Z 31901 - Combination Partner HIV Testing Strategies for HIV-positive and HIV-negative Pregnant Women: A Pilot Study
Phase: NA
Conditions: HIV
Sponsor: University of North Carolina, Chapel Hill

 
 
STUDY PROTOCOL 
 
 
Combination Partner HIV Testing Strategies for                                          
HIV-positive and HIV-negative Pregnant Women:  
A Pilot Study 
 
 
 
 
NCT number NCT04124536 
Document Date 6/17/2019 
 

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Combination Partner HIV Testing Strategies for HIV-positive and HIV-negative Pregnant 
Women: A Pilot Study 
 
 
  
Protocol version 1.2 
June 17th 2019 
 
 
 
 
Funded by: 
US National Institutes of Health  
R01 AI131060 
A dyad approach to combination HIV prevention in pregnancy for Zambia and Malawi 
 
 
 Protocol Co-Chairs:  
Wilbroad Mutale MBChB, MPhil, PhD 
Benjamin H. Chi, MD, MSc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
INVESTIGATORS AND SCIENTIFIC TEAM ............................................................................................ 4 
ABBREVIATIONS AND ACRONYMS ...................................................................................................... 6 
PROTOCOL SUMMARY .......................................................................................................................... 7 
1.0 INTRODUCTION ............................................................................................................................. 8 
2.0 STATEMENT OF THE PROBLEM .................................................................................................. 8 
3.0 RATIONALE .................................................................................................................................... 8 
4.0 LITERATURE REVIEW ................................................................................................................... 9 
4.1 Male partner HIV testing, couples HIV testing and counseling ................................................................... 9 
4.2 Evidenced-based strategies to increase partner HIV testing .................................................................... 10 
4.3 Our formative work ................................................................................................................................... 11 
5.0 RESEARCH QUESTION .............................................................................................................. 13 
6.0 OBJECTIVES AND OUTCOMES ................................................................................................. 14 
6.1 Primary and secondary objectives ............................................................................................................ 14 
6.2 Study Outcomes ........................................................................................................................................ 14 
7.0 HYPOTHESES .............................................................................................................................. 15 
8.0 METHODOLOGY .......................................................................................................................... 15 
8.1 Study design .............................................................................................................................................. 15 
8.2 Study site and study population ................................................................................................................ 15 
8.3 Selection of Participants ............................................................................................................................ 15 
8.5 Recruitment and enrollment procedures .................................................................................................. 16 
8.6 Study follow-up ......................................................................................................................................... 17 
8.7 Retention ................................................................................................................................................... 17 
8.8 Safety Monitoring ...................................................................................................................................... 18 
8.9 Qualitative Interviews ............................................................................................................................... 18 
8.10 Pre-intervention Phase ............................................................................................................................ 19 
8.11 Data Management and Storage .............................................................................................................. 19 
8.12 Sample Size .............................................................................................................................................. 20 
8.13 Data Analysis Plan ................................................................................................................................... 21 
8.13.1 General Approach: ............................................................................................................................... 21 
8.13.2 Analysis of the Primary Endpoint ......................................................................................................... 22 
8.13.3 Analysis of Secondary Endpoints .......................................................................................................... 22 
8.14 Analysis: qualitative component ............................................................................................................. 23 

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9.0 ETHICAL CONSIDERATIONS ...................................................................................................... 23 
9.1 Ethical approval ......................................................................................................................................... 23 
9.2 Informed consent ...................................................................................................................................... 23 
9.3 Data storage .............................................................................................................................................. 23 
9.4 Confidentiality ........................................................................................................................................... 24 
9.5 Potential risks of proposed research to study participants ....................................................................... 24 
9.6 Potential benefits of proposed research to study participants and others .............................................. 25 
9.7 Inclusion of children, sub-populations, and vulnerable populations ........................................................ 25 
9.8 Reimbursement/compensation ................................................................................................................ 25 
9.9 Dissemination of findings .......................................................................................................................... 25 
10.0 TIME FRAME .............................................................................................................................. 25 
11.0 BUDGET ..................................................................................................................................... 25 
12.0 REFERENCES ............................................................................................................................ 26 
13.0 APPENDICES ............................................................................................................................. 30 
 
 
 

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INVESTIGATORS AND SCIENTIFIC TEAM 
Protocol Chairs: 
Dr. Wilbroad Mutale MBChB, MPhil, PhD 
Department of Health Policy 
University of Zambia School of Public Health,  
Box 50110, Lusaka, Zambia 
Email: wmutale@yahoo.com  
 
Benjamin H. Chi, MD, MSc 
Division of Global Women’s Health 
Department of Obstetrics and Gynecology 
University of North Carolina at Chapel Hill 
111 Mason Farm Rd; CB 7577, 4300 MBRB 
Chapel Hill, NC 27599 
Email: bchi@med.unc.edu   
 
Investigator of Record (IOR) 
Kellie Freeborn, RN, NP-BC, MSc., PhD 
Division of Global Women’s Health 
Department of Obstetrics and Gynecology 
University of North Carolina at Chapel Hill 
111 Mason Farm Rd; CB 7577, 4300 MBRB 
Chapel Hill, NC 27599-7577 
Email: kellie.freeborn@med.unc.edu  
 
Co-Investigators: 
Margaret Kasaro, MBChB, MS 
 
 
 
 
 
UNC Global Projects - Zambia  
348 Independence Avenue 
Lusaka, Zambia 
Email: margaret.kasaro@unclusaka.org  
 
Andrew Kumwenda, MBChB, MPhil, MPH, MMed 
Department of Obstetrics and Gynaecology 
University of Zambia School of Medicine  
P.O. Box 50110 
Lusaka, Zambia.  
Email: andrew.kumwenda@unza.zm  
 
 
Oliver Mweemba, MPhil, PhD 
Department of Health Promotion and Education 
University of Zambia School of Public Health  
P.O. Box 50110 
Lusaka, Zambia 
Email: mweemba2@yahoo.com  

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Suzanne Maman, PhD 
Department of Health Behavior 
Gillings School of Global Public Health 
University of North Carolina at Chapel Hill 
135 Dauer Drive  
Chapel Hill, NC 27599 
Email: maman@email.unc.edu  
 
Kimberly Powers, PhD 
Department of Epidemiology  
Gillings School of Global Public Health 
University of North Carolina at Chapel Hill  
135 Dauer Drive  
Chapel Hill, NC 27599 
Email: powersk@email.unc.edu 
 
Nora Rosenberg, MSPH, PhD 
Department of Health Behavior 
Gillings School of Global Public Health 
University of North Carolina at Chapel Hill 
302 Rosenau Hall Campus Box 7440  
Chapel Hill, NC 27599 
Email: nrosenbe@email.unc.edu   
  
 
 
