
perpetration of unwanted oral sex (15%), sexual touching (14%), anal sex (8%), and vaginal sex (6%) via force 
or coercion.14 The synergistic relationship between HIV risk and IPV requires an integrated preventive 
intervention approach. Yet, no interventions we identified concomitantly target prevention of HIV risk and IPV 
perpetration among South African adolescents. Gender-tailoring to males is needed because of the majority of 
IPV is perpetrated by boys and men.15 Gender-tailoring facilitates males openly discussing attitudes, which  
may be more difficult when females are present.16 Developmental-tailoring is also needed because perpetration 
of violence most often begins during adolescence, and continues within multiple relationships across the 
lifespan.17-19 There are unique opportunities to capitalize on developmental aspects of adolescence for larger 
prevention gains including natural propensities such as forming and retaining preventive health behaviors; the 
power of positive peer influence to reinforce prevention; and building healthy male identity and gender norms 
critical to prevention. 
Our long-term goal is to prevent HIV and IPV perpetration using developmentally- and gender-tailored 
interventions for male adolescents. In this grant, our overall objective is to test the acceptability and feasibility 
Safe South Africa, an integrated intervention for preventing HIV-IPV perpetration for male adolescents 15-17 
years. We will create Safe South Africa by integrating best-evidence on adolescent HIV prevention20,21 into our 
existing Safe intervention,22-29 a developmentally tailored skills-based IPV prevention program with 
demonstrated promise among male adolescents. Our existing Safe intervention targets attitudes and behaviors 
that increase proclivity to IPV through evidence-driven social norms messaging combined with proactive 
bystander behavior training when witnessing inappropriate sexual aggression, IPV, or interpersonal violence 
among peers.23 Our rationale for this study is that the majority of existing interventions to address HIV-IPV 
synergies reduce risk for IPV victimization. An explicit focus on preventing IPV perpetration would tackle the 
root cause of violence related to HIV risk and complement existing risk reduction approaches. We propose 3 
aims: 
1. Development Aim: Create Safe South Africa, an integrated intervention for prevention of HIV and 
IPV perpetration. We begin by reviewing our existing empirically supported Safe intervention to identify 
content, structure, and delivery modalities needing refinement to ensure responsiveness in South Africa. 

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Then we integrate into Safe, best evidence on theoretical and behavioral adolescent HIV prevention to create 
Safe South Africa. We elicit feedback from k=3-5 focus groups with adolescent males on salience of 
adaptations.  
2. Acceptability Aim: Evaluate adolescent social norms relating to HIV and IPV risk within the school 
social ecology with N=100 adolescents to inform evidence-based messaging to be used within Safe 
South Africa, then test acceptability of Safe South Africa in an open pilot with N=20 male adolescents. 
We evaluate social norms relating to HIV and IPV risk to inform evidence-based social messaging tailored 
to adolescent intervention participants’ specific social ecology. Then we test acceptability including 
participant satisfaction with content, materials, and delivery for make final refinements to Safe South Africa.  
3. Feasibility Aim: Assess feasibility of Safe South Africa through a randomized controlled pilot trial 
with 1- and 6-month follow-up with N=60 male adolescents. We assess feasibility for a future R01 trial 
including rigor of facilitator implementation by evaluating fidelity and competence, recruitment strategies, 
and tracking and tracing success. As an exploratory secondary aim, we examine preliminary evidence for 
hypotheses that the intervention, relative to the control, will produce: (1) reductions in actual or intended 
HIV risk behaviors; (2) reductions in IPV frequency and decreased endorsement of IPV supportive attitudes; 
and (3) increased proactive bystander behavior for prevention of IPV perpetration. 
The expected outcomes of this study include acceptability and feasibility data that will inform a future fully-
powered RCT to test efficacy of Safe South Africa for preventing acquisition of HIV and IPV perpetration.  
 
STUDY SIGNIFICANCE 
The bi-directional relationship between HIV and IPV indicates the need for an integrated intervention. 
Several systematic reviews and meta-analyses identify causal and non-causal mechanisms linking HIV and IPV. 
Causal mechanisms linking increased HIV risk with sexual violence – one form of IPV – include increased 
vaginal or anal tissue trauma associated with increased infection risk. Non-causal mechanisms include positive 
correlation between HIV infection and those who perpetrate IPV30 and higher rates of HIV risk behaviors 
among IPV perpetrators including decreased condom use,31,32 concurrent and/or multiple sexual partners,31,33 
alcohol and substance use, and higher rates of sexually transmitted infections (STI) co-infection.34,35 HIV 
acquisition risk is significantly higher among individuals who have experienced IPV victimization. For 
example, a global systematic review and meta-analysis of 28 studies with N=331,468 women (including 4 
South African studies), indicated that any type of IPV [pooled RR (95% CI): 1.28 (1.00, 1.64)] was significantly 
associated with HIV infection in cohort studies, and that combination of physical and sexual IPV [pooled OR 
(95% CI): 2.00 (1.24, 3.22) and any type of IPV [pooled OR (95% CI): 1.41 (1.16, 1.73)] were significantly 
associated with HIV infection in cross-sectional data.36 A preventive intervention to address IPV perpetration 
naturally addresses sexual risk reduction and can yield HIV prevention benefits for potential perpetrators, and 
current or future partners. Adolescence offers an ideal life-course transition point for integrated HIV-IPV 
prevention interventions. South Africa provides an appropriate setting to advance the science of concurrent 
prevention of HIV risk and IPV given high global burdens of HIV and IPV.  
South Africa has the largest HIV epidemic of any country in the world,3 with adolescents accounting for 
the majority of new HIV infections.2 Among South African adolescents, HIV incidence increases rapidly during 
middle adolescence, from 0.25% in the 2-14 year age group to 1.49% in the 15-24 year age group.1 
Adolescents, especially middle adolescents aged 15-17 years, are naturally at increased risk due to normal 
developmental milestones.37 Initial sexual experiences frequently occur at this age, corresponding to increased 
risk for acquisition of HIV, other STIs, and IPV. Behavioral HIV prevention efforts are needed to complement 
emerging biomedical strategies because 40% of 15-24 year old South Africans did not think they are at risk for 
HIV, and only 26% correctly identified common modalities of HIV transmission and prevention.1 Given the 
gender-specific focus of our proposal (on male adolescents), we highlight data relevant to 15-17 year old males: 
data from a large South African birth cohort indicated by age 13, 74% of boys reported sexual foreplay or oral 
sex, and by age 15, approximately half engaged in penetrative sexual debut.38 We focus on adolescent males 
starting at age 15 because of the larger proportion of adolescents engaged in penetrative sexual debut by this 
age. South Africa also has a high global burden of IPV. The majority of IPV perpetrators are male, with over 1 
in 3 women (35.6%) experiencing intimate partner or non-partner sexual and/or physical violence in their 

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lifetime.39 Globally, the sub-Saharan African region, including South Africa, has the highest prevalence for both 
intimate partner and non-partner sexual and/or physical violence at 65.6% (95% CI: 53.6-77.7%)40 and 21% 
(95% CI: 4.5-37.5%) respectively.41 We recognize that violence occurs across the lifespan. However, preventive 
interventions are urgently needed during adolescence, especially in South Africa because 75% of adult 
perpetrators commit their first rape before the age of 2011,12 and 31.9% men report rape perpetration.10 We focus 
on prevention among adolescent males up to 17 years given this is the average age for first rape perpetration in 
South Africa.11,12 Alignment of age of sexual debut with age of perpetration underscores the need for preventive 
HIV-IPV interventions during adolescence. Given this young age, addressing interpersonal violence and sexual 
aggression is part of our comprehensive prevention because those who engage in these acts are more likely to 
engage in IPV.42  
Empirical data on IPV, especially adolescent sexual violence is rare; South Africa has one of few 
existing epidemiological surveys of adolescent sexual perpetration which identified a prevalence of 10%.43 Our 
own preliminary data indicates IPV perpetration is even higher among adolescents at risk for HIV based on 
results from an adolescent HIV prevention study (PI: Kuo) with N=200 adolescents 13-15 years of age recruited 
door-to-door from a South African community with 33.1% HIV prevalence.13,14,44-46 Self-reported perpetration 
was assessed using the Sexual Experiences Survey - Short Form Perpetration (SES-SFP) using audio computer-
assisted self-interviewing (A-CASI).47 Adolescents reported using coercion, incapacitation, force or threats of 
force to perpetrate unwanted oral sex at 15%, sexual touching at 14%, anal sex at 8%, and vaginal sex at 6%. 
Perpetration was more common among males, reinforcing the need for gender-tailored preventive intervention. 
Development of additional IPV perpetration prevention efforts are needed.15,48 When we disaggregated 
preliminary data by gender, males reported perpetrating at much higher rates than females including: oral sex 
(23%), sexual touching (18.4%), anal sex (11.6%), and vaginal sex (7%). Alarmingly, 14% of boys from our 
preliminary study engaged in repeat perpetration.14 Most common perpetration tactics included verbal coercion, 
followed by incapacitation, threats of violence, and physical assault. Attempted perpetration was also reported 
at alarming rates for this young age group including: vaginal (8%), oral (8%), and anal sex perpetration (5%).14  
Our intervention approach integrates prevention of both HIV risk and IPV perpetration, with a purposive 
focus on male adolescents as potential perpetrators. A focus on preventing IPV perpetration (focused on males) 
in relation to HIV, as opposed to reducing risk for IPV victimization (most often focused on females), is central 
to our effort to expand intervention approaches for HIV-IPV. Focusing on perpetration prevention rather than 
risk reduction permits us to tackle the root cause of violence early in adolescence. There were few randomized 
controlled trials (RCTs) for prevention of HIV and IPV perpetration in South Africa or other generalized HIV 
epidemic countries. This included the Stepping Stones intervention, a participatory learning intervention tested 
in a randomized controlled trial; the intervention demonstrated efficacy in reduction of HIV risk factors and 
reductions of male self-reported perpetration of violence.49,50 We were only able to find a handful of 
interventions that combined HIV-IPV in Southern Africa. All focused on risk reduction (rather than IPV 
perpetration prevention). In South Africa, PREPARE led by Dr. Mathews (M-PI of this study) was a multi-
component school-based intervention designed to decrease IPV and HIV risk behavior among adolescents. 
PREPARE was tested in a cluster RCT in 42 schools. The 21-session group-based intervention was 
accompanied by school health and school safety components. At the 12 month follow-up, intervention 
participants were less likely to report IPV victimization (35.1 vs. 40.9 %; OR: 0.77; 95 % CI 0.61–0.99) but had 
no changes in HIV risk.51 Also in South Africa, the IMAGE RCT investigated whether a microfinance 
intervention providing economic stability and complemented with education on male gender norms, domestic 
violence, sexuality and HIV could reduce IPV among adults. After two years, intervention participants reported 
lower risk of past-year physical or sexual violence by an intimate partner (adjusted risk ratio=0.45; 95% CI: 
0.23-0.91) but no changes in HIV incidence.52 In Uganda, the SASA! intervention tested in a cluster RCT in 
eight communities, targeted prevention of violence against women and HIV risk reduction by engaging 
communities in changing attitudes, norms and behaviors related to gender inequality, violence, and women’s 
increased HIV vulnerability.  At the four year follow-up, intervention group participants reported fewer events 
of sexual intimate partner violence (OR: 0.76, 95% CI: 0.33-1.72), and for HIV risk, fewer concurrent partners 
among men (OR: 0.57, 95% CI: 0.36 to 0.91).53 There was a fourth trial in Uganda that demonstrated efficacy 
of SHARE, an intervention to reduce IPV towards women and overall HIV incidence.54  However, PREPARE, 

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IMAGE, SASA!, and SHARE are risk reduction approaches focused on decreasing risk for victimization (as 
opposed to preventing perpetration which is our approach). The need to integrate best evidence on HIV 
prevention is indicated by the finding that no HIV and only limited HIV risk behavior change occurred in the 
trials. We detail how we will integrate the latest evidence on HIV prevention in our intervention under Methods, 
Aim 1.  
We also reviewed the literature to identify RCTs on prevention of IPV, especially sexual perpetration, in 
South Africa or other settings facing high HIV prevalence. In DeGue et al.’s 2014 systematic review of sexual 
violence prevention interventions, none integrated prevention of HIV, and no RCTs occurred in South Africa. 
DeGue’s review identified 140 outcome evaluations but only three RCTs55 All three RCTs were designed and 
tested in the USA where HIV prevalence is low.56-58 The study by Boba et al. 2009, took a structural 
intervention approach focusing on changing legislation and funding for law enforcement, prosecution, arrest 
policies, and programs to combat domestic violence and child abuse as well as social service support programs. 
The two other US interventions focused on adolescents; both Foshee et al.’s 2005 intervention, SAFE Dates, 
and Taylor et al.’s 2013 Shifting Boundaries intervention used combination intervention approaches of 
behavioral intervention with adolescents, with changes to school and community environments. Ellsberg et al.’s 
2015 review of evidence on prevention of violence against women and girls noted that group-based 
interventions in school settings have limited success the majority of evidence was generated in high income 
country settings. Our proposed study contributes to the evidence by examining a group-based approach in a 
school setting in South Africa (to contribute to the current geographic inequity in studies) and takes a male-
tailored approach and integrates bystander intervention elements (neither which were tried in SAFE Dates and 
Shifting Boundaries).48 Since DeGue et al.’s 2014 review, five additional RCTs have been identified. An 
adolescent dating violence intervention, Coaching Boys to Men, used bystander intervention among high school 
athletes in the USA and showed more likelihood to engage in bystander intervention but no changes in sexual, 
physical, or psychological perpetration behaviors. A study in India utilized an individual cognitive behavioral 
intervention approach and showed small but significant reductions in intimate partner perpetration.59 Another 
study in the Netherlands showed effective reductions in perpetration behavior using a cognitive behavioral 
therapy approach and a combined substance use and perpetration prevention approach.60 We decided not to 
adapt these US adolescent programs to South Africa given foci on changing school and community 
environments rather than peers, and because of no perpetration behavior change despite use of a bystander 
approach. A RCT in Kenya tested Your Moment of Truth, a bystander focused intervention for adolescent boys 
that showed efficacy in increasing intervention when witnessing violence.61 Finally, we identified one ongoing 
RCT for perpetration prevention in South Africa; Skhokho (Dr. Abrahams, expert consultant on our study was 
investigator on Skhokho) compares a school and family intervention versus a school intervention versus a 
control. We feel our proposal is distinct from Skhokho which does not integrate HIV prevention, and focuses on 
the family environment (rather than peers, as in our intervention).62 
 
