Pregnancy outcomes following self-reported and objective-measured exposure to oral preexposure prophylaxis in South Africa.

OBJECTIVE: To compare pregnancy outcomes using self-reported and objective levels of intracellular tenofovir diphosphate (TFV-DP) in pregnant women using preexposure prophylaxis (PrEP). DESIGN: We enrolled pregnant women >15 years without HIV at first antenatal care visit in an observational cohort study to compare pregnancy outcomes by PrEP use. METHODS: Exposure defined as: any PrEP use [tenofovir disoproxil and emtricitabine (TDF/FTC]) prescription + reported taking PrEP], or objectively-measured TFV-DP in dried blood spots in PrEP-using pregnant women. The primary outcome was a composite of pregnancy loss, preterm birth (<37weeks), low birthweight (<2500 g), small for gestational age ([SGA] ≤ tenth percentile), or neonatal death. Multivariable logistic regression models evaluated individual and composite adverse outcomes by self-reported or objectively measured PrEP use adjusting for age, gestational age, gravidity and socio-economic status. RESULTS: Between August 19 and February 23, we followed 1195 pregnant women and ascertained 1145 pregnancy outcomes (96%); 72% ( n  = 826) reported taking PrEP while pregnant, 16% did not take PrEP ( n  = 178), 12% were unconfirmed ( n  = 141). Overall, 94.5% ( n  = 1082) had singleton live births with a median birthweight of 3.2 kg [interquartile range (IQR) = 2.9-3.5], with no difference in pregnancy loss between self-reported PrEP exposed vs. unexposed [4.0 vs. 5.6%; adjusted odds ratio (aOR) = 0.65, 95% confidence interval (CI) = 0.32-1.47]. Composite adverse outcomes did not differ by reported PrEP use (20% for both groups; aOR = 1.07, 95% CI = 0.71-1.63). Comparing objective PrEP use (any TFV-DP vs. no TFV-DP or not on PrEP), adverse outcomes did not differ (aOR = 0.64, 95% CI = 0.39-1.04), nor did other outcomes including preterm birth nor SGA. CONCLUSIONS: Pregnancy outcomes did not differ by PrEP exposure (self-reported or objective), suggesting real-world efficacy that TDF/FTC as PrEP is safe in pregnancy.

Evaluating the use of oral pre-exposure prophylaxis among pregnant and postpartum adolescent girls and young women in Cape Town, South Africa.

Background: Adolescent girls and young women (AGYW) in South Africa are at a higher risk of acquiring HIV. Despite the increasing availability of daily oral pre-exposure prophylaxis (PrEP) for HIV prevention, knowledge on PrEP use during pregnancy and postpartum periods at antenatal care (ANC) facilities remains inadequate. Methods: Data from HIV-uninfected pregnant women in Cape Town, South Africa, were used in this study. These women aged 16-24 years were enrolled in the PrEP in pregnancy and postpartum (PrEP-PP) cohort study during their first ANC visit. Using the PrEP cascade framework, the outcomes of the study were PrEP initiation (prescribed tenofovir disoproxil fumarate and emtricitabine at baseline), continuation (returned for prescription), and persistence [quantifiable tenofovir diphosphate (TFV-DP) in dried blood samples]. The two primary exposures of this study were risk perception for HIV and baseline HIV risk score (0-5), which comprised condomless sex, more than one sexual partner, partner living with HIV or with unknown serostatus, laboratory-confirmed sexually transmitted infections (STIs), and hazardous alcohol use before pregnancy (Alcohol Use Disorders Identification Test for Consumption score ≥ 3). Logistic regression was used to examine the association between HIV risk and PrEP, adjusting for a priori confounders. Results: A total of 486 pregnant women were included in the study, of which 16% were "adolescents" (aged 16-18 years) and 84% were "young women" (aged 19-24 years). The adolescents initiated ANC later than the young women [median = 28 weeks (20-34) vs. 23 weeks (16-34), p = 0.04]. Approximately 41% of the AGYW were diagnosed with sexually transmitted infection at baseline. Overall, 83% of the AGYW initiated PrEP use during their first ANC. The percentage of PrEP continuation was 63% at 1 month, 54% at 3 months, and 39% at 6 months. Approximately 27% consistently continued PrEP use through 6 months, while 6% stopped and restarted on PrEP use at 6 months. With a higher risk score of HIV (≥2 vs. ≤1), the AGYW showed higher odds of PrEP continuation [adjusted odds ratio: 1.85 (95% CI: 1.12-3.03)] through 6 months, adjusting for potential confounders. Undergoing the postpartum period (vs. pregnant) and having lower sexual risk factors were found to be the barriers to PrEP continuation. TFV-DP concentration levels were detected among 49% of the AGYW, and 6% of these women had daily adherence to PrEP at 3 months. Conclusions: AGYW were found to have high oral PrEP initiation, but just over one-third of these women continued PrEP use through 6 months. Pregnant AGYW who had a higher risk of acquiring HIV (due to condomless sex, frequent sex, and STIs) were more likely to continue on PrEP use through the postpartum period. Pregnant and postpartum AGYW require counseling and other types of support, such as community delivery and peer support to improve their effective PrEP use through the postpartum period. Clinical Trial Number: ClinicalTrials.gov, NCT03826199.

