HIV Self-testing of Men to Increase Testing and Prevention Uptake Among Male Partners and Improve Postpartum ART Use in PMTCT B+ Programs in Uganda
Phase: NA
Conditions: ART Adherence, PMTCT, Linkage to Care, HIV, PrEP
Sponsor: University of Washington

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PROTOCOL 
 
 
 
 
HIV self-testing and PrEP to increase testing and prevention uptake among male partners 
and improve postpartum ART use in PMTCT B+ programs in Uganda 
 
 
Obumu Study 
 
 
Version 4.1 
 
22nd May 2020 
 
 
 
 
Funding: 
 
United States National Institute of Mental Health 
 
(R01 MH113434) 
 
 
 
 

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TABLE OF CONTENTS 
ACRONYMS AND ABBREVIATIONS ......................................................................................... 3 
STUDY TEAM .............................................................................................................................. 4 
SUMMARY ................................................................................................................................... 5 
Specific Aims ........................................................................................................................ 6 
BACKGROUND & RATIONALE .................................................................................................. 8 
STUDY METHODS ..................................................................................................................... 13 
Overall design ..................................................................................................................... 13 
Objectives ........................................................................................................................... 13 
Population ........................................................................................................................... 15 
Eligibility .............................................................................................................................. 15 
Sample size ........................................................................................................................ 15 
Recruitment ......................................................................................................................... 15 
Study screening .................................................................................................................. 16 
Study enrollment ................................................................................................................. 17 
Study procedures ................................................................................................................ 17 
Counseling about PrEP and ART ....................................................................................... 21 
PrEP medication and dispensation ..................................................................................... 22 
PrEP adherence .................................................................................................................. 22 
PrEP safety ......................................................................................................................... 23 
Retention ............................................................................................................................. 23 
HIV testing .......................................................................................................................... 23 
HIV seroconversion ............................................................................................................. 24 
Final study visit ................................................................................................................... 25 
Quantitative surveys ........................................................................................................... 25 
Data quality and management ............................................................................................ 25 
Qualitative data collection ................................................................................................... 25 
Qualitative data quality and management ........................................................................... 27 
Qualitative data analysis ..................................................................................................... 27 
DATA  ANALYSIS ...................................................................................................................... 28 
Sample size ........................................................................................................................ 28 
Outcome measurements ..................................................................................................... 29 
Statistical considerations .................................................................................................... 29 
DATA SHARING AND OWNERSHIP ........................................................................................ 30 
DISSEMINATION PLAN ............................................................................................................ 31 
HUMAN SUBJECTS CONSIDERATIONS ................................................................................. 31 
Informed consent ................................................................................................................ 31 
Risks ................................................................................................................................... 31 
Benefits ............................................................................................................................... 33 
Treatment for injury ............................................................................................................. 34 
Study records ...................................................................................................................... 34 
Confidentiality ..................................................................................................................... 34 
REFERENCES ........................................................................................................................... 39 
 
 
 

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ACRONYMS AND ABBREVIATIONS 
 
AE 
 
Adverse Event 
AIDS  
Acquired Immune Deficiency Syndrome 
ANC 
 
Antenatal Care 
ART 
 
Antiretroviral Therapy 
CHCT  
Couple HIV Counseling and Testing 
COVID  
Coronavirus disease  
CRF 
 
Case Report Form 
FTC/TDF 
Co-formulated Emtricitabine-TenofovirDisoproxil Fumarate 
HIV 
 
Human Immunodeficiency Virus 
HIVST  
HIV Self-testing 
HTS 
 
HIV Testing Services 
IDI 
 
In-depth Interview 
IRB 
 
Institutional Review Board 
IPV 
 
Intimate Partner Violence 
KCCA  
Kampala Capital City Authority 
MU-JHU 
Makerere University – Johns Hopkins University Research Collaboration 
OR 
 
Odds Ratio 
PMTCT 
Prevention of Mother-To-Child HIV Transmission  
PrEP  
Pre-Exposure Prophylaxis 
RA 
 
Research Assistant 
RCT 
 
Randomized Controlled Trial 
REDCap 
Research Electronic Data Capture 
SAE 
 
Serious Adverse Event 
SOC 
 
Standard of Care 
VCT 
 
Voluntary Counseling and Testing 
WHO  
World Health Organization 
 
 
 

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STUDY TEAM 
 
Infectious Diseases Institute, Uganda 
 
 
 
 
Elly Katabira, MBChB, FRCP 
Andrew Mujugira, MBChB, PhD 
Timothy Muwonge, MBChB, MPH 
Zikulah Namukwaya, MBChB, MPH 
 
 
University of Washington, Seattle, USA 
 
Connie Celum, MD, MPH 
 
Jared Baeten, MD, PhD 
 
Deborah Donnell, PhD 
 
Renee Heffron, PhD, MPH 
 
 
Harvard Medical School, Boston, USA 
 
 
 
Norma Ware, PhD 
Monique Wyatt, PhD 
 
 
University of Pennsylvania 
 
Harsha Thirumurthy, PhD 
 
 

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SUMMARY 
 
Uganda has the fifth highest HIV burden globally and one of the highest fertility rates in Africa. 
Prevention of mother-to-child HIV transmission Option B+ (PMTCT B+) is national policy in 
Uganda. To maximize the prevention and clinical benefits of PMTCT B+, the challenges of low 
HIV testing by male partners and high rates of post-partum discontinuation of antiretroviral therapy 
(ART), insufficient adherence, and incomplete viral suppression need to be addressed. Women 
may be more likely to continue ART long-term and have higher adherence post-partum if their 
partner is tested, there is mutual disclosure of HIV status, and their partner takes ART or PrEP, 
depending on his status. Innovative approaches are needed to allow men to test in settings other 
than busy antenatal clinics, preferably where they have privacy, are comfortable and do not miss 
work. Innovative HIV testing technology – HIV self-testing (HIVST) could increase male partner 
engagement in HIV testing, and uptake of prevention and care services through linkage to highly 
effective pre-exposure prophylaxis (PrEP) and ART for all HIV-positive men. This study has been 
designed to address this gap through an enhanced PMTCT B+ program with HIV self-testing, and 
linkage to PrEP or ART, for male partners. 
 
In a demonstration project we recently completed among mutually disclosed East African HIV 
serodiscordant couples (the Partners Demonstration Project), integrated ART and PrEP delivery  
with time-limited PrEP for the HIV-negative partner as a ‘bridge’ until the HIV-positive partner was 
on ART for six months, and achieved viral suppression, was very acceptable, achieved very high 
uptake and adherence to ART and PrEP, and nearly eliminated HIV transmission. This protocol 
builds on that demonstration project by evaluating whether PMTCT outcomes are improved by 
increasing uptake of HIV testing and PrEP among HIV-negative men whose pregnant partner is 
HIV-positive. PrEP for HIV-negative male partners of HIV-positive pregnant women provides 
highly effective prevention benefits during an important ‘season of risk’ when men may have 
higher HIV acquisition risk from their partner if she is viremic (during the first few months after 
ART initiation, post-partum ART discontinuation or due to viral resistance), or from outside 
partners.  
 
We will conduct a randomized trial to evaluate whether provision of oral HIV self-test kits to HIV-
positive pregnant women overcomes male partners’ reluctance to be tested in PMTCT clinics. 
Pregnant women will be trained in the use and interpretation of HIVST and given two oral fluid-
based HIVST kits to use with or give to their partners, along with information about HIV testing 
and prevention and care services. We will offer men confirmatory testing regardless of their HIV 
test result through HIVST, counseling, and if negative, PrEP and if positive, ART. We will provide 
counseling to minimize social harms of HIV self-testing, and additional counseling and referral to 
social support services when social harms occur. This project will address key challenges in 
PMTCT B+ programs, by evaluating innovative strategies to increase male partner involvement 
coupled with offering PrEP to HIV-negative men, ART to HIV-positive men, and encouraging post-
partum ART continuation and adherence among HIV-positive women. 
 
 
Design: 
Randomized clinical trial 
 
Up to 12 months of post-partum follow-up  
 
Population: 
HIV-positive pregnant women in Kampala, Uganda who have a male partner 
of unknown HIV status (approximately 500 women in total) 
 
 
Study Sites:  
Infectious Diseases Institute (IDI) Kasangati and collaborating antenatal care 
(ANC) clinics in Kampala, Uganda 

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Approach:  
We will recruit HIV-positive women ≥18 years accessing PMTCT B+ 
programs in Kampala, who have a male partner of unknown HIV status. 
Women will be randomized to the intervention (HIVST) or the control arm 
(invitation letters to deliver to partners to come to the ANC clinic where she 
receives care or IDI Kasangati for HIV testing). Women will be instructed in 
the use and interpretation of HIVST and be provided two HIVST kits to give 
to or use with their male partners. We will recommend that HIV-negative men 
use PrEP until their partner has been on ART for at least 6 months, and that 
HIV-positive men take ART. Specifically, PrEP as a bridge to ART will be 
offered to HIV-negative male partners as follows: when the HIV-positive 
pregnant partner is not yet taking ART, PrEP will be offered, and when 
the HIV-positive pregnant partner initiates ART, PrEP will be provided 
for the HIV-negative male partner for six months (i.e., when viral 
suppression in the HIV-positive partner would be expected to be 
typically achieved).This bridge to ART approach is detailed in Figure 1. 
Specific Aims 
 
Aim 1: 
Determine whether an enhanced PMTCT program with HIV self-testing for male 
partners and provision of PrEP to HIV-negative male partners increases the 
proportion of male partners who test for HIV and men who initiate PrEP. 
 
Innovations are needed to reach male partners for HIV testing that allow men to test 
where they are comfortable, which typically is not in busy antenatal clinics. Provision 
of HIV self-tests (HIVST) to pregnant women for their partners is safe, acceptable, 
and effective, and could facilitate partner testing, and increase uptake of PrEP by 
HIV-negative men and ART by HIV-positive men. HIVST is a promising approach to 
increasing partner and couples testing, which has not yet been evaluated in the 
context of PMTCT B+ programs. We will randomize 500 HIV-positive women 
initiating PMTCT B+ in Kampala in a 2:1 ratio to one of two partner testing strategies: 
1) HIVST kits (intervention) to give to or use with their partner, or 2) invitation letters 
for fast-track testing at the clinic (standard of care). Men who test will be offered 
confirmatory testing and counseling. Men who test HIV-positive will be linked to ART, 
and men who test HIV-negative will be offered PrEP for the first six months after his 
partner initiates ART through PMTCT. 
 
The co-primary outcomes are the proportion of male partners who test for HIV and 
the proportion of HIV-negative male partners who initiate PrEP. 
 
Aim 2: 
Evaluate whether HIV testing combined with PrEP and ART use among male 
partners increases effective post-partum ART use among HIV-infected 
Ugandan women in PMTCT B+. 
 
Pregnant HIV-positive women may be more likely to continue ART after delivery and 
have higher adherence post-partum if their partners are tested, there is mutual 
disclosure of HIV status, and their partner takes ART or PrEP, depending on his 
status. We will evaluate ART use and viral suppression at 12 months post-partum 
among the 500 HIV-positive pregnant women who are randomized to male partner 
testing strategies (Aim 1). In this observational analysis, we will use causal inference 
methods to assess whether the outcome (women’s viral load at 12 months post-

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partum) is improved by the exposure (male partner testing and engagement in HIV 
care or prevention–PrEP use among HIV-negative men and ART use among HIV-
positive men). 
 
The primary outcome is viral suppression at 12 months, as a measure of the 
woman’s effective ART use in the first 12 months post-partum and her adherence. 
Viral suppression will be defined as plasma viral load <400 copies/ml at 12 months 
post-partum. We will analyze the outcome (viral suppression in the female) by the 
male partner’s testing outcome and PrEP use among HIV-negative men. Secondary 
outcomes include a) post-partum adherence, as measured by pharmacy records, 
which will be used to measure ART dispensation, and women’s self-report about 
treatment interruptions; b) infant HIV status at 6 weeks as determined by PCR results 
(HIV infected/uninfected); and c) infant survival at 12 months as reported by the 
mother. 
 
