UNCPM 22323 - Supporting Oral Pre-exposure Prophylaxis Decision Making Among Pregnant Women in Lilongwe, Malawi: a Pilot Study
Phase: NA
Conditions: HIV Prevention
Sponsor: University of North Carolina, Chapel Hill

Study Protocol 
Study Title: Supporting Oral Pre-exposure Prophylaxis Decision 
Making Among Pregnant Women in Lilongwe, Malawi: A Pilot Study 
 
 
 
NCT number NCT06394323 
Document Date 02/23/2024 
 

 
 
 
Proposal Title:  
Supporting oral pre-exposure prophylaxis decision making among 
pregnant women in Lilongwe, Malawi: a pilot study 
 
 
PI: 
 
 
Lauren Hill, PhD MSPH (UNC-Chapel Hill, USA) 
 
 
Co-Investigators 
Friday Saidi, MBBS, MMed (UNC Project-Malawi) 
Benjamin Chi, MD MSc (UNC-Chapel Hill, USA) 
Carol Golin, MD (UNC-Chapel Hill, USA) 
Suzanne Maman, PhD (UNC-Chapel Hill, USA) 
Lisa Pearce, PhD (UNC-Chapel Hill, USA) 
 
 
 
Country Contact:  
Friday Saidi, UNC Project-Malawi 
Email:   
 
 fsaidi@unclilongwe.org 
Study contact phone number: +265 1 755 056 
 
Duration:  
 
2 Years 
 
 

 
 
TABLE OF CONTENTS 
TABLE OF ABBREVIATIONS ...................................................................................................................... 1 
1. ABSTRACT ............................................................................................................................................ 1 
2. BACKGROUND, PROBLEM STATEMENT AND JUSTIFICATION ............................................................. 1 
3. LITERATURE REVIEW ........................................................................................................................... 2 
3.1 HIV risk during pregnancy and breastfeeding ............................................................................... 2 
3.2 PrEP in pregnancy and breastfeeding ........................................................................................... 2 
3.3 The importance of shared decision-making for appropriate PrEP use ......................................... 3 
3.4 Our formative work ....................................................................................................................... 4 
4. STUDY OBJECTIVES AND OUTCOMES.................................................................................................. 5 
4.1 Objective and Aims ....................................................................................................................... 5 
4.2 Study Outcomes ............................................................................................................................ 5 
4.2.1 Primary outcomes .................................................................................................................. 5 
4.2.2 Secondary outcome ............................................................................................................... 5 
4.2.3 Exploratory outcomes ............................................................................................................ 5 
5. METHODOLOGY .................................................................................................................................. 6 
5.1 Study design .................................................................................................................................. 6 
5.3 Standard of care (control arm) ..................................................................................................... 7 
5.4 Eligibility criteria ............................................................................................................................ 8 
5.5 Place of study ................................................................................................................................ 8 
5.6 Target population.......................................................................................................................... 8 
5.7 Recruitment and enrollment procedures ..................................................................................... 9 
5.7.1 Recruitment procedures ........................................................................................................ 9 
5.7.2 Enrolment procedures ........................................................................................................... 9 
5.8 Study follow-up ............................................................................................................................. 9 
5.9 Assessment of study outcomes .................................................................................................. 10 
5.9.1 Assessment of primary outcomes ........................................................................................ 10 
5.9.2 Assessment of secondary outcomes .................................................................................... 10 
5.9.3 Assessment of exploratory outcomes .................................................................................. 11 
5.10 Retention .................................................................................................................................. 12 
5.11 Safety Monitoring ..................................................................................................................... 12 
5.12 Biological specimen collection and testing ............................................................................... 12 
5.13 Quality control and quality assurance procedures ................................................................... 13 
5.14 Data Management and Storage ................................................................................................ 13 
5.15 Sample size ................................................................................................................................ 13 
5.15.1 Precision calculations for continuous outcomes ............................................................... 13 

 
 
5.15.2 Precision calculations for binary outcomes ....................................................................... 14 
5.16 Data Analysis ............................................................................................................................. 15 
5.16.1 Analysis of primary endpoints ........................................................................................... 15 
5.16.2 Analysis of secondary endpoints ....................................................................................... 15 
5.16.3 Quantitative analysis of exploratory endpoints ................................................................. 16 
5.16.4 Qualitative analysis of IDIs (exploratory outcomes) .......................................................... 17 
6. ETHICAL CONSIDERATIONS ............................................................................................................... 18 
6.1 Ethical approval ........................................................................................................................... 18 
6.2 Informed consent ........................................................................................................................ 18 
6.3 Data storage ................................................................................................................................ 18 
6.4 Confidentiality ............................................................................................................................. 18 
6.5 Potential risks to participants ..................................................................................................... 18 
6.6 Protection Against Risks .............................................................................................................. 19 
6.7 Potential Benefits of Proposed Research to Human Subjects and Others ................................. 20 
6.8 Inclusion of children, sub-populations, and vulnerable populations ......................................... 20 
6.9 Reimbursement/compensation .................................................................................................. 20 
6.10 Dissemination of findings .......................................................................................................... 20 
7. WORK PLAN ....................................................................................................................................... 20 
REFERENCES .......................................................................................................................................... 21 
 
 

1 
 
TABLE OF ABBREVIATIONS 
 
Abbreviation 
Definition 
ANC 
Antenatal care 
DBS 
Dried blood spot 
HIV 
Human immunodeficiency virus 
IDI 
In-depth interview 
NHSRC 
National Health Science Research Committee 
PrEP 
Pre-exposure prophylaxis 
SDM 
Shared decision making 
SOC 
Standard of care 
SOP 
Standard Operating Procedure 
STI 
Sexually transmitted infection 
TDF-FTC 
Tenofovir disoproxil fumarate and emtricitabine 
TFVdp 
Tenofovir diphosphate 
WHO 
World Health Organization 
 
1. ABSTRACT  
 
An estimated 45% of mother-to-child HIV transmission in Malawi is attributable to acute 
maternal HIV infection during pregnancy and breastfeeding, indicating a critical need to 
address HIV risk during this period. Pre-exposure prophylaxis (PrEP) is a promising tool for 
the prevention of HIV acquisition during pregnancy and the postpartum period and is a 
recommended component of a comprehensive package of prevention of mother-to-child HIV 
transmission services. Yet, few strategies exist to promote person-centered shared decision-
making about PrEP use during pregnancy and breastfeeding despite the complexity of this 
decision and the importance of shared decision-making for medication adherence. To be able 
enable pregnant women to make shared decisions about PrEP use with their health care 
providers, person-centered counseling approaches are needed to help women determine if 
PrEP or an alternative HIV prevention method is most appropriate based on their values. 
Therefore, we propose a pilot study to evaluate a novel shared decision-making counseling 
approach for tailored to the needs of pregnant and breastfeeding women in Malawi. This 
intervention was developed on the basis of a previous formative study conducted in Lilongwe 
(NHSRC Protocol 20/01/2465), which consisted of a mixed methods study to understand 
women’s values and decision-making needs regarding PrEP uptake, and to refine the 
intervention through and participant feedback. In this pilot study we aim to evaluate the 
feasibility, acceptability, and appropriateness of the shared decision-making (SDM) 
intervention to support oral PrEP decision making among pregnant and breastfeeding women 
in Lilongwe. This pilot will inform a future efficacy trial to determine the effect of the SDM 
intervention on decisional satisfaction and adherence to PrEP. Thus, this study will ultimately 
contribute meaningfully to the successful delivery of PrEP in the context of antenatal care in 
Malawi to ensure that decision-making regarding PrEP use by pregnant and breastfeeding 
women is person-centered to encourage appropriate and adherent use. 
2. BACKGROUND, PROBLEM STATEMENT AND JUSTIFICATION 
 
Pre-exposure prophylaxis (PrEP) is a promising strategy to prevent HIV acquisition 
among pregnant and breastfeeding women; however, realizing this promise will require 
effective strategies to promote adherence. Prevention of HIV acquisition during pregnancy 
and the postpartum period is critical to preventing both horizontal and vertical transmission of 
HIV in sub-Saharan Africa. Women are at elevated HIV risk during this period1, and one-third 
to one-half of mother-to-child transmission of HIV is attributable to acute maternal infection2–
4. Oral PrEP with daily tenofovir-emtricitabine is highly effective in preventing HIV infection 

2 
 
when taken with high adherence5–7. WHO guidelines recommend offering oral PrEP to 
individuals at-risk for acquiring HIV, including pregnant and breastfeeding women8. To realize 
the potential of PrEP, strategies to promote adherence are urgently needed because of the 
sensitivity of PrEP’s effectiveness to user error: for protective drug levels during vaginal sex, 
a minimum of 85% adherence is required10. Women in PrEP trials have generally fallen short 
of this effective level, in some studies achieving a mean of only 24% adherence11–13.  
 
Ensuring user fit and motivation prior to PrEP initiation may be an important 
complement to conventional adherence support strategies. Poor adherence among 
women in the aforementioned PrEP trials was observed despite the inclusion of adherence 
counselling and support for participants14. Documented barriers to PrEP adherence among 
women have included poor fit with user lifestyles15–17, women’s difficulty using PrEP in the 
context of romantic relationships 15,18–20, and low motivation for PrEP use16. These findings 
highlight the fact that ensuring the appropriateness of PrEP for each potential user from the 
outset is essential. We need to help women decide which HIV prevention method best fits their 
needs and preferences, as this will be the method they will be most likely to use effectively 21. 
Strategies to support women’s decision-making about PrEP initiation are needed to ensure 
that it is informed and person-centred. 
 
Actively engaging women considering PrEP in shared decision-making may ensure 
user fit and promote adherence. Shared decision-making (SDM) is strongly recommended 
for preference-sensitive medical decisions for which multiple options are available with no 
distinctly superior option22. The SDM model provides a patient-centred approach to encourage 
an informed and active patient role in these decisions. By providing patients with knowledge 
about the options available to them, and helping them to clarify their needs and values relevant 
to the decision, SDM may improve adherence by ensuring user fit and promoting motivation 
and self-efficacy to adhere to the choice taken23–27. While SDM has been shown to promote 
adherence to other medications28, this promising approach needs to be evaluated for PrEP 
use. For novel tools like PrEP, decision support aids are particularly critical as clinicians often 
lack the skills or training to guide their patients through SDM. 
 