INNOVATION 
Our study offers several innovations. First, we develop our scientific understanding of developmentally 
appropriate preventive interventions to address the adolescent intersection of HIV behavioral and IPV 
perpetration risk. To our knowledge, this will be the first intervention to prevent adolescent HIV risk and IPV 
perpetration in an integrated manner and in a high priority global setting where prevalence of HIV and IPV is 
high. DeGue et al.’s 2014 systematic review of interventions to prevent perpetration detailed above failed to 
identify any RCTs showing efficacy in violence preventive interventions that were integrated with HIV. We 
were only able to find interventions that combined IPV risk reduction with HIV prevention in southern Africa. 
All three of these interventions – PREPARE (led by our M-PI Cathy Mathews), IMAGE, and SASA! – are IPV 
risk reduction approaches whereas our intervention specifically focuses on prevention, offering a complement to 
the existing intervention evidence base. We now integrate the most current global evidence on efficacious HIV 
preventive approaches for adolescents into a promising existing intervention for IPV. Second, the Safe 
intervention has shown promise in increasing bystander behavior, promoting change in attitudes and behaviors 
associated with IPV, interpersonal violence, and aggression. Such data indicate the promise of adapting to South 
Africa. Third, the proposed primary prevention program for IPV is highly innovative in that it targets the 

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specific risk and protective factors in the social ecology of IPV perpetration; a number of these risk and 
protective factors are aligned with our HIV prevention goals. Our previous work on Safe included the 
developmental tailoring of the intervention for adolescents, so now we can focus upon HIV and South African 
adaptations. Fourth, if found to be efficacious, Safe South Africa offers not only immediate prevention promise 
for adolescent males, but also offers long term promise by preventing negative consequences of HIV and IPV 
on current and future partners as these male adolescents proceed in their life-course. We purposively choose to 
test acceptability and effectiveness of this HIV-IPV preventive intervention in school settings because a 
systematic review has shown numerous challenges to reaching youth for sexual health services within health 
facility settings.63 Our approach may be congruent with policy changes including South Africa’s recent 
commitment to integrating health services into school settings and outlined in their national Integrated School 
Health Policy.64 The leads to our fourth innovation, that our intervention is directly policy relevant, consistent 
with the government policy encouraging structured after-school health-related activities as part of Integrated 
School Health Policy.  
 
C. PROPOSED INTERVENTION OVERVIEW 
Safe South Africa: Integrated adolescent intervention to prevent HIV risk and IPV perpetration 
This Clinical Trial Planning Grant tests the acceptability and feasibility of Safe South Africa with an 
approach that builds on adolescents’ natural desire for independence and responsibility as they transition to 
adulthood. Given the lack of integrated interventions for preventing adolescent HIV and IPV perpetration 
globally and in South Africa, we utilize a theoretically and empirically supported prevention strategy. 
Overview of proposed Safe South Africa intervention: The existing Safe intervention (tested 
previously in the USA by co-I Orchowski and consultant Berkowitz)22-29 will be adapted in this study to create 
the new Safe South Africa intervention. During Development Aim 1, we will integrate best-evidence HIV 
prevention strategies (HIV intervention elements described below). We retain two components of the existing 
Safe program in our new Safe South Africa intervention: (1) Part 1 is a survey with both male and female 
adolescents to evaluate IPV prevention needs within a specific social ecology (in this case peers within a 
school) and application of survey data into evidence-driven social norms messaging within the behavioral 
intervention that occurs as Part 2; and (2) Part 2, a group-based, facilitated behavioral intervention for 
prevention of HIV risk and IPV perpetration specifically tailored for male adolescents. The behavioral 
intervention is comprised of 2-hour sessions, held once a week for a total of two weeks. These 2-hour sessions 
comprise a behavioral intervention that includes the following core components (described in detail under the 
section titled “Core Components of the Safe South Africa intervention”):  information and behavioral skills 
practice to address HIV and STI prevention including HIV and STI content relating to prevention knowledge, 
attitudes and behaviors; information relating to linkages between HIV and IPV; formation and behavioral skills 
practice to address IPV prevention including debate, discussion, and information designed to improve victim 
empathy; debate, discussion, and information designed to support healthy norms regarding masculinity and 
deep understanding of consent; and development of bystander intervention skills with practice to boost self-
efficacy in future implementation of these skills.. The intervention also includes take-home activities to deepen 
behavioral engagement with week’s received session and to “prime the pump” for the upcoming week’s session.  
Theory driven and conceptual model of Safe South Africa: SAFE South Africa’s HIV risk 
prevention components will be based on Information-Motivation-Behavioral (IMB) theory. The change 
strategy of the HIV components of the intervention include: (1) increasing HIV knowledge around protective 
behaviors (i.e., information), (2) encouraging adolescents to implement protective behaviors through for 
example, formation of positive peer relationships that impact attitudes towards HIV risk, tying protective HIV 
behaviors to future goals (i.e., motivation), and (3) building self-efficacy for prevention behaviors including 
condom use, condom negotiation, and healthy sexual relationships (i.e., behavior).65-67 See below under 
Methods, Aim 1 for our proposed integration of best evidence HIV into the existing Safe Intervention. Safe 
South Africa’s prevention of IPV components will be based off a conceptual model called the Integrated 
Model of Sexual Assault and Acquaintance Rape. This conceptual model was originally proposed by Berkowitz 
(expert consultant).68,69 This conceptual model proposes interventions to prevent IPV, interpersonal violence, 
and sexual aggression are most salient when they target risk and protective factors across social ecology (i.e., 

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individual-, peer-, and community-level risk factors). At the individual level, adolescent males must consider 
their own potential for intimate and interpersonal violence (i.e., attitudes, beliefs and socialization experiences) 
and take a stand against violence perpetrated by others.70 Our HIV theoretical model (IMB) is aligned with the 
violence prevention social-ecological model. At the individual level we focus on changing personal attitudes 
and beliefs; this aspect of the violence prevention model is aligned with the “I - information” component of our 
HIV prevention theoretical model. For example, we educate adolescents on situational characteristics that may 
lead to misperception of sexual interest including “triggers”:71 Triggers might include a pre-existing relationship 
between the victim and perpetrator that may increase the likelihood that a young man feels justified to use 
coercive or aggressive behavior in order to obtain sex;72 misinterpretation of a variety of behaviors and 
situations, such as friendliness, the wearing of revealing clothing, and female attractiveness, as seductive and 
indicative of sexual interest, even when stimuli are subtle or ambiguous;73-75 assumptions that when a partner 
says “no” to sexual activity, they really mean “yes” (i.e., token resistance).76 Accordingly, this research suggests 
IPV prevention programs benefit from discussions of common assumptions (specific to different contexts) 
about gender, relationships, sexual situations, consent, and sexual communication. Towards this goal, we 
explore and challenge males’ attitudes and beliefs including stereotypical rape myths, adversarial views towards 
girls and women, and intimate partner and interpersonal violence.77-85  
We also address peer-level factors in our prevention model. At the peer level we use bystander 
intervention techniques.86-90 Positive peer pressure – as exerted through prosocial bystander action – can prevent 
IPV in others. Importantly, bystander behaviors can also reinforce the bystanders own prevention behaviors. 
The bystander approach has promise in correcting misperceptions about IPV91,92 and decreasing personal 
engagement in IPV, interpersonal violence, and aggression.23 This aspect of the violence prevention model is 
aligned with the “M-motivation” component of the HIV prevention theoretical model because bystander actions 
involve social learning where peer reinforcement results in self- and social-rewards for positive behaviors. We 
also build self-efficacy and behavioral skills, including for example, practice in assertive bystander 
communication (e.g., what to say, how to say it) and behavioral action (e.g., confronting and halting IPV 
behavior of peers, knowing who to contact for reporting and help in the case of suspected or actual IPV, linking 
peers and potential victims to appropriate services). This aspect of the violence prevention model is aligned 
with the “B-Behavior” component of the HIV prevention theoretical model.  
The final tier of the social-ecological model is community-level factors. To address community-level 
factors, we use a survey with both boys and girls to evaluate the social ecology of the community that 
adolescents are in (in this case, a community is defined as their peers within the school and thus specific to 
different settings). Data from the survey is used to create evidence-based social norms messaging used in our 
subsequent behavioral intervention with male adolescents.93,94 Our discussion of social norms with male 
adolescents (as derived from a survey of peers within their school) helps adolescents to interrogate their specific 
social ecology of risk that can serve to inhibit or encourage problem behavior.95 Social norms contribute to 
sexual violence in two ways. First, data suggest perpetrators are acting in ways that they (mis)perceive to be 
occurring within their community96 For example, men who perpetrate violence are apt to believe that other men 
ascribe to stereotypical gender role beliefs97 and support violence against women.98-100 Men who believe their 
friends are using coercive behavior to obtain sex are more likely to engage in sexually coercive behaviors 
themselves.101 Taken together, misperception of community norms regarding sexual activity in tandem with 
pressure to “fit” a (mis)perceived hyper-masculine ideal fosters an environment where sexual activity—even if 
coerced or forced—is falsely believed to be normative (with normative being defined differently for different 
contexts – in this case defined by the survey to be conducted in the school setting) and associated with increased 
status and acceptance.96,93 Social norms contribute to sexual violence by creating a false misperception of high 
rates of sexual violence existing in a community.102,103 Even non-perpetrators believe that peers harbor more 
rape myths than they actually do.104 People also underestimate the extent to which their peers feel 
uncomfortable with sexist or degrading language/actions towards women.70,91,105 These misperceptions about 
how many community members accept violence or how few would stand up against it, perpetuates violence by 
decreasing the likelihood that healthy community members stand up against the expression of inappropriate 
behavior in their community.16 Second, men who perpetrate acts of sexual aggression report feeling pressure to 
engage in sexually aggressive behavior in order to demonstrate their masculinity and avoid humiliation from 

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peers.106 This real or perceived pressure is a particularly salient factor for adolescents; notably, 85% of 
perpetrators, compared to 23% of non-perpetrators, described the “great and considerable” pressure to have sex 
in high school settings in the USA (data is not available in South Africa).107 Over-estimations of peer sexual 
activity contribute to high intentions to initiate early adolescent intercourse especially relevant to our HIV 
prevention aims,108 and pressure to be sexually active is a salient correlate of sexual assault perpetration.107 
Accordingly, our social norms messaging corrects misperceived norms as a community-level prevention 
strategy for both HIV and IPV109-112 by recognizing: 1) community norms influence behavior; 2) community 
norms are often misperceived (i.e., they are over- or under-estimated); 3) these misperceptions encourage 
individuals to adjust their attitudes and behaviors to confirm to what they incorrectly perceive to be true;113  and 
4) correcting these misperceptions allows individuals in a community to act in accordance with their actual 
beliefs, which are most often positive and health promoting.113 The social norms in our intervention will be 
defined by survey conducted in the preparatory stages of the study, and also via the participant debate and 
discussion that occurs as part of the intervention activities. Social norms theory proposes that when the actual 
norm of the peer group is revealed, individuals feel less pressure to engage in negative behaviors (sexual 
coercion, risk sex, etc.) and are more willing to intervene when witnessing inappropriate behavior.114 Following 
the acknowledgement that to be effective, prevention efforts must be positive, inclusive and empowering,115,116 
the social norms approach also emphasizes the importance of championing “positive behavior” rather than 
focusing on ameliorating “negative behavior.” The Integrated Model of Sexual Aggression suggests that 
prevention approaches can reduce proclivity for sexual aggression by providing opportunity to share discomfort 
with aspects of the traditional male gender role script, combined with discussion of more positive alternatives. 
The change strategies of the existing IPV prevention components of the intervention include: (1) understanding 
conditions of sexual consent; (2) increasing male empathy regarding the effects of IPV, interpersonal violence, 
and sexual aggression; (3) correcting misperceptions regarding IPV and interpersonal violence prevalence as 
well as prevalence of sex, and consequences of these misperceptions; (4) increasing use of bystander strategies; 
and (5) increasing awareness of risk for IPV, interpersonal violence, and aggressive behavior and links to HIV 
transmission.  
Hallmarks of the Safe South Africa intervention approach: The first hallmark of Safe South Africa 
is our gender-tailored approach. For HIV prevention, sensitive topics such as puberty, first relationships, and 
sexual negotiation are easier to discuss among male adolescents alone. For example, medical male 
circumcision, an important biomedical HIV prevention strategy for this age group, is also an important cultural 
marker of manhood among Xhosa males in South Africa. Culturally, this prevention approach is denoted as a 
topic that should only be discussed by men and boys.117-119 For IPV perpetration prevention, gender separation 
decreases defensiveness among participants and promotes salience of program content.  Fears of embarrassment 
make it difficult for males to openly discuss their attitudes when females are present.16 Given that only 
perpetrators can truly prevent violence, the importance of specifically engaging males in sexual assault 
prevention has been emphasized.16,120-124  We fill a gap in gender-tailored programming with our gender-
specific intervention approach since only 8% of existing sexual assault prevention efforts are directed toward 
males.15 The single-sex format of our intervention approach will allow boys to more effectively unearth and 
challenge misperceptions of social norms. Facilitators take a “non-expert” stance in order to avoid inciting 
defensiveness among participants. A second hallmark of the Safe South Africa Intervention is our age- and 
developmentally-tailored approach. Adolescence marks a life transition with developmental hallmarks that 
naturally increase propensity of HIV risk and IPV. For example, adolescence is marked by increases in 
impulsivity, increased risk taking,125 and exploration of sexual identities126 leading to naturally heightened 
sexual risk for HIV.127 Although developmental hallmarks create elevated risk for HIV and IPV, our approach 
uses other developmental hallmarks as prevention opportunities including: peer influence, habituation of 
behaviors, and identity formation including desire for recognition, leadership, and independence.128 This age is 
when formative first experiences in sexual behavior, sexual relationships, and peer relationships occur. We 
capitalize on formative experiences to habituate prevention behaviors for HIV and IPV. This age is when peer 
norms have a strong influence so we tap into positive peer norms for larger prevention gains. For example, our 
bystander prevention leverages positive peer pressure by positioning boys as allies in violence prevention. 
Given the vast majority of boys are not sexually aggressive and desire mutually respectful relationships,129 