Aim 3: 
Assess the acceptability of HIV self-testing and PrEP, as well as perceptions 
of ART adherence and HIV status disclosure during the COVID-19 pandemic, 
to pregnant women taking part in PMTCT B+ and to their male partners, using 
qualitative and quantitative methods.  
 
PMTCT B+ has the secondary benefit of reducing HIV transmission to male partners 
if HIV-positive women continue antiretroviral therapy (ART) long-term with high 
adherence. 
However, 
optimizing 
the 
effectiveness 
of 
PMTCT 
requires 
understanding factors that influence low uptake of HIV testing by male partners (~1/5 
of partners of women in Uganda PMTCT programs are tested for HIV). In addition, 
previous studies have indicated that 1/3-1/2 of African women discontinue ART after 
delivery, and the importance of disclosure and partners’ engagement in HIV care or 
prevention need to be assessed to determine how much those factors influence ART 
continuation post-partum. During the COVID-19 pandemic, both adherence to ART 
and initiation of status disclosure may be greatly impacted.  
 
We will use quantitative and qualitative methods to investigate acceptability of 
HIVST and PrEP. Additionally we may explore the perceptions of COVID-19 and 
the intersections of HIV status disclosure, male partner testing, and access to and 
experiences of HIV prevention and treatment during the pandemic. Quantitative 
behavioral data will be collected from the study cohort during clinic visits using 
multiple validated questionnaires. A structured interview administered to all HIV-
infected female partners at enrollment will ask about knowledge of the partner’s 
HIV status, disclosure, fertility desires, relationship power, and intimate partner 
violence. Up to 110 individual interviews will be conducted. A purposefully selected 
subsample of up to 90 individuals will take part in qualitative in-depth interviews to 
achieve in-depth understanding of the acceptability of HIV self-testing and PrEP 
use by male partners to women in PMTCT B+ and to male partners. In a sample of 
10 PMTCT providers, we will assess perspectives of HIVST, facilitated disclosure, 
male partner linkage to HIV care and prevention, and women’s ART use post-
partum. 
 
 
 
The goal of the qualitative analysis is to assess the acceptability of HIV self-testing 
and PrEP use by pregnant women in PMTCT B+, their male partners, and 
implementation perspectives of PMTCT providers. 
 
 

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BACKGROUND&RATIONALE 
 
The past five years have increased the pace of progress towards controlling the HIV epidemic 
and reducing the number of new perinatal and sexually transmitted infections occurring each year. 
The major reason is effective treatment and prevention through antiretrovirals – used by HIV-
positive individuals to treat HIV infection (ART) and prophylactically by HIV-negative individuals 
to prevent HIV infection (PrEP). However, much work remains to optimize ART and PrEP delivery 
to millions of people with and at high risk of HIV using strategies that will achieve the greatest 
effectiveness and coverage possible [3]. Uganda carries the fifth highest HIV burden in the world, 
with 1.6 million people living with HIV, and 140,000 new infections and 63,000 AIDS-related 
deaths in 2013 [4]. Uganda also has a high fertility rate (5.8 pregnancies per woman in 2015). A 
key driver of HIV incidence in Uganda is low utilization of antenatal and delivery services [5]. HIV-
positive women are more likely to complete the PMTCT cascade when male partners are tested 
and engaged in care [6]. To have a greater impact of PMTCT B+ on HIV trends in Uganda in the 
context of a high fertility rate, it is critical to increase male HIV testing and uptake of PrEP or ART 
and women’s post-partum ART continuation. 
 
PMTCT B+ and the need for higher rates of ART use and adherence post-partum  
 
Although there has been substantial progress in implementation of PMTCT B+, several 
challenges remain and need to be addressed, including post-partum ART continuation and 
adherence. These gaps and needs are highlighted by recent analyses from the PROMISE study, 
which was conducted in 52 clinical research sites in eight countries. The PROMISE study showed 
low acceptance of early ART among postpartum women globally (PROMISE studies 1077 
BF/FF/HS).  Women in PROMISE were informed of the benefits of early ART from the landmark 
START trial [7], but 33% did not accept early ART, citing concerns of i) wanting more time to 
consider ART and ii) stating she feels well [8]. Thus, despite intense ART education and HIV 
monitoring in a well-resourced clinical trial setting, one-third of women required additional 
counseling to start ART earlier for their own health. 
 
The PROMISE study also included a randomized comparison of stopping or continuing ART in 
1653 postpartum non-breastfeeding women with pre-ART CD4>400 cells/mm3 (PROMISE study 
1077HS). This study demonstrated clinical benefits of post-partum ART; women who were 
randomized to continue ART had a 32% lower risk of reaching the primary endpoint of time to an 
AIDS event, and a 44% lower risk of reaching an AIDS event or a WHO stage 2 or 3 event [9]. 
Importantly, among women randomized to continue ART, 23% had virologic failure; 86% of 
women with viremia did not have genotypic resistance, indicating non-adherence as the likely 
cause of their viremia[9]. Interventions to improve adherence are needed to achieve long-term 
benefits in post-partum women on ART.  
 
In contrast, in our recently completed demonstration project of integrated PrEP and ART delivery 
with 1013 high-risk HIV serodiscordant couples in Kenya and Uganda, the rate of viral 
suppression at 12 months was higher in women who initiated ART during pregnancy than for 
other indications (96% vs 87%, p=0.02) [10]. This finding merits further study for integrated PrEP 
and ART delivery in PMTCT B+ programs to improve effective ART use post-partum, when 
coupled with safe, acceptable, and effective strategies to increase HIV testing in male partners of 
unknown status, and to motivate male partners who test to use of PrEP or ART, based on their 
sero status and with effective linkage strategies. 
 
Low uptake of HIV testing by male partners: A barrier to PMTCT B+ success  
 

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HIV testing is consistently lower among African men than women, leading to a higher proportion 
of undiagnosed HIV infection among men [11, 12]. Women who learn they are HIV-positive, often 
in antenatal care, are sometimes unwilling to disclose their HIV status due to fear of domestic 
violence, stigmatization or divorce [13]. Safe and acceptable solutions to this challenge need to 
be identified in order to optimize the benefits of PMTCT for mothers and infants; past research 
has shown that HIV-positive women are more likely to complete the PMTCT cascade when their 
male partners are tested and engaged in care [6]. Male partner involvement increases condom 
use [14, 15], women’s utilization of antenatal services and HIV testing [16-18], obtaining HIV 
results [19],  ART use [14, 19, 20], adherence to infant feeding advice [21-24], infant HIV testing 
[25], and infant HIV-free survival [25, 26]. Despite these multiple benefits, studies from Africa have 
found that male partner testing rates remain low (16-54%) [14, 20, 27, 28]. Barriers to male partner 
involvement include fear of knowing one’s status, stigma [28, 29], men’s belief that their status is 
the same as their partners (i.e., testing by ‘proxy’) [23], cultural norms that men should not 
accompany their wives to antenatal care [13], negative attitudes of health care workers [30, 31] 
(i.e., not allowing men in antenatal clinics) [29, 30, 32], and men’s concern about time away from 
work and the impact on their income [29, 31-34]. 
 
Health system facilitators of male engagement in PMTCT 
 
Multiple interventions have tried to increase male involvement in PMTCT programs, including the 
provision of personalized invitation letters to men whose female partners have engaged with the 
program. Men often perceive invitation letters as a medical prescription, which increases their 
sense of obligation to attend [13]. However, partner return following receipt of official invitation 
letters is not high –36% in Kenya [35], 26-35% in South Africa [36], 28% in Malawi [37] and 16% 
in Uganda [38]. Couples HIV testing and counseling improves uptake of HIV testing and ART 
without increased risk of social harm, compared with individual counseling [14, 39]. Other 
approaches include offering ANC services for couples during weekends or non-working hours 
[13] and intra-partum HIV testing and counseling [40]. Couples testing, flexible hours, expedited 
clinic processing for women who bring male partners [40], male support groups [31] and peer 
sensitization of men [29]modestly increased male partner involvement in some PMTCT programs, 
but have not achieved substantially large increases in partner testing. 
 
Self-testing kits as innovation in HIV testing of male partners of pregnant HIV-positive women 
 
HIVST is a highly acceptable and innovative approach to increasing knowledge of HIV sero status 
among many populations that have limited access to or low uptake of HIV testing services [41-
43]. Studies conducted in high- and low-income settings have shown that self-tests can be used 
accurately by lay users [44], and that they overcome various barriers to facility-based testing [41, 
45].  Self-tests offer a low-cost way to increase access to testing among hard to reach persons 
such as male partners of pregnant women. This potential was demonstrated by our colleague, 
Dr. Thirumurthy, in a pilot of HIVST which offered multiple self-tests to HIV-negative women in 
antenatal and postpartum care in Kisumu, Kenya. Women were shown how to correctly use oral 
fluid-based self-tests, given three test kits with written and pictorial instructions, to distribute or 
use the tests with their male partner, based entirely on their discretion. Notably, over 90% of 
women distributed HIVST kits to their partners, and reported safer sexual decisions and rare 
social harms [46]. Acceptability indicators were very high; women reported HIVST kits were easy 
to use and their partners welcomed the opportunity to learn their HIV status conveniently and 
privately. To further evaluate this approach, Dr. Thirumurthy conducted a RCT of distribution of 
HIVST by pregnant and postpartum women to promote male partner and couples testing through 
antenatal clinics in Kisumu, Kenya [47]. Women in the intervention group received 2 oral fluid-
based HIVST, while those in the comparison group were given referral vouchers that invited their 

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partner for HIV testing at clinics, alone or as a couple. The primary outcome was whether their 
partner had sought HIV testing in the past 3 months. Significantly higher rates of male partner 
testing were achieved in the HIVST arm (91% compared to 51% in the control arm), and couples 
testing increased by 42% and disclosure by 39% [47]. 
 
In the context of PMTCT B+ programs, HIVST is a promising approach to increasing male partner 
and couples testing, which has not yet been evaluated. The Kenyan pilot of secondary distribution 
of HIVST to male partners of pregnant women had encouraging results; however, only a minority 
(4%) of the 600 women enrolled were HIV-positive and thus more information is needed about 
how to tailor this approach to HIV-infected women in PMTCT programs. Specific aspects that 
need to be better understood are HIV-positive pregnant women’s willingness and ability to 
motivate their male partner to test, which may differ from HIV-negative pregnant women, as well 
as social harms which may be more likely when male partners learn that their partner is HIV-
positive.  The importance of evaluating HIVST for male partners of women in PMTCT is that their 
male partners will either be HIV-negative (and thus in an HIV serodiscordant partnership where 
they could benefit from PrEP or voluntary medical male circumcision) or HIV-positive and need 
linkage to HIV care and ART. In summary, the feasibility and impact of secondary distribution of 
HIVST need to be evaluated in PMTCT B+ programs with the expectation that HIV-positive 
women will require additional counseling and support to broach HIVST with their partners.  
 
PMTCT B+ in Uganda  
 
Since PMTCT B+ became Ugandan national policy in late 2012, 94% of HIV positive pregnant 
women receive ART to reduce risk of mother-to-child transmission. Retention of women 6 months 
after ART initiation during pregnancy was 88%[48], and 90% on ART had undetectable viral load 
after >6 months of ART. While progress is being made in ART uptake among pregnant women in 
PMTCT B+ programs in Uganda, male engagement remains low (23%)[5].Mulago Hospital is the 
main referral hospital in Uganda, where ~23,000 pregnant women attended antenatal clinics in 
2015, 85% received an HIV test, and 3.3% were HIV positive with an average of 54 women 
initiating ART per month in PMTCT B+. Male partner involvement strategies at Mulago include 
invitation letters and phone calls to encourage HIV testing and assist with disclosure. Their 
experience with these strategies is mixed, as many invitation letters were not delivered. However, 
when letters were delivered, men showed up, eager to find out why the doctor wanted to see 
them. Partners who came to clinic were given priority and seen quickly, to boost retention, since 
the main complaint of men is the time to attend clinic. In the Mulago PMTCT program, however, 
only 19% of male partners were tested. Retention in care 12 months after ART initiation was only 
60% in 2015.  
 
Offering HIVST to women and facilitating men’s access to services are potential innovations to 
improve male partner testing and PMTCT outcomes. In Uganda, HIVST is currently limited to 
research studies. The Ugandan Ministry of Health (MoH) and Minister of Science, Technology 
and Innovation have expressed interest in HIVST projects, including this project which could 
improve PMTCT B+ outcomes. 
 