 
Katie Mollan, MS 
UNC Center for AIDS Research – Biostatistics Core 
School of Medicine 
University of North Carolina at Chapel Hill  
135 Dauer Drive  
Chapel Hill, NC 27599 
Email: kmollan@unc.edu  
 
Cassidy Claassen, MD, MPH 
Center for International Health, Education, and Biosecurity 
Institute for Human Virology at University of Maryland School of Medicine 
MGIC-Zambia, 6392 Dunduza Chisidza Crescent 
Lusaka, Zambia 
Email: cclaassen@ihv.umaryland.edu 
 
 
 
 
 
 
 

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ABBREVIATIONS AND ACRONYMS 
 
ANC 
Antenatal care 
ART 
Antiretroviral therapy 
CI 
Confidence interval 
HIV 
Human immunodeficiency virus 
SD- HIVST 
Secondary distribution of HIV self-test kits 
HTS 
HIV testing services 
IPV 
Intimate partner violence 
PrEP 
Pre-exposure prophylaxis 
PMTCT 
Prevention of mother to child transmission 
RR 
Relative risk 
SSI 
Semi-structured interviews 
 
 

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PROTOCOL SUMMARY 
Background: Despite intensive programmatic efforts, a significant proportion of pregnant 
women in Zambia do not know their partner’s HIV status. Being unaware of a partner’s HIV 
status represents a major barrier to HIV prevention and treatment efforts.  
Objective:  The overall objective of this study is to evaluate whether the addition of secondary 
distribution HIV self-test kits (SD-HIVST) to existing partner notification guidelines increases the 
proportion of male partners who access facility-based HIV testing services (HTS), when 
compared to the partner notification strategy alone.  
Design: Two parallel, unmasked, 1:1 pilot randomized controlled trials among pregnant women 
seeking ANC services in Lusaka, Zambia. We will compare two strategies for HIV testing of 
partners in parallel trials, one enrolling HIV-positive pregnant women and the other enrolling HIV-
negative pregnant women.  
Study Arms: Participants randomly assigned to the control arm will be asked to identify recent 
sexual partner(s) and these individuals will then be provided the existing partner notification 
strategies for HIV testing. Those randomized to the intervention arm will receive identical partner 
notification services; in addition, they will be offered HIV self-test kits (i.e., SD-HIVST)—and 
instructions on their use—for their partners.   
Population: Pregnant women 18 years of age or older over who enter antenatal care (ANC), 
stratified by HIV status. 
Study Site: Chipata Level 1 Hospital in Lusaka, Zambia.  
Duration and Follow up: The duration of recruitment is expected to be six months. The length 
of participant follow-up is 30 days from enrollment.  
Study Outcomes: The main outcome will be the proportion of primary male partners who 
complete facility-based HTS according to participant self-report.  The main outcome will be 
the proportion of primary male partners who complete facility-based HTS according to 
participant self-report. Secondary outcomes include: proportion of couples (pregnant 
woman and partner) who receive facility-based HTS together; incidence of social harms and 
other adverse events associated with the HIV testing approaches; participant uptake 
preferences and healthcare provider opinions about partner notification services and SD-HIVST; 
proportion of secondary male partners who complete HIV testing as reported by the 
pregnant woman; average number of partners tested to identify one HIV-positive partner and 
average number of SD-HIVST kits distributed to identify one HIV positive partner.  
Relevance: To achieve the goal of eliminating mother-to-child transmission of HIV in sub-
Saharan Africa by 2030 and to meet the ambitious targets set forth by international agencies 
(e.g., the “95-95-95” targets from UNAIDS1); there is an urgent need to scale up testing. Current 
guidelines in Zambia recommend both partner notification and SD-HIVST as strategies to 
increase HIV awareness; however, a combined approach has not been investigated for pregnant 
women and their partners. Due to the traditionally low rates of partner HIV testing in antenatal 
settings, such an approach could have immediate policy relevance nationally and regionally.   
 

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1.0 INTRODUCTION 
Despite the demonstrated effort to increase HIV testing in couples during the antenatal period, 
HIV testing among male partners of women attending antenatal care (ANC) has remained low.2 
In a systematic review of male partner testing strategies, Hensen and colleagues found rates to 
be as low as 5% within existing health services.3 Data from urban Zambia suggests that more 
than 60% of new infections occur within marriage or cohabiting relationships4 and 17% of 
pregnant couples in Lusaka are serodiscordant.5 Novel ways to engage men in HIV testing are 
crucial for the prevention of mother-to-child HIV transmission (PMTCT)6 and heterosexual HIV 
transmission. 
Increasing HIV testing programs in pregnant women has been shown to reduce mother-to-child 
HIV transmission rates.14-16 However, the benefit of testing programs extends further than 
protecting the mother and child. In couples where the female partner is HIV-positive, male 
partner HIV testing during the antenatal period has been shown to increase ART uptake,7 
adherence,2 and condom use.2 Expanding HIV testing services (HTS) to include the male 
partners of HIV-negative pregnant women may reduce the stigma associated with testing,8 
increase awareness of HIV status, and decrease transmission. Secondary distribution of HIV 
self-test kits (SD-HIVST), in particular, has been shown to  decrease in HIV testing stigma and 
increase male partner testing outside ANC settings.9  
We propose parallel pilot randomized controlled trials to assess whether the addition of SD-
HIVST to an existing strategy of partner notification increases partner testing in an antenatal 
setting. Although programs have emphasized such strategies among HIV-positive women, we 
will evaluate these two strategies (i.e., partner notification alone vs. partner notification plus SD-
HIVST) both in HIV-positive and HIV-negative antenatal populations. Understanding the 
performance, feasibility and acceptability of this strategy among pregnant women and their 
partners will help to inform broader HIV policy.  
2.0 STATEMENT OF THE PROBLEM 
PMTCT services have expanded rapidly and dramatically reduced pediatric HIV in sub-Saharan 
Africa. The rapid progression of scientific, programmatic, and policy advances have moved us 
closer to the “virtual elimination” of pediatric HIV.10 In many African settings, acceptance of 
antenatal HIV testing in health facilities is near universal.11 Despite the best programmatic 
efforts, however, a significant proportion of women are unable to bring their partners in for HIV 
testing and the partner HIV status remains unknown. This represents an important missed 
opportunity for HIV prevention, care, and treatment. 
3.0 RATIONALE 
In order to achieve the goal of eliminating mother-to-child transmission of HIV in sub-Saharan 
Africa by 2030—and to meet the ambitious 95-95-95 target set forth by UNAIDS1—new ways 
are needed to urgently scale up testing and counseling. Current HIV guidelines in Zambia 
recommend inclusion of HIV testing in routine screening for all pregnant women and their 
partners. 
In antenatal settings, a partner notification approach has been introduced for HIV-positive 
pregnant women, including client self-referral, provider contract referral, provider referral and/or 
a dual referral for identified partners. Despite the high HIV incidence rates observed during 