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engaging this majority as allies in prevention is vital to promoting cultural norms that thwart the behavior of the 
minority of coercive and aggressive boys and men, and engage the majority as proactive bystanders to intervene 
with peers and support victims. This age is when identity development occurs, and a preventive intervention can 
reinforce healthy male identity formation and gender norms. We build on the natural trajectory of identity 
development formation to instill healthy notions of manhood and gender relationship norms to facilitate long-
term life-course prevention.  
Core components of the Safe South Africa intervention:  
 Theory driven, best-evidence intervention approaches for adolescent HIV prevention: In Aim 1, we will 
integrate the latest rigorous evidence in efficacious interventions for adolescent HIV prevention into the 
existing Safe intervention to create Safe South Africa (described further in Methods). Our choice of adolescent 
HIV prevention components to integrate is guided by 4 global and South African specific systematic reviews 
and/or meta-analyses.20,130-132 It includes content on HIV and STI approaches to increase knowledge, attitudes 
and motivations, and behavior change related to HIV and STI prevention. This includes for example, age and 
location specific prevalence data, condom access and use, pre-exposure and post-exposure prophylaxis, 
medical male circumcision, contraception, HIV testing including testing with partners, HIV disclosure 
circumcision, early treatment seeking for STIs or HIV, and other relevant sexual and reproductive health 
information. We combine the latest evidence from these reviews with our own experience of adapting 
empirically supported interventions to the South African context, and in design and testing of South African 
adolescent HIV and IPV interventions. These reviews align with our IMB theory (described above). 
 Linkages between HIV and IPV: The intervention increases understanding of linkages between HIV and 
IPV including for example, risk behaviors related to both HIV transmission and IPV perpetration including 
condom use, number of partners, substance use, and existing STI infection.30-35 The intervention also 
addresses interpersonal violence and aggression, both linked to IPV and critical to address in prevention for 
this age group.  
 Victim Empathy: The intervention increases understanding of the impact of IPV by providing local and 
national statistics, discussing their perception of false accusations, and debunking rape myths. 
 Healthy Norms Regarding Masculinity: Peer violence and delinquent behaviors are strongly associated with 
IPV so the social norm components of the intervention creates more healthy norms regarding masculinity and 
encourages development of positive peer groups relevant to HIV-IPV prevention. The intervention involves 
interactive discussion of misperceptions of social norms, critiquing traditional male socialization as it relates 
to violence and sexual intimacy. This component is critical given that our preliminary data from the study 
described previously indicates that although rates of perpetration were as high as 15%, only 0.5% of 
adolescents defined their behavior as rape and 14% engaged in repeat perpetration.14 Participants are 
encouraged to share discomfort with aspects of traditional male gender roles and share positive alternatives.  
 Bystander Intervention Skills: Based on the bystander intervention approach,86-90 participants are 
encouraged to intervene when they witness other males engaging in inappropriate dating behavior, including 
an understanding of consent. Our bystander approach changes both the individual and socio-cultural context 
from one that supports coercive behavior to one that inhibits it. Since a relatively small group commit the 
majority of assaults,129 it is particularly important to engage all adolescents as proactive bystanders in 
changing the community norms that foster violence including risky sex and sexual violence. Participants will 
brainstorm responses to inappropriate behavior in a small group exercise and report responses back to the 
group. Misperceptions regarding males’ discomfort with the inappropriate behavior and language of other 
young men serve as barriers to intervening with other boys and men's behavior.16 Thus, misperceptions are 
deconstructed through accurate data and an experiential group exercise that reveals the norm of intolerance. 
Bystander approaches have both theoretical and empirical promise in perpetration prevention.22,24,88,90,133-136 
Strong Evidence of Existing Safe Intervention Promise  
Our investigative team has conducted three prior evaluations of the Men’s Workshop, which forms the 
foundation of the Safe intervention. The Men’s Workshop was developed and evaluated by Dr. Berkowitz 
(consultant) in concert with Drs. Orchowski (co-I), in a CDC-funded study for college men22. The Men’s 
Workshop showed efficacy in reducing perpetration of sexual aggression among young men (Gidycz, 
Orchowski & Berkowitz, 2011). The Men’s Workshop was then revised into the Safe intervention to address 

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alcohol as a risk factor for sexual aggression by Drs. Orchowski in work funded by NIAAA,23 and was deemed 
feasible, acceptable and promising among young men.28,29 We do not assume that this exact format will be 
acceptable or feasible in South Africa – our study will examine needs for adaptations and examine the 
feasibility and acceptability of an adapted intervention in depth to ensure that an intervention has been designed 
specifically for the South African populations and context in mind. Safe taps into the importance of the 
environmental, social (including the developmental influence of peers), and relational contexts in which 
adolescent perpetration occurs. Through CDC funding, the Men’s Workshop is also currently being tailored for 
administration among adolescent males in the USA. The Men’s Workshop showed 50% reductions in sexual 
assault perpetration among college men over four months22. Dr. Orchowski and Dr. Berkowitz trained and 
supervised interventionists in the prior trial (N = 635). In all, 83% returned for a four-month follow-up, and 
78% returned for a seven-month follow-up. These data reflect our ability to recruit and maintain adolescents 
and men in an evaluation of an intervention of similar format and comparable length. Notably, the sexual 
assault prevention workshop evaluated in this study was associated with a 50% decrease in rates of sexual 
assault perpetration among men in the treatment group, relative to the control. This was the first large-scale 
evaluation of a sexual assault prevention program that reduced rates of sexual aggression among men.  
 
D. INVESTIGATIVE TEAM 
Our multidisciplinary team consists of highly qualified, accomplished personnel with extensive experience in 
the areas of adolescent preventive interventions for HIV and IPV in South Africa and globally. Our 
investigative team currently has multiple projects in South Africa on adolescent HIV and IPV. Dr. Caroline Kuo 
(M-PI) will contribute social and behavioral expertise in adolescent HIV prevention including adaptation of 
empirically supported HIV interventions from outside of South Africa to South Africa, and in mixed-methods 
formative intervention development research that will yield appropriately tailored interventions for adolescents. 
She has 4 ongoing studies in Cape Town as an investigator (NIH grants: K01 NIMH 096646, R24 NICHD 
077976, R21 NIAID 116309, R21 NIAID118393) and 1 other study (iLink: Incentives for Linkage to Care for 
HIV positive individuals) in a mentor role. Dr. Kuo directly collaborates with Dr. Cathy Mathews on 2 of these 
studies (K01 NIMH 096646 and R24 NICHD 077976), and Dr. Harrison on 3 studies (R24 NICHD 077976, 
R21 NIAID118393 and iLink). Dr. Cathy Mathews (M-PI) is a public health scientist with expertise in 
adolescent interventions for HIV and IPV, and specializing in school-based intervention trial design and testing. 
Her research is specifically focused on testing interventions for scale-up in school and health systems, and 
designed to inform national policies related to adolescent sexual and reproductive health in South Africa. Dr. 
Abigail Harrison (co-I) will contribute her substantial expertise in qualitative sexual and reproductive health 
research with South African adolescents. She has served as M-PI or co-I for multiple NIH-funded awards in 
South Africa. She has investigated the social context of adolescent HIV risk and preventive behaviors in South 
Africa (R01 HD41721) and is experienced in the design and evaluation of interventions for adolescents (R01 
HD37343). Dr. Lindsay Orchowski (co-I) will bring her substantial expertise in the Safe violence preventive 
intervention being used in the study. She is PI of a large-scale, CDC-funded evaluation of sexual assault 
prevention programming for high school boys, as well as middle school boys. She is currently the PI of an 
NIAAA R34 grant designed to evaluate the Safe program for men in the military. She served as the study 
coordinator for a large-scale (N =1285), CDC-funded evaluation of sexual assault prevention programming 
(with Dr. Alan Berkowitz) and has published extensively on sexual assault risk reduction and prevention 
programs. Dr. Alan Berkowitz (consultant) is an expert in social norms theory, bystander intervention, and 
engaging men in sexual assault prevention. A collaborator on the design of the Men’s Workshop (which forms 
the basis of the Safe program), he has worked with Dr. Orchowski in three evaluations of the model. Dr. 
Naeemah Abrahams (consultant) is an expert in violence risk reduction and prevention in South Africa as well 
as gender norms and relationships. She brings significant content expertise in IPV and interpersonal violence 
research within South Africa and has extensive knowledge of the South African ethical challenges of violence 
research with adolescents. Dr. Kuo, Mathews, Abrahams and Orchowski recently collaborated on an edited 
volume on sexual violence which has been accepted for publication by Elsevier entitled, “Sexual Assault Risk 
Reduction and Resistance: Theory, Research, and Practice.” 
 

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E. METHODS 
In this proposed Clinical Trial Planning Grant, we will focus on testing the acceptability and feasibility of Safe 
South Africa in preparation for a future R01 clinical trial. Given the acceptability and feasibility aims of this 
study, we are underpowered to gather biomarker data on HIV and STI incidence but plan to incorporate 
collection of biologically verifiable data on HIV incidence – as aligned with NIH HIV research strategy in a 
future fully powered RCT. See study will take a total of 3 years from start to finish. For more details on the 
study timeline, including a breakdown of activities for the 3 study aims appears in Table 1: 
Language. All study materials and procedures will be conducted in English or isiXhosa, the local 
language in our school study sites. Study materials will be translated by a professional translator, then back-
translated to ensure accuracy. Participants will identify language of preference and multi-lingual research 
assistants (RAs) will conduct procedures in the preferred language. We draw from our established research 
networks to hire a team experienced in intervention development and testing research with adolescents 
including qualitative research and cognizant of linguistic precision needed in our research.  
Site Selection. We build on our team’s extensive experience conducting school-based interventions, adolescent 
HIV and IPV interventions, and prevention research in South Africa. We work off our established network of 
40 school research sites in Western Cape Province of South Africa, focusing on high schools in high HIV risk 
communities based off of M-PI, Dr. Mathews’ previous school-based research. We select the highest HIV 
prevalence schools from among 40 public high schools in Western Cape where we have previously worked with 
success in our school-based intervention trials with this age group.51,137-139 In each of these 40 schools, we have 
established relationships with school stakeholders including principals and other educators. These relationships 
allow us to run our after-school HIV-IPV prevention program on school premises. Dr. Mathews, in consultation 
with Dr. Abrahams will utilize their extensive experience to lead our team in the process of securing 
permissions to work within schools including the process of engagement and consultation with stakeholders 
such as referral sources, Department of Education, principals, the student Representative Council of Learners 
(RCLs), and School Governing Body (SGB). 
Table 1. Study Timeline 
Year 1 
Year 2 
Year 3 
3 month quarters 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 11 12 
Development Phase (Aim 1)  
Theoretical and empirical HIV prevention adaptation of 
    
 
 
 
 
 
 
 
 
Focus group discussions with adolescents 
 
   
 
 
 
 
 
 
 
 
Qualitative analysis to finalize intervention 
 
    
 
 
 
 
 
 
 
Acceptability Phase - Open Pilot (Aim 2) 
Translation and programming of electronic data systems 
 
 
 
 
  
 
 
 
 
 
 
Interventionist training and supervision  
 
 
 
 
 
   
 
 
 
 
Social ecology survey (N=100) with males and females in 
the school community 
 
 
 
 
 
  
 
 
 
 
 
Open Pilot (N = 20) with further Safe South Africa 
refinement 
 
 
 
 
 
 
  
 
 
 
 
Feasibility Phase – Trial RCT (Aim 3) 
Interventionist supervision 
 
 
 
 
 
 
    
 
 
Trial RCT (N = 60) 
 
 
 
 
 
 
    
 
 
1-month follow-up 
 
 
 
 
 
 
 
   
 
 
6-month follow-ups 
 
 
 
 
 
 
 
 
  
 
 
Outcome, mediation and moderation analysis 
 
 
 
 
 
 
 
 
 
 
 
 
Future Study Preparation Analysis Phase  
Preparation of manuscripts 
 
 
 
 
 
 
 
 
 
 
 
 
Submission of R01  
 
 
 
 
 
 
 
 
 
 
 
 