Antiretrovirals to reduce HIV infectiousness and acquisition 
 
The source of up to half of all new HIV infections in Africa is estimated to be among HIV 
serodiscordant couples – in which one partner is HIV-positive and the other is HIV-negative – a 
priority target population for HIV prevention interventions [49, 50]. Based on our experience in 
testing thousands of couples in East and southern Africa in past research studies, approximately 
half of male partners of HIV-positive women are expected to test HIV-negative and be in an HIV 

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serodiscordant partnership and half to test HIV-positive [51]. 
 
Following diagnosis of HIV serodiscordancy, couples face challenges as they strive to preserve 
their relationship and keep the HIV-negative partner uninfected amidst desires for intimate sex 
and safe pregnancy [52, 53],PrEP for the HIV-negative partner and ART for the HIV-positive 
partner can provide high levels of protection and a long-term solution for HIV serodiscordant 
couples [54, 55]. 
 
ART use by HIV-positive persons, with high adherence and maintenance of viral suppression, is 
the ultimate goal for long-term prevention of HIV transmission within HIV serodiscordant couples 
[7, 56]. The time between ART initiation and viral suppression (up to 6 months) [57], and common 
delays in ART initiation [58] are the period of highest HIV risk for HIV-negative partners. During 
this period PrEP can provides near complete protection to an HIV-negative person – the basis of 
an integrated PrEP and ART strategy [59]. Multiple randomized trials among different at-risk 
populations have demonstrated high efficacy of tenofovir-based PrEP [60-63]. 
 
The 2015 WHO guidelines recommend PrEP for people with substantial HIV risk, operationalized 
as populations with ≥3% annual HIV incidence, including HIV serodiscordant couples [64]. With 
release of WHO guidelines, there is growing enthusiasm for PrEP implementation in resource-
limited settings; Kenyan and South African drug authorities rapidly approved PrEP in 2015 [64, 
65]. Implementation plans have been developed in Kenya, South Africa, and are being developed 
in Uganda and other African countries. The focus for PrEP implementation is on innovative 
approaches to PrEP delivery for high-risk populations, such as HIV-negative male partners of 
women in PMTCT B+ programs. These implementation strategies require evaluating men’s 
willingness to be tested through innovative methods, their PrEP uptake, and women’s post-partum 
ART use and adherence. 
 
PrEP as an effective bridge to ART and viral suppression  
 
We tested the effectiveness of an integrated PrEP and ART strategy in our recently-completed 
Partners Demonstration Project among 
1,013 
ARV-naïve 
HIV 
serodiscordant 
couples at 4 sites in Uganda and Kenya, 
including IDI Kasangati in Kampala (NIMH 
R01 MH095507, Bill & Melinda Gates 
Foundation OPP1056051, USAID AID-
OAA-A-12-00023)[59]. In this model, PrEP 
provides protection against HIV acquisition 
prior to viral suppression in the HIV-
positive partner (Figure 1, Scenario 1). For 
couples in which the positive partner does 
not 
initiate 
ART 
immediately 
upon 
diagnosis, the period of HIV risk is 
extended, and PrEP is used for a longer 
period of time (Figure 1, Scenario 2). We 
recruited couples with a predicted HIV 
incidence of ≥3% [66], who would most 
benefit from PrEP as a bridge to ART.   
 
Overall, 97% of HIV-negative partners in the Partners Demonstration Project initiated PrEP and 
had high adherence with tenofovir detected in 82% of plasma samples. Similarly, we observed 

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high uptake and adherence to ART among HIV-infected 
partners; 91% initiated ART by 24 months with >90% viral 
suppression [59]. The integrated PrEP and ART strategy 
accelerates ART initiation; 90% of HIV-positive partners 
initiated ART within six months, compared to 50% in the 
Partners PrEP Study [58]. This integrated PrEP and ART 
strategy nearly eliminated HIV transmission with 95% 
reduction in HIV transmission (Figure 2); observed 
infections were compared to a counterfactual simulation 
model, bootstrapping data from the placebo arm of Partners 
PrEP, and sampling for the subset with a matching 
distribution of risk scores and follow-up [59]. High protection 
was observed among HIV-negative men (95% HIV 
reduction, p<0.0001), relevant to this project [67]. We found 
PrEP until the HIV-positive partner initiated ART was highly 
acceptable, safe and effective [1, 2]. Thus, the Partners Demonstration Project provided strong 
evidence of high adherence and effectiveness of time-limited PrEP among HIV serodiscordant 
couples who were counseled about their risk of HIV exposure, who were young and many wanted 
children, and were counseled about the efficacy of PrEP and ART. These findings provided critical 
data for PrEP guidelines by WHO [64, 68], Kenya [65], and Ugandan guidelines, which are in 
development. 
 
Relevant to this project, we also evaluated the feasibility and acceptability of HIVST among HIV-
negative persons on PrEP in a sub study of the Partners Demonstration Project. Specifically, we 
evaluated HIVST in Thika, Kenya, in which HIV-negative partners on PrEP were provided two 
oral HIVST kits to use monthly between their quarterly visits. We found very high acceptability, 
with 99% of users reporting that HIVST kits were easy to use, empowering, and reduced anxiety 
between quarterly clinic-based HIV testing [69].   
 
COVID-19 impact 
 
The COVID-19 pandemic entered Uganda in March 2019 and Uganda’s public health response 
implemented safety protocols such as shelter-in-place and transport restrictions, shortly after 
the first cases were confirmed. The impact of COVID-19 has disproportionately affected 
vulnerable populations, particularly pregnant women living with HIV, who face challenges in 
disclosure of their HIV status to their partners due to fear of loss of the partnership, economic 
support, and gender-based violence (GBV). This study will provide the opportunity to gather 
behavioral data on women’s experiences with ART adherence, status disclosure and additional 
challenges faced during prepartum and postpartum, during the COVID-19 pandemic.  
 
 
Summary  
 
This project will address key challenges in PMTCT B+ programs, by evaluating innovative 
strategies to increase male partner testing through secondary distribution of HIVST by the female 
partners to overcome men’s reluctance to test involvement in PMTCT. Confirmatory testing needs 
to follow with HIVST, and in the context of testing male partners of women in PMTCT B+, men 
who test will either learn that they are HIV negative and thus in an HIV serodiscordant partnership 
or HIV-positive. Thus, the linkages to HIV prevention and care are critical, and we will couple HIV 
testing with offering PrEP to HIV-negative men and ART to HIV-positive men and encouraging 
post-partum ART continuation and adherence among HIV-positive women.  
Figure 2. Observed vs expected HIV 
infections in the Partners 
Demonstration Project, with near 
elimination of HIV transmission[1, 2]. 
 
0"
1"
2"
3"
4"
5"
6"
EXPECTED"
N=83 infections 
incidence = 4.9  
(95% CI 3.9-6.0) 
OBSERVED"
N=4 infections 
incidence = 0.2  
(95% CI 0.1-0.6) 
95% reduction  
(95% CI 87-98%) 
P<0.0001 

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Version 4.1 , 22 May 2020 
13 
 
STUDY METHODS 
Overall design 
 
This is a randomized trial of HIV-positive pregnant women and their partners. The overall goal is 
to evaluate the impact of innovative strategies on male partner HIV testing, and engagement in 
HIV care and prevention among men, on post-partum ART continuation and adherence among 
HIV-positive women. We will recruit HIV-positive women in PMTCT B+ programs in Kampala to 
be randomized to: 1) the intervention arm in which they receive HIVST kits for their partners with 
self-instruction materials about HIVST, encouragement to seek confirmatory testing and 
counseling along with a voucher and referral, and brief educational materials about PrEP and 
ART, or 2) the control arm in which they receive invitation letters to deliver to their partners that 
invite men to fast-track HIV testing at the clinic, along with brief educational materials about PrEP 
and ART. Women in the intervention arm will be instructed in the use and interpretation of HIVST 
and be provided two HIVST kits to give to or use with their male partners. Male partners will 
receive an educational brochure outlining the benefits of HIV testing and ART or PrEP. We will 
recommend that HIV-negative men use PrEP until their partner has achieved viral suppression, 
and that HIV-positive men take ART.  
 
The co-primary outcomes of the study are the proportion of male partners who test and the 
proportion of HIV-negative male partners who take PrEP. The primary analysis is an intent to treat 
comparison by randomization arm of the primary outcome: proportion of women whose male 
partners who test HIV-uninfected and initiate PrEP within six months after their HIV-positive 
partner is randomized. A secondary outcome is an objective marker of PrEP adherence - tenofovir 
detection at 3 and 6 months - among men who initiate PrEP. 
 
The secondary outcome is the proportion of HIV-infected women who are virally suppressed at 
12 months post-partum, as the measure of continuation of ART and high adherence post-partum. 
We will also conduct observational analyses using marginal structural models to assess whether 
the HIV-positive woman’s viral load at 12 months post-partum is improved by male partner testing 
and engagement in HIV care or prevention (PrEP use among HIV-negative men or ART use 
among HIV-positive men). Quantitative and qualitative methods will be used to assess 
acceptability of HIVST in PMTCT, PrEP among male partners who test negative, and identify 
ways to minimize social harms. 
 
Objectives 
 
Aim 1: 
Determine whether an enhanced PMTCT program with HIV self-testing for male 
partners and provision of PrEP to HIV-negative male partners increases the 
proportion of male partners who test for HIV and men who initiate PrEP. 
 
Innovations are needed to reach male partners for HIV testing that allow men to test 
where they are comfortable, which typically is not in busy antenatal clinics. Provision 
of HIV self-tests (HIVST) to pregnant women for their partners is safe, acceptable, 
and effective, and could facilitate partner testing, and increase uptake of PrEP by 
HIV-negative men and ART by HIV-positive men. HIVST is a promising approach to 
increasing partner and couples testing, which has not yet been evaluated in the 

Obumu Study 
 
 
 
 
 
 
Version 4.1 , 22 May 2020 
14 
context of PMTCT B+ programs. We will randomize 500 HIV-positive women 
initiating PMTCT B+ in Kampala in a 2:1 ratio to one of two partner testing strategies: 
1) HIVST kits (intervention) to give to or use with their partner, or 2) invitation letters 
for fast-track testing at the clinic (standard of care). Men who test will be offered 
confirmatory testing and counseling. Men who test HIV-positive will be linked to ART, 
and men who test HIV-negative will be offered PrEP for the first six months after his 
partner initiates ART through PMTCT. 
 
The co-primary outcomes are the proportion of male partners who test for HIV and 
the proportion of HIV-negative men who initiate PrEP. The secondary outcome for 
this Aim is tenofovir detection at 3 and 6 months among men who use PrEP. 
 
Aim 2: 
Evaluate whether HIV testing combined with PrEP and ART use among male 
partners increases effective post-partum ART use among HIV-infected 
Ugandan women in PMTCT B+. 
 
Pregnant HIV-positive women may be more likely to continue ART after delivery and 
have higher adherence post-partum if their partners are tested, there is mutual 
disclosure of HIV status, and their partner takes ART or PrEP, depending on his 
status. We will evaluate ART use and viral suppression at 12 months post-partum 
among the 500 HIV-positive pregnant women who are randomized to male partner 
testing strategies (Aim 1). In this observational analysis, we will use causal inference 
methods to assess whether the outcome (women’s viral load at 12 months post-
partum) is improved by the exposure (male partner testing and engagement in HIV 
care or prevention – PrEP use among HIV-negative men and ART use among HIV-
positive men). 
 
The primary outcome is viral suppression at 12 months, as a measure of the 
woman’s effective ART use in the first 12 months post-partum and her adherence. 
Viral suppression will be defined as plasma viral load <400 copies/ml) at 12 months 
post-partum. Secondary outcomes include: a) post-partum adherence, as measured 
by pharmacy records will be used to measure ART dispensation and women’s self-
report about treatment interruptions; b) infant HIV status at 6 weeks as determined 
by PCR results(HIV-infected/uninfected);and c) infant survival at 12 months as 
reported by the mother.  
 