Problem statement: Pre-exposure prophylaxis (PrEP) represents an opportunity to 
dramatically reduce the elevated risk of HIV in pregnant and breastfeeding women in sub-
Saharan Africa, but shared decision making (SDM) about its use is essential to identify 
appropriate users and promote adherent use. No evidence-based approaches for PrEP 
shared decision making in pregnancy exist. Thus, we aim to fill this gap in the proposed pilot 
study to determine the feasibility, acceptability, and appropriateness of a novel SDM 
intervention and associated study procedures to inform a future efficacy trial. 
3. LITERATURE REVIEW 
 
3.1 HIV risk during pregnancy and breastfeeding 
Prevention of HIV infection during pregnancy and breastfeeding is a major HIV prevention 
priority because of the increased biological and behavioural risk factors for infection during 
this period29–32 and the danger that acute maternal HIV infection poses for transmission to the 
infant2,33–37. Indeed, in Malawi an estimated 45% of mother-to-child HIV transmission in Malawi 
is attributable to acute maternal HIV infection during pregnancy and breastfeeding, indicating 
a critical need to address HIV risk during this period38.  
3.2 PrEP in pregnancy and breastfeeding 
Following evidence that oral PrEP with daily tenofovir-emtricitabine effectively prevents HIV 
transmission5–7, and is safe during pregnancy and breastfeeding39, WHO and Malawi national 
guidelines recommend offering PrEP in standard PMTCT practice10. To date, however, little is 
known about how to identify appropriate PrEP users in antenatal settings and determine the 
appropriate PrEP method for each patient. The PrEP choice is highly preference sensitive22as 

3 
 
a given product may not be the right fit for every woman. Though many pregnant women in 
sub-Saharan Africa would be candidates for PrEP use according to HIV risk criteria (e.g., 
partner HIV status knowledge, STI history)33,40, women in PrEP trials who met HIV risk criteria 
and expressed an interest in PrEP often had low adherence11–13. This suggests that evaluated 
HIV risk alone is not in itself a sufficient motivator for women to adhere to PrEP. 
In randomized trials, oral pre-exposure prophylaxis (PrEP), in the form of daily tenofovir 
disoproxil fumarate and emtricitabine (TDF-FTC) has been shown to be effective for 
prevention of HIV acquisition5–7,41, including in women13,42. This intervention may be 
particularly well-suited for pregnancy and breastfeeding. Not only are HIV incidence rates 
exceedingly high during pregnancy but features that characterize this period may lead to 
greater PrEP adherence: high levels of institutional healthcare43, altruistic motivations towards 
the unborn fetus 44–46, a tradition of male partner engagement47, and a window of concentrated 
risk. In order to be effective, however, adherence is critical. 
TDF-FTC has been used in the context of pregnancy for both HIV and hepatitis B therapy, and 
has a strong track record for maternal and infant safety39. Data from PrEP trials have shown 
that TDF-FTC in the first trimester did not result in adverse outcomes at birth or in infant 
growth49. A smaller, open-label study—where women were given the option of continuing 
PrEP once they became pregnant—demonstrated similarly encouraging outcomes50. Studies 
in Kenya and Uganda suggest that PrEP can be safely used during breastfeeding with minimal 
infant drug exposure51.  In settings with high HIV incidence during pregnancy (i.e., greater than 
3.0 infections per 100 person-years), oral PrEP has been shown to be highly cost-effective 
across a range of modelling assumptions.52 TDF-FTC is approved by the Malawi ministry of 
health and available through standard of care. 
3.3 The importance of shared decision-making for appropriate PrEP use 
Because of the promise of PrEP for HIV prevention in pregnancy and breastfeeding and for 
PMTCT, there is a critical need to develop interventions to engage pregnant and breastfeeding 
women in PrEP use in ways that promote adherence to PrEP. To date, however, very little is 
known about how to engage pregnant women in PrEP use and how to identify appropriate 
PrEP users in this population. Though many pregnant women in sub-Saharan Africa would be 
candidates for PrEP use according to HIV risk criteria (e.g., partner HIV status knowledge, STI 
history)33,40, women in PrEP trials who met HIV risk criteria and expressed an interest in PrEP 
often had low adherence11–13. This suggests that evaluated HIV risk alone is not in itself a 
sufficient motivator for women to adhere to PrEP. 
User fit and motivation for PrEP use are integral to promoting adherence; a shared decision-
making process can help to ensure this fit and motivation. Unlike antiretroviral therapy, the 
decision to use PrEP is a highly preference-sensitive decision22; despite the advantage of 
PrEP as a woman-controlled method for HIV prevention, PrEP may not be the right HIV 
prevention fit for every woman. To promote this fit, a shared decision-making (SDM) process 
can be used to encourage values-congruent choices, or said otherwise, to reduce decisional 
conflict, defined as uncertainty about the best choice among competing options and discomfort 
with the decision taken53. SDM can reduce decisional conflict by increasing one’s sense of 
being informed about alternatives, benefits, and risks and by clarifying relevant personal 
values. The SDM model is both theoretically intended and empirically shown to promote 
values-congruent choices (low decisional conflict)23, as well as adherence to ART25–27, and 
treatments for depression and diabetes54,55. Shared decision-making in HIV care is well 
accepted and strongly desired by patients 56–58, and is associated with enhanced adherence 
to ART be promoting patient engagement, adherence self-efficacy, confidence in the 
treatment regimen, and satisfaction with the patient-provider relationship25,26. This effect on 
adherence can be understood by the fact that SDM is highly conducive to real and perceived 
choice autonomy, which is an essential precursor to intrinsic motivation for a behavior59. 
Decision-making theory suggests that adherence is more than a result of but rather a 
manifestation of real and perceived choice autonomy, which is optimally promoted through 

4 
 
shared decision-making21. This evidence points to the need for shared decision-making to 
identify appropriate PrEP users and to promote PrEP adherence. 
Antenatal care provides a unique opportunity to engage women in HIV prevention and PrEP 
use and is a context in which structured and guided decision aids are particularly needed. 
While women are engaged and motivated during pregnancy60, they are little engaged in health 
care outside of pregnancy. Because they usually lack previous exposure to healthcare and 
medical decision-making, women in ANC may feel poorly equipped to make decisions about 
HIV prevention options, making structured and guided decision processes particularly 
important61–63. For their part, ANC clinicians may feel poorly equipped to counsel women about 
potential PrEP use. In a recent formative study conducted by our team, ANC-based nurses 
expressed the need for additional training and communication materials to effectively counsel 
women about the decision to use PrEP. To overcome these communication barriers, SDM is 
specifically recommended for complex HIV prevention decisions64. Moreover, shared 
decision-making has been shown to be a feasible low-cost intervention, particularly when 
implemented using structured decision support aids65.  
To be able to implement the WHO guidelines to offer PrEP as a standard PMTCT service, we 
must ensure that limited resources for PrEP are targeted to those who are most likely to 
benefit. PrEP is a highly cost-effective HIV prevention strategy in low-resource settings52, yet 
funds to provide PrEP to pregnant and breastfeeding women are limited. Understanding how 
best to deliver PrEP to this population will be increasingly critical to inform policy in these 
settings. Given the limited resources available for PrEP, it will be essential that its provision 
be targeted to those women most likely to benefit from its use, as demonstrated by adherent 
use. 
3.4 Our formative work 
We have completed extensive formative research with pregnant women, male partners, and 
clinicians from the study site to develop the intervention for this pilot study. Formative evidence 
(regarding women’s values for PrEP decision making, the implications of these values for 
feelings regarding PrEP use, and preferences for partner involvement66) as well as key 
guidelines (Ottawa Decision Support Framework67 and International Patient Decision Aid 
Standards68) informed the PrEP SDM intervention, known as My Choice for HIV Prevention 
(MYCHOICE). In the formative study 66, we assessed women’s key values (motivations and 
concerns) for PrEP use. All participants wanted to protect themselves and their babies from 
HIV infection, 81% believed they were at risk for HIV, and 73% expressed concern about their 
partner's risk behaviours. Concerns included worries about potential harm to their babies 
(36%), themselves (32%), and being perceived as HIV-positive (24%). Qualitative insights 
highlighted motivations for PrEP use, such as protection for themselves and their unborn 
babies, while concerns encompassed potential harm to infants, side effects, stigma, and 
confusion about PrEP versus antiretroviral therapy. Participants often made autonomous 
choices and frequently disclosed them to partners. Limited family involvement was attributed 
to apprehensions about stigma and misunderstandings. Nevertheless, despite their varied 
concerns, participants overwhelmingly expressed enthusiasm for the HIV prevention benefits 
offered by PrEP. These formative findings along with SDM guidelines informed the content of 
the MYCHOICE intervention. The intervention has been refined through an iterative process 
of clinician and stakeholder feedback followed by feedback from 15 participants to refine the 
tool ahead of the proposed feasibility pilot study. During feedback interviews, women’s 
understanding of the intervention content was good. Scores for comprehension of HIV risk 
factors and prevention averaged 8.5 (range 5-10), 9.7 (range 7-10) for PrEP information, and 
9.2 for male and female condoms. The values clarification section had a mean comprehension 
score of 9.4. Furthermore, participants viewed the intervention content to be highly for 
decision-making (mean score of 10) and reported they would be likely to accept counselling 
using this tool during an ANC appointment (mean score of 9.7, range 7-10). Additionally, 
qualitative feedback revealed that all participants found the SDM tool acceptable and highly 
appropriate to support PrEP decision making. Additional Constructive feedback informed 

5 
 
improvements to enhance comprehension and utilization of the tool during pregnancy, and 
make the counselling content more efficient and acceptable (see 5.2 for full description of 
intervention content). 
 
4. STUDY OBJECTIVES AND OUTCOMES 
 
4.1 Objective and Aims 
The overall objective of this pilot study is to: 
 
Evaluate the feasibility (score of ≥4 among ≥80% of participants), acceptability (score 
of ≥4 among ≥80% of participants), and appropriateness (score of ≥4 among ≥80% of 
participants) of a shared decision-making intervention (MyChoice) to support 
personally appropriate decision making about oral PrEP use during pregnancy among 
100 women in antenatal care at Bwaila Hospital by the end of 2025. 
 
We will achieve this objective through three Specific Aims which will be completed through the 
pilot study: 
 
Aim 1: Evaluate the acceptability, appropriateness, and feasibility of the oral PrEP 
shared decision-making intervention. 
Aim 2: Assess the plausibility of intervention effects on a proximal cognitive endpoint 
(decisional conflict) in preparation for a future efficacy trial. 
Aim 3: Describe exploratory behavioral outcomes to better understand participant 
experiences during and following the intervention (PrEP uptake, PrEP adherence, 
Intervention fidelity, qualitative assessment of participant and implementer 
experiences). 
4.2 Study Outcomes 
Corresponding to the primary, secondary, and exploratory study objectives (above), we will 
assess the following primary secondary, and exploratory outcomes in this feasibility pilot study. 
 