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SPECIFIC AIM 1: DEVELOPMENT PHASE – HIV PREVENTION INTEGRATION AND ADOLESCENT FOCUS 
GROUPS 
Goals. In Development Phase (Aim 1) we will review our existing empirically supported Safe program 
to identify content, structure, and delivery modalities needing refinement and adaptation to South Africa. Then 
we will integrate best-evidence on theoretical and behavioral adolescent HIV prevention to create Safe South 
Africa. Finally, we will finalize adaptations guided by k=3-5 qualitative focus groups with adolescent males. 
Review of Existing Safe Intervention and Contextual Adaptations. We begin by evaluating the existing 
Safe intervention for adaptations needed for the South African context. Our focus of the adaptation process is to 
adapt content to be relevant to South African populations and settings. We also evaluate whether adaptations are 
needed to delivery approach (facilitators, setting, format of materials, activities). We also adapt based on the 
logical aspects that will affect the intervention such as location and scheduling keeping in mind the safety and 
ease of attendance by participants. We have specifically chosen this intervention because it has a conceptual 
model aligned with our chosen HIV prevention theory, has been empirically been developmentally adapted to 
adolescents in prior work, and also because of the potential for adaptation to South Africa. Specifically, the 
intervention has intensive but manageable numbers of sessions due to South African challenges related to 
poverty and community crime that might affect transport and attendance by participants. In our adaptation, we 
retain core active components of Safe, but examine material, content, and modalities of delivery that may result 
in non-response and non-engagement due to unique characteristics of the population and setting. We consider 
how high HIV prevalence, social determinants of HIV and IPV risk, culture, and language need to be integrated 
into material, content, and delivery, drawing from our experience of adapting or testing interventions for 
adolescents in South Africa.46,51,140-148 This will result in an initial draft of Safe South Africa. 
Theory and evidence-based adaptation for HIV. In the next phase, we will integrate the IPV 
perpetration and HIV prevention material. This stage will be guided by IMB theory-guided adaptation for an 
initial draft of Safe South Africa. Our choice of IMB theory-guided adaptation is further strengthened with 
integration of adolescent HIV prevention components based on 4 global and South African specific systematic 
reviews and/or meta-analyses that align with our theoretical IMB approach. The first meta-analysis evaluated 
effective HIV preventive interventions for South African youth aged 9-26 years. This meta-analysis was 
comprised of ten studies (k = 11; N = 22,788) and showed interventions were efficacious in delaying sexual 
intercourse (fixed-effects: d+s =0.07, 0.15), increasing condom use (fixed-effects: d+s =0.17, 0.19), reducing 
the number of sexual partners (fixed-effects: d+s =0.95, 0.44) relative to those in a control condition, and 
lowering incidence of HSV-2 (k = 2, d+ = 0.17, 95% CI = 0.09, 0.25).130 Based on this adolescent and youth 
South African review, we will include the following successful intervention components: delivery by facilitators 
who are not professionals (e.g., not nurses); delivery over fewer sessions (e.g. length was not important); 
content covering social norms and gender inequalities (synchronizing with our planned Safe South Africa 
intervention); and incorporation of intensive behavioral skills training such as condom use. The finding that 
number of sessions was not important, was relevant for our choice of the Safe intervention; we further examined 
whether brief interventions for HIV prevention have a clinically significant effect using a second meta-analysis. 
The second meta-analysis evaluated effectiveness of single-session behavioral interventions to prevent STIs. 
This meta-analysis was comprised of 29 single-session interventions (k = 20; N = 52,465) and showed 
intervention participants relative to controls had significantly lower risks with an odds ratio of 0.65 (95% 
CI=0.55-077) even when control groups were active controls (e.g. stringent controls where control participants 
received risk reduction materials). Because this meta-analysis indicated brief preventive (individual, group-
based, computer delivered) interventions can have clinical salience, we will focus on a brief but behaviorally 
intensive intervention in our approach.131 The third meta-analysis evaluated effectiveness of HIV interventions 
for adolescents 11-19 years globally and was comprised of 98 interventions (k = 67; N = 51,240). Results 
showed adolescents who received interventions compared to controls showed significant reductions in incident 
STIs, frequency of sex, number of partners, and significant increases in abstinence or delay of intercourse, 
condom use, safer sex communication skills, and acquisition of condoms. Based on this global adolescent HIV 
prevention review, we will include the following successful intervention components: motivational training for 
behavior change and condom skills training but no emphasis on abstinence given abstinence focused 
interventions were ineffective.20 The fourth global meta-analysis was on the efficacy of behavioral interventions 

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to increase condom use and reduce STIs. The meta-analysis was comprised of forty-two studies (k = 67; N = 
40,665 and showed intervention effects of increased condom use (d=0.17, 95% CI 0.04 to 0.29; Ι²=94%), fewer 
incidents of STIs (d=0.16, 95% CI 0.04 to 0.29; Ι²=90%) and lowered cases of HIV (d=0.46, 95% CI 0.13 to 
0.79; Ι²=99%). Based on this meta-analysis, we will include the following intervention components: for 
motivation, focusing on distal motivation components (i.e., future orientation for adolescents); and content with 
behavioral skills training (i.e., condom skills and interpersonal skills).132  
Sampling Plan, Recruitment, Inclusion/Exclusion. We describe the sampling plan including inclusion 
and exclusion criteria for recruitment, and retention strategies. Aim 1 involves focus groups (k=3-5) with male 
adolescents, 15-17 years of age.  We recruit male adolescents for k=3-5 adolescent focus groups to further 
refine our initial Safe South Africa intervention draft. Participant recruitment will follow procedures used 
previously in our research on best ethical procedures with adolescents in South Africa.149 We recruit a 
convenience sample of male adolescents through flyers providing contact details for study staff in the school 
setting and recruit in-person with permissions of school principals and teachers. Inclusion criteria include: (1) 
male adolescent; and (2) 15-17 years of age inclusive. Adolescents are excluded if parents do not provide 
consent or adolescents do not provide informed assent. 
Informed consent/assent. Interested adolescents will speak privately with the study team to gather 
parent contact details to proceed with the parental consent process. All interested adolescents will be sent home 
with written parental consent and adolescent assent forms. Study staff will speak with parents by phone or in 
person to secure consent. In our study, we use the term parent broadly to describe adults serving in a parental 
role and may include biological parents as well as surrogate parents (caregivers serving in the parental role). 
Diverse child caring arrangements are common in the South African context, where a large number of non-
biological caregivers take on the parental role. The South African Child Gauge 2013 Report by the Children's 
Institute shows that approximately a quarter of all children in South Africa do not live with either biological 
parent. More importantly, among the populations which we are working with (largely black African), 
approximately two-thirds of children do not live with either biological parent. Biological parents may not 
present in children's lives due to cultural norms, personal family choice, labor migration, parental neglect, social 
circumstances, etc. These diverse family structures result from historical adaptations due to separation of 
families during apartheid, economic migration, etc.150,151 Furthermore in our study setting, many children have 
experienced the death of biological parents due to HIV/AIDS or other causes. In HIV-affected communities, 
informal caregiving arrangements, in which non-biological individuals playing a parental role are particularly 
prevalent.152,153 We have utilized consent from adults serving in the parental role in our previous studies which 
have been reviewed and approved by South African universities (University of KwaZulu Natal, University of 
Cape Town and provincial Departments of Health and Education) and also by Oxford University. During this 
conversation, the parent will receive information on the study. Parents will have time to consider the 
information. Then they will be asked if they give consent for the adolescent to proceed with assent. Study staff 
will request a written informed consent form from each parent and prompt them to keep the second copy for 
their records. Then study staff will assess eligibility for adolescent focus groups. Inclusion criteria include: (1) 
male adolescent; and (2) 15-17 years of age inclusive. We will include adolescents regardless of sexual activity, 
HIV, or IPV status. This is because developmentally, prevention may alter the trajectory of possible 
engagement in new (not yet experienced) risk behaviors, or risk for those already engaged in unsafe behaviors. 
We consider all definitions of dating to be “intimate partners” at this young age. We are not specifically 
screening for intimacy in our eligibility in this study because South African data shows by age 13, 74% of boys 
reported sexual foreplay or oral sex, and age 15 is the median age for penetrative sexual debut.38 We will use 
this study to determine if a future fully powered randomized controlled trial needs a stricter eligibility criteria. 
Adolescents are excluded if parents do not provide consent or adolescents do not provide informed assent. If the 
potential participant meets the inclusion criteria for the study, we will inform them that they are eligible. If 
eligible, a participant locator form will be filled out to help schedule focus groups. Adolescents will be given an 
assent form at initial point of contact but go through assent procedures at the focus group to give additional time 
to consider assent. Our consent and assent procedures for this portion of the study and all subsequent portions 
include specific discussion of mandatory disclosures and reporting based on law which is also detailed in forms. 
We specifically acknowledge the significant potential harms and negative consequences that such disclosures 

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may present for participants and families if systems of reporting are initiated.  
Adolescent focus group procedures. We will conduct a total of k=3-5 male adolescent focus groups 
with final focus group numbers dependent upon data saturation. Each focus group will contain a minimum of 4, 
and maximum of 8 participants. We will begin each group by confirming receipt of consent forms from 
parents/caregivers, and verbally go over assent procedures followed by written assent. Assent procedures 
specifically detail permission for recording and the need to avoid use of real names. Then we will gather a brief 
socio-demographic survey to gather details on age, family situation, and behavioral data relating to HIV and 
IPV to contextualize focus group data. Each group will last approximately 1.5 hours; when combined with 
informed consent procedures and the demographic questionnaire, we anticipate that each participant will spend 
approximately 2 hours involved in the study. Two members of the study team will facilitate each group with 
one study team member directing the flow of discussion, and the other taking notes and prompting with 
additional questions as needed. Focus groups will follow the semi-structured agenda exploring the following 
themes: (1) perceptions of HIV including knowledge of protective behaviors, and barriers/facilitators to 
engaging in protective behaviors; (2) perceptions of IPV including attitudes and norms around gender roles, 
relationships, and violence; (3) exploration of community and context specific factors relating to HIV and IPV 
behaviors; (4) feedback on core elements of Safe South Africa, including appeal, clarity and appropriateness of 
content, especially newly adapted material and content; and (5) anticipated barriers/facilitators in uptake of the 
intervention including delivery preferences and suggestions for optimizing recruitment, data collection, and 
retention procedures. These specific thematic areas will guide our approach to adaptations made to the 
intervention model. Our goal is to ensure that we consider the design of an intervention that is appropriate for 
this male adolescents from South Africa in the specific setting where this intervention is being tested. These 
thematic areas will guide the intervention team in developing a final draft intervention to be trialed including 
areas such as content, material, format, timing, delivery, and more. All focus groups will take place in a private 
room in the school or community setting with compensation for time and transportation. Food and refreshments 
will also be offered during the focus groups. Focus group discussions will be recorded using a digital voice 
recorder (DVR). Audio files will be stored in the password-protected project drive.  Audio files will then be 
translated and transcribed verbatim by a transcriptionist. After transcription, the study team will edit out any 
information that might be used to identify a participant personally. A bilingual RA will compare 10% of 
transcripts to audio files for accuracy.  
Participant Reimbursement. At the close of the focus group, we will thank participants and provide 
reimbursement. Each participant will be provided with reimbursement of 75 Rand (approximately $7.50) 
(comprised of 50 Rand for time and 25 Rand for travel). This reimbursement may be provided in the form of a 
voucher. If the focus group is under-enrolled, we still offer a reimbursement for travel of 25 Rand.  
Analyses. We will conduct ongoing saturation analyses, based on iterative coding during data 
collection.154 Each audio recording is transcribed word-for-word and translated if necessary. Transcriptions are 
checked for accuracy and entered into NVivo. We will also enter all observational notes as memos. Data 
analysis is iterative including techniques of open and axial coding based on manual coding prior to coding in 
NVivo.155 We will distill qualitative intervention components into thematic categories to guide refinement of 
intervention material, content, and delivery for Aim 2. 
 
SPECIFIC AIM 2: ACCEPTABILITY PHASE – TEST ACCEPTABILITY OF SAFE SOUTH AFRICA IN OPEN PILOT 
TRIAL 
Goals. Acceptability Phase (Aim 2) involves two sets of data collection. First, we conduct a school-
wide survey of N=100 male and female adolescents, of any age (anticipated to be 13-18 years) to evaluate the 
social ecology of HIV and IPV risk (focusing on social norms of peers within the school). We will use survey 
data to create evidence-based social messaging tailored to address male adolescent’s specific social-ecological 
risk and protective factors for HIV and IPV – data from the survey used to generate content for debate and 
discussion within the behavioral intervention itself. Second, we will elicit feedback on Safe South Africa via an 
open pilot trial with N=20 male adolescents. This open pilot trial will assess acceptability including participant 

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satisfaction with intervention content, materials, and delivery prior to a more in-depth test of the intervention in 
the randomized pilot trial. 
Survey of Social Ecology. In preparation for later stages of Aim 2 and for Aim 3, we begin by 
conducting a school-wide survey to better understand the social ecology of the school community with N=100 
male and female adolescents. This survey comprises Part 1 (preparations for the Safe South Africa Intervention), 
by providing a data-driven evaluation of risk and protective factors for HIV and IPV. The results of the survey 
of social ecology will help to generate evidence-driven social norms messaging used as content for the 
intervention being tested in Part 2, the stage corresponding to actual roll-out of the male adolescent behavioral 
intervention (the open pilot test of the intervention and the randomized pilot trial of the intervention). For the 
survey, we will recruit a convenience sample of both male and female adolescents attending our chosen 
intervention school by visiting classrooms, briefly explaining the purpose of the anonymous survey. 
Recruitment for Survey. This survey will guide the development of intervention content that is 
specifically tailored to the adolescents that are the population being targeted in this intervention. The survey 
generates specific age and contextual data that will be integrated into a final intervention model that is adapted 
for the South African population and setting where the intervention is being tested. We will recruit a 
convenience sample of both male and female adolescents attending our chosen intervention school site by 
visiting classrooms, briefly explaining the purpose of the anonymous survey. Inclusion criteria include: (1) 
adolescents attending the high school will be included regardless of gender and age. Interested adolescents go 
through assent procedures if they are under 18 years of age. Adolescents are excluded if parents fail to provide 
consent or adolescents do not provide informed assent. We anticipate the age to be 13-18 years but school-going 
ages vary widely in South Africa due to delayed start of school and pass/fail criteria that may hold back students 
based on performance. We focus on all adolescents in the school environment. Although the target of the Safe 
South Africa intervention itself focuses on male adolescents 15-17 years of age (for the open pilot in the second 
half of Aim 2, and the randomized pilot trial in Aim 3), we feel that expanding our survey of social ecology to 
include all students regardless of age in the high school environment is warranted. We specifically chose to 
include adolescents who are both younger and older than our target intervention age group in this survey of the 
social ecology to provide a more complete picture of norms in the school community. This information on how 
norms develop and are shaped in the ages leading up to, and immediately after, our actual intervention target 
population age range of 15-17 years, is relevant to the developmental-tailoring of intervention content. We also 
purposively include females as well as males in this school ecology survey even though the intervention itself 
targets males. This is because norms around HIV risk behavior, IPV, and gender are not shaped only by male 
adolescents (who are the target of our gender-specific intervention). Females also shape the social ecology 
relating to HIV and IPV behaviors among males. As such, we feel that including females in the survey of social 
ecology will provide more detailed information on how both female and male perspectives shape the social 
environment including roles, norms, and expectations relating to male-specific HIV risk behavior and IPV 
perpetration. Thus, we feel that eliciting female, as well as male perspectives, in the social ecology survey 
during Aim 2 enriches the scientific data that we generate to refine the intervention that will be piloted in Aim 
3. 
Consent and assent for survey. After visiting classrooms to explain the purpose of the anonymous 
survey, we will follow the subsequent consent and assent process, which we have given careful consideration 
based on our own research of the most appropriate consent procedures for low-risk research with adolescents in 
school settings.156 We will follow active parental consent procedures for this anonymous school ecology survey. 
Our team will visit classrooms to describe the survey to students, explaining parents/caregivers need to indicate 
in writing whether they want their child to participant. We will provide parents/caregivers a letter about the 
nature of the research seeking their permission for their child’s participation, Then we revisit high school 
classes 1 week later. Then study staff will assess eligibility for adolescent surveys. Inclusion criteria include 
receipt of signed parental consent forms combined with the following: (1) adolescents attending the high school, 
anticipated to be 13-18 years of age. We include adolescents attending the school regardless of gender and age 
to get a full assessment of social ecology (rather than just focusing on 15-17 year old males). Interested 
adolescents go through assent procedures. Adolescents are excluded if parents provide dissent or adolescents do 
not provide informed assent. Then we provide a brief school social ecology climate survey assessing: (1) IPV 