Aim 3: 
Assess the acceptability of HIV self-testing and PrEP as well as the 
perceptions of ART adherence and HIV status disclosure during the COVID-19 
pandemic,  for pregnant women taking part in PMTCT B+ and their male 
partners, using qualitative and quantitative methods.  
 
PMTCT B+ has the secondary benefit of reducing HIV transmission to male partners 
if HIV-positive women continue antiretroviral therapy (ART) long-term with high 
adherence. 
However, 
optimizing 
the 
effectiveness 
of 
PMTCT 
requires 
understanding factors that influence low uptake of HIV testing by male partners (~1/5 
of partners of women in Uganda PMTCT programs are tested for HIV. In addition, 
previous studies have indicated that 1/3-1/2 of African women discontinue ART after 
delivery, and the importance of disclosure and partners’ engagement in HIV care or 
prevention need to be assessed to determine how much those factors influence ART 
continuation post-partum. During the COVID-19 pandemic, both adherence to ART 
and initiation of HIV status disclosure may be greatly impacted.  

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Version 4.1 , 22 May 2020 
15 
 
 
 
We will use quantitative and qualitative methods to investigate acceptability of HIVST 
and PrEP. Additionally we may explore the perceptions of COVID-19 and the 
intersections on status disclosure, male partner testing, and access to and 
experiences of HIV prevention and treatment during the pandemic. 
Quantitative behavioral data will be collected from the study cohort during clinic visits 
using multiple validated questionnaires. A structured interview administered to all 
HIV-infected female partners at enrollment will ask about knowledge of the partner’s 
HIV status, disclosure, fertility desires, relationship power, and intimate partner 
violence. Up to 110 individual interviews will be conducted. A purposefully selected 
subsample of up to 90 individuals will take part in qualitative in-depth interviews to 
achieve in-depth understanding of the acceptability of HIV self-testing and PrEP use 
by male partners to women in PMTCT B+ and to male partners. In a sample of 10 
PMTCT providers, we will assess perspectives about HIVST, facilitated disclosure, 
male partner linkage to HIV care, and women’s ART use post-partum. 
 
 
 
The goal of the qualitative analysis is to assess the acceptability of HIV self-testing 
and PrEP use by pregnant women in PMTCT B+, their male partners, and 
implementation perspectives of PMTCT providers. 
Population 
 
Five hundred HIV-positive pregnant women, ≥18 years of age, with male partners of unknown 
status, will be recruited from PMTCT B+ programs in Kampala. Women in the intervention arm 
will receive HIVST kits to give to or use with their partner. Women in the standard of care arm will 
receive invitation letters that invite the male partner to be tested at the clinic where their pregnant 
partner receives antenatal care, or at IDI Kasangati. 
Eligibility 
 
For all participants 
- 
Able and willing to provide written informed consent 
- 
Able and willing to provide adequate locator information for study retention purposes 
 
For women 
- 
Age ≥18  
- 
Currently pregnant 
- 
HIV-positive based on positive rapid HIV tests, according to national algorithm 
- 
Not currently enrolled in an HIV treatment study 
- 
Male partner not known to be HIV-positive orhas not tested in the past 3 months 
 
For men 
- 
In partnership with an HIV-positive pregnant woman in PMTCT B+ 
Sample size 
 
A total of 500 HIV-positive pregnant women and their male partners.  
Recruitment 
 

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16 
IDI Kasangati has long-established recruitment and retention strategies to identify and enroll 
research-naive participants for prospective follow up. Recruitment materials will be approved by 
the IRB before study initiation. Recruitment materials will educate women about the benefits of 
male partner testing, the probability of being HIV serodiscordant, and risks of post-partum ART 
discontinuation for the woman’s health and the possibility of HIV transmission to her baby and 
partner. 
 
Women attending antenatal care are offered HIV testing, and those who test positive are provided 
immediate ART according to Uganda national HIV treatment and prevention guidelines. 
Approximately, 50 HIV-positive women are identified per month. IDI Kasangati will work directly 
with collaborating health facilities, including antenatal care/PMTCT programs, to identify pregnant 
HIV-positive women attending PMTCT B+. Health care workers and study staff at collaborating 
clinics will provide general information sessions to inform potential participants. 
 
Study screening 
 
Women will be enrolled and followed at collaborating ANC clinics. Trained research staff will 
counsel potentially eligible women about the benefits of male partner testing, post-partum ART 
persistence, and possible participation in the study. Counseling messages will include: 
 
Reasons for male partners to be tested for HIV: 
• 
To know his status. 
• 
If he is infected that he does not infect others. 
• 
If he is positive, to help him to access care and treatment which will help him stay 
healthy longer. 
• 
If he is negative, to help him stay HIV negative. 
• 
To strengthen their relationship. 
• 
To avoid  testing by proxy since about half the time, he will have a different status than 
his partner. 
 
HIV status disclosure: 
• 
Does your partner know your status? 
• 
If no, and you are positive, what do you think might happen if you discuss this with your 
partner? 
• 
Where would you tell him? When would you tell him? 
• 
Encourage women to tell him a story about the antenatal clinic, how other women have 
encouraged their partners to test for HIV, which has been beneficial for the family by 
keeping both partners health longer and see what kind of reaction he has. 
• 
Importance of talking about HIV together with their partner so they can plan for the 
future. 
• 
Risk of HIV for their children. 
• 
Explore the possibilities of being sent away, relationship ending, violence, etc. 
 
Intimate partner violence: 
The counselor will collect the following information in a culturally appropriate way. 
• 
In the past month, has your current partner punched, slapped, kicked, bit you, or caused 
you any type of physical harm? 
• 
In the past month, has your current partner insulted, ignored or humiliated you, yelled at 
you, or made you feel ashamed or bad about yourself? 

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Version 4.1 , 22 May 2020 
17 
• 
In the past month, has your current partner forced you to have sex or perform any sexual 
act, or touched you sexually in any way that you did not want? 
• 
In the past month, has your current partner made you feel afraid, unsafe or in danger? 
• 
In the past month, has your current partner taken your money when you didn’t want him 
to, or prevented you from working outside the home? 
 
Women who indicate a willingness to participate will provide independent informed consent for 
study screening. Male partners who self-test for HIV and come to clinic for confirmatory testing or 
come for HIV testing in response to an invitation letter will be offered the opportunity to consent 
for screening. Men will consent to participate in the study and receive open label PrEP or ART, 
depending on HV status. Participants will be asked screening questions about their medical 
history, including specific questions about prior pregnancies, any medical problems, partner’s 
status, HIV testing, and whether they think violence would result from offering a HIVST kit to their 
partner.  
Study enrollment 
 
Each participant will be asked to provide independent informed consent for study participation.   
Women who meet eligibility criteria and are willing to participate in the study for 12 months post-
partum, will be consented and enrolled. Trained clinicians will perform physical exams, including 
measurement of blood pressure, height, and weight.  
 
Study procedures 
 
Specific study procedures are depicted in Figure 3 and detailed in Tables 5-7.  
 
 
Female partner randomization 
HIV-positive pregnant women will be randomized in a 2:1 ratio to provision of HIVST kits to use 
with their male partners or to take an invitation letter to their male partner to be tested at their 
ANC clinic, or if the male prefers, IDI Kasangati. The 2:1 randomization provides more data on 
male partner testing with HIVST, which would be useful in assessing uptake, social harms, and 

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18 
linkage to PrEP and ART. There is ample historical information about male partner testing with 
invitation letters; the objective of this protocol is to maximize the learning about implementation 
and outcomes with secondary distribution of HIVST through PMTCT B+.   
 
The randomization code and resulting randomization list will be generated and maintained by the 
study statistician or designee. A variable size block randomization scheme will be implemented 
to produce the randomization list and maintained by the study biostatistician. Thus, neither 
participants nor study staff will be blinded to each participant’s randomization group assignment. 
 
HIVST intervention group 
Pregnant women will be provided a brief demonstration of how to use the self-test, and will be 
given two oral fluid based HIV self-tests (Oraquick rapid HIV-1/2 test kit with developer fluid vial 
and stand) to take home with written and pictorial instructions translated into Luganda (the local 
language) about HIVST to share with their partner. The instructions will clearly indicate how to 
perform an oral swab, how long to wait to read results, and how to interpret the results. Women 
will receive information about HIV self-testing including reasons for suggesting usage of the self-
test to their partner, and strategies for introducing self-tests to their partners; however, it will also 
be emphasized that women are under no obligation to suggest to their partner or convince him to 
use the self-test. Because use of self-tests at home will mean that a trained counselor will not be 
present when women or their partners take the test, the counselor will discuss with women what 
messages might best suit her situation, so that she and her partner can use the self-tests correctly 
and safely on their own. A counselor will be available by phone if a woman in the self-test arm 
needs help explaining counselling messages to their partner. The messages and counseling that 
we will provide will adhere to Uganda National Guidelines for HIV Testing Services [70]. 
 
Counseling messages: 
 
• 
Knowing your partner’s status will help you make better decisions to protect your partner 
and unborn children from HIV. 
 
• 
This HIV self-test kit is an HIV test that you can use at home. We will show you how to 
use it, and you can take it home today to use yourself and to give to your partner to use.  
 
• 
We are giving you 2 HIV self-test kits and encourage you to give one to your partner, and 
use the second one for yourself, so that you test together.  
 
• 
We will ask if you have any questions or concerns about how you might want to talk to 
your partner about using the HIV self-test. If you think he may react violently, you should 
not bring up the topic with him or wait for an opportune time to do so. 
 
• 
This is how you could introduce the self-test kits to your husband/partner: 
 
a) 
Place the test kit where he is most likely to see it. When he inquires about it, say 
you went to the clinic and was taught about the new self-test-kit … and it is a good 
opportunity to test together. 
 
b) 
Gauge his mood, and if it is good, ask him about the last time he was tested/you 
tested as a couple, then tell him you were given HIV self-tests at the clinic and it is 
a good opportunity to test together. 
 

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Version 4.1 , 22 May 2020 
19 
c) 
Ask him whether he has heard about the new HIV test kit which uses oral fluid… 
then you could tell him that you were given some kits and it would be a good 
opportunity to test together and know each other’s HIV status. 
 
• 
If your partner agrees to self-test either with you or alone, remember that the test result is 
preliminary and should be confirmed at the clinic. 
 
• 
After you or your partner uses the self-test kit, you can keep the used test kit(s) until  
you return the used test kit to the clinic. 
 
• 
You are not required to use the test kits; it is a choice. It is also not mandatory to bring 
the used test kit back. 
 
Counselors will provide tailored messaging about HIV concordant positive or serodiscordant 
results, additional counseling as needed, encourage joint prevention decision making, and 
facilitate linkage to HIV prevention, treatment and care services.  
 
Each HIVST kit will include positively framed messages, informational materials, and a voucher 
with unique identifying numbers for men who use the self-test to come to a clinic for confirmatory 
testing. Test kits will also clearly indicate a 24-hour “helpline” to call in case questions arise about 
how to use the tests, obtain support in case of a reactive test, where to go for confirmatory testing, 
or where to seek additional counseling; this helpline will also be useful for providing additional 
support and referrals to women who may experience social harms. 
 
In addition, we will provide a brief educational sheet about the importance of their HIV testing as 
a first step; if they are HIV-positive they can stay healthy by taking ART and if they are HIV-
negative, they can remain HIV negative and healthy by taking PrEP. Both will help be beneficial 
for them and their family. 
 
Returned test strips will be used to verify use and not HIV test results. 
 
Minimizing probability of violence associated with participants’ offering HIV testing to sexual 
partners: 
To minimize the likelihood of social harms, including violence against HIV-positive pregnant 
women participants, trained study staff will talk to participants at the time of enrollment about the 
importance of using their discretion and assessing the risk of intimate partner violence (IPV) when 
deciding whether to introduce self-testing to their partners. Study staff will also talk to participants 
about strategies for introducing self-testing or voluntary counseling and testing (VCT) referral 
voucher to partners, including talking points. It will be emphasized to study participants that they 
are not obligated to distribute self-tests to their partners. Participants will be counseled to never 
offer a self-test or invitation letter to a partner who they will believe will become violent due to 
introducing HIV testing.  
 