4.2.1 Primary outcomes 
Primary outcomes will include participant reports of the perceptions regarding the 
intervention (assessed through questionnaire self-report): 
• 
Intervention acceptability (extent to which participants perceive the intervention to be 
agreeable, palatable, or satisfactory) 
• 
Intervention appropriateness (perceived relevance and usefulness to support 
decision making) 
• 
Intervention feasibility (extent to which the intervention is feasible or practical) 
 
4.2.2   Secondary outcome 
• 
Decisional Conflict assessed through validated scale (measure assessing 
perceptions of decision uncertainty, satisfaction, clarity of personal values, and 
support for decision-making) 
 
4.2.3 Exploratory outcomes 
• 
PrEP uptake (receipt of prescription as applicable) 
• 
Retention with functional PrEP adherence at month 2 (through study records and 
pharmacologic assessment) 
• 
Intervention fidelity (independent review of intervention sessions) 
• 
Qualitative perceptions of intervention and study procedure feasibility (from the 
perspective of participants, male partners, and study staff) 
 

6 
 
 
5. METHODOLOGY 
 
5.1 Study design 
We propose a pilot feasibility study of a shared decision making (SDM) intervention for 
pregnant women considering PrEP. 100 women will be randomized to receive either the SDM 
intervention addressing daily oral PrEP and alternative HIV prevention methods (condoms), 
or standard of care counselling addressing the same prevention methods. We will evaluate 
the feasibility, acceptability, and appropriateness of the intervention and associated study 
procedures. Women expressing interest in oral PrEP will be referred to government PrEP 
services. See Table 1 for a summary of the study design and Section 6 below further details 
of the study procedures. 
 
Table 1. Study design summary 
n 
100 women 
Intervention 
SDM counseling with choice of oral PrEP and/or condoms 
Follow-up duration 
3 months 
Primary endpoints 
Intervention acceptability 
Intervention appropriateness 
Intervention feasibility 
Secondary endpoints 
Decisional Conflict 
 
5.2 Study intervention 
The study intervention, My Choice for HIV Prevention (MyChoice), is a counselor-delivered 
shared decision-making approach for pregnant women considering PrEP. The intervention 
counseling will be delivered by trained study staff with a background in psychosocial 
counseling. The intervention consists of counseling facilitated by a SDM tool, following the 
steps in Table 2. The woman’s partner may be present depending on her preference. It begins 
with a review of HIV risk in pregnancy/breastfeeding including discussion of population-
specific risk factors which may apply to the participant. After understanding participant HIV 
risk and desire for HIV protection, the counselor presents HIV prevention options including 
oral PrEP, and internal and external condoms (discussing attributes and potential advantages 
and disadvantages of each method). This is followed by a values clarification exercise to 
identify which features of the competing options matter most to the participant (product 
attributes and personal and interpersonal implications of each method). The counselor reviews 
information about these valued features for each offered method. This information and checks 
to understand and address any unmet participant decision support needs serve as the basis 
for structured deliberation to collaboratively identify participant preferred method(s). The 
participant may defer or decline the decision, and may request a follow-up counseling visit to 
take more time to consider her preference or return with a partner or other supporter. If and 
when a decision is made, the counselor provides post-decision counseling including 
adherence counseling and disclosure counseling if desired. 

7 
 
 
Before the counseling visit, women will receive information about the content of the counseling 
and discuss whether or not they wish to have their partner or someone else (e.g., family 
member) participate in the counseling with them. The MyChoice counseling may be completed 
with or without the partner or another person they choose present depending on the 
participant’s preference. After completion of the main counseling, participants will receive brief 
adherence counseling for the HIV prevention method they have selected and additional post-
decision counseling as appropriate: for participants choosing PrEP, they will be asked if they 
hope to tell anyone about their decision. If yes, they will be offered coaching to support 
disclosure; for participant who have a partner living with HIV present, they will receive brief 
counseling on the continued importance of ART adherence and mutual support for ART and 
PrEP adherence (if applicable). While the counseling is intended to take place over one day, 
if the participant requests follow-up counseling (e.g., want more time to make a decision, wish 
to come back with a partner for a future session), reasonable accommodations will be made 
for the MyChoice counselor to meet with the participant a second time. 
 
Women choosing oral PrEP during the intervention counseling session will be referred to 
government services to initiate PrEP. 
 
5.3 Standard of care (control arm) 
Participants randomized to the control arm will PrEP counseling as based on the current 
standard of care (SOC). The SOC counseling will be delivered by a trained study staff 
member. The SOC counselor PrEP counseling according to national guidelines. 
Per current guidelines, the SOC counseling may include the following elements: An HIV risk 
assessment according to PrEP eligibility criteria; discussion of a combination prevention 
approach (PrEP and condoms) and risk reduction strategies. The women will receive 
comprehensive education on both the advantages and limitations of PrEP, including guidance 
on managing potential side effects. Subsequently, the counselor will assess the woman's 
eligibility, willingness, and readiness to start using PrEP.69 
Women choosing oral PrEP during the SOC counseling session will be referred to government 
services to initiate PrEP. 
 
Table 2. Shared Decision-Making Intervention Content 
Counselling 
component 
Content 
Pre-
counseling 
• Overview of counseling content 
• Discuss participant’s desire to include partner in counseling 
MYCHOICE Counseling 
HIV info & 
risk 
assessment 
• HIV risk in pregnancy and breastfeeding 
Evaluation of HIV risk criteria according to Malawian national guidelines 
HIV 
prevention 
options 
• Present oral PrEP, & condoms 
Features attributes and potential advantages and disadvantages of each 
Values 
clarification 
• Identify and discuss participant-valued features of available options (attributes, personal & 
interpersonal implications of each method) 
Structured 
deliberation 
• Assess and address unmet decision making needs 
• Collaboratively determine if participant is ready to make a decision, identify preferred method(s) 
Post-
decision 
counseling 
• Persistence/adherence counseling 
• Disclosure coaching if desired 
PrEP 
referral 
• If oral PrEP selected, referral to SOC services 
 
Post-
counseling 
• Adherence counseling for selected HIV prevention method 
• Disclosure support 
• Partner ART adherence counseling (if applicable) 

8 
 
5.4 Eligibility criteria 
 
The criteria for pregnant women participants is as follows: 
Inclusion criteria 
• 
Age 18 or older 
• 
Documented pregnancy by urine pregnancy test or physical exam 
• 
Documented negative HIV status within the past three months 
• 
Identified factor(s) for elevated risk for HIV acquisition per PrEP national eligibility 
guidelines 
• 
Willingness to remain in the study site’s catchment area over the course of study follow-
up and to comply with visit schedule 
• 
Ability and willingness to provide informed consent 
Exclusion criteria 
• 
Positive HIV test at time of screening 
• 
No identified HIV risk factors per national PrEP guidelines 
• 
Risk for intimate partner violence or social harms as a result of participation, in the 
judgement of the study personnel 
We will also conduct interviews with male partners and study staff to assess exploratory 
qualitative outcomes. All study staff will be eligible to participate in an interview. Male partners 
will be eligible to participate if they meet the following criteria: 
• 
Referred by a study participant as her romantic partner 
• 
Age 18 or older 
• 
Able and willing to provide informed consent 
5.5 Place of study 
The study will take place at a government health facility, Bwaila Hospital, a high-volume district 
facility run by the Malawi Ministry of Health. Approximately 1,500 babies are delivered each 
month at Bwaila and approximately 500 women present each month for immunization visits 
for their babies at 9 months after delivery. Bwaila Hospital has been providing PMTCT services 
since April 2002 and promoting male participation since 2007. 
 
5.6 Target population 
The primary population to be recruited for this study is HIV-negative pregnant women. For 
qualitative data collection only, we will also recruit male partners of these participants, and 
PrEP counselors and health care workers. We focus on pregnant women because of the 
elevated HIV risk faced by women in the perinatal period. 
 
We will recruit 100 women to participate in the pilot study. A subset of these participants will 
participate in qualitative interviews. Up to 20 male partners and up to 15 study staff will be 
recruited to participate in qualitative in-depth interviews. See a summary of the sample size 
by participant group below in Table 3. Qualitative sampling will continue until saturation is 
reached. 
 
Table 3. Sample size summary of by Study by type participant type 
Type of Participant  
n 
Pregnant women 
100 
(up to 30 complete IDIs) 
Male partners of PrEP users (IDIs 
only) 
Up to 20 
PrEP counsellors/Health care 
workers (IDIs only) 
Up to 15 

9 
 
 
5.7 Recruitment and enrollment procedures 
 
5.7.1 Recruitment procedures 
Staff will provide interested participants with study information and referral to the study. 
Potential participants will be identified at any point in their pregnancy. All women attending the 
study site who meet the eligibility criteria (section 5.4) will be invited to participate in the study. 
All participants will undergo an informed consent procedure to ensure they are well-informed 
about the study, its objectives, and its requirements (section 6.2). We will obtain locator 
information from the participant, including phone numbers, addresses, and directions. 
 
5.7.2 Enrolment procedures 
HIV-negative pregnant women eligible for the study and interested in participating will be 
scheduled to return for an enrolment visit within 1-2 weeks. Prospective participants who wish 
to complete the enrolment visit on the same day as screening or who need more time to return 
to for the enrolment visit will be reasonably accommodated. Participants will complete 
informed consent and be formally enrolled. We will collect social, demographic, medical, and 
behavioural information from all participants. We will obtain from the locator information from 
the participant, including phone numbers, addresses, and directions. Participants will be 
randomly assigned to one of two study arms (intervention or comparison). Statistical software 
will be used to generate a list of random assignments with a 1:1 ratio. To facilitate balance of 
intervention and SOC arms, permuted block randomization will be used.  The randomly 
generated arm assignments will be placed in opaque sealed envelopes and sequentially 
numbered with participant identification numbers. Participants will be blinded to their 
assignment, but study staff will not. 
 
5.8 Study follow-up 
Participants choosing oral PrEP during the counselling session in either intervention or 
comparison arm will receive an assisted referral to government PrEP services at the study site 
to initiate their selected PrEP method per national guidelines. No study drug will be 
administered. Initiation of oral PrEP (i.e., receipt of prescription) will be confirmed through 
clinic or pharmacy records, as well as information on reasons for non-initiation if applicable. 
 
We plan study follow-up visits at month 1, month 2, and month 3. Study visits will be scheduled 
to align with ANC/pharmacy visits whenever possible to minimize the number of trips needed 
at the clinic.  
 
Interviewer-administered questionnaires will be completed at the month 1 follow-up and the 
final follow-up visit (month 3). Questionnaires will assess study outcomes and associated 
social and behavioural measures to contextualize understanding of primary study outcomes. 
A subset of participants will complete in-depth qualitative interviews at month 1. Interviews will 
provide additional understanding of participant experiences with the intervention and 
experience using PrEP (if applicable). 
 
