Adherence to HIV Treatment Postpartum: The Implications of Transitions Among Women Living With HIV in South Africa
Phase: NA
Conditions: HIV, Pregnancy Related
Sponsor: Brown University

 
 
Study Protocol 
 
 
 
Adherence to HIV Treatment Postpartum: The Implications of Transitions 
Among Women Living with HIV in South Africa 
 
ClinicalTrials.gov #: NCT04846569 
 
Version 5.0 
 
 
November 5, 2021 
 
 
 
 
 
IRB Federalwide Assurance Numbers: 
• FWA00004460 (Brown University) 
• FWA00001637 (University of Cape Town) 
 
 
 
Study Sponsor: National Institute of Mental Health (K01MH112443) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Protocol Version 5, 5 November 2021 
Protocol Summary 
 
Adherence to HIV Treatment Postpartum: The Implications of Transitions Among Women 
Living with HIV in South Africa  
 
Study Aims: 
Aim 1: Identify contextual, interpersonal, clinic, and individual-level factors that 
influence women’s HIV treatment adherence during periods of key points of transition 
during pregnancy and postpartum, using longitudinal in-depth qualitative interviews 
among a cohort of pregnant women (N=25-30) following them up to 12 months 
postpartum.  
 
 
Aim 2: Evaluate the feasibility and preliminary efficacy of a Transition Theory-based 
ART adherence intervention for postpartum women living with HIV, using a small scale 
randomized controlled trial (RCT; N=60).  
 
Aim 3: Assess participants’ experiences of the intervention, perceived usefulness, and 
identify ways to refine the intervention for future evaluation, using in-depth individual 
interviews will be conducted with all participants in the intervention condition after 
follow-up assessments have been completed. 
 
 
Sample size for RCT: 62 participants consented; 43 randomized 
 
Study population: Adult (≥ 18 years), HIV-positive, pregnant (23-34 weeks) women attending 
antenatal services at the study site, prescribed ARVs 
 
Participating site: Gugulethu Midwife Obstetric Unit, Cape Town, South Africa 
 
Study design: Small-scale two-arm randomized control trial, assessing feasibility and 
preliminary efficacy. 
 
Study timeline for RCT: April 2021-December 2022  
 
Principal Investigator:  
Jennifer A Pellowski, PhD 
Assistant Professor of Behavioral and Social Sciences 
International Health Institute 
Brown University School of Public Health 
121 South Main St., Box G-S121-2 
Providence, RI 02903 
+1 (860) 908- 2406 
Jennifer_pellowski@brown.edu 
 
Co-Investigators/K01 Mentors: 
Landon Myer, MBChB, PhD  

Study Protocol Version 5, 5 November 2021 
Professor of Epidemiology and Biostatistics 
School of Public Health and Family Medicine  
University of Cape Town  
Cape Town, South Africa  
+27 (0)21 406 6661  
Landon.Myer@uct.ac.za 
 
Don Operario, PhD 
Professor, Behavioral and Social Sciences 
Brown University School of Public Health 
121 South Main St. 
Providence, RI 02903 
+1 (401) 863-6657 
Don_operario@brown.edu 
 
Mark Lurie, PhD 
Associate Professor, Epidemiology 
Brown University School of Public Health 
121 South Main St. 
Providence, RI 02903 
+1 (401) 863-7593 
Mark_lurie@brown.edu 
 
Susan Cu-Uvin, MD 
Professor, Obstetrics and Gynecology 
Alpert School of Medicine, Brown University 
+1 (401) 793-4775 
Scu-uvin@lifespan.org 
 
Abigail Harrison, PhD 
Associate Professor, Behavioral and Social Sciences 
Brown University School of Public Health 
121 South Main St. 
Providence, RI 02903 
+1 (401) 863-6201 
Abigail_harrison@brown.edu 
 
Christopher Colvin, PhD 
Adjust Associate Professor, Social and Behavioral Sciences 
School of Public Health and Family Medicine  
University of Cape Town  
Cape Town, South Africa  
+27 (0)21 650-1487 
c.j.colvin@uct.ac.za 
 
 

Study Protocol Version 5, 5 November 2021 
Lucia Knight, PhD 
Associate Professor and Division Head, Social and Behavioral Sciences 
School of Public Health and Family Medicine  
University of Cape Town  
Cape Town, South Africa  
+27 (0)72 770-7386 
lucia.knight@uct.ac.za 
 
 
Study Sponsor: National Institute of Mental Health (K01 112443) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Abstract From NIH Application 
Prevention of mother-to-child transmission (PMTCT) efforts have reduced the rates of vertical 
transmission to 2.7%, however, optimal antiretroviral therapy (ART) adherence remains a 
difficult goal to reach, particularly postpartum. The contribution of the proposed research is 
expected to be two-fold: 1) to gain an understanding of how influential contextual, interpersonal, 
clinic, and individual level factors change during key moments of transition during pregnancy 
and postpartum and influence ART adherence and 2) to develop bio-behavioral interventions to 
assist mothers in maintaining their adherence to ART postpartum. Candidate: I am a social 
psychologist with a background in ART adherence socially disadvantaged groups in the United 
States. I am applying for a five-year K01 Career Development Award to obtain training, 
mentorship, and research experience to become an expert in maternal health among women 
living with HIV in resource limited settings and an independent investigator capable of obtaining 
R01 funding. Mentoring: I have put together an exceptional mentoring team with extensive 
experience in HIV treatment and prevention research in South Africa that integrates 
epidemiology, qualitative methods, and clinical science. Drs. Don Operario and Mark Lurie will 
serve as co-Primary mentors and bring complementary expertise in international HIV behavioral 
intervention development and infectious disease epidemiology. In addition to my two Primary 
mentors, my co- mentors provide expertise in specific content areas and methodologies and are 
based in both the U.S. and South Africa (ZA). My co-mentorship team includes: Dr. Susan Cu-
Uvin (U.S.-based, clinical management of HIV, obstetrics and gynecology), Dr. Landon Myer 
(ZA-based, perinatal epidemiology, postpartum ART adherence), Dr. Abigail Harrison (U.S.-
based, longitudinal qualitative methods, sexual and reproductive health), and Dr. Christopher 
Colvin (ZA-based, qualitative methods, maternal child health). Training: Specific training in 
perinatal epidemiology, longitudinal qualitative methods, theory-based interventions, cross-
cultural intervention development and evaluation will be achieved through intensive mentored 
training, coursework, workshops and directed readings and primary ZA research. Guided by my 
excellent mentorship team, these training and research experiences will establish my independent 
investigator career as an expert in developing HIV treatment and prevention interventions to 
address maternal health in high impact, low resource settings, that take into account key 
moments of transition and change that impact health behaviors. Research: The goals of the 
proposed project are to (1) identify contextual, interpersonal, clinic, and individual level factors 
that influence women's HIV treatment adherence during key period of transition during 
pregnancy and postpartum; (2) evaluate a Transition Theory-based bio-behavioral intervention to 
improve ART adherence postpartum using a small scale randomized controlled trial; (3) assess 
participants' experiences of the intervention, perceived usefulness, and identify ways to refine the 
intervention for future evaluation 
 
 
 
Introduction 
 
It is a critical time in the South African HIV epidemic to increase HIV treatment 
adherence among postpartum mothers. During pregnancy and postpartum, women living with 
HIV are eight times more likely to die than women who are HIV negative.1 Prevention of 
mother-to-child transmission (PMTCT) efforts have reduced rates of vertical transmission to 
2.7% in South Africa (ZA),2 however, optimal postpartum adherence to HIV treatment, a key 

Study Protocol Version 5, 5 November 2021 
component of PMTCT, remains difficult.3,4 There are significant consequences of non-adherence 
postpartum including viral rebound,5-7 which increases infectiousness to sex partners8 and infants 
while breast-feeding,9 and an increased chance of drug resistance,10-14 which is particularly 
concerning in resource-limited settings where additional lines of ART may be limited.15 Women 
who are non-adherent are also at risk for AIDS-related complications, including tuberculosis,16 
candidiasis,17 and cytomegalovirus,18 which can create high-risk pregnancies and jeopardize 
maternal and infant health. 
Option B+ policies, which provide antiretroviral therapy (ART) to all HIV positive 
pregnant women for life, regardless of CD4 T cell count, have been adopted in many countries as 
a way to simplify health services and increase access and uptake.19,20 There is major concern, 
however, about suboptimal engagement in care postpartum after mothers transfer from antenatal 
clinics to regular adult HIV care and the ability for women to adjust to lifelong treatment.21-25 In 
Cape Town, ZA, 49% of women living with HIV have disengaged from care by six months 
postpartum26 and a meta-analysis3 of 51 studies found that only 53% of the women had optimal 
adherence postpartum. Additionally, it is hard to determine with precision when drop-offs in 
ART adherence occur due to the wide range of time points (3 days to 12 months) used to denote 
“postpartum” adherence in the literature.27-33 In order to fully capitalize on the potential that 
Option B+ has for simplifying HIV treatment, it is necessary to identify when and why women 
become non-adherent to ART and how influential factors may change as HIV positive mothers 
transition from pregnancy to postpartum.  
 