Having developed the training materials for study staff and implemented the intervention 
successfully in the Kenya pilot study, we are confident that these procedures help minimize the 
risks of social harms and intimate partner violence. We will also provide study participants with 
information on where they can seek help if they do experience violence or do need advice. We 
will establish a support telephone line (hotline) that study participants or their sexual partners can 
call at any time that will put them in touch with the study coordinator. The study coordinator will 
help arrange support for any woman experiencing violence. In our pilot study we set up a hotline 
similar to what is proposed here. 

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Version 4.1 , 22 May 2020 
20 
 
Minimizing probability of adverse reactions to test results and ensuring receipt of appropriate 
services: To ensure correct usage of self-tests (in the intervention group) and to minimize the 
probability of psychological distress due to HIV testing, we will include simple instruction materials 
with each self-test on how to use the tests, in English and Luganda. The self-test will include 
information listing VCT clinics in the area where free HIV testing and counseling is available, 
including the ANC clinic where his partner receives care and IDI Kasangati. Information will also 
be provided on clinics in the area where free HIV care and treatment is available. A support 
telephone line (hotline) will allow study participants or their sexual partner to call at any time in 
order to be in touch with study staff, who will be ready to provide additional information on where 
to seek further testing, care or treatment. 
 
Partner invitation group 
Women in the control arm will be provided invitation letters, the standard of care, to deliver to their 
partner to come for HIV testing to their ANC clinic for fast-track testing or at IDI Kasangati, alone 
or as a couple. As in the intervention group, each invitation letter will include positively framed 
messages to men about the opportunity to receive PrEP and ART if they get tested. Letters will 
also include information on how to contact a 24-hour “helpline” to talk with a counselor about the 
meaning of results and referrals. Invitation letters will have unique numbers to allow linkage of the 
man’s testing to his partner. Letters will be collected at collaborating ANC clinics. 
 
Antenatal and postnatal care 
Data collection will occur during standard of care antenatal/postnatal visits. HIV-positive pregnant 
women will access routine care at antenatal clinics according to guidelines for preventing and 
treating HIV infection in Uganda [71]. Pregnant women will have up to 4 antenatal visits before 
delivery: 1 visit in the first trimester, 1 visit in the second trimester and 2 visits in the third trimester. 
The standard-of-care antenatal package includes cotrimoxazole preventive therapy, nutrition 
assessment, iron, folic acid and multivitamin supplementation and screening for syphilis. Women 
newly initiating ART in PMTCT B+ will have same-day pre-ART adherence counselling and ART 
initiation (Table 1). They will have PMTCT B+ follow-up visit two weeks after initiating ART, and 
monthly visits for ART refills thereafter until delivery. Women will be offered delivery at a facility 
of their choice. After delivery, women will be followed quarterly for up to 12 months. 
 
Brief study questionnaires will be administered  will occur at the PMTCT visits to avoid separate 
study-specific visits.  Postnatal care and infant immunization visits will follow the routine maternal 
and child health (MCH) schedule. Viral load (VL) monitoring will include plasma HIV RNA levels 
at enrollment, 6 and 12 months post-partum. Blood samples will be batch-tested at collaborating 
laboratories. Women will be asked about interruptions in ART use. If the mother is stable on ART 
with good adherence and undetectable VL, post-partum visits will be quarterly thereafter. During 
clinic visits, women will complete interviewer-administered surveys to collect data on behavioral 
factors that could mediate women’s post-partum use of ART. Women will be provided their viral 
load results at the next visit with counseling about the relationship between adherence, viral load 
and transmission risk.  
 
Male partner procedures 
Male partners of women enrolled in the study will be recruited using established recruitment 
methods for serodiscordant couples. These strategies operationalize protocol-specified 
requirements and ensure participant privacy for eligibility determination. Men will be referred to 
their partner’s antenatal clinic or IDI Kasangati, either through invitation letters for HIV testing or 
following HIVST for confirmatory testing (Figure 4). Men will undergo informed consent for HIV 
testing and referral for HIV care and ART if they test HIV-positive or offered PrEP if they test HIV-

Obumu Study 
 
 
 
 
 
 
Version 4.1 , 22 May 2020 
21 
negative. Trained research staff will counsel potentially eligible men about possible participation 
in the study. Men who indicate a willingness to participate in the study for up to 12 months post-
partum will be offered an opportunity to undergo study screening. 
 
 
Counseling about PrEP and ART 
 
Participants will receive behavioral counseling on the effectiveness of ART and 6 months of PrEP 
to bridge to ART for HIV serodiscordant couples, post-partum ART continuation and adherence, 
PrEP benefits and adherence for HIV-negative male partners, and clinical and prevention benefits 
of ART for HIV-positive men. Counseling sessions will occur every 3 months, either to each 
partner individually or as a couple. Ad hoc sessions will be provided when requested by couples 
(Figure 5). Counselors will stress the importance of post-partum ART persistence with high 
adherence for clinical benefits and to prevent onward HIV transmission to breastfeeding infants 
and sexual partners.  
 
Table 1. Components of HIV prevention delivery for HIV serodiscordant couples as 
standard of care  public health clinics & enhanced PMTCT B+ with integrated ART and 
PrEP 
SOC services for HIV  
serodiscordant couples 
Additional components of integrated PrEP with PMTCT B+ 
Behavioral counseling 
Couples: counseling on HIV serodiscordance & efficacy of 
integrated PrEP and ART for (enrollment) 
Condom provision 
HIV-positive 
women: 
counseling 
on 
post-partum 
ART 
continuation & adherence for women (antenatal visits, 3,6, 9 and 
12 months) 
PrEP counseling & 
provision 
HIV-negative men: counseling about PrEP benefits & adherence 
(enrollment, quarterly visits through up to 12 months) 

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22 
6-monthly CD4 testing 
HIV-negative men: assessment of acute HIV infection, PrEP 
provision 
Annual HIV RNA testing, 
plus  
suspected virologic failure 
HIV-positive women: HIV RNA testing (enrollment, 6 & 12 
months) 
HIV negative men:6-monthly renal function monitoring, blood 
archive for tenofovir testing (3 & 6 months) 
HIV-positive men: assessment of ART use 
 
Counselors will assess men’s willingness to initiate PrEP or ART, willingness of women to 
continue ART post-partum, strategies to maintain daily adherence to PrEP and ART, the time-
limited use of PrEP, other HIV risk reduction strategies (condom use, medical male circumcision, 
and treatment of sexually transmitted infections), and couple communication. Male partners will 
be supported to make informed choices. Acute HIV symptoms will be assessed before PrEP 
dispensation. Medication refills with 3-month supplies, ART and PrEP adherence counseling, 
condoms, HIV testing, and lab monitoring (6-monthly creatinine, CD4 and HIV RNA testing) will 
be provided (Table 1). 
PrEP medication and dispensation 
 
PrEP will be offered to HIV-negative men according to national guidelines[71], and with the 
recommendation to take it for 6 months after their partner starts ART or until she is virally 
suppressed. Male partners will be assessed for acute HIV infection, counseled on PrEP and 
offered PrEP, if it is desired and there are no acute HIV symptoms. PrEP will be dispensed in a 
3-monthly supply. HIV testing will be conducted at each quarterly visit prior to providing PrEP 
refills. PrEP use will be suspended if HIV tests are positive or if acute HIV infection is suspected. 
Renal monitoring will occur on a 6-monthly basis. 
 
The study will provide open-label PrEP to HIV-negative male partners for 6 months or until their 
HIV-infected female partner is virally suppressed. Co-formulated FTC/TDF at 200 mg / 300 mg 
respectively will be used. The dose of FTC/TDF is the standard dose approved by the U.S. Food 
and Drug Administration. The study drug will be stored in accordance with the drug manufacturer’s 
recommendations. The pharmacy and storage facility will have locked, climate-controlled 
environments, with controlled humidity and temperature to remain within limits allowed by the 
manufacturer for drug storage. Counseling on the medications being used, their side effect 
profiles, how to take the study medication, what to do if side effects are experienced, and the 
importance of not sharing study medication to optimize potential efficacy will be provided.  
 
PrEP adherence 
 
High adherence is important for PrEP effectiveness in preventing HIV acquisition. Study staff also 
will provide brief adherence counseling at each scheduled visit, to mimic “real world” counseling. 
Data on adherence to the product use regimen will be collected via standardized interviewer-
administered questions to ascertain product use. PrEP use will be measured by dispensing 
records, and self-report through a validated 3-item questionnaire. Clinic and pharmacy records 
will be used to document PrEP prescriptions at the ANC clinics and IDI Kasangati, abstracted in 
real time from pharmacy records and entered into an electronic database. Adherence will also be 
assessed through tenofovir drug levels in male partners 3 and 6 months after PrEP initiation.   
 

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Version 4.1 , 22 May 2020 
23 
PrEP safety 
 
The Partners PrEP Study demonstrated that PrEP (including FTC/TDF) was safe for use in 
heterosexual men and women in Uganda. There were no statistically significant differences in the 
frequency of deaths, serious adverse events, adverse events overall, or key laboratory adverse 
events for those receiving PrEP compared to those receiving placebo [72].   
 
For the purposes of this study, only serious adverse events (SAEs) and adverse events Grade 3 
and above related to PrEP use will be obtained. All AEs that result in a clinical hold or permanent 
discontinuation of PrEP will be reported on the AE Log CRF regardless of grade. 
 
With appropriate permission of the participant, whenever possible, records from all non-study 
medical providers related to SAEs will be obtained and required data elements will be recorded 
on study CRFs. All participants reporting an AE will be followed clinically, until the AE resolves 
(returns to baseline) or stabilizes. 
 
Reporting on adverse events to relevant IRBs will be according to relevant regulations.   
 
Retention 
Retention measures for pregnant women and male partners will be those regularly used in 
previous PrEP studies at the IDI Kasangati – reminder calls, text messages, peer support, and 
home visits when individuals have several missed visits or an abnormal test result. Couples who 
break up will remain in the study but have separate clinic visits. We will continue to collect data 
about sexual behavior and PrEP and ART use. Research procedures for men will include 
behavioral questionnaires and blood collection to test for tenofovir drug concentration levels 
among men using PrEP. 
 
HIV testing 
 
HIV testing will be performed in accordance with Uganda HIV testing algorithms[73]. Men who 
are tested through HIVST will receive a voucher for confirmatory testing, either at the ANC where 
their partner receives care or at IDI Kasangati. HIV testing for men in the invitation letter arm and 
confirmatory testing for men in the HIVST arm will be accompanied by post-test counseling. All 
counseling and testing approaches will be in accordance with Uganda HIV counseling and testing 
guidelines.  
 
Procedures for HIV-positive men 
 
Men who are HIV-positive will receive ART adherence support, clinical monitoring and quarterly 
refills. A baseline CD4 count will be used to screen for risk of opportunistic infections. Treatment 
will be provided by local HIV care providers or at IDI Kasangati. The recommended first line 
regimen in Uganda is tenofovir-lamuvidine-efavirenz. Newly initiated partners shall be seen 
monthly for the first 3 months and quarterly therafter according to national guidelines. At these 
visits, adherence to ART, drug intolerance, side effects/toxicities and response to ART will be 
assessed. Viral load monitoring will occur at the 6 month visit (standard of care). Viral load results 
will be used to support adherence counseling.  
 
Follow up study procedures 

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24 
 
All data collection will be conducted in a private room in the participant’s preferred language, 
according to the participant’s fluency and preference. Women in the intervention and control 
groups will be asked about their partner’s testing and outcome at their PMTCT visits. Women in 
the intervention arm will be asked to bring the used HIV test strip to the ANC clinic or IDI 
Kasangati, where confirmatory testing will be offered. Clinic-based confirmatory testing for 
partners will confirm the accuracy of self-test results and identify false-positive results. Women 
whose partners have not tested will be encouraged to come with their partners to the ANC clinic 
or the IDI Kasangati to receive counseling about the importance of HIV testing, PrEP for men who 
are in HIV serodiscordant partnerships, ART for HIV-positive men, and intimate partner violence, 
efficacy of ART and PrEP, and her adherence for ART to reduce the risk of maternal-child 
transmission and sexual transmission. Women in the intervention and control groups whose 
partners do not come for testing, will be asked whether they discussed HIV testing with their 
partner, whether their partner was tested elsewhere, the outcome of his test, and whether any 
social harms resulted. 
 