Developing a male-specific counselling curriculum for HIV treatment in Malawi.

Men living with HIV in sub-Saharan Africa have sub-optimal engagement in antiretroviral therapy (ART) Programs. Generic ART counselling curriculum in Malawi does not meet men's needs and should be tailored to men. We developed a male-specific ART counselling curriculum, adapted from the Malawi Ministry of Health (MOH) curriculum based on literature review of men's needs and motivations for treatment. The curriculum was piloted through group counselling with men in 6 communities in Malawi, with focus group discussion (FGD) conducted immediately afterward (n=85 men) to assess knowledge of ART, motivators and barriers to care, and perceptions of the male-specific curriculum. Data were analysed in Atlas.ti using grounded theory. We conducted a half-day meeting with MOH and partner stakeholders to finalize the curriculum (n=5). The male-specific curriculum adapted three existing topics from generic counselling curriculum (status disclosure, treatment as prevention, and ART side effects) and added four new topics (how treatment contributes to men's goals, feeling healthy on treatment, navigating health systems, and self-compassion for the cyclical nature of lifelong treatment. Key motivators for men were embedded throughout the curriculum and included: family wellbeing, having additional children, financially stability, and earning/keeping respect. During the pilot, men reported having little understanding of how ART contributed to their personal goals prior to the male-specific counselling. Men were most interested in additional information about treatment as prevention, benefits of disclosure/social support beyond their sexual partner, how to navigate health systems, and side effects with new regimens. Respondents stated that the male-specific counselling challenged the idea that men were incapable of overcoming treatment barriers and lifelong medication. Male-specific ART counselling curriculum is needed to address men's specific needs. In Malawi context, topics should include: how treatment contributes to men's goals, navigating health systems, self-compassion/patience for lifelong treatment, and taking treatment while healthy.

Identifying efficient linkage strategies for men (IDEaL): a study protocol for an individually randomised control trial.

INTRODUCTION: Men in sub-Saharan Africa are less likely than women to initiate antiretroviral therapy (ART) and more likely to have longer cycles of disengagement from ART programmes. Treatment interventions that meet the unique needs of men are needed, but they must be scalable. We will test the impact of various interventions on 6-month retention in ART programmes among men living with HIV who are not currently engaged in care (never initiated ART and ART clients with treatment interruption). METHODS AND ANALYSIS: We will conduct a programmatic, individually randomised, non-blinded, controlled trial. 'Non-engaged' men will be randomised 1:1:1 to either a low-intensity, high-intensity or stepped arm. The low-intensity intervention includes one-time male-specific counseling+facility navigation only. The high-intensity intervention offers immediate outside-facility ART initiation+male-specific counselling+facility navigation for follow-up ART visits. In the stepped arm, intervention activities build in intensity over time for those who do not re-engage in care with the following steps: (1) one-time male-specific counselling+facility navigation→(2) ongoing male mentorship+facility navigation→(3) outside-facility ART initiation+male-specific counselling+facility navigation for follow-up ART visits. Our primary outcome is 6-month retention in care. Secondary outcomes include cost-effectiveness and rates of adverse events. The primary analysis will be intention to treat with all eligible men in the denominator and all men retained in care at 6 months in the numerator. The proportions achieving the primary outcome will be compared with a risk ratio, corresponding 95% CI and p value computed using binomial regression accounting for clustering at facility level. ETHICS AND DISSEMINATION: The Institutional Review Board of the University of California, Los Angeles and the National Health Sciences Research Council in Malawi have approved the trial protocol. Findings will be disseminated rapidly in national and international forums and in peer-reviewed journals and are expected to provide urgently needed information to other countries and donors. TRIAL REGISTRATION NUMBER: NCT05137210. DATE AND VERSION: 5 May 2023; version 3.