Pregnant and postpartum women are faced with individual, contextual, and systems-level 
facilitators and barriers to HIV treatment adherence.34,35 Evidence shows lower education,36 
difficulties managing the practical demands of ART,37 perceptions of being healthy, and the use 
of alcohol and drugs29,31 are associated with suboptimal adherence. A major gap in evidence, 
however, is that previous studies rarely distinguish between pregnancy and postpartum, 
providing little information about the changes that occur during this crucial transitional window 
period.35 A longitudinal perspective is necessary to accurately capture the complexities of 
women’s lives and how motivations and behaviors change across this transition from pregnancy 
to early motherhood.38 Additionally, balancing self-care with infant care, changes in familial 
roles, and finding out the infant’s HIV status are all associated with this transition and may 
influence adherence, however, discussion of these factors is minimal in the ART adherence 
literature.35 Furthermore, the extendibility of previous ART adherence interventions for general 
populations may not be appropriate for the special individual and contextual barriers that 
pregnant and postpartum mothers face.35 Globally, ART adherence interventions tailored for 
pregnant and postpartum women are severely lacking.39-41 
 
The contribution of this K01 research is expected to be two-fold: 1) to gain an 
understanding of how contextual, interpersonal, clinic, and individual level factors change during 
key moments of transition during pregnancy and postpartum and impact ART adherence and 2) 
to develop bio-behavioral interventions to assist mothers in maintaining their adherence to ART 
postpartum. The contribution of the proposed research will be significant because optimal ART 
adherence decreases rates of HIV transmission to infants and sexual partners, increases maternal 
general health and immune functioning, and decreases maternal mortality. Postpartum mothers 
are an ideal, high-risk population for achieving 90-90-90 targets, as they are already engaged 
within the health system and may be uniquely motivated by the life transition of birth.42 
 
Theoretical Framework. Transition Theory43 provides an innovative framework to 
guide the current research on HIV treatment adherence among pregnant and postpartum women. 

Study Protocol Version 5, 5 November 2021 
Transition Theory (Figure 1) allows us to characterize and describe the transitions that occur 
during this window period by clearly delineating the relevant personal and environmental 
characteristics that may facilitate or impede a successful transition, which could lead to sub-
optimal ART adherence. With Transition Theory, we can conceptualize pregnancy and 
postpartum among women living with HIV as a time with multiple related health and 
developmental transitions. Women experience transition into motherhood (for a first child) or 
transitions in family roles (for a subsequent child). These women will also experience other 
transitions such as receiving the results of their infants’ HIV PCR test and shifting their own 
healthcare from antenatal clinics to HIV care clinics. These transitions can present significant 
challenges for ART adherence. There are also properties of transition experiences that contribute 
to how well an individual is able to adhere to ART, including awareness about an impending 
transition – such as being aware for the need to transfer care to an HIV care clinic – and 
engagement in the processes inherent in the transition – such as seeking out information about 
infant care. Transition experiences influence outcomes, such as adherence to ART, via transition 
conditions. Transition conditions are personal and environmental factors that can facilitate or 
inhibit progress towards a successful transition. These conditions are: (a) personal meanings, 
including appraisals of the anticipated event and the effect it will have on an individual’s life, (b) 
cultural beliefs/attitudes, (c) socioeconomic status, (d) preparation for the transition, such as 
actively preparing for the infants’ arrival, (e) community factors including family and partner 
support and (f) societal factors such as marginalization of people living with HIV. Transition 
Theory also specifies potential intervention techniques, termed nursing therapeutics, including 
providing knowledge, role modeling, social support, and creating a healthier environment at the 
familial and community levels. This innovative framework will guide both the informative 
longitudinal qualitative phase (Aim 1) of this study as well as the development and evaluation of 
the intervention (Aims 2 & 3). 
This K01 application is innovative in several ways. First, this project focuses specifically 
on women living with HIV postpartum. Previous literature has largely been focused on pregnant 
women and child/mother dyads within the context of PMTCT and maternal ART adherence has 
often been considered a secondary outcome, particularly postpartum.44 Furthermore, there is a 
dearth of information regarding ART adherence beyond 6 weeks postpartum,45 which is too 
narrow a window period for understanding or targeting long-term treatment behaviors. This 
project aims to expand upon the current view of postpartum ART adherence by studying HIV 
treatment adherence and the factors that influence this behavior up to 12 months postpartum. In 
doing so, this project seeks to shift the current PMTCT research paradigm to focus on longer-
term engagement in care for women of reproductive age. Additionally, we will use Transition 
Theory to guide both the informative qualitative research phase and intervention development. 
This theory has been used to understand the process of first time motherhood and fatherhood46-48, 
chronic illness,49-52 cancer,53,54 and old age,55,56 and is a conceptual framework guiding mine and 
Dr. Operario’s current work on PrEP behaviors among young adults in ZA. However, Transition 
Theory has not been used to study PMTCT and HIV treatment among pregnant and postpartum 
women and is a novel contribution of the current work. This theory allows for the examination of 
behavior as personal and contextual factors change across time which provides new insights into 
how these factors impede adherence and represents a significant advantage over health behavior 
theories used to study ART adherence previously, particularly for this population.  
 
 

Study Protocol Version 5, 5 November 2021 
2. STUDY AIM & OBJECTIVES  
 
Study aim 
The objective of this study is to identify how influential factors change during key moments of 
transition during pregnancy and postpartum and to construct an intervention that effectively 
addresses these moments of transition to bolster ART adherence for mothers living with HIV. 
 
Study approach 
This study includes two phases: 
1. A longitudinal qualitative cohort to identify and characterize factors that influence 
women’s adherence behaviors as well as perceptions and motivations for continued 
treatment and engagement in care and examine participants’ preferences of adherence 
intervention structure and delivery, in order to shape the design components of the bio-
behavioral intervention. 
2. Conduct an open pilot and small scale RCT of the intervention to determine feasibility, 
and preliminary efficacy of the intervention to improve ART adherence among pregnant 
and postpartum women living with HIV and in-depth interviews with intervention 
participants to determine acceptability and to identify ways to refine the intervention for 
future evaluation.  
 
Note that Phase 1 received ethical approval from UCT HREC previously (HREC: 
344/2017). This protocol focuses on Phase 2 (Aims 2 & 3).  
 
For Phase 2, the key outcomes are: 
 
Primary Outcomes 
1. Feasibility: Feasibility will be assessed through the number of counseling sessions 
completed. 
2. Preliminary efficacy - ART Adherence: Preliminary efficacy will be assessed as the 
correlation between study arm and self-reported HIV adherence on the 3 item Wilson ART 
adherence scale (self-report, 3 item scale recoded as 0-100, 100 indicating perfect adherence in 
the past month) at 6 months postpartum. 
3. Preliminary efficacy- Retention in HIV services: Preliminary efficacy will be assessed 
as the correlation between study arm and retention in HIV services at 6 months postpartum. 
Retention in HIV services is measured by clinic records. Retention at 6 months postpartum is 
measured as attended HIV clinic appointment in the past 3 months. 
4. Preliminary efficacy-viral suppression: Preliminary efficacy will be assessed as the 
correlation between study arm and viral suppression at 6 months postpartum. Viral suppression 
will be measured by clinic records, with viral suppression defined as HIV viral load less than 200 
copies/mL. 
 