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pregnancy and breastfeeding,12 similar recommendations have not been evaluated for women 
who initially test HIV-negative. In addition, although SD-HIVST has also been endorsed by the 
Zambian Ministry of Health13, currently this strategy has not been incorporated into partner 
notification protocols. Given the general acceptability of SD-HIVST,14 including in antenatal 
populations,9,15 its incorporation has potential to further enhance existing HTS.  
The overall objective of this study is to evaluate whether the addition of SD-HIVST to existing 
partner notification guidelines increases the proportion of male partners who access facility-
based HTS, when compared to the partner notification strategy alone. In two parallel randomized 
trials, we will compare these two HIV testing strategies among partners of HIV- positive and HIV-
negative pregnant women. 
4.0 LITERATURE REVIEW 
4.1 Male partner HIV testing, couples HIV testing and counseling  
Increasing male partner HIV testing is recognized as a key component for PMTCT services.2 
Male partner involvement in ANC testing and counseling programs has positive effects on 
continued ANC attendance,16,17 PMTCT uptake,7,18 infant outcomes,19,20 and uptake of HIV 
prevention methods such as treatment as prevention21 and male circumcision.22 Aluisio and 
colleagues, for example, found that male involvement in PMTCT could reduce the risk of vertical 
transmission and the composite risk of infant HIV infection or mortality by as much as 40%.23  
In sub-Saharan Africa, where men are less likely to know their HIV status compared to women,7 
barriers to HIV testing exist at different levels. In their systematic review Morfaw and colleagues24 
identified factors associated with increased male partners HIV testing in PMTCT programs. 
These were categorized at the level of the health system, individual, and couple (Table 1). Novel 
ways to engage men—who often do not access institutional healthcare—in HTS are crucial for 
the elimination of HIV.25  
 
 
 

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Table 1: Facilitators to male involvement in HIV testing in ANC settings24  
Health System 
Individual 
Couples 
• Invitation letters 
• Offering counseling and testing 
for HIV at alternate sites 
• Offering counseling and testing 
for HIV within ANC settings 
• Availability of personnel to 
encourage testing and facilitate 
disclosure 
• Counseling services during 
non-working hours 
• Holding of open discussions on 
free prenatal testing for 
partners 
• Providing men time to 
consider PMTCT 
recommendations 
• Increased male knowledge 
of HIV and perceived 
benefits of PMTCT 
• Offering routine couples 
testing 
• Discussion of PMTCT within 
the couple 
• Change from voluntary 
counseling and testing to 
routine testing and counseling 
• Offering routine couples 
counseling 
 
The disclosure of HIV status between pregnant women and their partners is critical for HIV 
prevention and this important process begins with partner HIV testing. Previous studies have 
shown that when individuals are aware of their HIV status, they are more likely to take measures 
to reduce their risk of transmitting HIV to others.26 Couples who access HTS have been shown 
to benefit through increase relationship cohesion and normalization of HIV status; decrease 
intimate partner violence and stigma; increase uptake and adherence to antiretroviral therapy; 
increase relationship cohesion and normalization of HIV status;27 and decrease IPV and 
stigma.28-30  
4.2 Evidenced-based strategies to increase partner HIV testing 
A number of promising interventions have been studied to increase couples and male partner 
testing in ANC settings. Below, we highlight approaches that have garnered recent attention in 
the medical literature.2,31 Although each has been shown to be effective in clinical trials and 
implementation studies, no one approach has reached the high testing thresholds targeted by 
national programs or international agencies.1,13,32 
Use of partner notification services, either passive or active, for HIV testing is an established 
practice supported by a growing body of literature.33-35  In Malawi, for example, the use of  an 
invitation card increased the chances that a male partner would accompany the pregnant woman 
to her next antenatal visit (28% vs. 19%, p=0.02).36 The invitation approach was also found to 
be acceptable in Tanzania, where 54% of women returned with their partners after being issued 
an invitation letter; of these, 81% agreed to couples-based HIV testing.37 In South Africa, male 
partners receiving an invitation for HIV testing were more likely to undergo male partner testing, 
compared to those receiving an invitation for a pregnancy information session (32% vs. 11%, 
RR 2.82, 95% confidence interval [CI]: 2.14–3.72).38 In a randomized study, Rosenberg, et al. 
found that an invitation letter with follow-up contact tracing for partners resulted in a higher 
proportion of HIV testing among male partners compared to the standard of care (74% vs. 52%, 
p<0.001).39 Although male partner HIV testing rates were initially similar between the two arms, 
they increased considerably once contact tracing efforts began.  

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Another promising approach to increase male partner HIV testing is health care worker delivered 
home-based testing. This strategy extends the reach of health services into the community and 
may provide greater convenience and privacy. In Zambia, such activities have been incorporated 
into partner notification approaches—specifically for provider and dual referral—via community-
based healthcare providers.  A pair of randomized trials, both from Kenya, supports these 
findings. At 6 weeks postpartum, Osoti and colleagues reported higher rates of male partner 
engagement (89% vs. 37%, p<0.001) and male partner HIV testing (85% vs. 36%, p<0.001) in 
the home-based visit arm, compared to a clinic invitation alone.40 In secondary analysis, both 
the pregnant participants (54%) and male partners (68%) preferred home-based testing to 
traditional venues such as ANC or voluntary HIV testing and counseling sites. The majority (81% 
of men and 65% of women) would recommend this testing approach to others.41 Krakowiak42 
and colleagues reported similar findings. At 6 months postpartum, home-based education and 
HIV testing were associated with higher male partner testing (RR: 2.10, 95%CI: 1.81–2.42), 
testing as a couple (RR: 3.17, 95%CI: 2.53–3.98), and knowledge of male partner HIV status 
(RR: 3.38, 95%CI: 1.70–6.71), compared to clinic invitation alone.43 The intervention was also 
shown to be cost-effective in formal analyses.44 
Secondary distribution of HIV self-testing kits (SD-HIVST) is currently endorsed by the World 
Health Organization and Zambian HIV testing guidelines. 13,35 SD-HIVST is associated with an 
increased uptake and frequency of testing45 and it has the potential to increase HIV disclosure 
within couples. Benefits of the SD-HIVST strategy include increased convenience, shorter 
turnaround time for results, improved testing privacy, and greater sense of autonomy.9,46,47 
Additionally, SD-HIVST has been shown to reduce fears regarding lack of confidentiality and 
potential stigma and to increase facility-based confirmatory testing in male partners.46,48,49 In a 
recent survey study of adolescents and adults in Lusaka SD-HIVST was found to be acceptable 
and scale up of their use was recommended.9 SD-HIVST to pregnant women, for use by their 
male partners, is a relatively new approach, but early findings have been encouraging. In Kenya, 
a cohort study found the approach to be acceptable, with high proportions of distribution of self-
tests to partners during pregnancy (91%) and postpartum (86%).46 Although IPV was infrequent 
following the distribution of self-test kits (2 of 91 postpartum women, 0 of 53 antenatal 
participants), women who reported recent physical or sexual violence were less likely to report 
partner testing (adjusted RR: 0.10, 95%CI: 0.12–0.87) or couples testing (adjusted RR: 0.13, 
95%CI: 0.03–0.54).50 Results from a randomized study found that the SD-HIVST kits  to partners 
of a HIV positive index patient achieved higher reported partner testing rates than clinic invitation 
alone (91% vs. 52%, p<0.001).51 In this study, no participants reported IPV due to HIV testing.51 
In a recent survey study of adolescents and adults in Lusaka HIVST were found to be desirable 
and acceptable9 Further research is needed the regarding most efficient and effective use of this 
public health intervention in ANC settings.  
4.3 Our formative work 
Women in sub-Saharan Africa face an unacceptably high risk of acquiring HIV during pregnancy 
and breastfeeding. In a meta-analysis of 19 studies, Drake and colleagues reported a pooled 
incidence rate of 4.7/100 person-years (PY) (95%CI: 3.3–6.1) during pregnancy and 2.9/100 PY 
(95%CI: 1.8–4.0) while breastfeeding.12 During our formative research, we completed a new 
systematic review and meta-analysis to estimate the risk of HIV acquisition during pregnancy 
and the postpartum period in sub-Saharan Africa. Overall, 41 studies met our inclusion criteria. 
These represented 35 independent cohorts that contributed over 100,000 PY of follow-up.  The 