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and HIV behavior data; (2) predicted prevalence of IPV and sexual behaviors in their school; (3) norms and 
attitudes around sex, gender, and IPV. We then analyze this survey data and use this to generate content for the 
behavioral intervention materials and activities. We will conduct bivariate analyses using chi-square, Fisher’s 
exact and t-tests to examine the associations between participant demographic characteristics, and actual or 
predicted IPV behaviors. Then we will use multivariate regressions to identify variables predictive of IPV. 
Findings inform our social norms messages within the behavioral intervention, tailored to meet the specific 
HIV, IPV, interpersonal violence, and aggression prevention needs of adolescent’s social ecology. 
Training Intervention Facilitators. Our investigative team will train facilitators in preparation for the 
behavioral intervention that occurs as Part 2 of the Safe South Africa intervention. We will recruit facilitators 
through our pool of experienced adolescent HIV and IPV intervention facilitators used in our previous trials, 
supplemented by advertising, community-flyers, and outreach with NGOs/CBOs, community meetings, clinics, 
and schools. Training will involve 5 modules. Module 1 includes: 1) introductions and ice-breaking exercises, 
2) project overview and training objectives, 3) education regarding HIV prevention and IPV with a focus on 
perpetration prevention, communication, gender roles and social norms particularly in regards to sexual 
relationships, and sexual relationship negotiations. Module 2 focuses on intervention delivery skills: 1) public 
speaking and 2) communication of sensitive topics. Module 3 involves training in use of the intervention 
protocol guided by a manual: 1) demonstrations of intervention modules, 2) education on core intervention 
elements, and 3) role-play sessions. Module 4 involves: 1) testing implementation skills in short mock 
scenarios, 2) feedback from the PI. Module 5 involves role-playing participants in a mock intervention. We 
incorporate challenges that may arise during implementation including delivery of intervention content and 
inter-personal interactions to assess paraprofessional facilitators’ mastery of core skills and performance. We 
rank performance using the fidelity forms we will use in the trial. If an interventionist is not deemed qualified, 
additional training will be provided until competent. Interventionists who are deemed unqualified after 
additional training will be replaced. 
Open Pilot Trial. We will recruit N=20 male adolescent who meet study inclusion criteria to participate 
in the behavioral intervention that comprises Part 2 of the Safe South Africa intervention. This is the group-
based, facilitated behavioral intervention for prevention of HIV risk and IPV perpetration held in 2-hour 
sessions, once a week for a total of two weeks after school, on school premises. This after school program is a 
behavioral intervention that includes the following core components (described in detail under the section titled 
“Core Components of the Safe South Africa intervention”):  information and behavioral skills practice to 
address HIV and STI prevention including HIV and STI content relating to prevention knowledge, attitudes and 
behaviors; information relating to linkages between HIV and IPV; formation and behavioral skills practice to 
address IPV prevention including debate, discussion, and information designed to improve victim empathy; 
debate, discussion, and information designed to support healthy norms regarding masculinity and deep 
understanding of consent; and development of bystander intervention skills with practice to boost self-efficacy 
in future implementation of these skills.  
Recruitment for Open Pilot Trial. For the open pilot trial with N=20 adolescent males, 15-17 years, we 
recruit a convenience sample of male adolescents through flyers providing contact details for study staff in the 
school setting and recruit in-person with permissions of school principals and teachers. Inclusion criteria 
include: (1) male adolescent; and (2) 15-17 years of age inclusive. Adolescents are excluded if parents do not 
provide consent or adolescents do not provide informed assent. Retention is not an issue in Aim 2. Eligibility 
are same as Aim 1 Focus Groups. 
Consent and Assent for Open Pilot Trial. Consent and assent are the same as describe above for Aim 1. 
Interested adolescents will speak privately with the study team to gather parent contact details to proceed with 
the parental consent process. All interested adolescents are sent home with written parental consent and 
adolescent assent forms. Study staff will speak with parents/caregivers by phone or in person to secure consent. 
During this conversation, the parent will receive information on the study. Parents will have time to consider the 
information. Then they will be asked if they give consent for the adolescent to proceed with assent. Study staff 
will request a written informed consent form from parents and prompt them to keep the second copy for their 
records. Then study staff will assess eligibility. If the potential participant meets the inclusion criteria for the 
study, we will inform them that they are eligible. If eligible, a participant locator form will be filled out to help 

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schedule the intervention. Adolescents have been given an assent form at the initial point of contact but go 
through assent procedures prior to the intervention to give additional time to consider assent. We begin 
enrollment into the open pilot by confirming receipt of consent forms from parents/caregivers, and verbally go 
over assent procedures followed by written assent. 
Open Pilot Trial Procedures. For participant acceptability, participants will complete 3 sets of 
assessments. The first set of assessments will reflect the outcome questionnaire used at baseline, 1- and 6-
months (also used in Aim 3). The second set of assessments will be session and overall intervention satisfaction 
forms. These satisfaction forms gather opinions on content, material, delivery, format, length, time, and location 
(also used in Aim 3). The third set of assessments will evaluate participant opinions of final draft material and 
messages derived from the social-ecology survey (Part 1) including suggestions for refinement of images and 
social norms messages in a facilitated group discussion. Finally, our investigative team will evaluate fidelity, 
ranking integrity and competency of session delivery in real time (also used in Aim 3). Fidelity assessments will 
also be used in the trial RCT (Aim 3) but in this open pilot, rankings will be used to make final refinements to 
intervention facilitator training prior to launch of the trial RCT. These fidelity assessments will follow 
recommendations issued by the Treatment Fidelity Workgroup of the NIH Behavior Change Consortium to 
ensure rigorous coding of fidelity based on a standardized monitoring checklist to assess facilitator 
adherence/drift from fidelity.157 Measures and assessment timelines for Aims 2 and 3 appear in Table 2 
(below). 
Analysis and Further Intervention Refinement. We will check all forms for missing data in field and 
during entry, with at least 2 telephone calls to participants to get missing data. We will examine key variables 
for skewness, variability, missing data, and outliers, with transformations to achieve normality if needed. For 
our outcomes questionnaire (baseline version used in this pilot), we will examine descriptive statistics for main 
outcomes and mediators/moderators. This analysis will focus on correcting any errors prior to Aim 3 and 
trialing the data systems. Then, we will assess acceptability, setting 80% reporting positive ratings as a marker 
of acceptability and examining process data on satisfaction with format, length, etc. We will use this 
acceptability data to make final adjustments to the Safe South Africa intervention prior to Aim 3. We will assess 
fidelity of facilitator implementation, setting 80% as acceptable fidelity, and using data to make final 
adjustments to training.  
Reimbursement. For the brief school social ecology climate survey, adolescents will a pen/pencil (worth 
10 Rand) as appreciation. In the open pilot, adolescents will receive 50 Rand (consisting of 25 Rand to offset 
time and 25 Rand to offset travel costs) for the baseline outcome assessment, 60 Rand (consisting of 35 Rand to 
offset time and 25 Rand to offset travel costs) for the 1-month outcome assessment and 70 Rand (consisting of 
45 Rand to offset time and 25 Rand to offset travel costs) for the 6-month outcome assessment. In the open 
pilot, adolescents in the intervention arm only, also fill out questionnaires to help us evaluate the acceptability 
of the intervention; these questionnaires will occur after each session. Adolescents in will receive50 Rand 
(consisting of 25 Rand to offset time and 25 Rand to offset travel costs) for attending the enrollment session and 
the satisfaction assessments filled out in the first session. Adolescents in the intervention arm only, will also 
receive 60 Rand (consisting of 35 Rand to offset time and 25 Rand to offset travel costs) for filling out 
satisfaction assessments after the second session. The second session requires a slightly higher reimbursement 
rate because participants fill out both questionnaires on their satisfaction with the second session as well as the 
overall program.  
 
SPECIFIC AIM 3: FEASIBILITY PHASE – ASSESS FEASIBILITY OF SAFE SOUTH AFRICA IN TRIAL RCT 
Goals. In Feasibility Phase (Aim 3) we will assess feasibility for a future R01 trial including the rigor 
of facilitator implementation of the intervention protocol by evaluating fidelity and competence, recruitment 
strategies, and tracking and tracing success. We will assess feasibility by testing Safe South Africa in a 
randomized controlled pilot trial with 1- and 6-month follow-up. Participants include a sample of N=60 male 
adolescents who will receive a behavioral group-based intervention to prevent HIV risk, IPV perpetration, and 
increase bystander behavior). Intervention participants will be compared to a control of ordinary usual care. The 
ordinary usual care condition will consist of a packet of existing available brochures on HIV and other sexually 

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transmitted diseases including testing, prevention, and treatment; IPV prevention and intervention; and places to 
access prevention, care, and support for these outcomes and related health outcomes. This packet includes 
existing resources in South Africa including Childline (an adolescent tailored health resource), Stop Gender 
Based Violence helpline, HIV helpline, and the South African Depression and Anxiety Group 
(SADAG) helpline for mental health. We considered alternative treatments as a control but there are no existing 
rigorously tested HIV-IPV perpetration preventive interventions exist for adolescents in South Africa. This is 
not a treatment study but has a prevention focus. We explore preliminary evidence for hypotheses that the 
intervention, relative to the control, will produce the following outcomes: (1) reductions in actual or intended 
HIV risk behaviors; (2) reductions in IPV frequency and decreased endorsement of IPV supportive attitudes; 
and (3) increased proactive bystander behavior for prevention of IPV perpetration. 
Design. This is a randomized controlled trial where participants are prospectively assigned to two arms 
(Safe South Africa) versus the control of ordinary usual care. This will be a single blind study. Intervention 
participants will not be blinded to the condition they are in (the intervention group will receive the intervention 
first, with the control group given standard usual care. Study staff (e.g. intervention team) will not be blinded to 
the condition. Study staff (e.g., outcome assessment team) who assess outcomes after the experimental 
intervention has been delivered will be blinded to the condition participants have been assigned to. Blinding 
will be broken for data analysis. To reduce the risk of contamination, or that blinding will be broken by 
participants communicating to each other, we will request that participants in the intervention keep all activities 
and discussions to themselves. We will also assess whether blinding was successful by checking for 
contamination at the outcome assessments at 1- and 6-months. There is no chance that participants in the control 
group would participate mistakenly in the intervention so we assess for contamination in terms of sharing of 
intervention materials between the intervention and control group. Participants assigned to the control group 
will be screened for contamination. We will adjust for any contamination effects in analyses. Although this is a 
feasibility and acceptability trial, thus not designed to be fully powered to measure effects, we set out to create a 
study design that carefully adheres to elements outlined in the Consolidated Standards of Reporting Trials 
(CONSORT) Statement.158 This pilot study adheres to a single blind, randomized pilot trial design with the end 
goal of informing a future fully powered RCT corresponding to a Phase III clinical trial. 
Recruitment, eligibility, and informed consent/assent. We will recruit N=60 male adolescents (30 in 
each of 2 arms) to test Safe South Africa in a pilot RCT to generate data for a future fully-powered RCT. This 
pilot RCT consists of a behavioral group-based intervention (10-20 adolescents per group) delivered by a 
facilitator in 2-hour sessions, once a week for a total of two weeks after school, on school premises with take 
home activities to deepen behavioral practice and engagement. We implement recruitment, consent and assent 
procedures, and eligibility criteria same as Aim 1 (see above). Consent and assent procedures will occur twice 
during Aim 3. First, consent and assent will occur at the first point of contact, after screening for eligibility and 
prior to gathering baseline assessment. We seek consent and assent prior to gathering baseline assessment 
because this data will provide valuable feasibility and acceptability data on who is eligible for the community 
based intervention but who choose not to proceed to enrollment. Second, consent and assent will be sought at 
the enrollment session which includes a behavioral run-in an intensive methodological approach for discussing 
pros and cons of trial participation, detailed at the NIH Randomized Behavioral Clinical Trials Institute 
(attended by M-PI Kuo).159 This method focuses on thoroughly discussing ethical considerations prior to 
randomization (and in doing, also optimizing recruitment and retention in the trial). This procedure involves a 
discussion of pros and cons in the order shown in Figure 1 as part of study orientation, prior to randomization.  
 