Secondary Outcomes 
1. Adherence self-efficacy - confidence in taking medications: Adherence self-efficacy 
will be measured using the AACTG adherence self-efficacy scale, 15 items, using 5 point Likert 
scale ranging from not confident at all to very confident. Total scores range from 15-75, with 
higher scores indicating higher self-efficacy. 

Study Protocol Version 5, 5 November 2021 
2. Acceptability/Utility of the Intervention: Acceptability of the Transition Theory-based 
intervention, assessed during in-depth interviews among participants in the intervention 
condition to gauge general feelings of acceptability and perceived usefulness of the intervention. 
 
 
3. Study Design 
 
Overview 
We propose to address these objectives using a two phase design in which we identify how 
influential factors change during key moments of transition during pregnancy and postpartum 
and to construct an intervention that effectively addresses these moments of transition to bolster 
ART adherence and engagement in care for mothers living with HIV.  
 
Phase 1 (Aim 1) 
Phase 1 involved a longitudinal qualitative cohort design with interviews with 30 pregnant and 
postpartum women at 4 time points to identify contextual, interpersonal, clinic, and individual-
level factors that influence women’s HIV treatment adherence during periods of key points of 
transition during pregnancy and postpartum. (HREC 344/2017) 
 
 
Phase 2 (Aims 2 & 3) 
 
Aim 2: Evaluate the feasibility and preliminary efficacy of a Transition Theory-based 
ART adherence intervention for postpartum women living with HIV 
 
Informed by Aim 1, this intervention will be tested using an open pilot (n=5) and a small 
scale randomized controlled trial (RCT; n=60 to complete baseline). The purpose of the open 
pilot is to pretest all study procedures, particularly recruitment and retention, to increase the 
feasibility of the RCT, as well as to pilot test the intervention content. Primary hypothesis if the 
RCT: The intervention will be feasible to conduct with postpartum women living with HIV in 
Cape Town, South Africa. Secondary hypothesis: Postpartum women in the intervention 
condition will have better ART adherence than women in the control condition at follow-up.  
 
For the RCT, pregnant women living with HIV (n=60 to complete baseline; up to n=100 will be 
approached) will be approached to participate. Following informed consent, women will 
complete an enrollment study visit and will then be randomized to one of two arms: 
• Arm A (Transition theory-based intervention): Women randomized to this arm 
will receive monthly one-on-one meetings with a community health worker for 
four months during late pregnancy and early postpartum 
• Arm B (enhanced standard of care): Women randomized to this arm will receive 
one meeting with a community health worker in addition to the local standard of 
care.  
 
Women randomized to each arm will be asked to attend two additional assessment study visits at 
3- and 6-months postpartum. The primary outcome will be self-reported ART adherence and 
secondary outcomes will be retention in routine HIV care (from routine electronic medical 
records) and HIV viral load using dried blood spots.  
 

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Participation will have no impact on any aspect of women’s routine antenatal and obstetric care 
during pregnancy, or on any aspect of their postpartum care. In addition, participation will have 
no impact on their routine HIV care. Women randomised to the Transition intervention will 
receive the intervention separate from any routine medical visits. Women randomised to the 
enhanced standard of care will attend all routine medical visits and will receive one meeting with 
a community health worker separate from any routine medical visits.  
 
 
Aim 3: Assess participants’ experiences of the intervention, perceived usefulness, and 
identify ways to refine the intervention for future evaluation.  
 
This aim will be accomplished using in-depth individual interviews with all participants 
who were randomized to the intervention condition after all follow-up assessments have been 
completed (n= up to 30) 
 
The study schema is summarized in the diagram below: 
 
 
 
 
Setting 
The proposed study will take place in the community of Gugulethu in Cape Town. Aim 1 was 
successfully conducted in this community and our team has actively collaborated with local 
Aim 1: 
PAM Study: Longitudinal qualitative cohort with pregnant women living with HIV following them through 12 months postpartum 
(n=30)
Aim 2a: 
Open pilot of the Womandla Health intervention (n=5) 
Aim 2b: 
Small scale pilot: pregnant women living with HIV (n=60)
Randomly allocated to Womandla Health intervention or control and followed through 6 months postpartum 
Womandla Health
Intervention Arm (n=30)
•
Monthly one-on-one meetings 
with a community health 
worker (2 during pregnancy, 2 
postpartum)
•
HIV and antenatal/postpartum 
care through routine care 
services
Control Arm (n=30)
•
One meeting with a community 
health worker
•
HIV and antenatal/postpartum 
care through routine care 
services
Aim 3: 
In-depth interviews with women 
randomized to the intervention 
condition (n=up to 30)
Study assessment visits 
(conducted separately from 
routine care)
Enrolment
3 months postpartum 
(immediate post-test)
6 months postpartum

Study Protocol Version 5, 5 November 2021 
health services in this setting for over 10 years. The antenatal HIV prevalence rate in Gugulethu 
is between 26-30%. Participants will be recruited during pregnancy from the Gugulethu Midwife 
Obstetrics Unit (MOU), which is a public sector facility that serves more than 4800 pregnant and 
postpartum women annually.  
 
 
4. Study Population 
For Phase 2 of this study (Aims 2 & 3), inclusion criteria are as follows: 
• 18 years of age or older 
• HIV positive status (based on clinic records) 
• Confirmed pregnant (based on clinic records) and estimated to be 23-34 weeks gestation 
(clinic records or self-report) 
• Currently prescribed ART  
• Planning on remaining a resident of Cape Town for at least 6 months postpartum 
• Able to provide informed consent for research including: 
o Willingness to be randomly allocated to the Transition intervention or enhanced 
standard of care 
o Consent to have study personnel access medical records under confidential 
conditions and for the purposes of the study only 
o Consent to other study procedures, including follow-up for at least 6 months 
o Ability to speak isiXhosa or English 
Note: no restrictions will be made based on timing of HIV diagnosis or prior exposure to ART.  
 
Exclusion criteria include: 
• Failure to meet any of the inclusion criteria 
• Significant pre-existing psychiatric comorbidity at enrolment that may impact ability to 
consent according to the judgement of study personnel (including cognitive impairment 
or known psychotic disorder) 
Note: mothers will not be withdrawn from the study following foetal complications or death 
 
5. Recruitment 
Women attending the Gugulethu MOU who have documented HIV infection and clinical 
indication of pregnancy according to a provider will be told about the study by staff at the MOU. 
If women express interest in the study, they will be asked to approach study staff. Study staff 
will provide basic information about the study, and women who are interested in participating 
will be screened based on the inclusion/exclusion criteria detailed above. Women who are 
eligible will undertake the informed consent process described below. Study staff will emphasize 
that all study activities are entirely separate from routine antenatal/postpartum and HIV care and 
that refusal or withdrawal from the study will have no impact on their ability to access any of 
these services.  
 
6. Study Arms 
 
Open Pilot 
All women recruited for the open pilot (n=5) will receive the Transition intervention (see below). 
All open pilot participants will receive 4 monthly one-on-one meetings with the community 

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health worker. As a reminder the purpose of the open pilot is to pretest all study procedures, 
particularly recruitment and retention, to increase the feasibility of the RCT, as well as to pilot 
test the intervention content. Participants will fill out end of session questionnaires that inquire 
about specific content and design features of the intervention. This information will guide the 
next iteration of the intervention to be tested in the small-scale RCT.  
 
Randomized Controlled Trial Study Arms 
 
Enhanced standard of care 
Women randomized to the enhanced standard of care condition will receive the local standard of 
care plus a one-on-one meeting with the community health worker. All antenatal services at the 
Gugulethu MOU follow the local standard of care. Labor and delivery take place at either the 
MOU or nearby obstetric hospitals. Following delivery, all women make a routine postnatal visit 
to the Gugulethu MOU within 7 days postpartum; this is the only form of maternal postnatal care 
in this setting.  
 
HIV services are integrated into antenatal care at the Gugulethu MOU, but women are referred to 
their nearest ART clinic at their first postpartum clinic visit, following the local standard of care 
in this setting. Women attend ART visits 1-2 monthly in these services. Individual ART 
counselling is provided before ART initiation and again when clinicians identify adherence 
concerns. Infants are referred for routine infant care to local primary care clinics.  
 