Psychosocial determinants of pre-exposure prophylaxis use among pregnant adolescent girls and young women in Cape Town, South Africa: A qualitative study.

BACKGROUND: In South Africa, at least 7.5 million people (age ≥15 years) are living with Human Immunodeficiency Virus (HIV). In 2020, 220,000 new infections occurred, approximately one-third of which were among cisgender adolescent girls and women (age ≥15 years). The perspectives of pregnant adolescent girls and young women (AGYW) as key, targeted end-users of pre-exposure prophylaxis (PrEP) in this setting are not well known. METHODS: We purposively recruited participants enrolled in an ongoing cohort study at an urban antenatal clinic in Cape Town, South Africa for in-depth interviews between July-September 2020. We restricted our analysis to pregnant AGYW (age: 16-25 years) who initiated daily oral PrEP (Tenofovir/Emtricitabine) antenatally and self-reported either high PrEP persistence (≥25 days in the past 30 days and no missed PrEP collection), or low PrEP persistence and/or discontinuation (missing >5 days in the last 30 days or missed PrEP collection). The findings were organized thematically, per the adapted Health Behavior Model (2000), using Nvivo-v.1.5. RESULTS: We interviewed 18 AGYW (mean age = 22 years), at a mean of 14 weeks postpartum. Higher self-esteem and high-quality study provider-client relationships, including empathic psychosocial support, facilitated PrEP continuation. Reported barriers included unstable social structure characteristics (i.e., financial hardship) and individual factors (i.e., unintended pregnancy, parental rejection, and inadequate peer- and [non-cohabiting] partner support). Participants self-perceived a need for PrEP, feeling susceptible to non-consensual, forced sex, or considering partners' (presumed) sexual risk-taking. Limited community awareness regarding PrEP availability and/or perceived complexity in navigating health system access to PrEP, impede continuation. CONCLUSIONS: PrEP-focused healthcare access pathways for pregnant and postpartum AGYW need to be simplified. Further research is needed on health system determinants (i.e., structural barriers, provider-client interactions, and related outcomes) of oral PrEP utilization. In 2022, South Africa announced regulatory approval of long-acting PrEP options (i.e., the dapivirine ring for non-pregnant women and injectable cabotegravir, respectively); these may mitigate implementation barriers reported in this study. However, the safety and efficacy of long-acting PrEP (e.g., injectables, implants) among pregnant or breastfeeding women, specifically, remains to be confirmed in this setting.

Mobility and ART retention among men in Malawi: a mixed-methods study.

INTRODUCTION: Mobility is associated with worse outcomes across the HIV treatment cascade, especially among men. However, little is known about the mechanisms that link mobility and poor HIV outcomes and what types of mobility most increase the risk of treatment interruption among men in southern Africa. METHODS: From August 2021 to January 2022, we conducted a mixed-methods study with men living with HIV (MLHIV) but not currently receiving antiretroviral therapy (ART) in Malawi. Data collection was embedded within two larger trials (ENGAGE and IDEaL trials). We analysed baseline survey data of 223 men enrolled in the trials who reported being mobile (defined as spending ≥14 nights away from home in the past 12 months) using descriptive statistics and negative binomial regressions. We then recruited 32 men for in-depth interviews regarding their travel experiences and ART utilization. We analysed qualitative data using constant comparative methods. RESULTS: Survey data showed that 34% of men with treatment interruptions were mobile, with a median of 60 nights away from home in the past 12 months; 69% of trips were for income generation. More nights away from home in the past 12 months and having fewer household assets were associated with longer periods out of care. In interviews, men reported that travel was often unplanned, and men were highly vulnerable to exploitive employer demands, which led to missed appointments and ART interruption. Men made major efforts to stay in care but were often unable to access care on short notice, were denied ART refills at non-home facilities and/or were treated poorly by providers, creating substantial barriers to remaining in and returning to care. Men desired additional multi-month dispensing (MMD), the ability to refill treatment at any facility in Malawi, and streamlined pre-travel refills at home facilities. CONCLUSIONS: Men prioritize ART and struggle with the trade-offs between their own health and providing for their families. Mobility is an essential livelihood strategy for MLHIV in Malawi, but it creates conflict with ART retention, largely due to inflexible health systems. Targeted counselling and peer support, access to ART services anywhere in the country, and MMD may improve outcomes for mobile men.

Triple Benefit: Impact of an Integrated Early Childhood Development and PMTCT Intervention on ART Outcomes Among Mothers Living with HIV and Infants in Malawi-An Endline Evaluation.