At each follow-up visit, women who have chosen oral PrEP will undergo adherence 
assessment through self-report and pill counts. Furthermore, we will collect dried blood spots 
(DBS) at month 2 to assess adherence among all oral PrEP users. 
 
Table 4. Study visit schedule 
Procedure 
Screening 
Enrollment 
Visit 
Follow-up visits 
1 mo. 
2 mo. 
3 mo. 
Study introduction 
X 
 
 
 
 

10 
 
Eligibility assessment 
X 
 
 
 
 
Informed consent 
 
X 
 
 
 
SDM counseling (intervention) 
 
X 
 
 
 
Questionnaires 
 
X 
X 
 
X 
PrEP assisted referral 
 
X 
 
 
 
Qualitative interviews 
 
 
X 
 
X 
Adherence measurement (PrEP adopters only) 
Pill count/self-report 
 
 
X 
X 
X 
DBS 
 
 
 
X 
X 
 
5.9 Assessment of study outcomes 
 
5.9.1 Assessment of primary outcomes 
Primary study outcomes will be assessed in participant questionnaires at the enrollment visit. 
The outcomes will be assessed at the final follow-up visit to as well to understand how 
perceptions of the intervention have changed over time. 
Intervention Acceptability 
We will evaluate intervention acceptability, defined as the extent to which participants perceive 
the intervention to be agreeable, palatable, or satisfactory. Acceptability will be assessed 
through participant self-report using a validated 4-item scale. This scale measures how 
agreeable and satisfactory women find the intervention (responses rated on a 5-point Likert 
scale ranging from "Completely Disagree" to "Completely Agree"). This assessment will be 
conducted at both month 0 and month 2 using the Acceptability of Intervention Measure (AIM) 
scale 70  
 
Intervention Appropriateness 
We will also evaluate participant perceptions of Intervention appropriateness, defined as the 
perceived relevance and usefulness of the intervention to support decision making about HIV 
prevention methods. Appropriateness will be assessed through self-report using a validated 
4-item scale to measure women’s perceptions of its relevance and usefulness (responses 
rated on a 5-point Likert scale ranging from "Completely Disagree" to "Completely Agree")70.  
 
Intervention Feasibility 
We will also evaluate participant perceptions of Intervention appropriateness, defined as the 
extent to which the intervention is deemed feasible or practical from their perspective. This 
Feasibility of Intervention Measure will be administered at both month 0 and month 2. The 
items on the scale will be measured using a 5-point Likert scale, and individual responses will 
be averaged to create a score for each measure. Higher scores will indicate a greater level of 
feasibility70. 
 
5.9.2 Assessment of secondary outcomes 
Secondary outcomes will be assessed through study questionnaires and study records. 
 
Decisional Conflict 
The Decisional Conflict Scale (DCS) will be utilized to gauge women’s' perceptions of decision 
uncertainty, satisfaction, clarity of personal values, and support for decision-making. This 16-
item scale assesses these aspects on a 5-point scale, with scores totalling 100 points (mean 
rating multiplied by 25)70 717273,74A "low" DCS score will be identified using a cut-off of 25 out 
of 100, which has been linked to reduced decisional regret and enhanced choice retention. 

11 
 
DCS scores will be computed based on women’s responses to statements, where higher 
scores indicate greater decisional conflict, while lower scores indicate diminished conflict and 
heightened certainty in decision-making. The scale will be administered at the enrolment visit 
following completion of study counselling. 
 
5.9.3 Assessment of exploratory outcomes 
PrEP uptake 
We will assess PrEP uptake (i.e., receipt of oral PrEP prescription) among participants 
choosing PrEP during the intervention session. This will be assessed through clinic or 
pharmacy records. 
 
Retention with functional adherence 
Our clinical exploratory endpoint to be measured among participants taking up PrEP is 
retention in care with functional adherence to PrEP at two months. Retention will be assessed 
through study records. For participants taking up oral PrEP, functional adherence will be 
measured categorically according to Tenofovir diphosphate (TFVdp) quantified in dried blood 
spot (DBS) samples at the 2-month visit. 
 
Intervention Fidelity 
Intervention sessions will be digitally audio recorded with participant consent. A random subset 
of sessions will be reviewed by a study team member using a structured tool to assess 
intervention fidelity. Study staff will use recordings to evaluate the quality of counseling 
delivered (adherence to intended components and quality of counseling delivered) using a 
structured tool. Raters will score each section of the counseling and overall, with elements 
rated on a 5-point scale (0 “no effort” to 4 “exemplary effort”). 
 
Qualitative assessment of intervention & study procedure perceptions 
Qualitative in-depth interviews (IDIs) with study participants will be conducted at the visits 
designated above to explore women's satisfaction with study counseling, session quality, and 
feeling about their decision. Follow-up interviews will evaluate women’s experience using their 
selected HIV prevention method and the perceive impact of the study counseling on their 
current use of the selected product. Additional feedback on the intervention and study 
procedures will be gathered. 
 
Additional IDIs will be conducted with male partners and study staff to gather insights into their 
experiences with the intervention, different procedures, perceptions of integrating Shared 
Decision-Making (SDM) into routine care, and suggestions for procedural improvements. 
 
IDIs will be conducted by a locally recruited and trained research assistant fluent in Chichewa 
and English using semi-structured interview guides. Interviews will be digitally audio-recorded, 
transcribed, and translated to English for analysis. 
Table 5. Schedule of Evaluations 
 
Screening 
Enrollment 
Month 1 
Month 2 
Month 3 
Eligibility assessment 
 
 
 
 
 
Pregnancy status 
X 
 
 
 
 
HIV status 
X 
 
 
 
 
Additional eligibility criteria 
X 
 
 
 
 
Participant-reported 
assessments 
 
 
 
 
 
Questionnaires 
 
 
 
 
 
Demographic information 
 
X 
 
 
 
Intervention assessment 
 
X 
 
X 
 
Decisional conflict 
 
X 
 
 
 
Partner information 
 
X 
X 
X 
X 
Social harms 
 
X 
X 
X 
X 

12 
 
Qualitative interviews 
 
 
X 
 
X 
Adherence assessments 
 
 
 
 
 
PrEP uptake assessment 
 
 
X 
 
 
Oral PrEP 
 
 
 
 
 
Pill count 
 
 
X 
X 
X 
Self-report 
 
 
X 
X 
X 
DBS 
 
 
 
X 
 
 
5.10 Retention 
Once participants are enrolled in the trial, the study team will make efforts to retain them in 
follow-up to minimize bias associated with loss to follow-up. The study team will closely 
monitor retention rates and address any issues prospectively. Strategies to minimize attrition 
include: 
• 
Thorough explanation of the study visit schedule and procedures during informed consent. 
• 
Collection of detailed locator information at enrolment. 
• 
Use of appropriate and timely visit reminder mechanisms (including phone calls and text 
messages, if participants specifically agree). 
• 
Follow-up after missed visits, including home or alternative, off-site visits where possible. 
• 
Mobilization of trained outreach workers to complete in-person contact with participants at 
their homes and/or other locations. 
If participants elect to discontinue their involvement in the study, we will document their stated 
reason(s). These will be reported in any reports about the study cohort. 
5.11 Safety Monitoring 
At each study visit, study staff will evaluate participants for social harms and adverse events 
(AEs). A social harm will be defined as a non-medical untoward consequence of study 
participation, including: difficulties in personal relationships, stigma, or discrimination from 
family or community. An AE will be defined as any untoward medical occurrence in a study 
participant including any abnormal sign (e.g., abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the individual’s participation in the research, 
whether or not considered related to participation in the research. 
All adverse events and social harms will be documented, assessed for seriousness / severity, 
expectedness, and relatedness, and carefully monitored. The severity of events will be graded 
using the National Institute of Health’s Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events. We will also record information on all serious adverse events 
(SAEs) occurring in participants whether or not they are related to study participation, including 
AEs that: 
 
1. Result in hospital admission (unless hospitalization is preplanned, i.e. for delivery) 
or prolongation of existing hospitalization 
2. Are immediately life-threatening, including drug reactions that necessitate 
discontinuation of study participation, 
3. Cause significant, persistent, or permanent harm or disability, either physical or 
psychological, 
4. Result in death to mother or infant, or 
5. Are congenital anomalies or birth defects 
 
5.12 Biological specimen collection and testing 
To assess quantify drug concentrations to assess PrEP adherence among participants taking 
up oral PrEP, a participant blood specimen will be collected via venipuncture at the for 
applicable participants (those using oral PrEP). This specimen will be used to create a dried 

13 
 
blood spot (DBS) specimen at the local designated laboratory, prior to storage and shipment 
to the reference pharmacology laboratory for testing. 
All samples will be obtained from study participants by trained study staff according to 
approved standard operating procedures. All samples will be processed according to the 
assay manufacturers’ specifications. Specimens will be transported, processed, and 
temporarily housed at UNC Project Malawi (Lilongwe, Malawi) and shipped to UNC Chapel 
Hill for analysis. All laboratory testing will be performed by trained staff using standard 
operating procedures and according to specific assay manufacturers’ specifications. 
5.13 Quality control and quality assurance procedures 
Standard Operating Procedures (SOPs) following manufacturer’s protocols and detailing 
technical procedures involved (e.g. sample collection, processing and storage, assay 
procedures and how to interpret test results) will be developed and used by the study team. 
Tests will only be performed by certified laboratory personnel. Site coordinators will complete 
annual recertification. The certification process is an opportunity to ensure the highest 
specimen quality and standardize collection techniques. 
5.14 Data Management and Storage 
Data collected from each participant will include sociodemographic information, cognitive and 
behavioural self-reported information, qualitative transcripts, and relevant HIV and obstetrical 
history. Study data management (e.g., data transmission, query resolution, etc.) will follow site 
data management standard operating procedures. Study identification numbers will be used 
on all forms and communications related to the study. A separate confidential register will link 
study identification numbers and participant names. All data instruments and registers will be 
securely stored. Data will be entered into a custom-built database and, where possible, will be 
validated via double entry. Computers and tablets will be encrypted and password protected 
and their access restricted to authorized study personnel. Backups of the data will be made 
on a weekly basis. Data may be transmitted electronically to the study investigators through 
secure cloud-based servers. Study information will not be released without written permission 
of the participant, except when necessary for monitoring by the relevant ethical committees or 
their designees. Data will be disposed of after completion of the study per country guidelines. 
At that time, electronic records, including linkage codes and identifiers, will be deleted. Paper 
records will be shredded prior to disposal. 
All interviews will be digitally audio recorded, unless participants ask not to be recorded. The 
recording will be transcribed and translated to English for analysis. All identifiers will be 
redacted from the interview transcripts prior to analysis. Participants will be assigned a unique 
study ID number that will be used to capture data. Data will be kept in an encrypted computer 
with a password known only to the study staff. Audio files will be erased from the recorders 
after data are transferred into the computer. All study materials will be kept in a locked, 
fireproof safe cabinet in locked offices at the study sites. No participants will be identified in 
any report or publication about this study. 
 