As part of the enhanced standard of care condition, participants will also receive a one-on-one 
session during pregnancy with the community health worker. This session will include brief 
education about HIV, PMTCT, and ART, brief motivation interviewing for any adherence issues, 
as well as a basic assessment for any necessary referrals (i.e. psychological distress, substance 
use issues, food insecurity).  
 
 
Transition intervention/ CHW intervention 
This intervention draws on Transition Theory as an overarching framework (Figure below) and 
was developed using data provided by participants in Aim 1 as well as an extensive literature 
review.  
 
Theoretical underpinnings 
Transition Theory is a middle range nursing theory which posits that individuals in transition 
may be particularly susceptible to risks that impact their health (Chick & Meleis, 1986; Meleis, 
Sawyer, Massias, & Schumacher, 2000). Transition Theory allows us to characterize and 
describe the transitions that occur during this window period by clearly delineating the relevant 
personal and environmental characteristics that may facilitate or impede a successful transition, 
which could lead to sub-optimal ART adherence. With Transition Theory, we can conceptualize 
pregnancy and postpartum among women living with HIV as a time with multiple related health 
and developmental transitions. Women experience transition into motherhood (for a first child) 
or transitions in family roles (for a subsequent child). These women will also experience other 
transitions such as receiving the results of their infants’ HIV PCR test and shifting their own 
healthcare from antenatal clinics to HIV care clinics. These transitions can present significant 

Study Protocol Version 5, 5 November 2021 
challenges for ART adherence. There are also properties of transition experiences that contribute 
to how well an individual is able to adhere to ART, including awareness about an impending 
transition – such as being aware for the need to transfer care to an HIV care clinic – and 
engagement in the processes inherent in the transition – such as seeking out information about 
infant care. Transition experiences influence outcomes, such as adherence to ART, via transition 
conditions. Transition conditions are personal and environmental factors that can facilitate or 
inhibit progress towards a successful transition. These conditions are: (a) personal meanings, 
including appraisals of the anticipated event and the effect it will have on an individual’s life, (b) 
cultural beliefs and attitudes, (c) socioeconomic status, (d) preparation for the transition, such as 
actively preparing for the infants’ arrival, (e) community factors including family and partner 
support and (f) societal factors such as marginalization of people living with HIV.  
 
 
Transition Theory also specifies potential intervention techniques, termed nursing therapeutics, 
including providing knowledge, role modeling, social support, and creating a healthier 
environment at the familial and community levels. In the present intervention we use both the 
individual one-on-one sessions with the community health worker to enact these techniques.  
 
Qualitative Findings from Aim 2 
Preliminary analyses of the data from the longitudinal qualitative cohort (Aim 2) reveal a variety 
of facilitators and barriers to the transition from pregnancy to postpartum. Preliminary results 
from the pregnancy interview showed high adherence motivation. Anticipated barriers 
postpartum were employment/financial concerns, logistical concerns around childcare and 
breastfeeding, worries about vertical transmission and difficulties bonding. Additional concerns 
included forgetting their ART medications and confusion about where to receive HIV care 
postpartum. At 6 weeks postpartum, women reported experiencing many of the barriers that they 
had anticipated, particularly financial and logistical challenges. Adherence motivation remained 
high postpartum, but some women reported issues remembering to take medications while caring 
for infants. Most women seem to have successfully transitioned, at least in terms of the initial 
Nature of transitions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Transition conditions: Facilitators & 
Inhibitors 
 
 
 
 
 
 
 
 
 
 
 
 
 
Types 
Developmental 
Situational 
Health/Illness 
Organizational 
Patterns 
Single 
Multiple 
Sequential 
Simultaneous 
Related 
Unrelated 
Properties 
Awareness 
Engagement 
Change and difference 
Transition time span 
Critical points and events 
Personal 
Meanings 
Cultural Beliefs & attitudes 
Socioeconomic status 
Preparation & knowledge 
Community 
Society 
Patterns of response 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Process Indicators 
Feeling connected 
Interacting 
Location and being situated 
Developing confidence &  
      coping 
Outcome Indicators 
Mastery 
Fluid integrative identities 
Nursing Therapeutics 

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transition from pregnancy to early postpartum. Factors that appeared to facilitate this transition 
include supportive partners and families during pregnancy and postpartum and a sense of 
preparation during pregnancy. Factors that seemed to inhibit successful transition include 
unsupportive partners or a change in partner support from pregnancy to postpartum and lack of 
financial support. 
 
Given the wide ranging and multi-level factors that both inhibit and facilitate successful 
transitions from pregnancy to postpartum and subsequent adherence to ART, we felt that a 
typical manualized individual level intervention would not fully address the varying issues 
arising in these women’s lives. Our intervention design includes a one-on-one component with a 
community health worker who through motivational interviewing will help the participant 
identify her own individual barriers and her self-identified strategies for overcoming those 
barriers. Furthermore, the community health worker will be able to provide tangible support both 
in terms of referrals to other services (social services, governmental aid programs) as well as 
physically assisting with linkage to care and navigating clinical environments depending upon 
the needs of each individual participant.  
 
Furthermore, during the Time 4 interview we asked Aim 2 participants about their preferences 
for a number of different formats and intervention components. Of the 10 interviews that have 
been translated and transcribed thus far, all participants have spoken in favor of a group 
component of an intervention for pregnant and postpartum women living with HIV both for a 
sense of social support as well as to share experiences and provide advice to one another. 
Additionally, when asked to rank what topics they would like covered in an intervention for 
women like them (pregnant and postpartum women living with HIV) education and substance 
use came up amongst many participants, but there was little consensus on any additional topics. 
At least one participant mentioned each of the following: intimate partner violence, depression, 
strategies for taking ART, baby care (including caring for an HIV-exposed infant- nevirapine, 
testing, etc.), employment issues, HIV care transfers postpartum, social support, and family 
planning. The design of this study will allow for several topics common to many women to be 
discussed within the group setting but also allows for individual tailoring in the one-on-one 
session with the CHW, particularly for topics that may be sensitive to discuss in a group setting, 
such as substance use or IPV.  
 
Despite participants’ preference for a group component in light of the COVID-19 
pandemic, we will no longer including a group component to this study. 
 
Background Literature 
 
Our comprehensive review of the literature (Pellowski et al., 2019) supports a number of 
the findings from our qualitative work. Behavioral interventions for women living with HIV that 
contained a group component were more effective than interventions that did not include any 
group component. Furthermore, interventions that included some alteration of the healthcare 
system were also more effective than intervention that did not. Examples of types of alterations 
of the healthcare system included in this review were task-shifting from physician centered care 
to nurse/peer counselor care as well as the use of trained lay workers to deliver education, 
monitor barriers to ART adherence and to provide assistance in accessing healthcare, including 
accompanying women to the district hospital.  

Study Protocol Version 5, 5 November 2021 
 
Role of Community Health Workers 
 
This intervention draws on the growing cadre of community health workers within the 
South African health care system. A recent review (Schmitz et al., 2019) of HIV specific 
maternal and child health programmes delivered by lay health worker in Africa found a number 
of strategies utilized including: community engagement and sensitization, psychosocial support, 
linkage to care, encouraging women to bring their infants back for HIV testing and supporting 
default tracing. These interventions found improvements on community awareness of mother-to-
child transmission, condom use, clinic attendance/retention in care, and infant testing. However, 
very few of these interventions measured maternal ART adherence as an outcome. 
Current South African community health worker education does not include integrated 
training in maternal and child health and ART adherence focused on the transition from 
pregnancy to postpartum. This intervention would specifically provide additional training to 
community health workers in this area. Furthermore, this intervention will add to the literature by 
measuring ART adherence as a key outcome for a community health worker-based intervention.  
 
Proposed model 
 
After enrollment, participants will receive monthly one-on-one sessions. During the one-
on-one sessions, the CHW will utilize motivational interviewing to understand the biggest 
barriers to ART adherence in women’s lives and to assist the women in coming up with the best 
strategies or approaches. These sessions will also be used to assess if any referrals need to be 
made such as to social services or governmental aid programs. Importantly, there is no set 
agenda or topical areas that must be discussed within these sessions. The topics are entirely 
driven by the needs of the participant.  
 