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pooled HIV incidence rate during pregnancy and the postpartum period was 3.7/100PY (95% 
CI: 3.0-4.5), with no detected difference between pregnant and postpartum periods. This pooled 
incidence rate is consistent with cohort studies of female sex workers, men who have sex with 
men, and HIV serodiscordant couples.52-56 
We have developed a framework for HIV prevention during pregnancy and breastfeeding. In our 
framework (Figure 1), partner HIV status is used to stratify the population into six distinct groups 
(A-F). To optimally reduce horizontal and vertical HIV transmission during pregnancy, we argue 
that tailored interventions are needed. We hypothesized that three specific points along this 
dyad-based framework could have important downstream impact: (1) male partner HIV testing, 
(2) support for ART adherence, and (3) support for PrEP during pregnancy. 
 
Figure 1: Proposed framework for HIV prevention during pregnancy57 
To test this hypothesis, we developed a mathematical model describing horizontal and vertical 
HIV transmission during pregnancy within patient-partner and patient-infant dyads, respectively. 
The model was on based biological and behavioral inputs from literature estimates and ANC 
program data from Malawi and Zambia. The downstream impact of three main HIV prevention 
strategies, alone and in combination, was assessed by varying: (1) male partner HIV testing 
from a base-case value of 15% to a target of 35%; (2) suppressive ART for HIV-positive ANC 
patients and partners from a base-case of 70% to a target of 90%; and (3) adherent PrEP use 
for HIV-uninfected female ANC patients from a base-case of 0% to a target of 20%. Using this 
model, the percentage of horizontal and vertical HIV infections that could be averted relative to 
the current (base-case) scenario (see Table 2) were estimated as follows: 

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• Increasing male partner testing to 35% coverage was predicted to reduce horizontal and 
vertical transmissions by 16.7% and 15.1%, respectively (scenario 2); corresponding 
reductions with 20% female PrEP use were 13.4% and 12.1% (scenario 4). 
• Jointly increasing coverage of both male partner testing and female PrEP use by 20 
percentage points was predicted to reduce horizontal and vertical transmissions by ~one-
quarter (scenario 7); this reduction increased to ~one-third with a combination of these two 
interventions plus increasing suppressive ART (scenario 8). 
• Across scenarios, a 20-percentage-point increase in suppressive ART for HIV-positive 
patients and partners had only a modest incremental impact (scenarios 3 vs. 1, 5 vs. 2, 6 vs. 
4, 8 vs. 7).  
The modeling suggests that combination HIV prevention in ANC settings, particularly 
approaches that increase male partner testing and female PrEP use, could substantially reduce 
HIV incidence among pregnant women, their partners, and their newborns in sub-Saharan 
Africa. 
Table 2: Percentage of potential horizontal and vertical HIV infections averted 
Scenario 
% ANC patients’ 
male partners 
tested for HIV 
% HIV+ ANC patients & 
partners on 
suppressive ART 
% HIV− female 
ANC patients 
on PrEP 
% Horizontal 
transmissions* 
averted 
% Vertical 
transmissions 
averted 
 
 
 
 
 
 
1 
Current (15%) 
Current (70%) 
Current (0%) 
--- (Base case) 
--- (Base case) 
 
 
 
 
 
 
2 
↑ to 35% 
Current (70%) 
Current (0%) 
16.7% 
15.1% 
3 
Current (15%) 
↑ to 90% 
Current (0%) 
1.1% 
1.8% 
4 
Current (15%) 
Current (70%) 
↑ to 20% 
13.4% 
12.1% 
 
 
 
 
 
 
5 
↑ to 35% 
↑ to 90% 
Current (0%) 
21.5% 
19.9% 
6 
Current (15%) 
↑ to 90% 
↑ to 20% 
16.3% 
13.9% 
7 
↑ to 35% 
Current (70%) 
↑ to 20% 
27.8% 
25.1% 
 
 
 
 
 
 
8 
↑ to 35% 
↑ to 90% 
↑ to 20% 
32.1% 
29.2% 
 
 
 
 
 
 
* both female-to-male and male-to-female 
As part of our formative work, we also conducted qualitative research to better understand 
preferences for partner HIV testing. A total of 145 semi-structured interviews were conducted 
with pregnant women, their male partners, health care workers, and policymakers in Zambia and 
Malawi. Preliminary results indicated that novel testing modalities were considered acceptable; 
there did not appear to be a strong preference for one particular modality for male partner HIV 
testing. Convenience and the availability of alternate testing venues were viewed favorably by 
participants. Universally, concerns were raised about the potential for relationship conflict, 
including IPV, arising from the invitation for HIV testing. 
5.0 RESEARCH QUESTION 
In the antenatal setting, does the addition of SD-HIVST to existing guidelines for partner 
notification increase the proportion of male partners who access facility-based HTS? 
 