5.15 Sample size 
In this pilot study, the primary objective is to understand intervention acceptability, feasibility, 
and appropriateness. As such, the sample sizes are based on feasibility considerations. 
Despite this general approach, we provide estimated precision calculations for primary 
outcomes. 
 
5.15.1 Precision calculations for continuous outcomes 
For continuous measures, such as mean acceptability, appropriateness, and feasibility scores, 
or mean decisional conflict score, we used the t-distribution to estimate the level of precision 
we can expect to achieve given our various sample sizes and an expected 10% loss to follow-
up over the course of the study. Table 6 shows the precision we can expect for estimates of 
95% confidence intervals for mean acceptability, appropriateness, or feasibility at baseline 

14 
 
and at follow-up If we assume a common standard deviation of 0.9, we can expect a margin 
of error of ±0.256 points at baseline and ±0.270 points at follow-up on a 4-point scale. 
Likewise, Table 7 shows estimates of precision for 95% confidence intervals around mean 
decisional conflict score (DCS), except means will be estimated overall and by each arm. 
Here, if we assume a common standard deviation of 13.26, we can expect the margin of error 
for the 95% CI around the means to range from ±2.6 (pooled at baseline) to ±4.0 (by arm at 
follow-up) points on a 100-point scale. 
 
For primary outcomes, mean AIM, IAM, and FIM, assumed SD=0.9 for all measures based on 
Lavoie et al. Mean AIM, IAM, and FIM calculated among intervention arm only. 
Table 6. Expected precision for mean acceptability, appropriateness, or feasibility score 
among intervention arm 
 
Precision Estimate for 95% CI of Mean* 
 
Baseline (n=50) 
±0.256 
 
Follow-up (n=45)† 
±0.270 
*Assume SD=0.9 for mean acceptability, appropriateness, and feasibility scores (4-point scale); 
precision estimates for 95% confidence intervals obtained using t-distribution. 
†Assume 10% loss to follow-up by the end of study 
 
For secondary outcome, mean DCS, assumed SD=13.26 for each arm based on Vlemmix et al. 
Mean DCS will be calculated and compared by arm. 
Table 7. Expected precision for mean decisional conflict score, overall and by study arm 
 
Precision Estimate for 95% CI of Mean* 
Overall 
 
 
Baseline (n=100) 
±2.631 
 
Follow-up (n=90)† 
±2.777 
By arm 
 
 
Baseline (n=50) 
±3.768 
 
Follow-up (n=45)† 
±3.984 
*Assume SD=13.26  for mean decisional conflict score (100-point scale); precision estimates for 
95% confidence intervals obtained using t-distribution. 
†Assume 10% loss to follow-up by the end of study 
 
5.15.2 Precision calculations for binary outcomes 
To estimate the expected precision of our binomial outcomes, we used the normal 
approximation confidence limit approach and calculated the exact binomial 95% CI as a 
sensitivity approach. For our calculations we looked at both baseline and follow-up 
measurements, assuming 10% loss to follow-up over the course of the study. Table 8 presents 
the precision achieved for the outcomes of acceptability, appropriateness, or feasibility scores 
of 4 or greater with an expected proportion between 60-90% achieving mean scores above 
that threshold. The proportion of women with mean acceptability, appropriateness, and 
feasibility score ≥4 will be calculated only among women that received the intervention. By our 
estimates, we can expect to achieve a precision level levels in Table 8 below if 80% have high 
mean scores. Similarly, Table 9 shows estimates of precision for women with low vs. high 
mean decisional conflict scores (DCS, ≤25 vs. >25) with expected proportion of women with 
low DCS ranging from 50-90%. In this analysis, women will be assessed overall and by arm 
(intervention vs SOC). For example, we expect a ±7.8% precision if 80% of women in both 
arms (n=100) have DCS ≤25 at baseline with a 95% CI of 69-89%; at the end of study, we 
expect ±8.3% precision if we observe that 80% have a DCS of ≤25 (95% CI: 69-89%). 
 
Table 8. Expected precision for proportion of participants with high mean acceptability, 
appropriateness, or feasibility scores 
 
Observed Proportion with ≥4 Mean Score 
0.6 
0.7 
0.8 
0.9 
Baseline (n=50)† 
 
 
 
 
 
Approximate precision 
0.45-0.74 
0.55-0.92 
0.66-0.90 
0.78-0.97 

15 
 
 
Exact binomial 95% CI 
±0.136 
±0.127 
±0.111 
±0.083 
Follow-up (n=45)*† 
 
 
 
 
 
Approximate precision 
0.44-0.74 
0.53-0.82 
0.65-0.90 
0.76-0.96 
 
Exact binomial 95% CI 
±0.143 
±0.134 
±0.117 
±0.088 
*Assume 10% loss to follow-up; precision calculated using a normal distribution. 
†Estimates among intervention arm only. Pooled estimates include participants receiving 
intervention from (n=100 enrolled, 1:1 randomization) 
 
Table 9. Expected precision for proportion of participants with low mean decisional conflict 
score (DCS) 
 
Observed Proportion with ≤25 Mean DCS 
 
0.5 
0.6 
0.7 
0.8 
0.9 
Baseline (n=100)† 
 
 
 
 
 
 
Approximate precision 
0.39-0.62 
0.48-0.71 
0.58-0.79 
0.69-0.88 
0.82-0.96 
 
Exact binomial 95% CI 
±0.098 
±0.096 
±0.090 
±0.078 
±0.059 
Follow-up (n=90)*† 
 
 
 
 
 
 
Approximate precision 
0.38-0.63 
0.47-0.72 
0.58-0.81 
0.69-0.89 
0.80-0.96 
 
Exact binomial 95% CI 
±0.103 
±0.101 
±0.095 
±0.083 
±0.062 
By arm at baseline (n=50)† 
 
 
 
 
 
 
Approximate precision 
0.36-0.64 
0.45-0.74 
0.55-0.92 
0.66-0.90 
0.78-0.97 
 
Exact binomial 95% CI 
±0.139 
±0.136 
±0.127 
±0.111 
±0.083 
By arm at follow-up 
(n=45)*† 
 
 
 
 
 
 
Approximate precision 
0.34-0.64 
0.44-0.74 
0.53-0.82 
0.65-0.90 
0.76-0.96 
 
Exact binomial 95% CI 
±0.146 
±0.143 
±0.134 
±0.117 
±0.088 
*Assume 10% loss to follow-up; precision calculated using a normal distribution. 
†Estimates overall (n=100, 1:1 randomization), or by arm (n=50 per arm). 
 
5.16 Data Analysis  
Initial analysis will include descriptive analyses to characterize the sample on features such 
as demographics (e.g., age, marital status, income, education) and each outcome of interest. 
We will examine whether key sociodemographic features (age, income, education, marital 
status, gestational age, parity, perceived HIV risk, and experience of IPV) differ by study arm. 
Any characteristics differing significantly by arm will be included as covariates in sensitivity 
analyses comparing study arms; otherwise, primary analyses will be unadjusted 
 
Given the pilot nature of the study, emphasis will be put on estimation and precision of 
measured effects, rather than null hypothesis testing. An alpha=0.05 will be used throughout 
to compute 95% confidence intervals (CIs), with no adjustment for multiplicity. In the case of 
small cell counts or analyses of continuous data with n<30, exact statistical methods (e.g., 
exact CI for a risk difference) will be used. Given potential for precision loss with exact CI 
methods and the pilot nature of these studies, we will use large-sample methods (e.g., Wald 
CIs) when the nominal CI coverage level is tenable. 
 
Specific analyses for each study outcome are described in detail below. Detailed statistical 
analysis plans will be finalized prior to study outcome analysis. 
 
5.16.1 Analysis of primary endpoints 
Descriptive statistics will be calculated for primary outcomes of intervention acceptability, 
appropriateness, and feasibility among intervention arm participants. For each 4-item scale, 
item scores will be averaged to produce a composite score for each participant (range 1-5). 
Higher scores will indicate a greater level of acceptability, appropriateness, or feasibility, 
respectively. We will estimate the mean differences between arms for each primary outcome 
with a corresponding 95% confidence interval and p-value. 
 
5.16.2 Analysis of secondary endpoints 

16 
 
 
Decisional Conflict 
Decisional Conflict Scale (DCS) will be calculated according to published methods. A mean of 
the 16-item scale (rated on a 5-point scale) will be taken and multiplied by 25 to produce 
summary scores ranging from 0-100 points 71,74 Descriptively, summary scores will be 
presented descriptively (mean and SD across participants in each arm by study). We will 
compare DCS scores across in the SDM intervention condition to the SOC counselling control 
condition in an exploratory manner. We hypothesize that the intervention will be superior to 
the control, with intervention participants reporting at least an 8-point lower decisional conflict 
score on average than control participants. An intent-to-treat approach will be used to evaluate 
the effect of treatment on decisional conflict. We will first compare group means of decisional 
conflict scores by study arm and then examine the intervention’s effect on this outcome using 
a two-sample Welch’s t-test. If demographic variables related to decisional conflict differ 
substantively by study arm, we will instead use augmented inverse probability weights (AIPW) 
to perform doubly robust estimation of the average intervention effect to compare intervention 
vs. control (e.g., using the CAUSALTRT procedure in SAS software). Missing (unevaluable) 
data are anticipated to be uncommon (≤10%). Multiple imputation methods will be applied to 
address missing data if appropriate. 
 
Exploratory analyses will also be conducted with a dichotomous coding of DCS score 
according to published thresholds. A "low" DCS score will be identified using a cut-off of 25 
out of 100, which has been linked to reduced decisional regret and enhanced choice retention. 
DCS scores will be computed based on women’s responses to statements, where higher 
scores indicate greater decisional conflict, while lower scores indicate diminished conflict and 
heightened certainty in decision-making. 
 
5.16.3 Quantitative analysis of exploratory endpoints 
We will examine the intervention effect on retention and PrEP adherence in an exploratory 
fashion. In order to evaluate effectiveness, analyses will be conducted using an intention-to-
treat approach, with women analysed according to the arm they were randomly assigned.  
 
Given the pilot nature of these studies, emphasis will be put on estimation and precision of 
measured effects, rather than null hypothesis testing. An alpha=0.05 will be used throughout 
to compute 95% confidence intervals (CIs), with no adjustment for multiplicity. In the case of 
small cell counts (<5), 95% CI coverage properties of large-sample methods will be evaluated 
using exact statistical methods (e.g., exact CI for a risk difference) in sensitivity analyses. 
Given potential for precision loss with exact CI methods and the pilot nature of these studies, 
we will use large-sample methods (e.g., Wald CIs) when the nominal CI coverage level is 
tenable. 
 