Training for CHW 
We will hire a CHW who has experience working with both pregnant/postpartum women and 
persons living with HIV. Training specific to this interview will take place over the course for 2 
weeks. Week 1 will include training on motivational interviewing and Week 2 will focus on 
training in the specific topics to be covered in both the one-on-one meetings. Trainings will 
consist of mock intervention sessions to develop skills and provide a setting for role playing. 
These mock intervention sessions will be critiqued by the PI to ensure proficiency in the 
intervention content and consistency in delivery.  
 
Curriculum 
A manual will be provided to the CHW. For the one-on-one sessions, the manual will describe 
possible areas to investigate where women may be having difficulties and information about 
procedures for referrals and availability of resources in the local area.  
 
Educational materials will be adapted from the WHO and HHS/CDC Prevention of Mother-to-
Child Transmission of HIV (PMTCT) Generic Training Package.57 This training package was 
created as a comprehensive approach to the training of healthcare workers and provides 
guidelines for customized content to reflect local realities. 
 
 
Process measures 

Study Protocol Version 5, 5 November 2021 
The community health worker will complete logs for monitoring uptake and utilization of the 
intervention making note of session completion rates and dropouts. After individual sessions the 
CHW will also take extensive notes on topics focused on, common barriers experienced by 
women, and engagement within the sessions. 
 
We will also audio record all counseling sessions to assess fidelity to the intervention. All 
counseling sessions will be coded using validated measures that have been adapted for this study. 
58 59 
 
The following figure displays the differences in exposure between the Transition intervention 
and the enhanced standard of care as well as the assessments 
 
 
 
 
 
7. Study Procedures 
The purpose of the study measurement visits will be to evaluate the study objectives. These study 
measurement visits will be carried out separately from any routine care, including antenatal, 
postpartum, or HIV-related care.  
 
Following recruitment and informed consent, all participants will be assigned unique study 
identification numbers. Women will complete the enrolment study visit and will then be 
randomized to either the Transitions intervention or control (enhanced standard of care). 
 
Randomization 
Randomization will take place at the end of the enrolment study visit. Women will be randomly 
allocated to either the Transitions intervention or control using a 1:1 randomization scheme. 
Randomization numbers will be generated prior to the start of the study and will be placed in 
sequentially numbered opaque envelopes. Randomization envelopes will be stored in a locked 
cabinet in the study office at UCT and will be accessed by the project manager when a woman is 
fully consented and has completed the enrolment visit. Women will be informed of their random 
allocation at the end of the enrolment visit. Ideally, a one-on-one meeting with the CHW (first 
visit for those in the Transitions intervention, only visit for those in the enhanced standard of 
care) would occur the same day as enrolment to aid in retention. If this is not possible the CHW 
will contact the participant using tracing information detailed below to inform them of the date 
and time of the first or only one-on-one meeting.  
Month 1
Month 2
Month 3
Month 4
Month 5
Month 6
Month 7
Month 8
Postpartum 1 Postpartum 2 Postpartum 3 Postpartum 4 Postpartum 5 Postpartum 6
Assessments
Enrollment Appointment: Informed 
Consent, Baseline Survey Assessment, 
Locator Form
X
Follow-up Quantitative Survey
X
X
Follow-up DBS
X
Transition Intervention
One-on-one session with CHW
X
X
X
X
Group session (5-8 participants)
X
X
X
X
In-depth interviews
X
Enhanced Standard of Care
One-on-one session with CHW
X

Study Protocol Version 5, 5 November 2021 
 
Quantitative measures 
At each study measurement visit, a trained interviewer will administer questionnaire-based 
measures using paper and pencil. The trained interviewer will be blinded to participants’ 
allocation. All study measurement visits will be conducted at a space that is separate from 
routine care.  Most measures have been used previously by our group in this setting (see 
references in Table of measures, below), and have been translated into isiXhosa and back-
translated into English following standard procedures. An additional scale46 developed to 
measure the theoretical constructs of Transition Theory has been adapted for use with women 
living with HIV for this study and will be translated into isiXhosa and back-translated to English 
prior to use in the trial.  
 
Linkage of routinely collected clinical data 
Our team has extensive experience in utilizing data from routinely collected electronic medical 
records in this setting, including for ART and PMTCT outcome assessment. 60,61 Data will be 
requested from the Western Cape Provincial Data Centre, and we will use participants’ 
provincial folder number (requested as part of tracing information) to facilitate an accurate 
electronic data request. Permission to review electronic clinical records of participants will be 
included in informed consent documents. Following standard procedures, we will request 
approval from the Provincial Department of Health to access electronic medical records. 
Established procedures are in place to ensure patient confidentiality. The project manager will 
link these data to participants’ unique participant identifiers. 
 
For the primary outcomes obtained from routine medical records (engagement in care and HIV 
viral suppression), we will use the following definitions: 
• Engagement in care will be classified as any evidence of engagement in routine HIV 
services, including evidence of: HIV visit attendance; ART collection at a pharmacy; 
laboratory testing of HIV viral load or CD4 cell count 
• HIV viral suppression will be classified as a viral load <200 copies/mL  
 
For the primary outcome, we will use a window of up to 3 months around the 6-month 
postpartum study visit. In cases where there is evidence of multiple HIV viral load results in this 
window, we will use the result closest to the 6-month postpartum study visit for the primary 
outcome. For women who are lost to follow-up, we will use the median time of visits attended 
among those who are retained at study measurement visits to assess engagement in care and HIV 
viral suppression. As the primary outcome data will come from routine medical records, all 
women will have outcome data regardless of retention at study measurement visits. 
 
Routinely collected clinical data will be linked with the written permission of (a) the participant 
(via informed consent), (b) the research oversight body of the Provincial Government of the 
Western Cape including the Provincial Data Centre, and (c) the HREC. Established procedures 
are in place to ensure patient confidentiality.  
 
Aim 3 Qualitative Component 
In-depth interviews will be conducted with participants randomized to the intervention condition 
(n=up to 30) after the completion of follow-ups in order to assess participants’ experiences of the 

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intervention, perceived usefulness, and identify ways to refine the intervention for future 
evaluation. Participants will complete a separate informed consent form for the qualitative 
interview. Extra efforts will be made to capture participants who were not retained in the 
intervention to gain insight into elements of the intervention that may have contributed to 
disengagement from the intervention and to generate ideas for boosting retention in future 
evaluations. 
 
The goal of these interviews is to evaluate the participants’ views of the acceptability of the 
intervention and how useful they felt the intervention was with respect to medication adherence 
and retention in care. Content from these interviews will also allow us to better understand the 
quantitative outcomes of the intervention, regardless of the efficacy of the intervention. The in-
depth interviews may also inform selection of future mediator or moderator variables to test in a 
full-scale RCT. 
 
 
All study measures are detailed in the table below.

Study Protocol Version 5, 5 November 2021 
 
  
Measure 
Enrolment 
3 months 
postpartum  
6 months 
postpartum 
Quantitative component 
Sociodemographic characteristics 
Tool developed and used by our team previously 60 
X 
  
  
Pregnancy intentions 
London Measure of Unplanned Pregnancy and measures of family 
planning use and fertility intentions 63 
X 
X 
X 
Used by our team previously 64 
Maternal health 
Tool developed and used by our team previously 60 
X 
X 
X 
Includes measures of self-reported health issues and health service use 
Child questionnaire 
Tool developed and used by our team previously 60 
  
X 
X 
Includes measures of breastfeeding, health issues and health service 
use 
Non-disclosure 
Tool developed and used by our team previously 65 
X 
X 
X 
Partner questionnaire  
Tool developed and used by our team previously 
Includes measures of relationship status, partner HIV testing, and 
partner substance use 
X 
X 
X 
COVID-19 impacts of engagement in 
care 
Items are detailed below this table 
 
X 
X 
X 
Intimate partner violence 
WHO Violence Against Women Questionnaire 66 
X 
X 
X 
Used by our team previously 67 
Depressive symptoms 
Edinburgh Postnatal Depression Scale 68 
X 
X 
X 
Used by our team previously 67 69  
Substance use 
Alcohol Use Disorders Identification Test 70 
X 
X 
X 
Drug Use Disorders Identification Test 71 
Both used by our team previously 67 72 
Adherence self-efficacy 
Adherence Self-Efficacy 73 
X 
X 
X 
Used by our team previously 74 
Self-reported adherence 
Tool developed and used by our team previously 75 and the Visual 
Analog Scale 76 
X 
X 
X 
Includes measures of side effects and self-reported adherence  
Pregnancy and Postnatal Well-being in 
Transition Questionnaire 
Validated tool that we adapted for HIV 46 
X 
X 
X 
Includes measures of Transition Theory constructs  
Alcohol-ART toxicity beliefs 
Tool validated in Cape Town 77 
X 
X 
X 
Includes measures of beliefs about mixing alcohol and ART 
Routine medical data 
Maternal health service use 
Accessed from routine medical records 
X 
Infant health service use 
Accessed from routine medical records 
X 
HIV viral load results 
Accessed from routine medical records 
X 
Qualitative Component 
 