We conducted a programmatic, observational cohort study with mother-infant pairs (MIPs) enrolled in prevention-of-mother-to-child-transmission (PMTCT) programs in Malawi to assess the feasibility and potential HIV-related benefits of integrating Early Childhood Development (ECD) services into PMTCT programs. Six health facilities were included in the intervention. We offered ECD counseling from the WHO/UNICEF Care for Child Development package in PMTCT waiting spaces while MIPs waited for PMTCT and broader treatment consultations. Primary outcomes were mothers' retention in HIV care at 12 months and infant HIV testing at 6 weeks and 12 months after birth. Routine facility-level data from six comparison health facilities were collected as an adhoc standard of care comparison and used to calculate the cost of delivering the intervention. A total of 607 MIPs were enrolled in the integrated ECD-PMTCT intervention between June 2018 and December 2019. The average age of MIPs was 30 years and 7 weeks respectively. We found that 86% of mothers attended ≥ 5 of the 8 ECD sessions over the course of 12 months; 88% of intervention mothers were retained in PMTCT versus 59% of mothers in comparison health facilities, and 96% of intervention infants were tested for HIV by six weeks compared to 66% of infants in comparison health facilities. Costing data demonstrated the financial feasibility of integrating ECD and PMTCT programs in government health facilities in Malawi. Integrating ECD into PMTCT programs was feasible, acceptable, resulted in better programmatic outcomes for both mothers and infants. Further investigation is required to determine optimal delivery design for scale-up.

Engaging men through HIV self-testing with differentiated care to improve ART initiation and viral suppression among men in Malawi (ENGAGE): A study protocol for a randomized control trial.

BACKGROUND: Men experience twice the mortality of women while on ART in sub-Saharan Africa (SSA) largely due to late HIV diagnosis and poor retention. Here we propose to conduct an individually randomized control trial (RCT) to investigate the impact of three-month home-based ART (hbART) on viral suppression among men who were not engaged in care. METHODS AND DESIGN: A programmatic, individually randomized non-blinded, non-inferiority-controlled trial design (ClinicalTrials.org NCT04858243). Through medical chart reviews we will identify "non-engaged" men living with HIV, ≥15years of age who are not currently engaged in ART care, including (1) men who have tested HIV-positive and have not initiated ART within 7 days; (2) men who have initiated ART but are at risk of immediate default; and (3) men who have defaulted from ART. With 1:1 computer block randomization to either hbART or facility-based ART (fbART) arms, we will recruit men from 10-15 high-burden health facilities in central and southern Malawi. The hbART intervention will consist of 3 home-visits in a 3-month period by a certified male study nurse ART provider. In the fbART arm, male participants will be offered counselling at male participant's home, or a nearby location that is preferred by participants, followed with an escort to the local health facility and facility navigation. The primary outcome is the proportion of men who are virally suppressed at 6-months after ART initiation. Assuming primary outcome achievement of 24.0% and 33.6% in the two arms, 350 men per arm will provide 80% power to detect the stated difference. DISCUSSION: Identifying effective ART strategies that are convenient and accessible for men in SSA is a priority in the HIV world. Men may not (re-)engage in facility-based care due to a myriad of barriers. Two previous trials investigated the impact of hbART on viral suppression in the general population whereas this trial focuses on men. Additionally, this trial involves a longer duration of hbART i.e., three months compared to two weeks allowing men more time to overcome the initial psychological denial of taking ART.

Understanding the Unique Barriers and Facilitators that Affect Men's Initiation and Retention in HIV Care: A Qualitative Study to Inform Interventions for Men Across the Treatment Cascade in Malawi.

Men in sub-Saharan Africa are underrepresented in antiretroviral therapy (ART) programs. Our secondary analysis of 40 in-depth interviews with Malawian men living with HIV examined barriers and facilitators for ART initiation versus retention. Interviewees included men who never initiated or initiated ART late (initiation respondents, n = 19); and men who initiated ART but were late for an appointment (retention respondents, n = 21). Transcribed interviews were coded using deductive and inductive coding techniques and analyzed using constant comparison methods. Long wait times, frequent facility visits, and insufficient in-clinic privacy were barriers for initiation and retention. Poor knowledge of ART was primarily a barrier for initiation; unexpected travel was a barrier for retention. Key facilitators for initiation and retention included previous positive experiences with health facilities. Having examples of successful men using ART primarily facilitated initiation; support from spouses and male peers facilitated retention. Results may inform interventions to increase men's engagement in ART services.