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6.0 OBJECTIVES AND OUTCOMES 
The overall objective of this study is to evaluate whether the addition of SD-HIVST to existing 
partner notification guidelines increases the proportion of male partners who access facility-
based HTS, when compared to the partner notification strategy alone. In two parallel randomized 
trials, we will compare the two HIV testing strategies among partners of HIV- positive and HIV-
negative pregnant women. 
6.1 Primary and secondary objectives 
Our primary objective is: 
1) To evaluate whether a combination of partner notification plus SD-HIVST increases 
primary male partner HIV testing when compared to partner notification alone. 
Our secondary objectives are: 
1) To evaluate whether a combination of partner notification plus SD-HIVST increases 
couple HIV testing when compared to partner notification alone. 
2) To identify social harms and other adverse events associated with the HIV testing 
approaches. 
3) To explore acceptability and feasibility of partner notification and SD-HIVST among 
female participants and healthcare workers. 
Our exploratory objectives are: 
1) To evaluate whether a combination of partner notification plus SD-HIVST increases HIV 
testing among secondary male partners when compared to partner notification alone.  
2) To estimate the relative yield of identifying HIV-positive partners with each partner HIV 
testing strategy.  
6.2 Study Outcomes 
Our primary outcome is: 
• Proportion of primary male partners who complete facility-based HTS by participant 
self-report. The current Zambian guidelines require confirmatory testing by a trained 
healthcare provider following HIV self-testing. The requirement of facility-based HTS 
ensures that testing is performed appropriately and that counseling messages are 
provided according to current guidelines. 
Our secondary outcomes include: 
• Proportion of couples (pregnant woman and partner) who receive facility-based HTS 
together. 
• Incidence of social harms and other adverse events associated with the HIV testing 
approaches. 
• Participant uptake, preferences and healthcare provider opinions about partner 
notification services and SD-HIVST.  
• Proportion of secondary male partners who complete HIV testing as reported by the 
pregnant woman. 
• Average number of partners tested to identify one HIV-positive partner.  
Average number of SD-HIVST kits distributed to identify one HIV positive partner. 

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7.0 HYPOTHESES 
1) For both HIV-positive and HIV-negative women, the addition of SD-HIVST to partner 
notification will increase the proportion of primary male partners who access HTS.  
2) For both HIV-positive and HIV-negative women, the addition of SD-HIVST to partner 
notification will increase the proportion of couples who access HTS. 
3) The addition of SD-HIVST to partner notification will not increase the incidence of reported 
social harms. 
4) For both HIV-positive and HIV-negative women, SD-HIVST will be acceptable to patients 
and feasible in antenatal care settings. 
 
8.0 METHODOLOGY  
8.1 Study design  
Two parallel, unmasked, 1:1 pilot randomized controlled trials among pregnant women seeking 
ANC services in Lusaka, Zambia. We will compare partner HIV testing uptake using partner 
notification only and partner notification plus SD-HIVST, among partners of HIV-positive and 
HIV-negative pregnant women. 
8.2 Study site and study population 
Chipata Level 1 Hospital is a government health facility run by the Lusaka District Health 
Management. Serving a population of over 100,000, the ANC clinic is very busy, with an average 
of 400-450 new patients and 900-1000 return visits each month. Similar to other health facilities 
in the Lusaka district, the HIV prevalence in the antenatal clinic is ~10-15%.  
8.3 Selection of Participants 
We will recruit women receiving ANC who meet the following criteria: 
• 18 years of age or older 
• Pregnant at time of enrollment based on antenatal record   
• Documented HIV status (either positive or negative) in antenatal record 
• Reports at least one current sexual partner 
• Willingness to provide her own contact information 
• Ability and willingness to provide informed consent  
• Intent to remain in current geographical area of residence for the duration of follow-up 
activities 
• Willingness to adhere to study procedures 
Women who express concerns about IPV or social harms as a result of participation during the 
screening process will not be included. Women who have previously enrolled in the study will 
not be permitted to enroll again. 
Following informed consent, participants will be enrolled into one of two parallel randomized 
trials based on their HIV status. 
 

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8.4 Study Intervention 
All women enrolled will receive partner notification services based on the current 
recommendations for HIV positive women in ANC settings.13  This includes the elicitation of 
primary and secondary male partners via interview with the pregnant woman. According to the 
2018 Zambian Consolidated HIV Guidelines13, four types of partner notification should be 
offered: 
• Client self-referral - clients are encouraged by providers to disclose their HIV status to 
their sexual partner(s) by themselves, and to suggest HTS to the partner(s)  
• Provider contract referral - clients enter into a contract with a trained provider and 
agree to disclose their status by themselves and to refer their partner(s) to HTS within a 
specific time period. If the partner(s) of the HIV-positive individual do not access HTS or 
contact the health provider within that period, then the provider will contact the 
partner(s) directly and offer voluntary HTS. 
• Provider referral - the health care provider confidentially contacts the person’s 
partner(s) directly and offers the partner(s) voluntary HTS. 
• Dual referral – a health care provider accompanies and provides support to clients 
when they disclose their status to their partner(s). The provider also offers HTS to the 
partner(s).  
While partner notification is currently offered to HIV-positive pregnant women only, in this study 
we will also adapt these referral services for pregnant women testing HIV-negative.  
 
HIV-positive and HIV-negative participants in the intervention arms will be offered SD-HIVST in 
addition to partner notification. The HIV self-test kits are oral swabs and are currently included 
in the Zambian national guidelines for HIV testing. We will be offering an integrated strategy of 
both partner notification and SD-HIVST. Participants will be instructed on the use of the HIV-
self-test kits at home or alternative site,13 and provided HIV self-test kits for themselves and 
each reported sexual partner. The SD-HIVST will be promoted as a screening test; regardless 
of the results—and according to the Zambian HIV guidelines—all participants will be strongly 
encouraged to receive HTS at the study clinic. The women will receive verbal and written 
instructions on the use of an HIVST as per current guidelines.13 This will include: 
 
1) How to perform the test and interpret the result correctly; 
2) Where to access HIV testing services and further support services; and  
3) How to safely dispose of the used test-kits. 
8.5 Recruitment and enrollment procedures 
Staff will provide interested participants with additional information and referral to the study. 
Potential participants will be identified at any point in their pregnancy. All women attending the 
ANC clinic at Chipata Level 1 Hospital who meet the eligibility criteria as listed in section 8.3 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 9.2). After informed consent is 
obtained, we will collect social, demographic, medical, and behavioral information from all 
participants.  We will obtain from the pregnant woman locator information—including phone 