At each follow up visit, questionnaires will be administered to assess sexual behavior, self-
perceived risk, partner testing status, intimate partner violence, relationship power, future fertility 
desires, self-efficacy, stigma, facilitators and barriers to ART and PrEP (Table 2). 
 
Table 2. Data collection to longitudinally assess behavioral factors related to PrEP and 
ART use 
among HIV serodiscordant couples in PMTCT B+ 
Behavioral data 
Assessment tool 
HIV-positive women 
Facilitators and barriers to ART use 
and adherence in women (Aim 2) 
Tool piloted in Partners Demonstration Project and 
past qualitative and quantitative work[59, 74] 
Sexual behavior with study partner and 
other partners 
Tool piloted in multiple couples-based HIV prevention 
services[59, 75] 
Internalized stigma 
Internalized AIDS-related stigma scale [76] 
Fertility desires 
Tool piloted in multiple couples-based HIV prevention 
services [59, 75] 
Relationship power 
Sexual Relationship Power Scale [77] 
Intimate partner violence 
Conflict Tactics Scale [78, 79] 
Alcohol use 
Rapid Alcohol Screen [78] 
Self-efficacy of ART use 
HIV Medication Self-Efficacy Scale [80] 
HIV-negative men 
HIV prevention preferences among 
men (Aim 1) 
Tool piloted in multiple couples-based HV prevention 
studies [59, 75] 
Self-perceived risk of HIV 
Tool piloted in multiple couples-based HIV prevention 
services [59, 75] 
Sexual behavior with study partner and 
other partners 
Tool piloted in multiple couples-based HIV prevention 
services [59, 75] 
HIV-positive men 
Sexual behavior with study partner and 
other partners 
Tool piloted in multiple couples-based HIV prevention 
services [59, 75] 
 
HIV seroconversion 
 
Study staff will counsel male partners who seroconvert on PrEP and refer them to local HIV care 

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providers for ongoing-care and initiation of antiretroviral therapy according to Uganda treatment 
guidelines. Seroconverters will be asked to remain in the study until completion of the follow up 
period in order to implement data collection relevant to secondary outcomes -- antiretroviral 
resistance, plasma viral load and CD4 after HIV seroconversion. 
 
Final study visit 
 
Women and male partners will be followed for 12 months post-partum. At 12 months post-partum 
or when a participant discontinues study participation, they will have a final study visit. Study 
procedures at this visit will be similar to other follow up visits. All study participants on ART will 
continue receiving care at a public health clinic of their choice. Participants on PrEP will be 
referred for care if PrEP becomes available through the public health system.  
 
Quantitative surveys 
 
A structured interview administered to all HIV-infected female partners at enrollment will ask 
about knowledge of the partner’s HIV status, disclosure, fertility desires, relationship power, and 
intimate partner violence. At the enrollment visit for male partners, a structured questionnaire will 
be administered addressing HIV testing history and experience with HIV testing through the 
PMTCT program. At six months following enrollment, a structured questionnaire will be 
administered to women and men about acceptability of HIVST and social harms and benefits 
associated with HIVST and PrEP for male partners.  Data will be collected during in person visits, 
or by phone in accordance with safety guidelines during the COVID-19 pandemic.    
 
Data quality and management 
 
Health information about the mother and child during pregnancy, delivery and after delivery will 
be documented. Clinic and pharmacy records will be used to document PrEP prescriptions, 
abstracted in real time from pharmacy records to tablet-based case report forms and entered into 
an electronic database. Automated legal range checks will be programmed to reduce data entry 
errors and internal quality control reports will be run monthly. Our team has experience using this 
data capture method in other studies of HIV prevention.  
 
Qualitative data collection 
 
Qualitative data collection will consist of individual in-depth interviews (IDIs), field observations, 
and focus group discussions (FGDs).  
 
IDIs 
The qualitative sample of study participants will be stratified by study arm. Specifically, we will 
carry out 1) up to 50 interviews with male partners 2) up to 60 interviews with pregnant women 
and 3) PMTCT and HIV providers (up to 10). For interviews with men and women, we will 
oversample those who are in the intervention arm.  
 
Individual in-depth interviews will be conducted with individuals in the qualitative subsample to 

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elicit data on acceptability of HIV self-testing and PrEP for male partners (and on the control 
condition). Some participants may be asked to complete a second in-depth interview, to assess 
their experience in the study over time. Interviews will be “minimally structured“, i.e. guided by 
topics (rather than pre-designated, open-ended questions) tailored to each group. Examples of 
topics for interviews with male partners are:  
 
a) History of HIV testing;  
b) History of relationship with his partner in PMTCT B+;  
c) Response to receiving an HIVST or letter of invitation to test;  
d) Response to the offer of PrEP for prevention (for individuals with negative test results). 
 
Examples of topics to be covered in the interviews with women in PMTCT B+ are:  
 
1) The “story” of providing the HIV self-testing kit or the letter of invitation to test to their partner  
2) Description of the partner’s response 
3) Partner follow-up in terms of confirmatory HIV testing and/or PrEP 
4) Impact on the relationship (including social harms) 
5) Impact on feelings about ART use post-partum 
 
Examples of topics to be covered in the interviews with PMTCT providers are:  
 
1) Perceptions of influences on  male partner testing in the context of PMTCT B+ ; 
2) Experiences of implementing male partner testing in the context of PMTCT B+; 
3) Perceived responses of male partners to self-testing, and the reasons behind these responses; 
4) Perceived responses to the offer of PrEP for male partners who test negative; 
5) Patterns of and influences on ART adherence for pregnant women during pregnancy and post-
partum; 
6) Perceived impact of HIV testing and subsequent initiation of PrEP or ART by male partners  on 
ART  adherence for pregnant and post-partum women; and 
7) Perspectives on how to facilitate disclosure and minimize social harms in these couples. 
 
During in-depth interviews with PMTCT providers, male partners and women, we may explore 
the perceptions of COVID-19 and the intersections on status disclosure, male partner testing, 
and adherence to HIV prevention and treatment during the pandemic.  
 
Interview procedures: In-depth interviews will be conducted by gender-matched Ugandan 
research assistants (RA). The RA’s have been trained in methods of qualitative interviewing by 
Dr. Wyatt, who heads the qualitative team with Dr. Ware. Interviews will usually be scheduled 1–
3 months following provision of the HIVST kit or letter of invitation to test, but may take place at a 
later time during study participation. They will be conducted where conversations cannot be 
overheard. Interviews will be conducted in the interviewee’s language of preference (English or 
Luganda). Provider interviews will be conducted in English. Interviews will be audio-recorded with 
permission. Participation will be recognized with a small reimbursement, based on local 
standards. Compensation for travel to the interview will be provided where appropriate.  
 
Producing the interview data: The interview data for this study will consist of up to 120 written 
transcripts. Immediately following each interview session, the interviewer will produce an exact 
electronic write-up of the interview in English, using audio-recording and notes taken during the 
interview as guides. We have developed this approach of direct transcription into English from 
local languages over many years of qualitative research in Africa and find it produces an accurate 
transcript while also saving time and resources. We will use Express Scribe, an audio-recording 

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27 
transcription computer software program, which facilitates transcription.  
 
Field Observations 
This study will use field observations to provide additional, complementary information on 
implementation of the HIV self-testing intervention (and control condition). Field observations are 
a well-established data collection technique in qualitative research that involve the presence of a 
researcher in a naturalistic setting, the witnessing of events and activities of interest, and often 
some degree of participation [81]. Observations provide a direct view of the event under study 
and thus complement the mediated perspective obtained through IDIs. Dr. Ware has been using 
field observations with success in her qualitative HIV research in sub-Saharan Africa for the past 
several years. The qualitative component of this study will include 20 observations of interactions 
between pregnant women and providers in PMTCT B+ clinic visits where HIV self-testing kits or 
letters of invitation to test are distributed. Field observations will be conducted by a Ugandan 
qualitative RA, trained and experienced in this approach to qualitative data collection. 
Observations will be conducted until 20 observations have been completed. Each observation 
session will last 2-3 hours. To minimize bias in collecting observational data, dates of observations 
will be randomly selected. Verbal consent is obtained to conduct observations, which is done by 
the Ugandan RA. Observations are recorded as field notes, which do not contain identifying 
information and serve as formal records for analysis.   
 
Focus Group Discussions 
 
Female and male participants will be asked to join focus group discussions designed for the study 
staff to gather feedback on how they can best support participants during their study involvement. 
Participants will sign a separate consent form before joining the focus group discussions. We will 
use FGDs for qualitative data collection, including understanding the major issues related to HIV 
self-testing and status disclosure, assessing variation in testing and disclosure experiences, 
eliciting attitudes and beliefs and understanding differences between participants. 
Qualitative data quality and management 
 
Data in the form of interview transcripts and field notes will be continuously reviewed for content, 
clarity, detail, and grammar by Dr. Ware’s research group. Feedback on quality and suggestions 
for improvement will be provided to the RA through regular supervision. Upon completion, 
transcripts and field notes will be routed electronically to Boston, using a secure file transfer 
system. Data will be stored on secure servers at the Harvard Medical School and at IDI Kasangati.  
Qualitative data analysis 
 
The goal of the qualitative analysis is to assess the acceptability of HIV self-testing and PrEP for 
male partners to pregnant women in PMTCT B+ and to male partners. The construct of 
acceptability is broadly defined to target not only participants’ feelings and attitudes toward the 
intervention, but also their broader experiences with intervention components. The qualitative 
analysis will address “how” and “why” questions about intervention dynamics to inform future 
dissemination and intervention examples of questions to be answered through analysis of the 
qualitative data are: 
 
1) When participating male partners completed an HIV test, what were the reasons?  
2) When participating male partners did not test, what were the reasons?   
3) In what ways, if any, did the availability of HIV self-testing kits influence the decision to test?  

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4) In what ways, if any, did receiving a letter of invitation influence men’s decision to test?   
5) In what ways, if any, did self-testing or letters of invitation impact men’s decisions for or against 
initiation of PrEP and/or ART, for male partners who tested for HIV? 
 
We will use an inductive, content analytic approach [82] to data analysis, with coding and category 
construction as core analytic activities. The qualitative data set consists of up to 110 interview 
transcripts and 20 observation field notes. Analysis will begin with open-coding through review of 
20% of the data to identify sections of text suggestive of acceptability. These sections of text will 
be labeled, defined, and illustrated to become codes, and assembled into a codebook. The 
codebook will be used for data coding, using the software program Atlas.ti to organize the coding 
process. Coding will be conducted by the Uganda RA and Emily Pisarski. Data will be sorted by 
codes to identify themes corresponding to specific aspects of acceptability. The coded data will 
also be compared by code across groups to investigate systematic inter-group differences in 
perspectives of male partners, pregnant women and providers. Differences will be reported in 
descriptive categories. The final step in analysis is to develop descriptive categories. Categories 
will consist of a label, an operational definition and text specifying the category content, with 
illustrations through excerpts from interview transcripts or field notes. The categories will 
represent answers to the analytic questions specified above. Qualitative results will be compared 
with quantitative data on intervention acceptability collected as part of Aim 3. Qualitative data will 
be used to help interpret the results of the randomized trial.  
 
DATA  ANALYSIS 
Sample size 
Aim 1: The sample size was selected to ensure high power for the PrEP outcome as well as the 
male partner testing. Table 3shows a range of assumptions for the proportion of men who are 
HIV-uninfected (60-70%), and the test uptake in the standard of care arm (20-30%, as observed 
in MU-JHU’s program) and Enhanced testing arms (55-66%).  
 
Table 3. Sample size calculations for comparison of 
proportion of 
HIV-negative men on PrEP by arm  (Aim 1) 
Proportion of 
HIV-negative 
men 
HIV test uptake 
Sample size to achieve 
SOC Enhanced 80% power 90% power 
60% 
20% 
55% 
162 
216 
60% 
20% 
65% 
103 
138 
60% 
30% 
55% 
379 
508 
60% 
30% 
65% 
203 
271 
70% 
20% 
55% 
133 
178 
70% 
20% 
65% 
84 
112 
70% 
30% 
55% 
312 
417 
70% 
30% 
65% 
165 
221 
Randomization is 2:1 for Enhanced: SOC. Assumes 95% 
retention, 80% PrEP uptake 
 
Assuming PrEP uptake in HIV-negative men is 80% and 60% of the men are HIV-uninfected, with 
a sample size of 500 we would have almost 90% power to detect an increase in PrEP use resulting 
from a change from 30% to 55% in test uptake. With 500 women, the power for assessing an 
increase in HIV test uptake exceeds 95% across a range of assumptions in Table 3. 