Sexual Risk among Pregnant Women at Risk of HIV Infection in Cape Town, South Africa: What Does Alcohol Have to Do with It?

This study examines baseline associations between alcohol use and HIV sexual risk among a cohort of HIV-uninfected pregnant women (n = 1201) residing in a high HIV burdened community in Cape Town, South Africa. Alcohol use was measured using a modified version of the Alcohol Use Disorder Identification Test (AUDIT). HIV sexual risk was measured through a composite variable of four risk factors: diagnosis with a STI, self-report of > 1 recent sex partners, partner HIV serostatus (unknown or HIV+) and condomless sex at last sex. Any past year alcohol use prior to pregnancy was reported by half of participants (50%); 6.0% reported alcohol use during pregnancy. Alcohol use prior to pregnancy was associated with increased odds of being at high risk of HIV (aOR = 1.33, 95% CI 1.05-1.68, for 2 risks and aOR = 1.47, 95% CI 0.95-2.27 for 3 risks). In addition to reducing alcohol use, several other strategies to address HIV sexual risk were identified. Evidence-based interventions to address alcohol use and other HIV sexual risk behaviors during pregnancy in South Africa are desperately needed. Qualitative work exploring individual and community level drivers of alcohol use among pregnant and breastfeeding women in this setting could support development of a culturally tailored intervention to address these issues in this population.

Adherence challenges with daily oral pre-exposure prophylaxis during pregnancy and the postpartum period in South African women: a cohort study.

INTRODUCTION: Daily oral pre-exposure prophylaxis (PrEP) can reduce HIV acquisition. However, prevention effectiveness requires daily adherence prior to and during periods of sexual activity. Little is known about pharmacologic measures of PrEP adherence during pregnancy and postpartum and the factors related to optimal adherence during periods of sexual activity in this population. METHODS: Between August 2019 and October 2021, we enrolled pregnant women without HIV at their first antenatal care visit followed-up through 12 months postpartum. Eligible women ≥16 years old received HIV prevention counselling and were offered oral PrEP (TDF-FTC). We quantified tenofovir-diphosphate (TFV-DP) in dried blood spots in women who reported taking PrEP in the past 30 days (at quarterly follow-up visits). We used regression models with generalized estimating equations to evaluate correlates of TFV-DP (any vs. none, and ≥2 vs. <2 doses/week), adjusting for maternal age and pregnancy status. RESULTS AND DISCUSSION: In 382 women who started PrEP in pregnancy, returned for follow-up and reported PrEP use in the past 30 days, the median age was 27 years (interquartile range [IQR] = 23-32), and the median time on PrEP was 168 days (IQR = 84-252 days). Half of the samples had quantifiable TFV-DP at any time point (52%), declining from 67% of pregnant women 3 months post-initiation to 31% of postpartum women by 12 months. Overall, 72% had concentrations corresponding to <2 doses/week; 25% ≥2 doses/week; 3% 7 doses/week. Concentrations were lower in postpartum versus pregnancy (age-adjusted odds ratio [aOR] = 0.44; 95% confidence interval [CI] = 0.35-0.54). The correlation of self-reported adherence and TFV-DP ranged from -0.07 in pregnancy to 0.25 in postpartum women. Variables associated with having quantifiable TFV-DP included partner living with HIV/unknown serostatus (aOR = 1.50; 95% CI = 1.01-2.22), and reported frequency of sexual activity in the past month (aOR sex >5/month vs. no sex or <5 times/month = 2.11; 95% CI = 1.58-2.82) adjusting for age and pregnancy versus postpartum status. TFV-DP concentrations declined over follow-up time (aOR for 6 vs. 3 months = 0.49; 95% CI = 0.36-0.67). CONCLUSIONS: Objectively measured adherence to PrEP was low overall and did not correlate with self-reported use. There is an urgent need for objective adherence measures to support clinical decision-making as well as adherence support interventions as part of PrEP services for pregnant and postpartum women at risk of HIV.

Men care too: a qualitative study examining women's perceptions of fathers' engagement in early childhood development (ECD) during an ECD program for HIV-positive mothers in Malawi.