 
 
 
 
 
 
 
The idea of this behavioral run-in is to provide a more in-depth orientation session after participants have been 
Figure 1: Study orientation and ethical discussion 
 
Enrolling in the study 
NOT enrolling in the study 
Pros of  
participation 
3 – Discuss third pros of 
enrolling in the study 
2 – Discuss second pros of 
not enrolling in the study 
Cons of  
participation 
4 – Discuss last cons of 
enrolling in the study 
1 – Discuss first cons of not 
enrolling in the study 

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given time to consider the study in depth (following an initial consent and assent at baseline). In this behavioral 
run-in, we provide a thorough discussion of ethical considerations to complement traditional consent/assent 
procedures. This discussion focuses upon eliciting potential participants’ perspectives of pros and cons of their 
potential trial enrollment to help them consider risks and benefits thoroughly, to explicitly acknowledges study 
challenges, and to engage in a meaningful interactive dialogue to overcome any misunderstandings of the study 
(including confusion on trial design and objectives, prevention misconception, and other ethical challenges 
documented by studies on related topics in similar settings).160,161 The approach avoids a “hard sell” or “pro-
change” positions, but instead, focuses on enriching the informed consent and assent process to ensure 
meaningful informed and voluntary consent and assent.  
Randomization & Retention. We will randomize adolescents in this 2-arm trial to an intervention arm 
(testing our Safe South Africa intervention, n=30) or a control arm (n=30) from a different school consisting of 
ordinary usual care (information on existing community resources for HIV and IPV). We considered comparing 
to a more stringent control, such as an existing rigorously empirical preventative interventions targeting 
prevention of HIV-IPV perpetration but this does not exist for adolescents in South Africa. We will randomize 
based on permuted blocked randomization chosen off careful consideration of randomization possibilities and 
training received at the NIH Randomized Behavioral Clinical Trials Institute. Permuted blocks will be based off 
of varying block lengths. This process will be repeated until target baseline enrollment is achieved. To retain 
participants, one data enterer will devote 50% time to tracking including: 1) at baseline, documenting multiple 
participant contact details and three individuals who know how to contact the family; 2) monthly contact via 
telephone or text; 3) follow up at least five times using different days, times, and methods. These strategies 
were successful in maintaining 100% attrition in Dr. Kuo’s recent acceptability and feasibility trial with 
adolescents of similar age and similar South African communities.  
Assessments. All measures utilized in the current study are well established, with adequate reliability 
and validity and tested in our prior studies. See Table 2. 
Table 2: Outcome Measures and Assessment Timeline 
Outcome 
Measures 
Baseline 
Session 
1
Session 
2
1-month 
6-month 
Acceptability 
• Session Evaluation Form162 
• Client Satisfaction Questionnaire163 
 
 
 
 
 
HIV Risk Behavior & 
Intentions: HIV and STI 
status; HIV testing; 
frequency sex; number and 
type of partners; use of 
condoms 
• Items taken from South African trials & NIH’s 
Adolescent Medicine Trials 
Network for HIV/AIDS Interventions 
 
 
 
 
 
IPV Perpetration 
Behaviors:  type, 
frequency and severity of 
IPV; sexual perpetration 
and aggression, dating 
violence 
• Childhood Sexual Victimization Questionnaire 
(CSVQ)164,165  
• Sexual Experiences (SES-SFP)47 
• Assault Characteristics Questionnaire (ACQ)164 
• Conflict in Adolescent Dating Relationships166 
 
 
 
 
 
Bystander Intervention 
Behaviors: proactive 
bystander behavior; 
bystander efficacy and 
readiness 
• Sexual Social Norms Inventory (SSNI)167 
• Bystander Behavior Scale168-170 (BBS) 
• Intent to Help Scale (IHS) 168,170  
• Bystander Efficacy Scale169,170 (BES) 
• Interpersonal Reactivity Index (IRI)171 
• Stages of Change Scale (SOC) 90,172,173 
 
 
 
 
 

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All administration systems (paper and smartphone modalities) and data software come with rigorous human 
subjects protections (Teleform, SurveyToGo, Filemaker). All have worked well as international data systems in 
our previous collaborative USA-South African trials. We conduct a first set of assessments to evaluate 
acceptability using paper forms which will be scanned into computerized data using TeleForm Software. 
Acceptability will be evaluated with session satisfaction and overall intervention satisfaction forms. These 
satisfaction forms gather opinions on content, material, delivery, format, length, time, and location. We conduct 
a second set of assessments to evaluate feasibility. We will examine the rigor of the intervention by evaluating 
fidelity for 10-15% of total sessions using a neutral coder, ranking integrity and competency of session delivery 
in real time, and following recommendations issued by the Treatment Fidelity Workgroup of the NIH Behavior 
Change Consortium157 We also track recruitment, retention, and attrition data using FileMaker Software to 
inform future studies. This will include gathering characteristics on who is eligible (from baseline data) but do 
not attend the enrollment session; data on who fills out baseline, post 1-month, and 6-month assessments; as 
well as who attends scheduled intervention sessions. The count-down clock for the 1- and 6- month post 
intervention assessment will occur after the last intervention session has occurred. We will also conduct exit 
questionnaires for early exiters and full completers probing for: 1) intervention drop out/facilitators including 
logistical, job or family related barriers, 2) perceived burden of intervention and assessment, and 3) satisfaction 
with interactions with the research team in scheduling, etc. For early exiters who we are unable to identify at 
intervention sessions, we will complete exit evaluations by phone. We will conduct a third set of assessments 
for our exploratory aims, our examination of direction of outcomes regarding whether the intervention, relative 
to the control, will produce: (1) reductions in actual or intended HIV risk behaviors; (2) reductions in IPV 
frequency and decreased endorsement of IPV supportive attitudes; and (3) increased proactive bystander 
behavior for prevention of IPV perpetration. For these assessments we use an outcome questionnaire at 
baseline, 1- and 6-months. We collect outcomes on a smartphone using SurveyToGo, anticipating assessments 
lasting 1-1.5 hours. To diminish social reporting bias we administer questions via earphones plugged into 
smartphone devices using A-CASI. 
Reimbursement. Adolescents will receive 50 Rand (consisting of 25 Rand to offset time and 25 Rand to 
offset travel costs) for the baseline outcome assessment, 60 Rand (consisting of 35 Rand to offset time and 25 
• Decisional Balance Scale (DB) 169 
Co-variates: socio-
demographics; economic 
status; household 
characteristics 
• Items from the South African 2011 Census 
Questionnaire & World Health Organization Food 
Security Questionnaire 174 
• Verbal Autopsy Questionnaire for AIDS 
orphanhood175 
 
 
 
 
 
Mechanisms & 
Moderators: 
• HIV knowledge; HIV 
stigma; condom attitudes, 
self-efficacy, and skills; 
family interactions 
• Resilience; mental health; 
substance use 
• Sexual aggression norms; 
endorsement rape myths, 
traditional gender roles; 
social norms regarding 
violence; identification of 
sexual consent; empathy 
for victims 
• South African HIV Knowledge176; AIDS Related 
Stigma Scale and Internalized AIDS-Related 
Stigma Scale (IA-RSS)177,178; Condom Attitudes 
Scale - Adolescents (CAS-A)179; Condom Use 
Self-Efficacy Scale (CUSES)180; Condom-use 
skills checklist181; Alabama Parenting 
Questionnaire-Short Form182 
• Connor-Davidson Resilience Scale (CD-RISC)183; 
Center for Epidemiologic Studies Scale - Revised 
(CESD-R)184,185; Alcohol Use Disorders 
Identification Test (AUDIT-C)186; Drug Use 
Disorders Identification Test (DUDIT)187 
• Illinois Rape Myth Acceptance Scale (IRMAS) 
188; Hypergender Ideology Scale—Short Form 
(HIS)189; Boeringer’s Social Norms Measure 
(BSN)190; Marlowe-Crowne Social Desirability 
Scale (MCSDS191; consent scenarios23 
 
 
 
 
 

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Rand to offset travel costs) for the 1-month outcome assessment, and 70 Rand (consisting of 45 Rand to offset 
time and 25 Rand to offset travel costs) for the 6-month outcome assessment. In addition, adolescents will 
receive 50 Rand (consisting of 25 Rand to offset time and 25 Rand to offset travel costs) for the enrollment 
session and filling out the satisfaction assessments that occur after the first session Adolescents in the 
intervention arm only, will receive 60 Rand (consisting of 35 Rand for time and 25 Rand for travel) for 
satisfaction assessments filled out after the second session.).  
Sample Size and Power Considerations. The primary objective of this pilot is to test feasibility, 
acceptability, and generate meaningful effect size estimates for a future fully-powered RCT. A fully-powered 
study is not our aim. We believe 60 adolescents (30 adolescents per arm) is adequate to examine feasibility and 
acceptability. We increase sample size by 10% as a conservative estimate during baseline recruitment to 66 
adolescents to account for loss to attrition; our previous HIV intervention trial with similar aged adolescents in 
similar settings had 100% retention at the last follow-up timepoint.45,192 We considered sample size needed 
based on the goals of increased condom use at last sex by a third or double as shown in other adolescent HIV 
behavioral trials,20,193,194 and reduced sexual assault by half as shown in our previous trials of the SAFE 
intervention. To examine moderate effects (e.g., 0.50) we would need 200 adolescents, or 100 adolescents per 
arm, beyond the scope of this pilot. Thus, we focus on rigorously testing acceptability and feasibility.  
Analysis. For acceptability, we conduct the same analysis as described for Aim 2, setting 80% reporting 
positive ratings as a marker of acceptability and examining process data on satisfaction with clarity, structure, 
content, delivery, location, and timing of the intervention. For feasibility, we evaluate fidelity, setting 80% 
fidelity as a marker of acceptability. We also evaluate feasibility in regards to attendance rates, treatment 
retention rate, retention during outcome timepoints, and balance during randomization. For these data, 
individual ANOVA will be conducted to compare groups (SAFE South Africa vs. Control) on the continuous 
variables of number of sessions attended. For treatment retention rate (dichotomous), a chi-square analysis will 
be used. For success of random assignment in equating groups, we compare groups on demographic 
characteristics and primary risk factors for HIV and IPV. If groups differ on any variables that show a relation 
to outcomes, outcome analyses will be conducted both with and without adjusting for these covariates. For trial 
outcomes, preliminary analyses will include studies of patterns of missing data, dropout rates, and correlations 
effect size estimates with small samples have large standard errors so we use pilot data to assess hypothesized 
intervention effects.195 We will examine key variables for skewness, variability, missing data, and outliers, with 
transformations to achieve normality if needed.  We will examine descriptive statistics for main outcomes and 
mediators with extreme scores or deviations from normality to be addressed in subsequent analyses. Baseline 
differences between groups on demographic variables will be examined using t-tests and variables that show 
differences will be included as covariates in outcome analyses. Generalized estimating equations (GEE) will be 
used to compare intervention and control group on the main study outcomes following intention-to-treat 
principles. In exploratory analysis, we look at directions of hypothesized effects for our outcomes. While we are 
underpowered to test mediation effects directly, we will explore differences between study arms in 
hypothesized mediating and moderating variables. We will obtain the between treatment condition effect size 
estimates (with 95% confidence intervals) at each assessment (e.g., Cohen’s d or h) to help determine necessary 
sample size for future fully-powered RCT.196 
Dissemination. In addition to peer review papers and conference presentations, we will develop research 
briefs for adolescents, school stakeholders, and policy makers. In Year 3, we will submit an R01 application for 
a fully powered clinical trial to test the efficacy of Safe South Africa. 
 
F. OTHER ETHICAL CONSIDERATIONS 
Additional ethical reviews. We have submitted an ethical review application to Brown University and 
provide their letter providing detail that we are able to proceed with Aim 1 with a planned re-review prior to 
Aim 2 and 3 (see Appendices). 
 
Inclusion of Children. This study will include children. In Aim 1, we will include male adolescents 
aged 15-17 years (inclusive) for focus groups. In Aim 2, we will include male and female adolescents ages 13-
18 (inclusive) for a brief school climate survey, and male adolescents aged 15-17 years (inclusive) for an open 

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pilot trial of the intervention. In Aim 3, we will include male adolescents aged 15-17 years (inclusive) for a 
randomized controlled pilot trial of the intervention. The topic under investigation necessitates inclusion of 
adolescents; we are developing and testing the acceptability and feasibility of an intervention tailored to meet 
the specific HIV and IPV prevention needs of adolescents. Without adolescent participants, we will be unable to 
accomplish the study objective of developing knowledge on the acceptability and feasibility of SAFE South 
Africa, a male adolescent-tailored intervention to prevent HIV risk behaviors and IPV perpetration. We 
recognize that children may be a vulnerable group, and extreme care is required to ensure protection and 
empowerment amongst participants but that exclusion of this group would significantly prohibit scientific 
development in topic areas of great importance to the health and wellbeing of this group. To ensure informed 
consent and assent, we will clarify what information will be kept confidential and what will be disclosed to 
another party. We also build upon our team’s extensive research and clinical experience working with 
adolescents living with HIV in South Africa as well as our team’s experience conducting HIV behavioral 
research with vulnerable populations affected by HIV in South Africa and other international settings. We 
provide additional protections in consent and assent procedures. All informed assent forms will be read aloud in 
participants’ chosen language and participants will also be provided copies. To ensure that children do not feel 
obliged to participate in the research, emphasis will be placed on their ability to refuse to participate, or to cease 
participation at any point during the research. As has been the practice in our previous studies with this 
vulnerable population, our research team is trained to recognize that any avoidance by children of the research 
will be taken as evidence of failure to assent. For adolescents, during the parental informed consent procedures 
and during the adolescent informed assent procedures, we emphasize that all information shared with us will 
remain confidential except for life-threatening disclosures or disclosures which falls under legally mandated 
reporting to police, social services, and IRB including perpetration with identifiable rape or sexual assault 
victims, being a victim of rape, sexual, emotional, or physical abuse which falls under legally mandated 
reporting to police, social services, and IRB. 
Collaborating Sites. All primary data collection occurs in South Africa, based out of the South African 
Medical Research Council (SAMRC) via a contractual arrangement with Brown University. Dr. Mathews, M-PI 
is based at SAMRC. Data will be obtained, managed, and protected through a data agreement between Brown 
University and SAMRC. M-PI’s Drs. Kuo and Mathews will oversee all standard operating procedures 
including study protocols including ethics; quality control and assurance; and data collection, management, and 
analyses procedures. In regards to data collection, data will be protected by unique research identification 
numbers (RINs). Data will be managed in the following manner. First, documents identifying participants by 
name will be included on password-protected computers and files. Second, these identifiable data will be kept 
separate from documents containing other participant data. Third, electronic data will be further protected by 
nCrypted Cloud software which offers two-way encryption with secure access controlled by PIs (who can turn 
on and off access to password protected files from a central location and wipe data remotely on electronic 
devices). Fourth, paper documents relating to patient data will be kept in locked cabinets accessible only to 
essential study personnel. For data analyses, analyses procedures will only focus on data associated with RIN. 
All other identifiers will be expunged from transcripts. Any names or pseudonyms used during focus groups 
will be replaced with the RIN. To guard against accidental data loss, the project data will be backed up. 
Access to Individually Identifiable Information & Data Collection, Management, and Protections. 
Only PIs, co-Is and other essential project staff will have access to project data. Drs. Orchowski, Abrahams, and 
Berkowitz will only have access to de-identified participant data. All data will be protected by unique RINs. 
Identifiable data will be kept separate from documents containing other participant data. Paper documents 
relating to participant data will be kept in locked cabinets accessible only to essential study personnel. Data will 
also be backed up by the data enterer and transferred via two-way encryption via the nCrypted Cloud program 
for PIs and Co-Is to oversee for quality control.  Participants’ names will never appear in any report resulting 
from the project. Electronic data, including digital voice recordings and data collected via ACASI on our 
electronic computer devices (android smartphones) will have several protections. Staff will be trained in 
procedures for maintaining confidentiality of participant information. Data analyses will only focus on data 
associated with RIN. All other identifiers will be expunged from transcripts. To ensure data quality, we will 
implement several quality procedures. These include the following procedures: 1) for quantitative data, quality 