Missing (unevaluable) data are anticipated to be uncommon (≤10%). The primary analyses 
are based on a composite endpoint of being retained in care with functional PrEP use, and 
thus complete case analyses will be conducted. Women who are not retained in care will be 
counted in the denominator for the primary analysis. Sensitivity analyses will exclude women 
who were not retained in care. 
 
PrEP uptake 
Uptake of oral PrEP will be described as the proportion of participants with record of receipt 
of an oral PrEP prescription. 
 
Retention + Functional Adherence 
Our clinical exploratory endpoint to be measured among participants taking up PrEP is 
retention in care with functional adherence to PrEP at two months. We will assess adherence 
to oral PrEP among participants taking it up through Tenofovir diphosphate (TFVdp) 
concentrations in participant dried blood spot (DBS) samples. TFVdp will be measured using 

17 
 
established liquid-chromatography tandem mass spectrometry methods75 Using published 
thresholds76, TFVdp concentrations will be categorized as in Table 10 below. Emtricitabine 
triphosphate (FTCtp) concentrations will also be quantified and may be interpreted in an 
exploratory manner (e.g., in the event that TFVdp is below the level of quantification). 
Participants will be considered for this composite outcome if they have any record of oral PrEP 
initiation following study assisted referral. Participants retained at two months meeting the 
relevant definition of functional adherence (below) will be categorized as retained with 
functional adherence. 
 
Table 10. Adherence interpretation of TFVdp concentration levels 
Interpretation 
DBS TFVdp fmol/punch 
Pregnant participants 
Postpartum participants* 
~7 doses/week 
≥650 
≥1050 
2-6 doses/week 
200-649 
300-1049 
<2 doses/week 
<200 
<300 
*participants will be enrolled during pregnancy but may deliver prior to the month 2 visit when this outcome is assessed 
 
Treatment effect on PrEP adherence among participants adopting PrEP will be explored as 
sample size and rates of adoption permit. We will compare the proportion of the sample 
retained in care with functional PrEP adherence at 2-month follow-up between the two 
randomization arms using a linear-binomial model. Women who are not retained for 2-month 
follow-up will be counted as failures and will contribute to the analysis denominator. From the 
linear-binomial model, the site-adjusted risk difference of being retained and in care with 
functional PrEP for the intervention arm versus the control arm will be calculated, along with 
a corresponding 95% CI. 
 
In addition to the primary analysis, assessing functional PrEP adherence as binary outcome, 
secondary analyses will compare the adherence categories between the study arms using a 
Wilcoxon rank-sum test. This analysis will be restricted to women with an evaluable adherence 
score. 
 
Intervention Fidelity 
To assess intervention fidelity, we will quantify intervention fidelity in a series of items rated by 
a study team member on a 5-point scale. A random subset (~20%) of these sessions will be 
audited by a study team member using a fidelity assessment tool that includes objective and 
subjective measures. These assessments will help to characterize the quality of 
implementation over the course of study participation. Fidelity to the intervention will be 
assessed through study staff audits of counseling sessions on including quality of counseling 
delivered (adherence to intended components and quality of counseling delivered), for of each 
section of the counseling and overall, with elements rated on a 5-point scale (0 “no effort” to 4 
“exemplary effort”). Ratings for each section of the scoring instrument tool will be averaged 
and summarized descriptively (including mean scores and standard deviations) to report 
fidelity to the intervention. 
 
5.16.4 Qualitative analysis of IDIs (exploratory outcomes) 
Thematic analysis will be used to analyse the qualitative data. The transcripts will be 
transcribed and translated into English. Analysis will consist of: 1) Reading for Content: We 
will read the data until content becomes intimately familiar. As data are reviewed emergent 
themes will be noted. 2) Coding: A list of codes will be created and documented in a codebook 
based on identified themes in addition to structural codes corresponding to initial interview 
questions. Two coders will independently code each transcript. To ensure inter-coder 
reliability, 10% of data will be double-coded; 3) Data reduction: We will review the data related 
to each code to identify principal sub-themes that reflect finer distinctions in the data. This 
entails taking an inventory of what is related to a given code, observing the variation or 

18 
 
richness of each theme, and noting differences between individuals or among subgroups; 4) 
Data display and comparison: Matrices that categorize and display data will be used to help 
facilitate comparisons across the sampling groups. 
 
 
6. ETHICAL CONSIDERATIONS 
 
6.1 Ethical approval 
All study participants will be fully informed of the study procedures described above. Prior to 
study activation, for each participating site, ethical approval will be sought from the relevant 
institutional review boards / research ethics committees, national authorities, and other 
regulatory authorities. 
 
6.2 Informed consent 
All participants will be consented prior to participation and during the consent process they will 
be reminded that their participation is voluntary. Discussions with prospective participants and 
informed consent procedures will be conducted in private to protect patient confidentiality. We 
will obtain written informed consent from all participants. The study procedures, risks, and 
benefits will be discussed and we will answer all questions prior to obtaining consent. The 
consent forms will be translated into relevant local languages and back-translated into English 
to assure accurate translation. For illiterate participants, a literate impartial witness will be 
present during the entire consent process to ensure that all of the relevant information has 
been provided and the participant voluntarily gives consent. Eligible women who do not wish 
to participate in this study will continue to receive ANC care according to local clinical 
standards. We will obtain signed permission from the pregnant woman to collect locator 
information, including phone numbers, addresses, and directions. Permission for collection of 
locator information and contract tracing will be per usual practice at the clinic. 
6.3 Data storage 
The confidentiality of all study records will be safeguarded to the extent legally possible. To 
maintain participant confidentiality, all laboratory specimens, reports, study data and 
administrative forms will be identified by a coded number only. All databases will be secured 
with password-protected access systems, and computer entries will be identified by coded 
number only. Forms, lists, logbooks, appointment books, and any other listings or data forms 
that link participant ID numbers to other identifying information will be stored in a separate, 
locked fireproof safe cabinet in a locked local office. For the data collected through audio 
recordings, all audio files will be deleted from the recorders after data are transferred into a 
computer. Study-related computers, tablets, audio tapes, field notes, and other study materials 
will be kept in a locked cabinet in a locked local office. All data analysis will be performed using 
datasets which have only study ID numbers as unique identifiers. 
6.4 Confidentiality 
Measures will be taken to ensure safety of data and confidentiality of all our study participants. 
All participants will be assigned a unique study ID number. The interview guides will not 
capture names of the participants but only their ID number. No study participant will be 
identified in any report or publication about this study. However, for quality control and safety 
purposes, data that we collect may be reviewed by the sponsor of this study (i.e. United States 
National Institute of Health), the ethical and regulatory committees in Malawi and at the 
University of North Carolina at Chapel Hill. Clinical information with individual identifiers will 
not be released without the written permission of the participant. We expect these procedures 
to adequately protect participant confidentiality. 
6.5 Potential risks to participants 
No study drug will be administered thus all risks to participants relate to risks relevant to 
counseling and study assessment procedures. The risk to participants in this study is minimal. 
The main risk is possible discomfort to participants in answering question about themselves 

19 
 
and their decisions or actions related to PrEP. All participants will be asked to provide written 
informed consent before participation in the study. During the consent process, we will inform 
all participants that they may stop at any time and may ask the interviewer to skip any 
questions they do not feel comfortable answering.  
Participation in clinical research includes the risks of loss of confidentiality and discomfort with 
the personal nature of questions, particularly when discussing HIV infection or sexual 
behaviors. At each step in the study, we will protect participant privacy and confidentiality to 
reduce these risks (e.g., consenting participants in a private setting, not including names on 
case report forms, etc.). Although investigators will make every effort to protect participant 
privacy and confidentiality, it is possible that participant involvement in the study could become 
known to others, and that social harms may result (i.e., as participants could become known 
as HIV-positive). Participants will be given a phone number they can call at any time if they 
need assistance or feel they are at risk of harm. 
Venipuncture is sometimes associated with discomfort. Venipuncture may lead to 
discomfort, dizziness, bruising, swelling, and rarely, an infection at the venipuncture site. 
 
6.6 Protection Against Risks 
Risks to the participant will be minimized by thorough training and supervision of all staff. 
Participants’ privacy will be assured by conducting interviews, surveys, and other forms of 
data collection in a private location, for example, in a private room at the health facility. The 
confidentiality of all study records will be safeguarded to the extent legally possible. All study 
data, reports, and administrative forms will be identified by a coded number only to maintain 
participant confidentiality. All databases will be secured with password-protected access 
systems, and computer entries will be identified by coded number only. Forms, lists, logbooks, 
appointment books, audio-recordings, and any other data forms that link participant ID 
numbers to other identifying information will be stored in a separate, locked cabinet. All data 
analysis will be done on transcripts which have only the study number as a unique identifier. 
Clinical information with individual identifiers will not be released without the written permission 
of the participant. 
 
Participant name and contact information are the only individually identifiable private 
information that will be collected specifically for our project. Data will be entered into a 
protected electronic database and all analytic datasets will have only the study number as a 
unique identifier. Forms, logbooks, appointment books, and any other data forms that link 
participant ID numbers to other identifying information will be stored in a separate, locked file 
cabinet. Clinical information with individual identifiers will not be released without the written 
permission of the participant. Data collection forms, electronic databases, and printed data will 
only be supplied to appropriate study staff on an as-needed basis. Any publication about this 
research study will omit names and any other identifying information. 
 
Paper copies of consent forms, observation forms, exit interviews, and surveys will be kept in 
a locked room at the UNC Project office in Lilongwe. Only staff and researchers directly 
involved in processing and analyzing data will have access and will be allowed to transfer the 
data to electronic databases. Voice recordings and electronic databases will be stored in 
computers with password protection. Any computers used will also be encrypted. Each 
participant will be assigned a unique identification number, which will be used in databases 
and on transcriptions instead of any identifying information. Paper copies and original voice 
recordings will be stored for 3 years after the completion of the publications from this research. 
 
We expect these procedures to adequately protect participant confidentiality. However, it is 
possible that a participant’s study participation could become known to people in the 
community and may result in stigma or discrimination. Should that occur, study staff will work 

20 
 
with the participant and their family as appropriate to resolve the situation in whatever manner 
is preferred. All study procedures carry minimal risks. 
 