OBJECTIVES: Integrated early childhood development (ECD) and prevention of mother-to-child transmission (PMTCT) interventions rarely target fathers, a missed opportunity given existing research demonstrating that father involvement improves maternal and child outcomes. We aimed to explore mother's perceptions of fathers' buy-in to an integrated PMTCT-ECD programme, any impact the programme had on couple dynamics, and perceived barriers to fathers' involvement in ECD activities. DESIGN: Qualitative study using individual in-depth interviews with mothers participating in a PMTCT-ECD programme. Interviews assessed mothers' perceptions of father buy-in and engagement in the programme and ECD activities. Data were coded using inductive and deductive strategies and analysed using constant comparison methods in Atlas.ti V.1.6. SETTING: Four health facilities in Malawi where PMTCT services were provided. PARTICIPANTS: Study participants were mothers infected with HIV who were enrolled in the PMTCT-ECD programme for >6 months. INTERVENTIONS: The PMTCT-ECD intervention provided ECD education and counselling sessions during routine PMTCT visits for mothers infected with HIV and their infants (infant age 1.5-24 months). The intervention did not target fathers, but mothers were encouraged to share information with them. RESULTS: Interviews were conducted with 29 mothers. Almost all mothers discussed the PMTCT-ECD intervention with male partners. Most mothers reported that fathers viewed ECD as valuable and practised ECD activities at home. Several reported improved partner relationships and increased communication due to the intervention. However, most mothers believed fathers would not attend the PMTCT-ECD intervention due to concerns regarding HIV-related stigma at PMTCT clinics, time required to attend and perceptions that the intervention was intended for women. CONCLUSIONS: Fathers were interested in an integrated PMTCT-ECD programme and actively practised ECD activities at home, but felt uncomfortable visiting PMTCT clinics. Interventions should consider direct community outreach or implementing ECD programmes at facility entry points where men frequent, such as outpatient departments.

Stepped care to optimize pre-exposure prophylaxis (PrEP) effectiveness in pregnant and postpartum women (SCOPE-PP) in South Africa: a randomized control trial.

BACKGROUND: HIV incidence among pregnant and postpartum women remains high in South Africa. Pre-exposure prophylaxis (PrEP) use remains suboptimal in this population, particularly during the postpartum period when women's engagement with routine clinic visits outside PrEP decreases. Key barriers to sustained PrEP use include the need for ongoing contact with the health facility and suboptimal counseling around effective PrEP use. METHODS: Stepped Care to Optimize PrEP Effectiveness in Pregnant and Postpartum women (SCOPE-PP), is a two-stepped unblinded, individually randomized controlled trial (RCT) that aims to optimize peripartum and postpartum PrEP use by providing a stepped package of evidence-based interventions. We will enroll 650 pregnant women (> 25 weeks pregnant) who access PrEP at a busy antenatal clinic in Cape Town at the time of recruitment and follow them for 15 months. We will enroll and individually randomize pregnant women > 16 years who are not living with HIV who are either on PrEP or interested in starting PrEP during pregnancy. In step 1, we will evaluate the impact of enhanced adherence counselling and biofeedback (using urine tenofovir tests for biofeedback) and rapid PrEP collection (to reduce time required) on PrEP use in early peripartum compared to standard of care (SOC) (n = 325 per arm). The primary outcome is PrEP persistence per urine tenofovir levels and dried blood spots of tenofovir diphosphate (TFV-DP) after 6-months. The second step will enroll and individually randomize participants from Step 1 who discontinue taking PrEP or have poor persistence in Step 1 but want to continue PrEP. Step 2 will test the impact of enhanced counseling and biofeedback plus rapid PrEP collection compared to community PrEP delivery with HIV self-testing on PrEP use (n = up to 325 postpartum women). The primary outcome is PrEP continuation and persistence 6-months following second randomization (~ 9-months postpartum). Finally, we will estimate the cost effectiveness of SCOPE-PP vs. SOC per primary outcomes and disability-adjusted life-years (DALYs) averted in both Step 1 and 2 using micro-costing with trial- and model-based economic evaluation. DISCUSSION: This study will provide novel insights into optimal strategies for delivering PrEP to peripartum and postpartum women in this high-incidence setting. TRIAL REGISTRATION: NCT05322629 : Date of registration: April 12, 2022.

Improving ART initiation among men who use HIV self-testing in Malawi: a qualitative study.