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checking weekly with our experienced data team for synchronization electronic data, and backup of this data; 2) 
for qualitative data, transferring of digital files to computers checking of DVR recordings within 48 hours; after 
transcriptions, a check of transcripts for accuracy and to facilitate cleaning of transcripts. 
We use several data systems to protect our data. First is Filemaker, our tracking database. This is stored 
on Brown University’s encrypted server and this database is only available to staff tracking participants. It is 
password protected (in addition to accessibly only by a password protected computer. We also utilize 
SurveyToGo Software (http://www.dooblo.net/stgi/surveytogo.aspx). SurveyToGo will be used to screen for 
eligibility, and to collect data at baseline, 6- and 12-months. Data center security is protected by state-of-the-art 
servers hosted by Amazon AWS. Amazon AWS datacenters are housed at nondescript facilities protected by 
biometric locks and round-the-clock interior and exterior surveillance monitoring. Data center is limited to 
authorized personnel, who must pass a two-factor authentication a minimum of two times to access the 
datacenter floors. The software and infrastructure are updated regularly with anti-virus protection and regular 
security updates. Network security includes an enterprise-level firewall that protects two way data flows. This 
includes SSL encryption to protect device to server communications and management applications to server 
communications. SSL certificates are also utilized and al data passes through a checkpoint firewall product to 
prevent network attacks. All network traffic is stopped at the firewall and monitored with Intrusion Detection 
and Prevention Systems. Data is strictly regulated. This includes security measures to ensure that data is tied to, 
owned by, and accessible only by our project team for each specific project. Access to SurveyToGo system for 
our project team and project is done via user name and password which authenticates authorized access. In 
addition, we can grant various levels of security and access with delineated rights to data in the project. This 
role based security can provide a combination of access features including combinations of the following: 
creating users for the SurveyToGo project, managing storage of data, managing rights to access, viewing rights. 
This includes the ability for our project team to delete and wipe all data from SurveyToGo servers. Data 
collection security includes the ability to collect data from the field (in our case using android devices that are 
password protected and with ncrypted cloud security). SurveyToGo data systems on Android devices will route 
encrypted data to a secured local database; this data is automatically uploaded to the SurveyToGo remote server 
and deleted from the device whenever network is detected. If network fails, data can still be collected in offline 
scenarios and is fully encrypted in this scenario. SurveyToGo allows us to disable devices that may be lost or 
stolen by de-linking devices to the specific SurveyToGo project immediately or using the auto-sync option of 
10 minutes to pull any remaining data from the device. Data stored on a PC includes a built-in encryption 
mechanism of the Microsoft SQL Mobile to encrypted data on the local hard drive of the machine. We use a 
scanned TeleForm system for paper data collection. All paper versions are stored in locked study cabinets in 
project offices upon scanning. The scanned versions are stored on Ncrypted Cloud which offers similar state of 
the art protection as detailed for SurveyToGo. Ncrypted Cloud includes double encryption, zipping of files, 
password protected entry to folders and files each and every time or once, authorization of every user by the PI. 
This program also allows the PI to track which authorized individual has accessed files and when and changes 
that have occurred including deletions, copies. The PI can bar all copying or set limits to copying of files. 
Importantly, data is wipeable via “unlink” function from a central location in case of theft or loss. To guard 
against accidental data loss, the project data will also be backed up.  
Potential Risks to Subjects. This research includes a number of potential risks. We highlight these and 
the steps we take to minimize risk. 
1) Sensitive Information. Participants may feel uncomfortable with the sensitive nature of some of the survey 
and/or interviews or research staff’s questions. For example, we ask about sexual and reproductive health 
questions. To minimize discomfort, we use a highly trained team (hiring from our pilot study team) who 
have experience conducting sensitive research to gather outcomes data. We also use a computerized mobile 
smartphone to collect data, which offers privacy both visually and in regards to sound in our deployment of 
Audio Computer-Assisted Self-Interviewing Software (ACASI) for sensitive questions to limit social 
desirability bias in participant reporting of data. The scientific team will train and supervise the RAs in these 
procedures and techniques to gather data sensitively. If any such moments of sensitivity occur during the 
study, the M-PIs will be available for consultation. Further, if participants experience discomfort, they will 
be given the option of taking a break, or rescheduling. Further, any distress will be minimized by assurances 

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that participants can refuse to provide any data and that they can withdraw from the study at any time 
without penalty. For group based intervention sessions, we will protect against the risk of loss of 
confidentiality during the group intervention by extensively training intervention facilitators in the 
importance of maintaining confidentiality of participant information. Topics discussed in the program are 
personal and sensitive in nature. Participants may disclose personal information in the group programs that 
other participants may not otherwise have known. Although participants will not be encouraged to do so, 
participants may also disclose sexual experiences and prior engagement in coercive sexual behavior during a 
group session.  To minimize these risks, the interventionists will detail under what circumstances they will 
maintain confidentiality (and when they will not due to legally mandated disclosures). Furthermore, 
interventionists will minimize participant disclosure within the group session. Participants will be informed 
that they may refuse to participate in the group at any time. Consistent with standards of practice for 
administering group interventions, the interventionists will emphasize the importance of group members 
protecting one another’s confidentiality in the group and throughout the course of the study. Prior to 
participating in the group, participants will be provided with a statement noting the nature of the group 
process. Some participants may choose to attend the groups but not make verbal comments during the 
sessions. Participants will also sign an agreement of group confidentiality, which reinforces the confidential 
nature of group discussions. However, we cannot guarantee protection of confidentiality by other group 
members and will make this clear.  
2) There is a small risk of loss of privacy or confidentiality of data, including sensitive data on sexual 
behaviors, other risk behaviors, and psychological characteristics. This risk increases in the focus group 
discussion (in Aim 1). We take this risk seriously, and we will take steps to protect participants' identities. 
As outlined in the previous section, we will ensure that all personal identifiers are removed from the data 
and any publications arising from the study. We will make clear prior to the start of the focus group 
discussion that we cannot guarantee the absolute confidentiality of participant statements made in the group 
setting, and we will encourage them to use aliases for the group discussion. The informed consent and 
assent documents will highlight confidentiality risks. We will inform both adolescents and parent during the 
informed consent and assent process that we will not share information about anything disclosed in focus 
groups unless in a case of self or other harm and legally mandated reporting requirements.  We will ensure 
that personal identifiers are never included in any research or analytical datasets, or any publications arising 
from the study. The informed consent documents will bring confidentiality risks to participants' attention 
and situations under which disclosure can occur (and to who). Names and any other specific personal 
identifiers will not be included in any datasets: only a unique participant RIN. Tracking information 
(including names and telephone numbers) will be available solely to the project staff in charge of planning 
and organizing follow-up visits. We explain the extensive data protections put into place for our data above.  
3) Participants may experience stigma or discrimination due to sexual behaviors, self-report HIV status, or IPV 
perpetration behaviors. We have taken steps to minimize the risk due to association with our pilot study 
through careful wording of the consent and assent forms emphasizing prevention (meaning participants are 
not selected based on IPV perpetration of HIV status) and through careful discussion of participation in 
group settings and the limits we have in protecting information disclosed in group settings with other 
participants being present. We also put in place data handling, storage, and analysis practices to protect 
participants’ anonymity. We will provide training for all project staff on the needs and strategies for 
maximizing participants’ anonymity. 
4) Psychological distress or retribution: Thus are concerns including risk of retribution against perpetrators 
disclosing in these studies. The risk of retribution against boys disclosing perpetration is guarded against by 
using self-completion for disclosure of acts that are socially stigmatizing or involve violence. The other 
concern is psychological distress; those who have raped or perpetration sexual assault can find discussing it 
makes them realise that it was wrong. The scientific team has extensive experience in interviewing 
participants, including adolescents around these topics and rarely have participants reacted to these types of 
questions with more than temporary embarrassment or mild discomfort in group discussion because they 
can decide what to discuss. For other data collection, we gather data using sensitive self-report methods 
including anonymized surveys and ACASI. The scientific team will train and supervise the RAs in these 

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procedures and techniques to gather data sensitively. If any such moments of sensitivity occur during the 
study, the M-PIs will be available for consultation. Further, if participants experience emotional discomfort, 
they will be given the option of taking a break or rescheduling the focus group discussion or other data 
collection for another date and time. Further, any distress will be minimized by assurances that participants 
can refuse to answer any particular question they do not feel comfortable addressing and withdraw from the 
study at any time without penalty. For consent and assent procedures for Aims 1, we will spend significant 
time discussing what topics will be covered, particularly highlighting what questions will explore including 
HIV-status, perpetration behaviors. We will emphasize that adolescents can halt participation at any time 
without consequence. We will also emphasize that although study staff will protect confidentiality of 
participants, this is not guaranteed in group settings. We also highlight the legal norms that would require 
break in confidentiality, and who information would be reported to as laid out by South African law. We 
balance these legal norms from South Africa on protecting the best interests of the child. For some data, we 
collect it anonymously (as in the school climate survey in Aim 2), participants will be guaranteed that the 
information will be kept confidential with no reporting given the anonymized data. In other cases of data for 
our other Aims, we follow the limits to confidentiality detailed above. Although our study protocol does not 
specifically probe for identifiable victims of perpetration, we recognize that there is the small chance 
adolescents will disclose this, unprompted by our team and requiring reporting. In anticipation of any 
possibility of serious adverse events, we will refer adolescents to appropriate HIV support, mental health, 
and social support services, and for various psychological issues to the specific DCAPs within catchment 
areas after gaining permission for research from the Department of Education. In our weekly team meetings, 
we explicitly probe for any unanticipated ethical situations which do not need immediate emergency 
attention. All ethical emergencies requiring urgent attention are reported to the PIs immediately. All 
procedures will be reviewed by institutional IRBs.  
Planned Procedures for Protecting Against or Minimizing Potential Risks 
 
Overview. For adolescents, during assent procedures, and for parents during consent procedures, we 
highlight the legal norms that would require break in confidentiality, and who information would be reported to. 
For both adolescents in focus groups, we will minimize loss of privacy by limiting access to individually 
identifiable information using unique RINs on all paper, electronic data, and analyses. Electronic data, including 
digital voice recordings and data collected via ACASI will have several protections. First, all data will be stored 
on password-protected computers including smartphones and files. Second, all files on project computers and 
android smartphones will be further protected by nCrypted Cloud software which offers two-way encryption 
with secure access controlled by PIs (who can turn on and off access to password protected files from a central 
location) and wipe all data from devices remotely in the case of theft. NCrypted Cloud also enables the PIs to 
control who has access, who can move files from the secured and encrypted cloud serve onto local hard drives 
(including computers, smartphones, and external harddrives), and whether and how files can be moved between 
providing absolute control over data management and monitoring. Third, all staff will be trained in procedures 
for maintaining confidentiality of participant information. We are also prepared to address any distress that may 
arise by referring to South African’s mental health care within their free public health systems. All serious 
adverse events will be reported to IRB and NIH. Overall internal monitoring of the safety of human subjects 
will be conducted by the M-PIs. For non-emergency issues, a weekly meeting will be held to address study 
progress, recruitment and retention, data collection, and other factors related to human subjects and meetings 
will be held more often if necessary.  
Unanticipated Problems or Adverse Events. If an Unanticipated Problems or a Serious Adverse Event 
occurs at the study site and is more likely than not related to the research activity, and places participants or 
others at a greater risk of harm than was previously known or recognized, the M-PIs will report the event in 
writing using the appropriate forms to IRB. The M-PIs will also report Serious Adverse Events in writing to the 
sponsor. The M-PIs will review the Adverse Event report with the entire study team and gather any information 
needed to investigate the event and to determine subsequent action.  The M-PIs will document and report any 
subsequent action to IRBs. We will also generate a brief report of Adverse Events for the study record each 
year, and we will forward the report to Brown University IRB, SA MRC HREC, and NIH. 

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Potential Benefits of the Proposed Research to Human Subject and Others. There may be little or no 
direct benefit to participants from the study. Some possible benefits may include informing HIV and IPV 
prevention science. Adolescent participants will be given information on HIV, IPV, general health, and social 
services and referrals if necessary. The risks associated with this research are reasonable in relation to the 
anticipated benefits of advancing empirical knowledge adolescent prevention approaches for this high priority 
population and setting.  
Importance of Knowledge to be Gained. To our knowledge, this will be the first intervention to prevent 
adolescent HIV risk and IPV perpetration in an integrated manner and in a high impact setting (South Africa).  
 
Data and Safety Monitoring Plan 
Data Protected by Unique Research ID Number (RIN). Every individual that expresses interest in 
our study and is deemed eligible will be assigned a RIN. All data they provide will be identifiable only by the 
RIN, which will not contain any personal identifiers. During this study, we will take precautions to separate any 
documents that identify participants by name from documents that contain participant data. Documents that 
identify participants by name will include the password-protected file containing participants’ signed informed 
consent/assent forms and signed documentation that participants have received reimbursement. These 
documents will be kept entirely separate from any documents containing participant data. Paper documents that 
identify participants by name will be kept in locked cabinets in the offices of study personnel. Data will also be 
backed up on a weekly basis and transferred via two-way encryption via the nCrypted Cloud program for PIs 
and Co-I to oversee for quality control. Participants’ names will never appear in any report resulting from the 
project.  
Electronic data, including digital voice recordings and data collected via ACASI on android 
smartphones will have several protections. First, all data will be stored on password-protected computers and 
phones and files on these electronic devices will store data within electronic files that are further protected via 
nCrypted Cloud, approved by Brown’s Computing, including their information security division. NCrypted 
Cloud software offers two-way encryption with secure access controlled by M-PIs (who can turn on and off 
access to password protected files from a central location) and wipe all data from devices. NCrypted Cloud also 
enables the M-PIs to control who has access, who can move files from the secured and encrypted cloud serve 
onto local hard drives (including computers, smartphones, and external hard drives), and whether and how files 
can be moved between  providing absolute control over data management and monitoring. Third, all staff will 
be trained in procedures for maintaining confidentiality of participant information. Fourth, audiotapes will be 
transferred to a secure computer within 48 hours of recording. Encrypted data on the nCrypted Cloud server can 
be downloaded daily from any location in the world (via secure password) and if authorized by the PIs, saved to 
password protected hard-drives on computers dedicated solely to the project. Data analyses will only focus on 
data associated with RIN. All other identifiers will be expunged from transcripts.  Any names or pseudonyms 
used during focus groups will be replaced with the RIN.  To guard against accidental data loss, the project data 
will be backed up onto a secure server weekly.  
Encouraging Focus Group Participants to Maintain Confidentiality. At the start of each focus 
group, we will emphasize the need for confidentiality and discuss the need for participants to refrain from 
sharing others' comments with any other person after the group ends. We cannot completely safeguard the 
confidentiality of participants' statements during focus group sessions, because these sessions involve multiple 
participants. We will state this fact explicitly when we obtain informed consent and assent from focus group 
participants. We will strongly encourage focus group participants to use aliases during the group discussion to 
protect their names.  
Training in Confidentiality. The M-PIs will provide the study team with training in all ethical 
procedures including informed consent/assent, maintaining confidentiality, and protecting confidential data. 
This training includes for example, the importance of securing participants' privacy, the separation of data from 
identifiers, and protocols for using locked offices, filing cabinets, and password-protected files to avoid 
unauthorized use of participant data. The study team will meet regularly to discuss protocols for maintaining 
participants' privacy. The study team will also follow institutional policies at Brown University for requiring 
mandatory training in human subjects protection before conducting any study activities.  