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Aim 2: Under the range of assumptions for HIV testing uptake in Aim 1, the overall HIV test uptake 
will be in the range 43-53% (Table 4) and the number of enrolled women with partners who test 
and begin ART or PrEP ranges from ~150-200. Assuming power for the causal inference can be 
approximated by logistic regression, we would have ~80% power to detect an OR of 1.75 or 
higher, assuming women have 50% ART continuation and viral suppression when male partners 
do not initiate PrEP or ART. If the number of women with partners who test is between 220-270, 
we would have approximately 85% power to detect an OR of 1.75.  
 
Table 4. Power approximation for assessing impact of partner PrEP/ART use on 
women’s viral suppression 
Overall HIV  
test uptake 
HIV prevalence 
in male partners 
HIV+ men on ART 
or HIV- men on 
PrEP 
Not on ART 
or PrEP 
OR=1.75 
OR=2.0 
43% 
0.4 
147 
353 
78% 
92% 
47% 
0.3 
166 
334 
81% 
94% 
50% 
0.4 
170 
330 
80% 
94% 
53% 
0.3 
189 
311 
83% 
95% 
Randomization is 2:1 for Enhanced: SOC. Assumes 95% retention, 80% PrEP uptake and 
50% ART persistence 
Outcome measurements 
 
Aim 1: Women who are randomized will have key outcomes assessed at scheduled visits. The 
co-primary outcomes will be HIV testing by the male partner, as measured by questionnaires 
administered to women in clinic, and PrEP by 6 months after the woman initiated ART. The Kenya 
pilot indicated minimal bias in self-report of male partner testing. The secondary outcome is PrEP 
adherence among the male partners who initiate PrEP, based on detectable blood tenofovir levels 
at 3 and 6 months after PrEP initiation. PrEP use will also be measured by pharmacy records 
where men are dispensed PrEP (e.g.at the ANC or IDI Kasangati), and self-report through a 
validated 3-item questionnaire[83]. We will assess HIV seroconversion but expect a low rate. 
 
Aim 2: The exposures of interest are male partner testing, PrEP initiation and ART initiation (Table 
2). The primary outcome is the woman’s viral load at 12 months post-partum. Viral suppression 
will be defined as plasma viral load <400 copies/ml). For the secondary outcomes, pharmacy 
records will be used to measure ART dispensation and women will be asked at quarterly visits 
about treatment interruptions[83]. Secondary outcomes include infant HIV status at 6 weeks (HIV-
infected/uninfected) which will be ascertained from ANC records, and infant survival at 12 months 
as reported by the mother at her 12-month post-partum visit. 
 
Capture of cohort clinical data  
 
Data on male partner HIV testing and female partner ART use and viral load will be obtained from 
case report forms. Clinic and pharmacy records will be used to document PrEP prescriptions, 
abstracted in real time from pharmacy records to paper-based case report forms and entered into 
an electronic database. Automated legal range checks will be programmed to reduce data entry 
errors and internal quality control reports will be run monthly. 
Statistical considerations 
 

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Aim 1: The primary analysis will be an intent to treat comparison by randomization arm of the 
primary outcome: the proportion of women whose male partners who test for HIV and the 
proportion of HIV-negative men who take PrEP within six months after their HIV-positive partner 
is randomized. The secondary outcome is tenofovir detection at 3 and 6 months among men who 
use PrEP. 
 
Aim 2: Our primary analysis will assess the effect of male partner’s PrEP or ART use on women’s 
ART continuation and viral suppression at 12-month post-partum period, as the measure of her 
ART continuation and adherence. This intent of the analysis is to assess the impact of the male 
partner’s current (time-dependent) PrEP or ART use on the women’s current ART use and viral 
suppression. Since initiation of PrEP or ART is secondary to the randomized HIV testing 
intervention, causal inference methods will be used to assess the impact of male partner HIV 
testing and PrEP or ART use on post-partum ART continuation. We will calculate standardized-
inverse-probability weights with logistic regression [84], to predict the probability of current male 
PrEP or ART use at each visit as predicted by the instrumental variable HIV testing randomization, 
and potential time-varying confounders (Table 3), including sexual behavior, future fertility 
desires, relationship power dynamics, intimate partner violence, alcohol use, and baseline 
demographics and duration of ART pre-partum. These weights will then be used in a pooled 
logistic regression model of partners’ PrEP or ART exposure as predictors of: 1) ART continuation 
and 2) viral suppression. In a separate set of models, we will examine the direct effect of male 
testing, overall and separately for HIV-positive and HIV-negative men, on the woman’s ART 
continuation and viral suppression. We will also explore an instrumental variables approach to 
causal estimation, given the expected role of randomization in male partners’ initiation of PrEP 
and ART in Aim 1[85]. 
 
DATA SHARING AND OWNERSHIP 
 
During the conduct of the trial, the study database will remain confidential. After study completion, 
access to data will follow requirements of the Infectious Diseases Institute, National Institutes of 
Health and the University of Washington. The University of Washington International Clinical 
Research Center has a Manuscripts and Ancillary Studies Committee established to enable data 
and specimen collaborative work from studies conducted through the research group. Intellectual 
property and data generated under the proposed project will be administered in accordance with 
Uganda, University of Washington and NIH policies, including the National Guidelines for 
Research involving Humans as Research Participants (2014) and the NIH Data Sharing Policy 
and Implementation Guidance of March 5, 2003. 
 
Materials 
generated 
under 
the 
project 
will 
be 
disseminated 
in 
accordance 
with 
University/participating institutional and NIH policies. Depending on such policies, materials may 
be transferred to others under the terms of a material transfer agreement. Access to databases 
generated under the project will be available for educational, research and non-profit purposes 
as approved by the relevant IRBs. Publication of data shall occur during the project, if appropriate, 
or at the end of the project, consistent with normal scientific practices. We will publish our findings 
in a timely fashion and will present unpublished data at appropriate research conferences. We 
are committed to collaboration in complex disease research and will participate in data-pooling 
studies as allowed by our currently established consent forms and IRBs. 
 
Data obtained from this research study are the property of the Infectious Diseases Institute of 
Makerere University and the University of Washington International Clinical Research Center. 

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31 
Local researchers shall have unrestricted access rights to datasets collected through this 
collaborative research project in accordance with Uganda guidelines. 
 
DISSEMINATION PLAN 
 
Dissemination of study results will follow principles of good participatory practice. Study results 
will be disseminated through presentations to study participants, stakeholders and policy makers, 
and published in conference abstracts and peer-reviewed journals. Participants will be informed 
that if they so desire, they will be contacted at the end of the study for the purpose of informing 
them about study results. Trial results will also be shared with the community advisory board, the 
Ministry of Health, implementing partners and civil society groups with interest in reproductive 
health. 
 
HUMAN SUBJECTS CONSIDERATIONS 
 
The study protocol, site-specific informed consent forms, participant education and recruitment 
materials, and other requested documents — and any subsequent modifications — will be 
reviewed and approved by the IRBs/ECs responsible for oversight of research conducted at the 
study site. Subsequent to initial review and approval, the responsible IRBs/ECs will review the 
study at least annually.   
Informed consent 
 
Written informed consent will be obtained from each study participant prior to both screening and 
enrollment. Participants will be offered copies of the informed consent forms. The study site will 
draft informed consent forms that describe the purpose of screening and of the study, the 
procedures to be followed, and the risks and benefits of participation, in accordance with all 
applicable regulations, based on the consent forms provided in the Appendix. The site will 
translate the forms into the local language and verify the accuracy of the translation by performing 
an independent back-translation, which will be reviewed and approved by the International Clinical 
Research Center at the University of Washington. 
Risks 
Confidentiality. Although the study site will make every effort to protect participant privacy and 
confidentiality, it is possible that participants' involvement in the study could become known to 
others, and that social harms may result (i.e., because participants could become known as 
participating in a trial involving HIV-positive persons). For example, participants could be treated 
unfairly or discriminated against, or could have problems being accepted by their families and/or 
communities. There is additionally the potential of confidentiality with regards to virtual data 
collection over the phone. Phone visits may occur, to comply with national safety guidelines in 
response to COVID-19. Study staff are well trained in protecting patient confidentiality, and will 
ask several introductory questions to confirm the identity of the participant before continuing with 
study visits. Phone visits will only occur if participants feel comfortable answering study questions 
virtually, and they do not foresee any safety related concerns. 
 
HIV testing. Participants may become embarrassed, worried, or anxious when completing their 
HIV risk assessment and/or receiving HIV counseling. They also may become worried or anxious 
while waiting for their (or their partner’s) HIV test results. Couples-based counseling and 

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discussions of study participation may raise issues between partners, particularly related to blame 
(from HIV-negative men) and potential termination of the partnership. Participants who learn that 
they have HIV may experience anxiety or depression related to their test results. Individual and 
couples-based HIV counseling will be provided by counselors and clinicians who have been 
trained in specific issues related to HIV serodiscordant couples, including stigma, blame, methods 
to avoid transmission, and available support services. 
 
Social harm. Intimate Partner Violence (IPV) following HIV status disclosure is an important 
consideration for couple studies. In a Kenyan study, women who experienced recent IPV were 
less likely to report partner self-testing (adjusted relative risk ratio [a RRR] 0.10; 95% CI: 0.02-
0.47) or couple testing (a RRR 0.13; 95% CI: 0.03-0.54)[86]. Recent partner violence was not 
significantly associated with male partner self-testing or couple testing. However, couple testing 
was less likely if the male partner had a neutral or negative reaction to the offer of a self-test (aOR 
0.32; 95% CI: 0.12-0.87) or was not easily persuaded to use a self-test (a OR 0.25; 95% CI: 0.09-
0.76). 
 
We have extensive experience with counseling >1700 couples over the past decade at the IDI-
Kasangati research site. In a study that utilized data from our site, IPV was reported in 2.7% of 
visits by HIV-infected women and in 2.2% of visits by HIV-uninfected women [87]. In the Partners 
PrEP Study, HIV-uninfected women in serodiscordant partnerships reported IPV at 0.7% of study 
visits [88]. Serodiscordant couples perceive PrEP as a solution to the “discordance dilemma” - 
the desire to avoid HIV acquisition while preserving the relationship. PrEP users benefit from the 
adherence support of infected partners on ART, and this mutual reinforcement motivates couples 
who wish to stay together to do so [52].  
 
The majority of women receive support and understanding from their partners when they disclose 
their HIV status. Fewer than 5% of couples separate or divorce after disclosure of an HIV positive 
test [89]. A study in South Africa found no evidence that inviting male partners to ANC and HTS 
increased risk of self-reported IPV in women or men when compared to letters inviting male 
partners for pregnancy information sessions [36]. Overall, no association between HIV status and 
IPV was demonstrated in an analysis of data from Demographic and Health Surveys conducted 
in Kenya, Liberia, Malawi, Mali, Rwanda, Zambia and Zimbabwe [90].  
 
While HIVST studies indicate several benefits and minimal risk of harm, intended or unintended 
physical, economic, emotional or psychosocial injury could occur before, during or after HIV 
testing [91]. Women may experience social harm from partners after discussing and/or performing 
HIVST. In a Kenyan cohort study, two of 178 pregnant or postpartum women reported verbal 
abuse following a reactive HIV self-test result [46]. Few instances of violence or harm have been 
reported in HIVST randomized trials, but these occurred prior to partner notification[92-94], 
suggesting that HIVST may not directly influence the risk of IPV. This finding is consistent with 
systematic reviews of harm in studies of HIVST [95], couple testing [96], and other forms of HIV 
testing [97]. 
 
Phlebotomy. Participants may experience discomfort or pain when undergoing phlebotomy. They 
also may feel dizzy or faint, and/or develop a bruise, swelling, or infection where the needle is 
inserted.  
 