6.7 Potential Benefits of Proposed Research to Human Subjects and Others 
Participants will not benefit personally from participating in this research. The results of this 
study may benefit society as the results can be used to develop a decision-making aid to help 
pregnant women, their partners, and clinicians make decisions about PrEP use. An improved 
decision-making process may lead to more appropriate and adherence PrEP use, which may 
ultimately serve to prevent HIV infection during pregnancy and mother-to-child transmission 
of HIV. 
6.8 Inclusion of children, sub-populations, and vulnerable populations 
This study focuses on the outcomes of pregnant and breastfeeding women; as such, they 
must be included in our study population. Prisoners will be excluded as they receive care at 
separate facilities. 
6.9 Reimbursement/compensation 
There is no cost to participate in the study. Participants will be provided with transport 
reimbursement for each study visit, according to local research standards. 
6.10 Dissemination of findings 
Study findings will be disseminated through appropriate local channels, including academic 
and public health research symposia. We will report findings to relevant local authorities in 
Malawi. One or more publications will also be submitted to a peer-reviewed journal. Our study 
team plans to publish the study results whether positive or negative. The study participants’ 
privacy and confidentiality will be strictly maintained in all results dissemination or publication 
activities. 
7. WORK PLAN 
 
In the table below, we show our proposed timeline for the study activities (2 year study period) 
 
  
Y1 
Y2 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Study 
startup 
Study site & data 
systems setup 
X 
 
 
 
 
 
 
 
Protocol training 
X 
 
 
 
 
 
 
 
Instrument 
piloting 
X 
 
 
 
 
 
 
 
Pilot 
study 
Enrollment & 
intervention 
 
X 
X 
 
 
 
 
 
Follow up 
 
 
X 
X 
 
 
 
 
Fidelity 
assessment 
 
 
X 
X 
 
 
 
 
Analysis & Reporting 
 
 
 
X 
X 
X 
 
 
Data cleaning 
 
 
 
X 
X 
 
 
 
Quantitative analysis 
 
 
 
 
X 
X 
 
 
Qualitative analysis 
 
 
 
 
 
X 
X 
 
Results dissemination (local 
meetings, conferences) 
 
 
 
 
 
 
X 
X 
Publications 
 
 
 
 
 
 
X 
X 
 

21 
 
 
REFERENCES 
1.    Drake AL, Wagner A, Richardson B, John-Stewart G. Incident HIV during pregnancy 
and postpartum and risk of mother-to-child HIV transmission: a systematic review and 
meta-analysis. PLoS Med. 2014;11(2):e1001608. doi:10.1371/journal.pmed.1001608 
2.    Johnson NB, Hayes LD, Brown K, Hoo EC, Ethier KA, Centers for Disease Control 
and Prevention (CDC). CDC National Health Report: leading causes of morbidity and 
mortality and associated behavioral risk and protective factors--United States, 2005-
2013. MMWR Suppl. 2014;63(4):3-27. 
3.    Dinh T-H, Delaney KP, Goga A, et al. Impact of Maternal HIV Seroconversion during 
Pregnancy on Early Mother to Child Transmission of HIV (MTCT) Measured at 4-8 
Weeks Postpartum in South Africa 2011-2012: A National Population-Based 
Evaluation. PLoS ONE. 2015;10(5):e0125525. doi:10.1371/journal.pone.0125525 
4.    Lu L, Motswere-Chirwa C, Legwaila K. Abstract 15: HIV incidence in women during 
the first postpartum year: implications for PMTCT programs Francistown, Botswana, 
2010. 3rd International Workshop on HIV Pediatrics Rome, Italy: Reviews in Antiviral 
Therapy and Infectious Diseases 2011_8. 17. 
5.    Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in 
heterosexual men and women. N Engl J Med. 2012;367(5):399-410. 
doi:10.1056/NEJMoa1108524 
6.    Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure 
prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 
2012;367(5):423-434. doi:10.1056/NEJMoa1110711 
7.    Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV 
prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587-2599. 
doi:10.1056/NEJMoa1011205 
8.    World Health Organization. Preventing HIV during pregnancy and breastfeeding in 
the context of PrEP. Accessed September 13, 2023. 
https://www.who.int/publications/i/item/WHO-HIV-2017.09 
9.    Delany-Moretlwe S, Hughes JP, Bock P, et al. Cabotegravir for the prevention of HIV-
1 in women: results from HPTN 084, a phase 3, randomised clinical trial. Lancet. 
2022;399(10337):1779-1789. doi:10.1016/S0140-6736(22)00538-4 
10.   Cottrell ML, Yang KH, Prince HMA, et al. A translational pharmacology approach to 
predicting outcomes of preexposure prophylaxis against HIV in men and women using 
tenofovir disoproxil fumarate with or without emtricitabine. J Infect Dis. 
2016;214(1):55-64. doi:10.1093/infdis/jiw077 
11.   Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-Based Preexposure 
Prophylaxis for HIV Infection Among African Women. Obstet Gynecol Surv. 
2015;70(7):444-446. doi:10.1097/01.ogx.0000466878.37011.6f 
12.   Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection 
among African women. N Engl J Med. 2012;367(5):411-422. 
doi:10.1056/NEJMoa1202614 

22 
 
13.   Thomson KA, Baeten JM, Mugo NR, Bekker L-G, Celum CL, Heffron R. Tenofovir-
based oral preexposure prophylaxis prevents HIV infection among women. Curr Opin 
HIV AIDS. 2016;11(1):18-26. doi:10.1097/COH.0000000000000207 
14.   Amico KR, Mansoor LE, Corneli A, Torjesen K, van der Straten A. Adherence support 
approaches in biomedical HIV prevention trials: experiences, insights and future 
directions from four multisite prevention trials. AIDS Behav. 2013;17(6):2143-2155. 
doi:10.1007/s10461-013-0429-9 
15.   Corneli A, Perry B, McKenna K, et al. Participants’ Explanations for Nonadherence in 
the FEM-PrEP Clinical Trial. J Acquir Immune Defic Syndr. 2016;71(4):452-461. 
doi:10.1097/QAI.0000000000000880 
16.   van der Straten A, Stadler J, Montgomery E, et al. Women’s experiences with oral 
and vaginal pre-exposure prophylaxis: the VOICE-C qualitative study in 
Johannesburg, South Africa. PLoS ONE. 2014;9(2):e89118. 
doi:10.1371/journal.pone.0089118 
17.   Madrasi K, Chaturvedula A, Haberer JE, et al. Markov mixed effects modeling using 
electronic adherence monitoring records identifies influential covariates to HIV 
preexposure prophylaxis. J Clin Pharmacol. 2017;57(5):606-615. 
doi:10.1002/jcph.843 
18.   Amico KR, Wallace M, Bekker L-G, et al. Experiences with HPTN 067/ADAPT Study-
Provided Open-Label PrEP Among Women in Cape Town: Facilitators and Barriers 
Within a Mutuality Framework. AIDS Behav. 2017;21(5):1361-1375. 
doi:10.1007/s10461-016-1458-y 
19.   Ware NC, Wyatt MA, Haberer JE, et al. What’s love got to do with it? Explaining 
adherence to oral antiretroviral pre-exposure prophylaxis for HIV-serodiscordant 
couples. J Acquir Immune Defic Syndr. 2012;59(5):463-468. 
doi:10.1097/QAI.0b013e31824a060b 
20.   Roberts ST, Haberer J, Celum C, et al. Intimate Partner Violence and Adherence to 
HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant 
Relationships: A Prospective Cohort Study. J Acquir Immune Defic Syndr. 
2016;73(3):313-322. doi:10.1097/QAI.0000000000001093 
21.   Sandman L, Granger BB, Ekman I, Munthe C. Adherence, shared decision-making 
and patient autonomy. Med Health Care Philos. 2012;15(2):115-127. 
doi:10.1007/s11019-011-9336-x 
22.   Elwyn G, Frosch D, Rollnick S. Dual equipoise shared decision making: definitions for 
decision and behaviour support interventions. Implement Sci. 2009;4:75. 
doi:10.1186/1748-5908-4-75 
23.   Shay LA, Lafata JE. Where is the evidence? A systematic review of shared decision 
making and patient outcomes. Med Decis Making. 2015;35(1):114-131. 
doi:10.1177/0272989X14551638 
24.   Street RL, Makoul G, Arora NK, Epstein RM. How does communication heal? 
Pathways linking clinician-patient communication to health outcomes. Patient Educ 
Couns. 2009;74(3):295-301. doi:10.1016/j.pec.2008.11.015 
25.   Beach MC, Duggan PS, Moore RD. Is patients’ preferred involvement in health 
decisions related to outcomes for patients with HIV? J Gen Intern Med. 
2007;22(8):1119-1124. doi:10.1007/s11606-007-0241-1 

23 
 
26.   García PR, Côté JK. Factors Affecting Adherence to Antiretroviral Therapy in People 
Living with HIV/AIDS. Journal of the Association of Nurses in AIDS Care. 
2003;14(4):37-45. doi:10.1177/1055329003252424 
27.   Enriquez M, McKinsey DS. Strategies to improve HIV treatment adherence in 
developed countries: clinical management at the individual level. HIV AIDS (Auckl). 
2011;3:45-51. doi:10.2147/HIV.S8993 
28.   Guadagnoli E, Ward P. Patient participation in decision-making. Soc Sci Med. 
1998;47(3):329-339. doi:10.1016/s0277-9536(98)00059-8 
29.   Morrison C, Fichorova RN, Mauck C, et al. Cervical inflammation and immunity 
associated with hormonal contraception, pregnancy, and HIV-1 seroconversion. J 
Acquir Immune Defic Syndr. 2014;66(2):109-117. 
doi:10.1097/QAI.0000000000000103 
30.   MacIntyre DA, Chandiramani M, Lee YS, et al. The vaginal microbiome during 
pregnancy and the postpartum period in a European population. Sci Rep. 
2015;5:8988. doi:10.1038/srep08988 
31.   Businge CB, Longo-Mbenza B, Mathews V. Risk factors for incident HIV infection 
among antenatal mothers in rural Eastern Cape, South Africa. Glob Health Action. 
2016;9:29060. doi:10.3402/gha.v9.29060 
32.   Peltzer K, Mlambo G. Sexual HIV risk behaviour and associated factors among 
pregnant women in Mpumalanga, South Africa. BMC Pregnancy Childbirth. 
2013;13:57. doi:10.1186/1471-2393-13-57 
33.   Pintye J, Drake AL, Kinuthia J, et al. A risk assessment tool for identifying pregnant 
and postpartum women who may benefit from preexposure prophylaxis. Clin Infect 
Dis. 2017;64(6):751-758. doi:10.1093/cid/ciw850 
34.   Liang X, Garland S, Hartley S, et al. Attitudes and acceptance of potential changes in 
cervical screening: Views of obstetricians and gynaecologists. BJOG-AN 
INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY. 
2015;122:80. 
35.   Humphrey JH, Marinda E, Mutasa K, et al. Mother to child transmission of HIV 
among Zimbabwean women who seroconverted postnatally: prospective cohort study. 
BMJ. 2010;341:c6580. doi:10.1136/bmj.c6580 
36.   Dunn DT, Newell ML, Ades AE, Peckham CS. Risk of human immunodeficiency virus 
type 1 transmission through breastfeeding. Lancet. 1992;340(8819):585-588. 
doi:10.1016/0140-6736(92)92115-v 
37.   Van de Perre P, Simonon A, Msellati P, et al. Postnatal transmission of human 
immunodeficiency virus type 1 from mother to infant. A prospective cohort study in 
Kigali, Rwanda. N Engl J Med. 1991;325(9):593-598. 
doi:10.1056/NEJM199108293250901 
38.   HIV/AIDS Joint United Nations Programme on. Improving UNAIDS’paediatric and 
adolescent estimates. Geneva, Swizerland: UNAIDS. 2019. 
39.   Mofenson LM, Baggaley RC, Mameletzis I. Tenofovir disoproxil fumarate safety for 
women and their infants during pregnancy and breastfeeding. AIDS. 2017;31(2):213-
232. doi:10.1097/QAD.0000000000001313 