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numbers, addresses, and directions—for her and her partner.  Information about partner(s) will 
be collected as reported by the female participant.  
Participants will be randomly assigned to one of two study arms. The study statistician will use 
statistical software to generate a list of random assignments with a 1:1 ratio. The randomly 
generated numbers will be placed in opaque sealed envelopes and sequentially numbered  with 
participant identification numbers58.  
All participants will be asked to identify sexual partner(s). Participants with multiple partners will 
be asked to designate their primary partner—defined as whomever the participant designates 
as their primary partner, e.g. husband or boyfriend—and secondary partners—defined as any 
other sexual partners. Study staff will discuss the partner notification strategies (see section 8.4) 
for each partner and help the participant to devise a partner notification plan.  
Participants assigned to the intervention arm will receive structured counseling about HIVST and 
its potential role in engaging male partners in HIV testing. These women will be offered oral HIV 
self-test kits, one for themselves and one for each reported partner. For those who agree to try 
SD-HIVST, clinic staff will provide instructions about their use, their interpretation, and disposal 
of used test kits, as per current Zambian guidelines (see section 8.4). We will emphasize the 
role of the oral HIV self-testing kits as a screening measure and the need for facility-based 
confirmatory testing.  
Regardless of study arm, participants and their partners will be encouraged to complete facility-
based HTS as soon as possible—ideally in the first two weeks and within the first 30 days (our 
primary outcome). Participants will be given a schedule of possible times for facility-based HTS 
at the study site. These will include regular clinic hours; based on participant demand, we may 
add weekend and/or off-hour time periods. Such services would be equally available to 
participants randomized to either study arm. Participants who experience any social harms for 
example, experiencing emotional, economic, legal or physical harm from a family member, 
friend, people at work, police officer or other people   will be asked to return earlier and provided 
a designated study contact number for emergencies.  
Prior to discharge, all participants will be given a follow-up appointment at 30 days. We will 
emphasize the importance of this exit visit, even if their partners did not complete HTS or use 
the HIV self-test kit.  
8.6 Study follow-up 
At approximately 30 days from enrollment, participants will be asked to return for an exit visit. 
We will collect information about their experience with the partner notification strategies and 
whether their partners completed facility-based HTS either at the study or an alternate site. We 
will ask about any perceived social harms and their potential association with the partner 
notification strategies or SD-HIVST. For those in the intervention arm, we will also collect 
quantitative information about SD-HIVST, including acceptability, preferences, and actual use. 
This information will be collected at the end of the visit, after other measures pertaining to both 
arms are collected. A random sample of these women (HIV-positive and HIV-negative) from both 
arms will be invited to participate in the qualitative research component (see section 8.9). 
8.7 Retention  

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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. Given the relatively short follow-up 
duration for follow-up (30 days), we expect this to be achievable. 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 enrollment.  
• 
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 if agreed upon. 
• 
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. 
8.8 Safety Monitoring  
At each study visit, study staff will evaluate participants for social harms. 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. We will use 
standardized instruments to screen for these adverse events, with follow-up counseling and/or 
support as needed. For severe cases, we will make referrals to local government agencies and 
provide additional resources (e.g., transport) to minimize barriers to seeking out such services. 
 
8.9 Qualitative Interviews 
To provide a more in-depth understanding of the acceptability and feasibility of the HIV testing 
strategy we will recruit up to 20 participants from each arm (40 overall) to participate in semi-
structured interviews (SSIs). Within each study arm, up to 20 will be HIV-negative participants 
and up to 20 will be HIV-positive participants. In order to provide insight into the factors that 
affect male partner HIV testing, we will interview women from both arms whose partners did or 
did not complete HIV testing, see Table 3.  
In addition, to gain insight into the feasibility of the intervention, we will also conduct SSIs with 
healthcare workers engaged in providing the study intervention. We will recruit up to 10 
healthcare workers to participate in SSI. Selected healthcare workers (including study 
personnel) should be involved in the counseling and instruction for combined partner notification-
HIVST arm.   
All participants must be age 18 years or older and demonstrate the ability and willingness to 
provide informed consent. Additional eligibility criteria for women are listed in Section 9.2. The 
SSIs will be conducted in rooms at or near the clinic that provide sufficient privacy to ensure 
confidentiality of information and are quiet enough to enable audio recording of the interviews. 
Trained female Zambian interviewers will use interview guides to explore key themes, including 
the acceptability of the HIV testing approach, barriers and facilitators to the approach, and 

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potential social harms. The SSIs will explore participants’ experiences with the HIV testing 
approach. Each SSI is expected to last 30-60 minutes.  
Table 3 SSI Interviews per arm  
 
HIV+ participant HIV- participant 
Control arm 
 
 
Partner tested 
5 
5 
5 
5 
Partner did not test 
Intervention Arm  
 
 
Partner tested 
Partner did not test 
5 
5 
5 
5 
Total 
20 
20 
 
8.10 Pre-intervention Phase 
Prior to activation of the main study, we will implement a pre-intervention phase for both HIV-
positive and HIV-negative pregnant women. We will recruit women meeting the eligibility criteria 
for the main study (Section 8.3). Similar to those participants, these individuals will be educated 
about the study; provide informed consent; answer specific questions about HIV testing history 
and sexual risk behaviors; and then return approximately 30 days later to report partner HIV 
testing. We will not provide any interventions for partner HIV testing as described in Section 8.4. 
Instead, we will educate women about partner HIV testing and encourage them to utilize existing 
clinical services at the study facility. Overall, we plan to enroll up to 100 participants in this pre-
intervention phase, split between HIV-positive and HIV-negative pregnant women. Based on 
antenatal clinic volumes at Chipata District Hospital, the duration of enrollment for this pre-
intervention phase is expected to be 4-8 weeks. 
 
This pre-intervention phase is intended to accomplish two goals. First, it will allow the study team 
to refine study procedures— including recruitment, informed consent, data collection, and follow-
up— prior to the full enrollment of the main study. Second, this exercise will allow us to gather 
important preliminary data about partner HIV testing within the current standard of care. Although 
not powered for precision or specific comparisons, this preliminary data will help us to 
understand the impact of partner HIV testing procedures offered in the study clinic. These data 
will be used to provide context to the main trial, but are not part of the a priori comparisons in 
the analysis plan. 
 
 
8.11 Data Management and Storage  
Data collected from each participant will include sociodemographic information, relevant HIV and 
obstetrical history, and results of HIV testing.  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 will be validated via double entry.  Computers will be 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-

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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 following sponsor recommendations. Data will be disposed 
of after completion of the study per sponsor guidelines. At that time, electronic records, including 
linkage codes and identifiers, will be deleted. Paper records will be shredded prior to disposal. 
 