INTRODUCTION: HIV self-testing (HIVST) increases HIV testing uptake among men; however, the linkage to antiretroviral therapy (ART) among HIVST users is low. Innovative strategies for ART initiation are needed, yet little is known about the unique barriers to care experienced by male HIVST users, and what ART-related interventions men desire. METHODS: We conducted semi-structured in-depth interviews with cisgender men (≥15 years) in Malawi who tested HIV positive using HIVST between 2018 and 2020, as well as interviews with their female partners (≥15 years) who distributed the HIVST kits. Medical records from seven facilities were used to identify respondents. We included men who received HIVST from a health facility (primary distribution) and from sexual partners (secondary distribution). Interview guides focused on unique barriers to ART initiation following HIVST and desired interventions to improve linkage and initiation. Interviews were audio recorded, translated and transcribed to English, and analysed using constant comparison methods in Atlas.ti v.8.4. Themes were compared by HIVST distribution strategy. Data were collected between 2019 and 2020. RESULTS: Twenty-seven respondents were interviewed: eight male/female dyads (16 respondents), eight men without a female partner and three women who represented men who did not participate in the study. Among the 19 men represented (16 men interviewed in person, three represented by secondary report from female partners), seven received HIVST through primary distribution, 12 through secondary distribution. Six men never initiated ART (all secondary HIVST distribution). Barriers to ART initiation centred on the absence of healthcare workers at the time of diagnosis and included lack of external motivation for linkage to care (men had to motivate themselves) and lack of counselling before and after testing (leaving ART-related fears and misconceptions unaddressed)--the latter was especially true for secondary HIVST distribution. Desired interventions were similar across distribution strategies and included ongoing peer mentorship for normalizing treatment adherence, counselling messages tailored to men, outside-facility services for convenience and privacy, and facility navigation to help men understand how to navigate ART clinics. CONCLUSIONS: Male HIVST users face unique challenges to ART initiation, especially those receiving HIVST through secondary distribution. Male-tailored interventions are desired by men and may help overcome barriers to care.

Barriers to Oral HIV Pre-exposure Prophylaxis (PrEP) Adherence Among Pregnant and Post-partum Women from Cape Town, South Africa.

Cisgender women, particularly pregnant and postpartum women in Eastern and Southern Africa, face an unacceptably high risk of HIV acquisition. Oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention that can reduce HIV acquisition and vertical transmission. In this qualitative study, we interviewed 21 postpartum women from Cape Town, South Africa who initiated PrEP during pregnancy and who self-reported low PrEP adherence or missed > 1 PrEP follow-up collection. We identified multiple overlapping barriers to PrEP continuation and/or adherence. Individual factors included forgetting to take PrEP daily, being away from home when PrEP should be taken, anticipated stigma and limited disclosure of PrEP use. Women also reported pill-related factors such as side effects and having to take PrEP in addition to other tablets during pregnancy and the postpartum period. Facility-related barriers included logistics around PrEP collection especially when not in antenatal care, as well as transport and financial barriers.

Early pre-exposure prophylaxis (PrEP) initiation and continuation among pregnant and postpartum women in antenatal care in Cape Town, South Africa.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is a safe and effective prevention strategy to reduce women's risk of HIV in pregnancy and postpartum. Effective PrEP protection requires daily PrEP adherence, but little is known about maternal PrEP continuation and factors that influence PrEP use. METHODS: The PrEP in pregnancy and postpartum (PrEP-PP) study enrolled consenting pregnant, HIV-negative women at first antenatal care (ANC) visit with follow-up through 12 months postpartum. Eligible and consenting women and girls ≥16 years received HIV prevention counselling and were offered PrEP. Interviewers collected socio-demographic and behavioural data from participants at each visit. We analysed the proportion of women who initiated PrEP and the proportion who continued PrEP after 3 months with associated correlates by estimating the prevalence ratio adjusting for a priori confounders. RESULTS: Between August 2019 and October 2021, we enrolled 1201 pregnant women (median gestation 21 weeks; age 26 years); 84% of women initiated PrEP at their first ANC visit (n = 1014); 55% were married or cohabiting. Overall, 66% of women on PrEP returned for a repeat prescription at 1 month; 58% returned at 3 months (n = 493 of 844). Almost one-half of women on PrEP reported a side effect at 1 month, mostly nausea/vomiting. Women on PrEP in the first and second trimesters had higher odds of reporting side effects (aOR 2.61; 95% CI 1.17-5.84) versus postpartum women. Women who reported side effects continued with PrEP less than those who did not report side effects (aPR = 0.87; 95% CI 0.77-0.97). Women with ≥1 previous pregnancy (aPR = 0.76; 95% CI 0.57-1.01) or were postpartum (aPR 0.85; 95% CI 0.75-0.97) were less likely to continue PrEP compared to women who were primigravid or pregnant. Women who reported having an HIV+ partner (aPR = 1.45; 95% CI 1.13-1.85) or high HIV risk perception (aPR = 1.20, 95% CI = 1.01-1.41) were more likely to continue on PrEP than those who had HIV-negative partners or low risk perception. CONCLUSIONS: PrEP initiation and early continuation were high in this setting, compared to other studies in women. Being postpartum and experiencing side effects were associated with lower PrEP continuation, presenting opportunities for counselling on early transient side effects. Interventions for postpartum women on PrEP are needed.