PrEP medication. Risks and side effects related to PrEP include: occurring in a minority of 
individuals taking PrEP - gastrointestinal intolerance, such as nausea, diarrhea or vomiting, 
flatulence; rare but serious - lactic acidosis/ severe hepatomegaly with steatosis, renal 
impairment, including cases of acute renal failure and Fanconi’s syndrome (renal tubular injury 

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with severe hypophosphatemia), increase in bone metabolism leading to osteopenia, 
hypersensitivity reaction.   
 
Qualitative interviews. The risks of participating in the qualitative interviews are minimal. It is 
possible that participants might become tired during the interview. They may also find some of 
the questions uncomfortable or hard to answer. In the observation sessions, it is possible that 
individuals may feel uncomfortable being observed. 
Benefits 
 
The primary aim of this study is to evaluate the impact of innovative strategies on male partner 
HIV testing, engagement in HIV care and prevention among men, and on post-partum ART 
continuation and adherence among HIV-positive women. HIV prevention practices, according to 
Ugandan guidelines, will be provided to all participants enrolled in this study. This will include risk 
reduction counseling, treatment of sexually transmitted infections (STIs), condoms, and referral 
for medical male circumcision. If prevention strategies are modified during the course of study 
conduct (e.g. PrEP becomes available through the public health system), participants will be 
counseled and referred for these strategies as well.   
 
HIV-positive women will benefit from male partner testing, facilitated disclosure and ART 
counseling. HIV-negative male partner participants will benefit by having free access to PrEP 
during the study period, until 6 months after their partner initiates ART. Participants may benefit 
from ongoing access to prevention services. There may be no other direct benefits to participants 
in this study. However, participants and others also may benefit in the future from information 
learned from this study.   
 
All participants will be provided with HIV prevention services, including condoms, STI treatment, 
and ongoing support, including counseling and referral to other support services. 
 
Care for HIV-positive male partners 
 
This study will identify male partners who are infected with HIV, either as part of testing male 
partners of unknown status, or during follow-up of initially HIV-negative men. Study staff will 
provide participants with their HIV test results in the context of post-test counseling. Men identified 
as HIV-positive will be referred for HIV clinical care, including primary care and antiretroviral 
therapy, according to Ugandan guidelines. During the course of the study, it is possible that 
guidelines will change regarding clinical care of persons with HIV (including optimal therapy, 
prophylaxis, etc.).  At all times during the study, treatment and referral practices for HIV-positive 
persons in the study will adhere to national ART guidelines. After the study ends, HIV-positive 
participants will be provided referrals to other care programs for ongoing HIV primary care. This 
type of care will also be offered to initially HIV-negative study participants who become infected 
during follow-up.  
 
Benefits to the community 
 
An important goal of this study is to achieve the study objectives in a way that provides benefits 
to the community that endure beyond the proposed study lifetime regardless of the specific 
outcome of the study.  Some of these community benefits are listed below: 
 
Couples HIV counseling and testing (CHCT): Infrastructure to effectively counsel and test couples 
for HIV will be needed for this study to effectively recruit male partners. CHCT capacity developed 

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at the study site in collaboration with existing local VCT programs through training of local 
counselors is a beneficial resource to the community well after the study is completed. Given 
recent data that 70% of incident HIV cases are transmitted from regular partners, creating 
awareness, increasing demand, providing couples VCT and providing ART and PrEP will reduce 
transmission of HIV among couples. This will have consequent benefits to the family and 
community by maintaining one healthy partner. 
 
Development of male-friendly HIV testing and linkage to HIV care and prevention within real world 
PMTCT B+ settings: This study aims to provide HIV prevention policy makers with information on 
how to best engage male partners in PMTCT B+ programs. In addition to the provision of this 
biomedical method, the study site will provide CHCT, and routine adherence counseling. The 
outcome of the study will be evidence upon which to based policy guidelines for improving male 
involvement in PMTCT in Uganda and nearby countries with similar HIV prevention needs.  
 
Treatment for injury 
If a study participant is injured while participating in this study, they will be offered care at the 
study clinic, free of charge until their injury is cured or stabilizes.  Participants will be encouraged 
to tell members of the team of researchers if they feel they have been injured because of taking 
part in this study. Those who require medical care that the study clinic cannot provide will be 
referred by the study doctors to the appropriate services or organizations that can provide care 
for the injury. This referral will be covered by the University of Washington comprehensive liability 
program. 
 
Study records 
 
Site Investigators will maintain, and store in a secure manner, complete, accurate, and current 
study records throughout the study. The investigator will retain all study records for at least five 
years after completion of the study. Study records include administrative documentation and 
regulatory documentation as well as documentation related to each participant screened and/or 
enrolled in the study, including informed consent forms, locator forms, case report forms, 
notations of all contacts with the participant, and all other source documents. Logs linking 
participant name to study identification number and other identifying information in study files will 
be retained for five years after the study is completed; after that time, the link will be destroyed. 
Participants may consent to storage of samples for future research; any future research must be 
approved by overseeing Institutional Review Boards.  
Confidentiality 
 
Every effort will be made to protect participant privacy and confidentiality to the extent possible.  
Personal identifying information will be retained at the study site. The study site will establish a 
standard operating procedure for confidentiality protection that reflects the local study 
implementation plan and the input of study staff and community representatives to identify 
potential confidentiality issues and strategies to address them. In addition to local considerations, 
the protections described below will be implemented at the study site.   
 
All study-related information will be stored securely at the study site. All participant information 
will be stored in areas with limited access. Data collection, administrative forms, laboratory 

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35 
specimens, and other reports will be identified only by a coded number to maintain participant 
confidentiality. All records that contain names or other personal identifiers, such as locator forms 
and informed consent forms, will be stored separately from study records identified by code 
number. All local databases will be secured with password-protected access systems. Forms, 
lists, logbooks, appointment books, and any other listings that link participant ID numbers to other 
identifying information will be stored in a separate, locked file in an area with limited access. 
 
Participants’ study information will not be released without their written permission, except as 
necessary for oversight by: 
 
The National HIV/AIDS Research Committee  
The Uganda National Council for Science and Technology 
The Uganda National Drug Authority 
Uganda Ministry of Health 
The University of Washington 
Harvard Medical School 
The United States National Institutes of Health 
 

Obumu Study 
 
 
 
 
 
 
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36 
 
Table 5.  Procedures for HIV-positive pregnant women 
*Standard of care 
Study staff will perform study specific procedures at collaborating clinics 
 
LEGEND 
[ ] as indicated 
T = trimester 
Del = delivery 
 
 
 
ANTENATAL 
POSTNATAL 
 
T1 T2 
T3 
T4 
M3 
M6 M9 M12 
ADMINISTRATIVE AND REGULATORY 
PROCEDURES 
 
 
 
 
 
 
 
 
Obtain written informed consent 
[X] [X] 
[X] 
[X] 
 
 
 
 
Assign participant identification number 
[X] [X] 
[X] 
[X] 
 
 
 
 
Assess eligibility 
[X] [X] 
[X] 
[X] 
 
 
 
 
Collect/update locator information 
[X] [X] 
[X] 
[X] 
X 
X 
X 
X 
Collect/update demographic information 
[X] [X] 
[X] 
[X] 
 
 
 
 
Obtain random allocation 
[X] [X] 
[X] 
[X] 
 
 
 
 
Schedule next visit 
[X] [X] 
[X] 
[X] 
X 
X 
X 
 
COUNSELING 
 
 
 
 
 
 
 
 
HIV/STI risk reduction counseling, condom provision 
[X] [X] 
[X] 
[X] 
X 
X 
X 
X  
Counseling (ART adherence, clinical & prevention 
benefits) 
[X] [X] 
[X] 
[X] 
X 
X 
X 
X 
CLINICAL PROCEDURES 
 
 
 
 
 
 
 
 
Provide HIV test results 
[X] [X] 
[X] 
[X] 
 
 
 
 
Medical history 
[X] [X] 
[X] 
[X] 
X 
X 
X 
X 
Perform physical exam 
[X] [X] 
[X] 
[X] 
[X] 
[X] [X] [X] 
STI syndromic assessment and management 
[X] [X] 
[X] 
[X] 
[X] 
[X] [X] [X] 
Referral for / provision of ART according to national 
guidelines 
[X] [X] 
[X] 
[X] 
X 
X 
X 
X 
PMTCT PROCEDURES* 
 
 
 
 
 
 
 
 
Antenatal care package 
[X] [X] 
[X] 
[X] 
 
 
 
 
Postnatal care package 
 
 
 
 
[X] 
[X] [X] [X] 
Infant HIV status at 6 weeks 
 
 
 
 
X 
 
 
 
Infant survival at 12 months post-partum 
 
 
 
 
 
 
 
X 
LABORATORY PROCEDURES 
 
 
 
 
 
 
 
 
Syphilis testing 
X 
[X] 
[X] 
[X] 
 
 
 
 
HIV serology 
X 
[X] 
[X] 
[X] 
 
 
 
 
Plasma HIV viral load 
 
 
 
 
 
X 
 
X 

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37 
Table 6.  Procedures for male partners 
 
 
[ ] as indicated 
             *Three months after study enrollment 
+Visits up to 12 months postpartum 
 
 
 
E M3* M6 M9 M12 [M]+ 
ADMINISTRATIVE AND REGULATORY 
PROCEDURES 
 
 
 
 
 
 
Obtain written informed consent 
 
 
 
 
 
 
CLINIC PROCEDURES 
 
 
 
 
 
 
Confirmatory testing (self-test arm) 
X 
 
 
 
 
 
Initial testing (invitation letter arm) 
X 
 
 
 
 
 
Provide HIVtest results and post-test counseling 
X 
 
 
 
 
 
Medical history 
X 
X 
X 
X 
X 
 
Perform physical exam 
X 
[X] [X] [X] [X] [X] 
STI syndromic assessment and management 
X 
[X] [X] [X] [X] [X] 
Syphilis testing 
X 
 
 
 
 
 
HIV-NEGATIVE MEN 
 
 
 
 
 
 
Provide HIV test results 
 
X 
X 
X 
X 
[X] 
Hepatitis B surface antigen 
X 
 
 
 
 
 
Creatinine 
X 
 
X 
 
[X] [X] 
PrEPprovision 
X 
X 
X 
[X] [X] [X] 
Blood sample archive for tenofovir levels (if on PrEP)  
 
X 
X 
 
 
 
HIV-POSITIVE MEN 
 
 
 
 
 
 
Referral for / provision of ART according to national 
guidelines 
X 
X 
X 
X 
X 
[X] 
Assess ART use and linkage/retention in care 
 
X 
X 
X 
X 
[X] 
Plasma HIV viral load 
X 
 
X 
 
[X] [X] 

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38 
 
Table 7.  Procedures for HIV seroconverters among HIV-negative male partners who initiate 
PrEP 
 
HIV-negative men who seroconvert to HIV will have one set of samples collected as close in 
time to the seroconversion visit as possible (ideally, either at the SC or SC<1 month visits). 
Samples to be collected are: 
 
 
CD4 count 
Viral load 
Plasma archive (for tenofovir and resistance assays) 
 
 
 
 
 
Possible 
seroconversion 
visit (≥1 rapid HIV 
test positive) 
Follow-up to 
possible 
seroconversio
n (ideally 
within one 
month of 
possible 
seroconversio
n) 
M3 M6 
ADMINISTRATIVE, BEHAVIORAL AND REGULATORY PROCEDURES 
 
 
Provide HIV counseling, including couples counseling 
X 
X 
X 
X 
CLINICAL PROCEDURES 
 
 
Collect medical history 
X 
X 
 
X 
Perform physical exam 
X 
 
X 
X 
Collect blood specimen 
X 
X 
X 
X 
Stop PrEP, if applicable 
X 
 
 
 
Provide test results 
X 
X 
 
 
Refer for HIV care 
 
X 
 
 
Assess linkage to care 
 
 
X 
X 
LABORATORY PROCEDURES 
 
 
CD4 count 
X 
X 
X 
X 
HIV plasma viral load 
X 
X 
X 
X 
HIV serology (confirmatory EIA) 
X 
 
 
 
Serum, plasma archive for HIV resistance assays,  
PrEP levels (batched testing) 
X 
X 
X 
X 

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