8.12 Sample Size 
We propose two randomized trials, each based on the pregnant women’s HIV status. Enrollment 
into two parallel trials—rather than single trial with pre-defined strata—is justified by our 
expectation of different baseline HIV testing rates in the control arm and the potential for different 
effect sizes according to the pregnant women’s HIV status. Our sample size calculations are 
guided by three main considerations:  
(i) In this pilot phase, the studies are powered to detect large, transformative differences in 
partner HIV testing rates, while evaluating feasibility and acceptability of the interventions.  
 (ii) While we make educated assumptions about the baseline HIV testing rates in the control 
arm for both HIV-positive and HIV-negative women, there are currently a dearth of reliable data 
about HIV testing rates following partner notification, particularly in a programmatic settings. If 
the intervention were shown to be clinically promising (regardless of statistical “significance”), 
point estimates and confidence intervals from the pilot trial will help us to inform the design of a 
larger definitive study.  
(iii) In line with the objectives of a pilot study, we seek to obtain preliminary results in relatively 
short period of time. The sample sizes also consider the capacity for enrollment over a six-month 
window, based on known ANC patient volumes and HIV prevalence among the antenatal 
population.  
In the trial of HIV-positive pregnant women, we anticipate 20% of male partners will test under 
the partner notification strategy alone (i.e., the control arm). With the addition of SD-HIVST, we 
expect to see a 25% absolute increase (i.e., to 45%) in partner HIV testing rates. With a 
significance level of 0.05, power of 80%, and an adjustment for 5% missing data and attrition, 
we will enroll 116 total HIV-positive pregnant women into the trial (58 per arm). 
In the trial of HIV-negative pregnant women, we anticipate 10% of male partners will test under 
the partner notification strategy alone (i.e., the control arm). With the addition of SD-HIVST, we 
expect to see a 15% absolute increase (i.e., to 25%) in partner HIV testing rates. With a 
significance level of 0.05, power of 80%, and an adjustment for 5% missing data and attrition, 
we will enroll 210 total HIV-negative pregnant women into the trial (105 per arm).  
We recognize there is uncertainty about baseline partner testing rates for both proposed trials. 
Among HIV-positive pregnant women, partner notification services have been implemented, but 
were only recently introduced. For this reason, there are few reliable data about its uptake in the 
programmatic setting. To our knowledge, partner notification approaches—as proposed in this 
study—have not been previously studied in HIV-negative pregnant populations. As a result, no 
empiric data about its uptake currently exist. For this reason, for both trials, we show the 
calculated power across a range of assumptions for the control arm and a range of possible 
effect sizes in Table 4. 

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Table 4. Statistical power and precision for male partner HIV testing RCTs 
 
& Assuming 5% missing data / attrition (e.g., loss-to-follow-up). @ Significance level, alpha = 0.05, using a likelihood ratio chi-
square test for two proportions (Power Procedure, SAS/STAT version 14.3) 
The targeted effect sizes between the two trials differ. In order to inform Zambia HIV testing 
guidelines among HIV-positive pregnant women, the effect size would need to be higher to justify 
further investment into the partner notification plus SD-HIVST. We have powered the trial for 
HIV-negative pregnant women to detect smaller absolute differences in testing rates (15% 
difference) because a dearth of empiric data exists for partner notification-based strategies in 
this population, with or without SD-HIVST. Also, based on our formative research, we reasoned 
that partners of HIV-negative pregnant women may have comparatively lower motivation for 
returning to the clinic for facility-based HTS, especially if HIV self-testing outside the clinic was 
HIV-negative. 
 
8.13 Data Analysis Plan 
 
8.13.1 General Approach:  
Two randomized controlled trials will be conducted simultaneously, for HIV positive and HIV 
negative pregnant women, separately. All primary and secondary endpoints will be evaluated 
separately for each trial, unless stated otherwise. We anticipate the RCT of HIV negative women 
may enroll and complete sooner than the RCT for HIV positive women. In the unanticipated case 
that results are homogeneous between the two trials with respect to the estimated risk difference, 
and policy implications are similar for the two populations, the two trials can be combined in a 
weighted analysis to generalize the findings to the target population of pregnant women in 
Zambia (or Lusaka, more specifically).59,60 In such a weighted analysis, we anticipate the HIV 
negative women would have higher weights (on average) to account for the overrepresentation 
of HIV positive women in the combined trials, as compared to the target population of pregnant 
women. Additional patient characteristics available in the larger ANC population would also be 
used for estimating generalizability weights.  
 
 
 
 
Assumed probability 
of partner HIV testing 
 
Example results (in expectation) 
N tested / N evaluable (%) 
Population 
N 
enrolled 
total& 
N 
evaluable 
per arm 
Control 
Intervention 
Power@ 
Intervention 
Control 
Difference in 
probabilities 
(95% CI) 
HIV 
positive 
women 
116 
55 
20% 
40% 
63% 
22/55 (40%) 
11/55 (20%) 
20 (3.1, 37%) 
 
116 
55 
20% 
45% 
80% 
25/55 (45%) 
11/55 (20%) 
25 (8.4, 42%) 
 
116 
55 
20% 
50% 
91% 
28/55 (51%) 
11/55 (20%) 
31 (14, 48%) 
HIV 
negative 
women 
210 
99 
10% 
22% 
64% 
22/99 (22%) 
10/99 (10%) 
12 (2.0, 22%) 
 
210 
99 
10% 
25% 
80% 
25/99 (25%) 
10/99 (10%) 
15 (4.7, 26%) 
210 
99 
10% 
30% 
94% 
30/99 (30%) 
10/99 (10%) 
20 (9.3, 31%) 

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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 significance level will be 
used throughout (i.e., 95% confidence intervals) with no adjustment for multiple testing. Missing 
data are anticipated to be uncommon (≤5% missing); a complete case analysis will be used 
unless the missing data proportion is >10%. In the case of missing data for >10% of individuals, 
inverse probability weighting for missingness or multiple imputation will be used to account for 
data missing at random (missing conditional upon measured covariates and outcomes). Missing 
data patterns will be evaluated blinded to study arm and outcome. If data are suspected to be 
missing not at random, this will be described with the study results as a limitation.  
Analyses will be conducted using an intention-to-treat approach, with women analyzed 
according to the arm they were randomly assigned to regardless of their subsequent use or non-
use of the SD-HIVST kits. The post-randomization use of SD-HIVST kits is a participant or 
couple-driven choice and will be recorded in both arms. If there is unanticipated cross-over or 
lack of SD-HIVST uptake, exploratory analyses may use marginal structural models to estimate 
an “as-treated” effect of SD-HIVST uptake upon the primary endpoint.  
8.13.2 Analysis of the Primary Endpoint 
The proportion of primary male partners who complete facility-based HTS within 30 days of 
enrollment will be compared between study arms using an estimated difference in probabilities 
(i.e., risk difference) and a corresponding 95% CI (with the control arm as the referent group). 
The primary outcome is measured by participant self-report and the partner recorded as the 
primary male partner will be pre-specified before randomization. An adjusted analysis will be 
conducted using a linear-binomial model to account for chance imbalances in key male partner 
characteristics (e.g., perceived engagement in index participant’s healthcare, distance from 
home to nearest health facility, day-time work schedule) that may influence HIV testing 
behaviors.  
We will further evaluate our primary outcome (i.e., facility-based HTS) using a time-to-event 
analysis over the 30-day follow-up, comparing between the two study arms descriptively using 
Kaplan-Meier curves. A Cox proportional hazards model or restricted mean survival time 
analysis61,62  will be used for covariate adjusted analyses and formal comparison between the 
study arms. 
8.13.3 Analysis of Secondary Endpoints 
The proportion of couples who receive facility-based HTS will be analyzed using the same 
approach as described above for the primary endpoint. A couple receiving facility-based 
HTS will be defined as both members of the couple participating in HTS together. 
In secondary analyses, facility-based HTS and HIVST uptake will be evaluated among all sexual 
partners (primary and secondary) reported to the study, and will be handled as clustered binary 
data. These outcomes will be either directly observed by the study staff or self-reported by the 
pregnant woman participating in the study. Multiple partners of the same pregnant woman will 
be handled as a cluster using generalized estimating equations (GEE); the analysis will be 
conducted at the partner level.62 If feasible, a linear-binomial model fit with GEE will be used; 
otherwise a probability ratio (i.e., risk ratio) will be estimated using a log-binomial model fit with 
GEE. The mean (arithmetic average) number of partners tested to identify one HIV positive 
partner will be estimated with a corresponding 95% CI among all male partners (with the control 