24 
 
40.   Pintye J, Singa B, Wanyonyi K, et al. Preexposure Prophylaxis for Human 
Immunodeficiency Virus (HIV) Prevention Among HIV-uninfected Pregnant Women: 
Estimated Coverage Using Risk-based Versus Regional Prevalence Approaches. Sex 
Transm Dis. 2018;45(12):e98-e100. doi:10.1097/OLQ.0000000000000898 
41.   Fonner VA, Dalglish SL, Kennedy CE, et al. Effectiveness and safety of oral HIV 
preexposure prophylaxis for all populations. AIDS. 2016;30(12):1973-1983. 
doi:10.1097/QAD.0000000000001145 
42.   Murnane PM, Celum C, Mugo N, et al. Efficacy of preexposure prophylaxis for HIV-1 
prevention among high-risk heterosexuals: subgroup analyses from a randomized 
trial. AIDS. 2013;27(13):2155-2160. doi:10.1097/QAD.0b013e3283629037 
43.   Malawi. Malawi Demographic and Health Survey, 2010. Malawi Demographic and 
Health Survey, 2010. 2011. 
44.   Mellins CA, Chu C, Malee K, et al. Adherence to antiretroviral treatment among 
pregnant and postpartum HIV-infected women. AIDS Care. 2008;20(8):958-968. 
doi:10.1080/09540120701767208 
45.   Vaz MJR, Barros SMO, Palacios R, et al. HIV-infected pregnant women have greater 
adherence with antiretroviral drugs than non-pregnant women. Int J STD AIDS. 
2007;18(1):28-32. doi:10.1258/095646207779949808 
46.   Sullivan KM, Ford ES, Azrak MF, Mokdad AH. Multivitamin Use in Pregnant and 
Nonpregnant Women: Results from the Behavioral Risk Factor Surveillance System. 
Public Health Rep. 2009;124(3):384-390. doi:10.1177/003335490912400307 
47.   Ambia J, Mandala J. A systematic review of interventions to improve prevention of 
mother-to-child HIV transmission service delivery and promote retention. J Int AIDS 
Soc. 2016;19(1):20309. doi:10.7448/IAS.19.1.20309 
48.   Guidelines on Long-Acting Injectable Cabotegravir for HIV Prevention. World Health 
Organization; 2022. 
49.   Mugo NR, Hong T, Celum C, et al. Pregnancy incidence and outcomes among 
women receiving preexposure prophylaxis for HIV prevention: a randomized clinical 
trial. JAMA. 2014;312(4):362-371. doi:10.1001/jama.2014.8735 
50.   Heffron R, Mugo N, Hong T, et al. Pregnancy outcomes and infant growth among 
babies with in-utero exposure to tenofovir-based preexposure prophylaxis for HIV 
prevention. AIDS. 2018;32(12):1707-1713. doi:10.1097/QAD.0000000000001867 
51.   Mugwanya KK, Hendrix CW, Mugo NR, et al. Pre-exposure Prophylaxis Use by 
Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of 
Antiretroviral Excretion in Breast Milk and Infant Absorption. PLoS Med. 
2016;13(9):e1002132. doi:10.1371/journal.pmed.1002132 
52.   Price JT, Wheeler SB, Stranix-Chibanda L, et al. Cost-Effectiveness of Pre-exposure 
HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa. J Acquir 
Immune Defic Syndr. 2016;72 Suppl 2(Suppl 2):S145-53. 
doi:10.1097/QAI.0000000000001063 
53.   Decision making: A psychological analysis of conflict, choice, and commitment. Eval 
Program Plann. 1978;1(2):167. doi:10.1016/0149-7189(78)90042-3 

25 
 
54.   Loh A, Simon D, Wills CE, Kriston L, Niebling W, Härter M. The effects of a shared 
decision-making intervention in primary care of depression: a cluster-randomized 
controlled trial. Patient Educ Couns. 2007;67(3):324-332. 
doi:10.1016/j.pec.2007.03.023 
55.   Schoenthaler AM, Schwartz BS, Wood C, Stewart WF. Patient and physician factors 
associated with adherence to diabetes medications. Diabetes Educ. 2012;38(3):397-
408. doi:10.1177/0145721712440333 
56.   Kumar R, Korthuis PT, Saha S, et al. Decision-making role preferences among 
patients with HIV: associations with patient and provider characteristics and 
communication behaviors. J Gen Intern Med. 2010;25(6):517-523. 
doi:10.1007/s11606-010-1275-3 
57.   Kremer H, Ironson G, Schneiderman N, Hautzinger M. "It’s my body’’: does patient 
involvement in decision making reduce decisional conflict? Med Decis Making. 
2007;27(5):522-532. doi:10.1177/0272989X07306782 
58.   Deber RB, Kraetschmer N, Urowitz S, Sharpe N. Do people want to be autonomous 
patients? Preferred roles in treatment decision-making in several patient populations. 
Health Expect. 2007;10(3):248-258. doi:10.1111/j.1369-7625.2007.00441.x 
59.   Ryan RM, Deci EL. Self-determination theory and the facilitation of intrinsic 
motivation, social development, and well-being. Am Psychol. 2000;55(1):68-78. 
doi:10.1037/0003-066X.55.1.68 
60.   Zambia. Zambia: Demographic and Health Survey, 2013-14. Zambia: Demographic 
and Health Survey, 2013-14. 2015;1. 
61.   Watson-Jones D, Balira R, Ross DA, Weiss HA, Mabey D. Missed opportunities: poor 
linkage into ongoing care for HIV-positive pregnant women in Mwanza, Tanzania. 
PLoS ONE. 2012;7(7):e40091. doi:10.1371/journal.pone.0040091 
62.   Kalichman SC, Cherry C, Kalichman MO, et al. Randomized clinical trial of HIV 
treatment adherence counseling interventions for people living with HIV and limited 
health literacy. J Acquir Immune Defic Syndr. 2013;63(1):42-50. 
doi:10.1097/QAI.0b013e318286ce49 
63.   Williams S, Renju J, Ghilardi L, Wringe A. Scaling a waterfall: a meta-ethnography of 
adolescent progression through the stages of HIV care in sub-Saharan Africa. J Int 
AIDS Soc. 2017;20(1):21922. doi:10.7448/IAS.20.1.21922 
64.   Seidman DL, Weber S, Cohan D. Offering pre-exposure prophylaxis for HIV 
prevention to pregnant and postpartum women: a clinical approach. J Int AIDS Soc. 
2017;20(Suppl 1):21295. doi:10.7448/IAS.20.2.21295 
65.   Stacey D, Légaré F, Lewis K, et al. Decision aids for people facing health treatment 
or screening decisions. Cochrane Database Syst Rev. 2017;4(4):CD001431. 
doi:10.1002/14651858.CD001431.pub5 
66.   Hill LM, Golin CE, Saidi F, et al. Understanding PrEP decision making among 
pregnant women in Lilongwe, Malawi: A mixed-methods study. J Int AIDS Soc. 
2022;25(9):e26007. doi:10.1002/jia2.26007 
67.   O’Connor AM, Drake ER, Fiset V, Graham ID, Laupacis A, Tugwell P. The Ottawa 
patient decision aids. Eff Clin Pract. 1999;2(4):163-170. 

26 
 
68.   Elwyn G, O’Connor A, Stacey D, et al. Developing a quality criteria framework for 
patient decision aids: online international Delphi consensus process. BMJ. 
2006;333(7565):417. doi:10.1136/bmj.38926.629329.AE 
69.   Malawi National Oral Pre-Exposure Prophylaxis (PrEP) Guidelines - Malawi National 
PrEP Guidelines - Document Management System. Accessed September 13, 2023. 
https://dms.hiv.health.gov.mw/dataset/malawi-national-oral-pre-exposure-prophylaxis-
prep-guidelines/resource/f5be8a13-c3a9-46e8-afb6-fef0a0912c2f 
70.   Weiner BJ, Lewis CC, Stanick C, et al. Psychometric assessment of three newly 
developed implementation outcome measures. Implement Sci. 2017;12(1):108. 
doi:10.1186/s13012-017-0635-3 
71.   O’Connor AM. Validation of a decisional conflict scale. Med Decis Making. 
1995;15(1):25-30. doi:10.1177/0272989X9501500105 
72.   Garvelink MM, Boland L, Klein K, et al. Decisional Conflict Scale Use over 20 Years: 
The Anniversary Review. Med Decis Making. 2019;39(4):301-314. 
doi:10.1177/0272989X19851345 
73.   Knops AM, Goossens A, Ubbink DT, Legemate DA, Stalpers LJ, Bossuyt PM. 
Interpreting patient decisional conflict scores: behavior and emotions in decisions 
about treatment. Med Decis Making. 2013;33(1):78-84. 
doi:10.1177/0272989X12453500 
74.   Sun Q. Predicting Downstream Effects of High Decisional Conflict: Meta-Analyses of 
the Decisional Conflict Scale. 2005. 
75.   Schauer AP, Sykes C, Cottrell ML, Prince H, Kashuba ADM. Validation of an LC-
MS/MS assay to simultaneously monitor the intracellular active metabolites of 
tenofovir, emtricitabine, and lamivudine in dried blood spots. J Pharm Biomed Anal. 
2018;149:40-45. doi:10.1016/j.jpba.2017.10.030 
76.   Stranix-Chibanda L, Anderson PL, Kacanek D, et al. Tenofovir Diphosphate 
Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and 
Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan 
Africa. Clin Infect Dis. 2021;73(7):e1893-e1900. doi:10.1093/cid/ciaa1872