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Protocols for Audio Files. Focus group discussions will be recorded on digital voice recorders. Given 
our precautions to maintain confidentiality, the risk of a confidentiality breach related to recorded data is 
minimal, and that it is reasonable in relation to the benefits to be gained by recording focus groups. This risk is 
also reasonable in relation to the importance of the knowledge to be gained from our study. After each day of 
recording, the group facilitator will transfer all new recordings to a project drive on a password-protected 
computer. He or she will label files with the number of each focus group and ensure that files are password-
protected. To guard against accidental data loss, the project data will be backed up weekly. All original 
recordings will be removed from the digital voice ecorders immediately after transferring the recording to a 
password protected and secure project drive and before starting a new focus group. Transcript files will also be 
stored securely in password-protected files, on password-protected computers. The transcript file has been 
"cleaned" after it has been reviewed by project staff who participated in the focus group for accuracy, and to 
expunge any identifying information other than a participant's RIN (e.g., name, address, name of school, etc.). 
After a transcript file has been "cleaned", this will be the primary document for analysis in NVIVO. RAs will 
receive ongoing supervision and training in regular meetings, which will also ensure continued compliance with 
data safety protocols. The M-PIs will be responsible for ensuring that study protocols for maintaining 
confidentiality are followed. Serious adverse events will be reported to and written reports will also be provided 
NIH.  
Data and Safety Monitoring. Aim 1 is comprised of qualitative focus groups. Aim 2 is an open pilot of 
our intervention to assess acceptability. Aim 3 is a randomized controlled pilot trial of our intervention to assess 
feasibility. For both Aim 2 and Aim 3, this is a pilot of a prevention trial (thus not a treatment) and not requiring 
interim analysis for safety and monitoring. Thus our focus is on identifying Unanticipated Problem or a Serious 
Adverse Events that may occurs at the study site and is more likely than not related to the research activity, and 
places participants or others at a greater risk of harm than was previously known or recognized.  
M-PIs are responsible for monitoring the safety and efficacy of this trial and complying with the 
reporting requirements. The safety of participants will be monitored during each contact with study participants.  
There will also be regular team meetings monitoring of the safety of participants. If Serious Adverse Events, 
Unanticipated Problems occur, M-PIs will report the event in writing using the appropriate forms to IRB. For 
Serious Adverse Events that require clinical care, referral for appropriate care for subjects will be conducted for 
them to access care within South Africa’s free at point of care public health care system.  
 The M-PIs will review the Adverse Event report with the entire study team and gather any information 
needed to investigate the event and to determine subsequent action.  The M-PIs will document and report any 
subsequent action to IRBs. We will also generate a report of Adverse Events for the study record each year, and 
we will forward the report to Brown University IRB, SA MRC HREC and NIH. 
 
G. 
MANAGEMENT DETAILS 
Staff and Scientific Collaboration 
Our multidisciplinary team consists of highly qualified, accomplished personnel with extensive 
experience in the areas of adolescent preventive interventions for HIV and IPV in South Africa and globally. 
Our investigative team currently has multiple projects in South Africa on adolescent HIV and IPV. Dr. Caroline 
Kuo (M-PI) will contribute social and behavioral expertise in adolescent HIV prevention including adaptation 
of empirically supported HIV interventions from outside of South Africa to South Africa, and in mixed-methods 
formative intervention development research that will yield appropriately tailored interventions for adolescents. 
She has 4 ongoing studies in Cape Town as an investigator (NIH grants: K01 NIMH 096646, R24 NICHD 
077976, R21 NIAID 116309, R21 NIAID118393) and 1 other study (iLink: Incentives for Linkage to Care for 
HIV positive individuals) in a mentor role. Dr. Kuo directly collaborates with Dr. Cathy Mathews on 2 of these 
studies (K01 NIMH 096646 and R24 NICHD 077976), and Dr. Harrison on 3 studies (R24 NICHD 077976, 
R21 NIAID118393 and iLink). Dr. Cathy Mathews (M-PI) is a public health scientist with expertise in 
adolescent interventions for HIV and IPV, and specializing in school-based intervention trial design and testing. 
Her research is specifically focused on testing interventions for scale-up in school and health systems, and de-
signed to inform national policies related to adolescent sexual and reproductive health in South Africa. Dr. 

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Abigail Harrison (co-I) will contribute her substantial expertise in qualitative sexual and reproductive health 
research with South African adolescents. She has served as M-PI or co-I for multiple NIH-funded awards in 
South Africa. She has investigated the social context of adolescent HIV risk and preventive behaviors in South 
Africa (R01 HD41721) and is experienced in the design and evaluation of interventions for adolescents (R01 
HD37343). Dr. Lindsay Orchowski (co-I) will bring her substantial expertise in the Safe violence preventive 
intervention being used in the study. She is PI of a large-scale, CDC-funded evaluation of sexual assault 
prevention programming for high school boys, as well as middle school boys. She is currently the PI of an 
NIAAA R34 grant designed to evaluate the Safe program for men in the military. She served as the study 
coordinator for a large-scale (N =1285), CDC-funded evaluation of sexual assault prevention programming 
(with Dr. Alan Berkowitz) and has published extensively on sexual assault risk reduction and prevention 
programs. Dr. Alan Berkowitz (consultant) is an expert in social norms theory, bystander intervention, and 
engaging men in sexual assault prevention. A collaborator on the design of the Men’s Workshop (which forms 
the basis of the Safe pro-gram), he has worked with Dr. Orchowski in three evaluations of the model. Dr. 
Naeemah Abrahams (consult-ant) is an expert in violence risk reduction and prevention in South Africa as well 
as gender norms and relation-ships. She brings significant content expertise in IPV and interpersonal violence 
research within South Africa and has extensive knowledge of the South African ethical challenges of violence 
research with adolescents. Dr. Kuo, Mathews, Abrahams and Orchowski recently collaborated on an edited 
volume on sexual violence which has been accepted for publication by Elsevier entitled, “Sexual Assault Risk 
Reduction and Resistance: Theory, Research, and Practice.” 
 
Management Approach 
We propose a multiple PI leadership plan that involves sharing responsibility by two M-PIs, Dr. 
Caroline Kuo (Brown University) and Dr. Catherine Mathews (Medical Research Council). This scientific 
collaboration is stronger than a study conducted by either the USA-based or South African-based team alone. 
We are able to consolidate expertise with South African adolescents at risk for HIV and IPV. This collaboration 
also illustrates our philosophy of multidisciplinary and equitable international research partnerships. Dr. Kuo 
contributes significant expertise in adolescent behavioral and social risk. She also brings expertise in mixed-
methods for intervention development and adaptation of empirically supported programs to the South African 
context as well as international data systems and mobile data collection in South African community contexts. 
Her experience will facilitate tracking and tracing of adolescents for collection of data in the community setting, 
and high quality data collection from adolescents on sensitive topics. Dr. Mathews contributes significant 
experience in adolescent HIV, sexual and reproductive health, and IPV. She brings vast expertise in intervention 
trial design, implementation, analyses, and dissemination for maximum health systems and policy impact. She 
is also an expert in trial implementation among South African adolescents in school settings.  
Dr. Kuo will have oversight of Brown University activities including the subcontract to the University of 
Cape and submission of reports to NIH. Dr. Mathews will have oversight over Medical Research Council sub-
contract activities, in close collaboration with Dr. Kuo. Project progress will be summarized weekly in order 
coordinate scientific, fiscal and administrative management of the project, setting priorities for allocation of 
resources and funds. Together, Drs. Kuo and Mathews will ensure adequate systems, working with their 
experienced institutional financial and grants management teams, to ensure that grant activities are in 
compliance with US laws, and DHHS and NIH policies, including biosafety, the protection of Human Subjects, 
data and facilities, as well as parallel applicable laws and policies in South Africa. In the case of unanticipated 
serious adverse events, and with the permission of children and parents, we will refer to services by tapping into 
the extensive social service and clinical networks that we have worked with for adolescent health in South 
Africa including both Drs. Kuo and Mathew’s respective affiliation with the Medical School at University of 
Cape Town. 
Authorship for peer-reviewed manuscripts, book-chapters, scientific conference presentations, policy 
and clinical briefs, and child-friendly dissemination briefs resulting from project activities will be determined 
prior to creating drafts for these outputs. Authorship will be negotiated based on the relative scientific 
contributions of the PIs, Co-I, consultants, and key personnel, following international guidelines set by the 
International Committee of Medical Journal Editors (ICMJE). All decisions regarding the technical aspects of 

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the project will be decided jointly in weekly Skype meetings by the M-PIs and Co-Is.  In the unlikely case of 
conflicting opinions regarding the technical approach of the study, the M-PIs, Drs. Kuo and Mathews will 
consult with co-Is (Drs. Harrison and Orchowski). 
 
Facilities 
The South African Medical Research Council (SAMRC) will serve as the South African site for this 
proposed study. Dr. Catherine Mathews (M-PI) is Chief Specialist Scientist and Director of the Health Systems 
Re-search Unit. She is co-Director of the Adolescent Health Research Unit at the University of Cape Town. She 
is a member of the Cochrane Sexually Transmitted Infections Review Group. She also holds an appointment as 
Honorary Associate Professor in the School of Public Health and Family Medicine and in the Department of 
Psychiatry and Mental Health at University of Cape Town. Dr. Mathews shared appointment at the University 
of Cape Town has provided many opportunities to collaborate with Drs. Kuo and Harrison. Dr. Kuo (M-PI) also 
holds an appointment in the Department of Psychiatry and Mental Health at the University of Cape Town; Dr. 
Harrison (co-I) also holds an appointment in the School of Public Health and Family Medicine at University of 
Cape Town. Dr. Naeemah Abrahams (expert consultant) is Chief Specialist Scientist and Deputy Unit Director 
of the Gender and Health Research Unit, also based at the SAMRC. She also holds an appointment as Honorary 
Associate Professor with University of Cape Town’s Faculty of Health Sciences in the School of Health and 
Rehabilitation Sciences, as well as Extraordinary Professor with University of Western Cape’s Faculty of 
Community Health Sciences in the School of Public Health. 
The SAMRC is a South African and international leader in research on adolescents including HIV, 
adolescent sexual and reproductive health, and IPV. There is strong interdisciplinary collaboration between 
research units at SAMRC, with Dr. Mathews’ and Abrahams’ respective units located adjacent to each other 
and their offices several doors away from each other. Such close physical proximity facilitates collaboration on 
this proposed study. SAMRC provides an exceptional research environment, particularly in regards to HIV and 
IPV including sexual violence prevention research. The SAMRC was established in 1969 with a man-date to 
improve the health of the South African population, through research, development and technology transfer, so 
that people can enjoy a better quality of life. Both Drs. Mathews and Abrahams bring decades of experience and 
hold leadership positions in research units within SAMRC focused on adolescent HIV and sexual health and 
IPV research.   
SAMRC offers a full administrative and grants management staff to assist in pre- and post-award 
management. Speaking to SAMRC’s capacity to address post-award financial management, including review, 
approval and processing of all transactions associated with the sub-contract of this award, SAMRC currently 
manages over 100 active research grants. The Professional Sup-port Services team at SAMRC manages all its 
research contracts by complying to all research contract conditions as well as statutory and legislative 
requirements. 
SAMRC has robust access to a physical library housed on their campus as well as electronic access to 
the majority of academic databases related to this proposal. Investigators from SAMRC will also utilize their 
affiliations at University of Cape Town to access library resources (where both Drs. Mathews and Abrahams 
have appointments). University of Cape Town has 9 libraries spanning across three campuses including a 
dedicated Health Sciences Library. The University of Cape Town library system houses 1.2 million volumes. 
Journal volume holdings alone consist of over 72,000 e-journal titles and more than 28,500 print journal titles. 
In addition, University of Cape Town faculty and students have access to 190 high-quality electronic databases. 
The libraries have fully staffed user service desks with knowledgeable library professionals to assist with 
research needs.  
SAMRC will provide fully equipped office space dedicated to Drs. Mathews and Abrahams and their 
research team. The SAMRC research campus is secured at all times with both physical security and 24 hour 
security personnel. All offices are secured and include locked filing cabinets. SAMRC offices are fully 
equipped with high speed laser printers, scanners, fax machines, and photocopy machines.  
Computing at SAMRC is linked to high-speed networks. SAMRC has a fully staffed information 
technology support team. We have coordinated our information technology teams to facilitate. SAMRC also 
offers a wide range of applications for office computers including the software needed for research (i.e., 

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Microsoft Office, NVIVO, SPSS, etc.). Data will be captured onto password protected computers and backed up 
daily onto a secure server. Data on this server can be downloaded daily from any location in the world using 
two-way encryption and saved to password protected computers dedicated solely to the project. Data will also 
be backed up onto an encrypted hard-drive on a weekly basis and transferred via two-way encrypted files to the 
M-PI’s quality control. Drs. Mathews, Kuo, and Harrison have worked extensively on past collaborative pro-
jects to develop a user-centered, real time data system capable of collecting secure human subjects data in an 
adolescent friendly manner. 
  
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