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and intervention arms pooled, and also summarized by arm). This analysis will also be 
conducted among solely primary partners. The arithmetic mean number of SD-HIVST kits 
distributed to identify one HIV positive partner will be estimated with a corresponding 95% CI 
among the intervention arm only; this analysis will take into account all HIVST kits given to the 
women, including those she might use to retest her own status. 
Incidence of social harms and other adverse events associated with the partner notification or 
SD-HIVST approaches will be estimated and individual events will be described using line 
listings. Participant uptake and preferences and healthcare provider opinions about partner 
notification services and SD-HIVST will be described using frequency tables and summary 
statistics. Retention in the study for 30 days of follow-up will be described using frequency tables, 
and reasons for study drop-out will be tabulated. Any participant deaths will be recorded along 
with the contributing cause(s) of death. 
8.14 Analysis: qualitative component 
The SSI audio recordings will be transcribed and translated for analysis. All identifiers will be 
redacted from the interview transcripts prior to analysis. Although we propose sample sizes for 
each group based on prior experience, the final number interviewed will be determined by 
theoretical saturation. Data will be analyzed using techniques that include coding, memoing, and 
matrices to summarize and interpret key patterns in the data. Comparative and thematic 
analyses will be used to provide an in-depth understanding of the experiences related to HIV 
testing. 
9.0 ETHICAL CONSIDERATIONS 
9.1 Ethical approval 
All study participants will be fully informed of the study procedures described above. Ethical 
approval for this study will be sought from the UNZA Ethical Review Committee and the 
Institutional Review Board at UNC. Ethical approval will also be sought from the National Health 
Authority in accordance with the National Health Research Act. 
9.2 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 local languages (Nyanja and Bemba) 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 HIV and ANC treatment according to local 
clinical standards. We will obtain signed permission from the pregnant woman to collect locator 
information—including phone numbers, addresses, and directions—for her and her partner. 
Permission for collection of locator information and contract tracing will be per usual practice at 
the clinic. 
9.3 Data storage  

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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. The computers together with audio tapes, field notes, and all other study materials 
will be kept in a locked, fireproof safe cabinet in a locked local office. All data analysis will be 
performed using datasets which have only study ID numbers as unique identifiers.  
9.4 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 
Allergy and Infectious Diseases), the ethical and regulatory committees in Zambia, 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. 
9.5 Potential risks of proposed research to study participants  
Risks to participants in this study are minimal and do not differ significantly from the risks inherent 
in the local standard of care for pregnant women, their partners, and their infants. Oral HIV-self 
test kits are currently included in the Zambian national guidelines and are being utilized in 
programmatic settings. As such, their use outside of research settings should not pose additional 
risk. In addition, the importance of confirmatory HIV testing at a health facility will be emphasized 
to all study participants. This approach is recommended by the national HIV testing policy and 
serves as the primary outcome of our study. In this way, the risk of inaccurate HIV test results 
should be minimized. In addition, we do not expect more than minimal risks during the one-on-
one interview. Participants may feel uncomfortable when being interviewed, but will have the 
opportunity to skip or refuse to answer any questions that they do not want to answer. It is 
expected that this study will expose subjects to minimal risks.  
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-
infected). There is a risk that sexual partners will react adversely to the participants’ suggestions 
of self-test usage, or to the test result itself. To minimize this risk, we will provide detailed 
information on the need for confirmatory testing and the availability of HIV care and treatment 
for HIV-infected persons. Participants will also be given a phone number they can call at any 

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time if they need assistance or feel they are at risk of harm. We will not enroll women who self-
report concern that their partner may hurt them if they suggest using the HIV self-test or home-
based testing and in addition we will refer men and women who experience violence to IPV 
services. 
9.6 Potential benefits of proposed research to study participants and others  
The benefits to participants include increased knowledge about their partner’s HIV status, which 
in turn may serve to reduce their own, their partner’s and their infant’s risk of HIV infection. The 
knowledge gained from this study will also help inform policy makers and HIV prevention 
programs about the potential role that expanding HIV testing services can play in increasing 
awareness of HIV status and reducing the number of new HIV infections. 
9.7 Inclusion of children, sub-populations, and vulnerable populations  
This study focuses on the outcomes of pregnant women and their partners. Newborn infants are 
not included in the study per se, though they may derive indirect benefit from participation via 
increased partner HIV testing. Prisoners will be excluded as they receive care at separate 
facilities. 
9.8 Reimbursement/compensation 
There is no cost to participating in the study. Participants completing the exit questionnaire will 
be provided transport reimbursement that will be approximately (but not less than) $5 USD. To 
maintain operational feasibility, we will ensure that exchange rates are updated at regular 
intervals. We may also round up the disbursement amount to the nearest ZMW denomination.  
9.9 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 entities, including the 
Zambian Ministry of Health, the UNZA Biomedical Research Ethics Committee, and the National 
Health Research Authority. One or more publications will also be submitted to a peer-reviewed 
journal. Our study team plan 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. 
10.0 TIME FRAME  
Table 4: Study Time Frame  
 
Month 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Site training 
X 
 
 
 
 
 
 
 
 
Enrollment 
 
X 
X 
X 
X 
X 
X 
 
 
Follow-up visit 
 
 
X 
X 
X 
X 
X 
X 
 
Dissemination of findings 
 
 
 
 
 
 
 
 
X 
11.0 BUDGET 
Table 5: Study Budget 
Item 
Cost in USD  
Cost in ZMK 
Operational Costs 
 4,144 
49,446 
Materials and Supplies 
10,200 
121,707 

Combination Partner HIV Testing Strategies for HIV-positive and HIV-negative Pregnant Women 
Page 26 of 30 
UNZA Protocol v1.2 | June 17th 2019 
Field Personnel  
57,100 
681,317 
Compensation for 
Participants 
 1,830 
21,836 
Total Estimated Costs 
73,274 
874,306 
 
 
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13.0 APPENDICES  
1. Informed Consent Forms (ICF) 
• Pre-Intervention Phase  
• 
Control and Intervention Arms 
• 
Qualitative interviews 
2. Semi Structured Interview Guides  
• 1 female participants in control arm 
• 1 female participants in intervention arm 
• 1 Health Care Workers 
3.Questionairre