 

Study Protocol Version 5, 5 November 2021 
In-depth interviews (IDI) 
IDI guide, conducted with all participants randomized to the 
intervention 
After all study procedures and assessments 
have been completed 
 
 
COVID-19 impacts of engagement in care 
 
1. Because of the COVID-19 pandemic, did you miss an appointment at your clinic for HIV treatment or care in the last 3 months? (Yes/No) 
 
2. How do you access/have you accessed your ART tablets/your HIV medication during lockdown? (1=I buy them from someone on the street, 2=I get them from the 
clinic/hospital as I used to, 3= I borrow pills from a friend/household member/neighbor) 
 
3. Has accessing your ART tablets/your HIV medications during lockdown been more challenging than before COVID-19? (Yes/No) 
 
4. Are you worried that you will run out of ART tablets/your HIV medications because of challenges associated with COVID-19 (i.e. lockdown, don’t want to go to the 
clinic during COVID-19) (Yes/No)

Study Protocol Version 5, 5 November 2021 
Identification of health needs during study procedures 
At every study measurement visit, any woman found to have an unmet health need (whether 
medical, obstetric, postpartum family planning, or related to mental health or substance use) will 
be referred to the relevant service within the Gugulethu Community Health Centre or higher 
levels of care, as appropriate. In particular: 
• Any woman found to have defaulted ART will be re-referred to her most recently attended 
ART service. 
• Any woman found to be non-adherent to ART at any study measurement visit will receive 
intensive counselling on ART use, and will be referred to the relevant ART service for 
follow-up. 
• Any woman found to be experiencing domestic or partner violence in any form will be 
referred to the main local NGO supporting victims of domestic violence and the South 
African Police Service with follow-up to ensure adequate attention. 
• If any infant health care needs are identified, the infant will be referred to the appropriate 
paediatric health services via the Gugulethu Community Health Centre. 
 
All referral processes are documented in an SOP for Referrals. 
 
Staff training 
Prior to initiation of the study, all staff that will have contact with participants will take part in a 
multi-day study-specific training. The curriculum of the training will include: rationale, purpose 
and scientific objectives of the study; study design and methodology; conduct of study 
assessments, tracking of participants, completion of study forms, and data collection; staff 
responsibilities; recruiting participants; procedures for enrolling participants into the study; 
randomization; universal precautions; communication skills; safety in the field; ethical guidelines 
for research including participants’ rights; procedures for obtaining informed consent; and 
confidentiality requirements. Study staff will receive hands-on training, including mock 
interviews. Study staff will be given opportunities to practice both the English and isiXhosa 
versions of all assessments. 
 
In addition, all staff members will complete training related to Good Clinical Practice and 
Human Subjects Protection. All staff who through the course of their work will have knowledge 
of, or access to, personal information about participants will be required to complete training on 
confidentiality and will sign a confidentiality agreement before the start of data collection.  
 
All staff will be trained on the SOP for Referrals as well as management of crisis situations, 
including reports of abuse and domestic violence, that may be disclosed during study 
participation.  
 
For all study staff, there will be additional training days scheduled during the study for refresher 
training. During these refresher trainings, study staff will review study procedures.  
 
Contamination and masking 
Contamination between groups is a concern and blinding participants to this type of psychosocial 
intervention is not possible. Contamination would mean that women in the enhanced standard of 
care control group may be aware of the Transitions interview, or vice-versa, and change their 

Study Protocol Version 5, 5 November 2021 
behaviours related to their own ART use or retention in care. Some of the primary outcomes 
(retention in ART care and HIV viral suppression) are objective, thus reducing detection bias. 
Self-reported ART adherence is subjective and thus we acknowledge that this measure may be 
biased, however, other behavioral interventions (particularly pilot interventions) have utilized 
self-reported adherence to understand the behavioral antecedent to viral suppression. Insofar as 
possible, we will mask study personnel involved in the study measurement visits; in particular, 
the interviewer administering study measures will be blinded to participants’ allocation All study 
measurement visits will be conducted at a space that is separate from routine care.  
 
8. Participant retention 
 
Study follow-up & retention 
Participants will be followed for 8 months (6 months postpartum). Participants in both arms will 
attend study measurement visits at enrollment, 3 months postpartum, and 6 months postpartum. 
These visits will be scheduled and conducted separately from any routine care. Retention 
activities will focus on study measurement visits. At enrolment, the interviewer will collect 
detailed tracing information, including participants’ full names, addresses, all telephone details; 
the names, addresses and contact details for two individuals who the participant lives with, and 
one alternate individual who the participant does not live with. Participants will also be asked to 
provide their provincial folder number used on routine medical records, for linkage with 
electronic medical records. At the 3-month postpartum follow-up visit, participants will be asked 
to update their contact information if needed. Throughout the study, tracing information will be 
kept in locked filing cabinets, separate from other participant information. 
 
Following established procedures, we will maintain a simple electronic visit schedule database in 
Microsoft Access for the study team. Based on participant visits logged in the database, a 
schedule of expected participant study measurement visits is generated that can be used to 
provide reminders to participants before visits, or identify missed study visits that require 
tracing. The database will contain only unique participant identification numbers, and reference 
to the tracing information (kept in a locked study cabinet in the project office) will be made by 
the study coordinator. Following our previous approach, retention activities will include 
reminder phone calls to participants prior to study measurement visits. For women who do not 
attend scheduled study visits, we will attempt to contact the participant via telephone. If 
unsuccessful, we will contact one of the pre-designated alternate individuals. If telephone 
attempts fail, fieldworkers will visit the home address of the participant to trace the participant in 
person. Note that all participant tracing efforts by fieldworkers (via phone or home visit) do not 
mention the reason for the contact, or anything regarding HIV/AIDS or ART, under any 
circumstances (even if the participant themselves is traced). All contacts simply request that the 
participant come to the clinic the next working day for a health-related issue. 
 
Participants will only be traced by study staff if they are found to have missed a study 
measurement visit. Tracing of participants who default routine care will be managed by public 
sector health services. However, if a participant is found to have defaulted ART at a study visit, 
study staff will urgently refer the participant to the service which they last attended. 
 
Participant withdrawal 

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All participants may refuse or voluntarily withdraw from the study for any reason and at any 
time. As part of the informed consent process, staff will state specifically that participation in the 
study is voluntary and that a participant may refuse participation or withdraw from study 
participation at any time. Participants will be told that withdrawal from the study will have no 
effect on their access to health facilities providing any services. All study staff will be trained to 
ensure that participants have a firm understanding of this concept at the time of the informed 
consent process, and the informed consent forms will include a statement to this effect.  
 
9. Analytic considerations 
 
Sample size considerations: pilot study 
The overall goal of this pilot study is to determine feasibility and potential efficacy to support 
future larger, fully-powered tests of the intervention’s efficacy. We fully acknowledge the 
exploratory nature of this pilot. With a sample size of 60, between two groups, 2 follow-up 
measurements, controlling for self-reported baseline adherence, p=0.05, we will have 29% power 
of finding a small effect (Cohen’s d=0.30), 65% power of finding a moderate effect (d=0.50), 
and 98% power of finding a large effect (d=0.80). This study will be underpowered to find 
significant small and moderate effects however, we will be able to calculate an effect size and 
the direction of its impact to support a larger scale test of the intervention.  
 
The facility that is participating in this study, the Gugulethu MOU, sees approximately 4800 
pregnant and postpartum women annually, with an antenatal HIV prevalence of 28%. Thus, we 
do not anticipate difficulty recruiting this sample within the allotted timeframe. 
 
Sample size considerations: In-depth Interviews (Aim 3) 
We propose to interview all of the women randomized to the intervention condition (n=up to 30). 
Based on our follow-up rates for the longitudinal qualitative cohort (HREC 344/2017), we 
anticipate at least an 80% retention rate at 6 months postpartum, which equates to an anticipated 
24 participants completing in-depth interviews. Based on our previous experiences working with 
this population, we feel that 24 participants will be enough to reach saturation on key themes 
related to acceptability of the intervention.  
 
Data management 
The study includes data from four sources: (1) interviewer-administered questionnaires; (2) 
routine electronic medical records; (3) dried blood spots; and (4) IDI with participants 
randomized to the intervention condition. The collection of data will be conducted by (1) a 
fieldworker; (2) the project manager; (3) lab-based researcher; and (4) a qualitative interviewer, 
respectively. Procedures for data collection (regardless of source) will be outlined in SOPs. We 
have a bank of well-developed SOPs that our group has developed for previous studies. All data 
management will take place at UCT following procedures established by our group for multiple 
previous studies. 
 
Quantitative data will be captured into a custom designed Microsoft Access database. The 
database will be password-protected following standard password safety procedures, and will be 
maintained in a firewall-protected UCT server with daily backups. The database will be designed 
and maintained by the project manager. The study coordinator will direct queries and data 

Study Protocol Version 5, 5 November 2021 
quality assurance (QA)/quality control (QC) activities, and supervise data entry, with oversight 
from the project manager. Data QA will be in the form of robust database structure and platform, 
and ‘front-end’ data checks including real-time database queries. QC will be through data 
checking scripts to identify out-of-range values, logic violations and missing observations. 
Queries will be resolved based on reference to the completed questionnaires in question; all data 
queries and responses will be logged, and edits will be implemented through separate program 
files. 
 
Qualitative data from IDI will be transcribed verbatim and translated into English. Translations 
will use unique participant identifiers, not participant names. All electronic files will be 
encrypted and password protected. 
 
Data analysis 
Quantitative data will be exported to Stata Version 14.0 (Stata Corporation, College Station, 
Texas) for analysis. We will analyze all primary and secondary outcomes preliminarily using 
simple means and standard deviations and point-biserial correlations to estimate effect sizes 
where appropriate. For outcomes that are indicative of a possible difference by condition, we will 
utilize more advanced analytic techniques, i.e generalized estimating equations (GEE), as 
follows: 
 
To compare the impact of intervention condition on self-reported ART adherence, engagement in 
ART services and HIV viral suppression, we will utilize a series of generalized estimating 
equations (GEE) using Poisson distributions where appropriate. Outcome analyses will control 
for baseline self-reported adherence and any baseline differences on demographic variables. 
Intervention condition, time of assessment, and condition*time interaction will be entered as 
model effects. We will use GEEs to predict key psychosocial outcomes (adherence self-efficacy) 
by intervention condition. If there is evidence of an intervention effect we will explore factors 
that may modify intervention effects, we will compare intervention effects within subgroups of 
women based on key demographic clinical and psychosocial characteristics.  
 
To determine feasibility, we will calculate rates for session attendance, as well as retention, 
withdraws, and assessment completion.  
 
To determine acceptability of the intervention, we will use NVivo (QSR International Pty Ltd) to 
conduct our qualitative analysis. Data analysis will be iterative including open coding, axial 
coding, marginal remarks, constant comparison, and memo-writing. Analyses will be brought to 
the larger research team for critique and interrogation which will result in further queries and 
data checks to ensure appropriate interpretation of the qualitative data.  
 
10. Ethical considerations 
 
Ethical review 
The study protocol, informed consent forms and data collection tools will be reviewed and 
approved by the Faculty of Health Sciences Human Research Ethics Committee (HREC) at 
UCT. Subsequent to the initial review and approval, the HREC will review progress of the study 
at least annually.  

Study Protocol Version 5, 5 November 2021 
 
Preliminary research in this setting 
As described above, our team has collaborated with district and provincial health services 
in the community of Gugulethu for >10 years, including the Gugulethu MOU at which this 
research will be based. During this time, we have formed strong local relationships including 
with a community advisory board. In Phase 1 of this study we found a variety of facilitators and 
barriers to the transition from pregnancy to postpartum for women living with HIV. Barriers 
included employment/financial concerns, logistical concerns around childcare and breastfeeding, 
worries about vertical transmission and difficulties bonding, forgetting ART medications, 
confusion about postpartum HIV care. Factors that appeared to facilitate this transition include 
supportive partners and families during pregnancy and postpartum and a sense of preparation 
during pregnancy. Given the wide-ranging and multi-level factors that both inhibit and facilitate 
successful transitions from pregnancy to postpartum and subsequent adherence to ART, we feel 
that a component of the intervention that includes a one-on-one component with a community 
health worker who through motivational interviewing will help the participant identify her own 
individual barriers and her self-identified strategies for overcoming those barriers in needed. 
Furthermore, the community health worker will be able to provide tangible support both in terms 
of referrals to other services (social services, governmental aid programs) as well as physically 
assisting with linkage to care and navigating clinical environments depending upon the needs of 
each individual participant. Additionally, when asked about formats of potential interventions, 
women spoke in favour of a group component of the intervention with other women living with 
HIV to provide both a sense of social support as well as to share experiences and provide advice 
to one another. 
 
Informed consent 
 
After eligibility is confirmed, all participants will complete informed consent prior to 
enrollment. All informed consent procedures will follow protocol approved by the University of 
Cape Town HREC and the Brown University IRB. The consent process will be conducted with a 
staff member fluent in both English and isiXhosa who has been trained in research ethics and the 
specific consenting protocol for this study. The consent process will be conducted in the 
language of the participant’s choosing. The informed consent process will highlight the specific 
risks associated with the study, including discomfort from in-depth discussions of HIV infection 
and mother-to-child transmission and risk of breaches in confidentiality. The participants will be 
informed about the precautions put in place to reduce the risk of breaches in confidentiality 
including: the use of unique PIDs on all research data and that her name will not be used in 
relation to her data and that all data will be kept safe in a locked filing cabinet or password-
protected computer in a locked office. It will also be noted that research study staff are not 
doctors, nurses, or any other type of trained medical personnel and, thus, cannot diagnose, treat, 
or change medications. The participant will be allowed to ask questions and the staff member 
will probe for complete understanding during key points of the consent form. The participant 
will be allowed to take as much time as she needs to make a decision and she will be reminded 
that her participation is completely voluntary, will not impact her medical care in any way, and if 
she does decide that she would like to participate she may change her mind at any time without 
penalty. All participants will be provided the contact numbers of the Principal Investigator Dr. 
Pellowski and University of Cape Town HREC chairs to answer questions that the participant 
might have about the study or one’s rights as a human subject. Completed, signed consent forms 

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will be kept in a locked filing cabinet in our secured research office. The participant will be 
allowed to take a copy of the consent form home to have as a reference, but will also be 
reminded that someone finding the form may result in a breach of confidentiality.  
 
Potential Risks to Participants 
 
 There are several potential risks in participant in this study. Discussing sensitive topics 
such as pregnancy and HIV infection may cause psychological distress. Study staff will be 
trained in counseling and will continually monitor the participant for signs of distress. If signs of 
distress are apparent, the interviewer will offer to pause the session until the participant feels 
well enough to carry on. The participant will also be reminded that they may stop the session or 
un-enroll from the study at any time without penalty. If needed, referrals will be made to social 
services. We will also emphasize that participants may pause the interview at any time or may 
un-enroll from the study at any time without penalty. 
 
To reduce risks of accidental disclosure of HIV status, all study activities (i.e. eligibility 
screening, interviews, assessments) will take place in a private room. During recruitment, 
eligibility questions will be embedded in a larger set of foil questions so that ineligible 
individuals will not be able to decipher why they were not eligible for the study. All data 
collected will not contain the name of the participant and will instead be identified by their 
unique PID number. All data will be stored in locked file cabinets and encrypted computers. 
Although this study is centered around HIV medications and adherence behaviors, study staff 
will not be prescribing medications and they will not change dosing of medications in any way. 
Optimal adherence to medications will always be encouraged. If the participant discloses issues 
with side effects or HIV symptoms, study staff will refer the participant back to their HIV care 
doctor. 
 
Additionally, during the consent process, risks of breaches in confidentiality will be 
highlighted including legal norms that would require a break in confidentiality. All ethical issues 
requiring urgent attention will be reported to the PI immediately. All unanticipated ethical 
situations that do not need immediate attention will be discussing the weekly team meeting. 
 
Protections Against small risk of loss of privacy or confidentiality of data. All interview 
cohort participants will be assigned a unique participant ID (PID). These PIDs will be used to 
identify participants on all research materials, surveys, transcripts, tracking forms and all 
databases. Separate from research records, an identifier key will be created to link the PID to 
participant names and contact information in order to facilitate follow-up with participants. This 
identifier key will only contain contact information and will NOT include any research data and 
it will be stored separately from any research data or research-related forms (e.g. informed 
consent forms). All research data, research-related forms, and the identifier key will be secured 
in a locked cabinet or a password protected and encrypted laptop in a locked room. Data will also 
be backed up daily by a designated staff member and transferred a firewall protected secure UCT 
server. Only the PI, mentors, and essential project staff will have access to any project data. 
Participants’ names or other individually identifying information will never appear in any report 
resulting from this project.  
 
Electronic data, including digital voice recordings, will have several protections: (1) all 
data will be stored on password-protected computers; (2) all files on project computers will be 
protected through encryption; (3) all study staff will be trained in participant data confidentiality 
protocols and will be consistently monitored by the PI on data safety and confidentiality; (4) 
audio files generated from the qualitative interviews will be designated with a code to ensure 

Study Protocol Version 5, 5 November 2021 
name confidentiality and delivered securely to the transcribers who will establish a memorandum 
of understanding (MOU) to ensure their compliance with confidentiality procedures (e.g. 
maintaining files on an encrypted computer in a locked office when not being actively 
transcribed, deleting all identifiers from the transcripts and using the unique PID). 
For qualitative data collected in the in-depth interviews (i.e. transcripts), all identifiers 
within the text will be replaced with the PID. To ensure data quality of qualitative data, DVR 
recordings of the interviews will reviewed within 48 hours of the interview by the PI or study 
manager. Additionally, after the data is transcribed, transcripts will be checked for accuracy 
against the voice data files. Voice files will be destroyed after transcripts are thoroughly checked 
for accuracy.  
Training in Confidentiality. The PIs will provide the study team with training in all 
ethical procedures including informed consent, 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 for requiring mandatory training in human subjects 
protection before conducting any study activities.  
 
Alternative Treatments. The purpose of this study is to expand upon the standard of care 
for pregnant and postpartum women living with HIV. Participation or non-participation will not 
impact health care or clinic services in any way.  
 
Addressing Risks to Participants 
Planned Procedures for Protecting Against or Minimizing Potential Risks. We will 
minimize discomfort associated with discussing potentially distressing topics (e.g. pregnancy, 
HIV infection, mother-to-child transmission of HIV) by notifying eligible individuals about the 
types of topics that will be discussed prior to signing the consent form. Participants will also be 
reminded that they can discontinue participation in the study at any time. Additionally, staff 
members will be trained procedures to minimize distress within the interview and will be trained 
in how to identify discomfort in the participant. If a participant appears to be becoming too 
distressed, the staff member will offer to pause the assessment. These procedures will also be 
used in the counseling sessions to minimize the distress of those enrolled in the behavioral trial.  
We will minimize breaches in confidentiality by using unique PIDs on all data resulting 
from this project and will not use identifying information (i.e. participants’ names) in databases 
or forms that contain data. We will also let participants know that they may use a pseudonym in 
the interview to keep their identity unknown on the recording. Regardless, all names and other 
identifying information will be expunged from the transcripts of the interviews. All data 
generated from this project will be kept in a locked filing cabinet or a password-protected 
computer in a locked office. To minimize the risks of accidental HIV status disclosure, all study 
procedures will occur in a private room.  
Additional Considerations for Pregnant Women. As a research project, we will have no 
part in making medical decisions regarding the health of the pregnant woman or her fetus, 
including but not limited to determination of the viability of the fetus or need for inducing labor. 
Additionally, we will have not part in making any diagnoses related to pregnancy or other 
conditions such as preeclampsia or cytomegalovirus. Although we will be conducting a study 
about medication adherence during pregnancy and postpartum, we will not change medication 

Study Protocol Version 5, 5 November 2021 
prescriptions. If a participant complains about their current prescriptions or states that they would 
like to stop their prescription, they will be told by the study staff to continue taking their 
medications as prescribed and instructed to bring these concerns to their antenatal care physician 
for the protection of themselves and their fetus. Because this study will be conducted in a health 
care setting, study staff will remind study participants that we are not related to their pregnancy 
or HIV care in any capacity, when necessary. 
Medical or Professional Intervention in Event of Adverse Event. Although we do not 
anticipate any events in need of medical intervention associated with our study activities, due to 
our special population of pregnant and postpartum women living with HIV we do recognize the 
need for some safeguards. All participants will be under the care of a physician as our study site 
is based in a SA-DOH clinic (Gugulethu MOU) and prescription of ART is an eligibility criteria 
of our study. We will emphasize that research staff members are not medically trained and 
medical concerns should be discussed with the participant’s doctor. If a medical event does arise 
during our research activities (e.g. labor pains), with the participant’s permission, we will consult 
with the medical staff in the clinic and transfer her to their care, if necessary. All adverse events 
will be immediately reported to the PI. Serious adverse events will be reported to the University 
of Cape Town HREC and Brown IRB by phone and followed by a written report of notification 
within 24 hours of the event. The PI will also notify the NIH Program officer and will report 
adverse event in writing to the NIH funding institute. The Adverse event will also be reviewed 
with co-Primary Mentors Drs. Lurie and Operario with input from the entire mentorship team to 
determine subsequent actions and if revisions to current protocols are needed.  
 
Benefits 
 
Direct Benefit 
 
There may be little or no direct benefit to participants from this study. For those enrolled 
in the intervention we hope that receiving support from a community health worker and support 
from other women living with HIV may lead to improvements in ART adherence and 
engagement in care, however, this benefit is unknown. All participants will be given information 
on HIV infection, pregnancy, and preventing mother-to-child transmission of HIV as well as 
references to local health and social services. Referrals to more intensive resources will be made 
as needed. The risks associated with this research are reasonable in relation to the anticipated 
benefits of advancing empirical knowledge about ART adherence during the transition from 
pregnancy to postpartum and behavioral intervention approaches to improve ART adherence for 
this high priority population and setting.  
 
Indirect Benefit 
 
This study will fill key gaps in scientific knowledge about behavioral ART adherence 
interventions for pregnant and postpartum women living with HIV. In the literature there are few 
behavioural intervention that have been effective in increasing ART adherence and retention in 
care among postpartum women. Given this lack of effective interventions, there are significant 
indirect benefits to filling key gaps in scientific knowledge and, if the intervention is successful, 
this study has the potential to lead to the roll out of this intervention for pregnant and postpartum 
women living with HIV, which could benefit the population as a whole. Thus, the risks of the 
proposed study are reasonable and balanced by the potential contribution of providing important 
information that can advance our knowledge of ART adherence among pregnant and postpartum 

Study Protocol Version 5, 5 November 2021 
women and whether or not the proposed behavioral intervention will aid in increasing ART 
adherence during this critical time for HIV treatment and prevention.  
 
Compensation 
At each study measurement visit, participants will be given R20 in cash for transport costs and 
R80 in the form of grocery vouchers for their time and effort. At the final study measurement 
visit, women will be given a small gift up to the value of R100 for their child. Refreshments will 
be provided at all study measurement visits and at the one-on-one sessions. No reimbursement 
will be given for attendance at the one-on-on sessions for the intervention arm but participants 
will be reimbursed for their transportation costs for each session (R20). 
 
Internal monitoring 
The study team involved in day-to-day activities will meet weekly to discuss progress and 
operational aspects, led by the principal investigator; and the project manager will report back to 
the principal investigator and core team of study investigators on a weekly basis. Quarterly 
teleconferences will be held with the scientific advisory board for their specific inputs into the 
study. 
 
Use of information and publications 
Publication or presentation of the results of this study will be agreed upon in collaboration with 
the study investigators. Note that the funding agency has no input in the decision to present or 
publish study data or the nature of the data that are presented or published. 
 
 
 
 
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