Pre-exposure Prophylaxis Recent Adherence With Real-Time Adherence Feedback and Partner Human Immunodeficiency Virus Self-Testing: A Pilot Trial Among Postpartum Women.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is safe and effective in postpartum women. Human immunodeficiency virus self-testing (HIVST) for male partners combined with biofeedback counseling through real-time adherence measures may improve PrEP use among postpartum women. METHODS: Between August 2020 and April 2021, we randomized postpartum women who initiated PrEP in pregnancy 1:1 to the intervention group (HIVST + biofeedback counseling after urine tenofovir test) or to standard of care ([SOC] facility-based human immunodeficiency virus [HIV] tests and routine counseling without biofeedback). The outcomes of interest were PrEP adherence in the past 48-72 hours via urine tenofovir tests and partner HIV testing, measured 1-month after randomization. Secondary outcomes included the proportion of partners who tested for HIV and the discrepancy between self-reported PrEP adherence and urine tenofovir result. RESULTS: We enrolled 106 women (median age = 26 years). At enrollment, 72% of women reported missing <2 doses in the past 7 days; 36% of women had tenofovir present in her urine. One month after enrollment, 62% (n = 33) of women in the intervention arm had tenofovir present in their urine compared to 34% (n = 18) in SOC (risk ratio [RR] = 1.83; 95% confidence interval [CI] = 1.19-2.82; P = .001). Two thirds of women in the intervention arm reported that her partner tested for HIV (66%; n = 35), compared to 17% (n = 9) in SOC (RR = 3.89; 95% CI = 2.08-7.27; P < .001). Self-reported PrEP adherence (took PrEP >5 of last week) with no tenofovir in urine test was lower in the intervention group (17% vs 46%; RR = 0.33; 95% CI = 0.17-0.67; P = .03). No social or clinical adverse events were reported in the intervention arm. CONCLUSIONS: The HIVST for partners and biofeedback counseling increased levels of recent PrEP adherence, pointing to the importance of these interventions to support PrEP use in this population.

Maternal PrEP Use in HIV-Uninfected Pregnant Women in South Africa: Role of Stigma in PrEP Initiation, Retention and Adherence.

Pregnant women in sub-Saharan Africa are at high risk of HIV acquisition and require effective methods to prevent HIV. In a cohort of pregnant women offered Pre-exposure prophylaxis (PrEP), we evaluate the relationship between internalized and anticipated stigma and PrEP initiation at first antenatal visit, 3-month continuation and adherence using multivariable logistic regression. High internalized and anticipated PrEP stigma are associated with lower PrEP care initiation at first antenatal visit (aOR internalized stigma = 0.06; 95% CI = 0.03-0.11 and aOR anticipated stigma = 0.55; 95% CI = 0.31-1.00) compared to women with low reported stigma, after controlling for covariates. Women whose partners have not been tested for HIV or whose serostatus remains unknown have 1.6-times odds of PrEP retention at 3-months compared to women whose partners have been tested (aOR = 1.60; 95% CI = 1.02-2.52) after adjusting for covariates. PrEP counseling and maternal PrEP interventions must consider individual- and relational-level interventions to overcome anticipated PrEP stigma and other barriers to PrEP initiation and adherence.

"I had Made the Decision, and No One was Going to Stop Me" -Facilitators of PrEP Adherence During Pregnancy and Postpartum in Cape Town, South Africa.

PrEP is safe and effective but requires adherence during potential HIV exposure, yet the facilitators of long-term maternal adherence are not well understood. We conducted semi-structured interviews with 25 postpartum women who reported high adherence (PrEP use ≥ 25 days in last 30-days and never missed a PrEP prescription in pregnancy/postpartum period) within a PrEP service for pregnant and postpartum women. A thematic approach guided an iterative process of coding and analysis. Themes identified as drivers of optimal PrEP use were HIV risk perception, mainly because of partner's behaviors and unknown serostatus, and a strong desire to have a baby free of HIV. Reported disclosure of PrEP use facilitated PrEP adherence. Women discussed having partner and family support, which included reminders to take PrEP daily. Primary barriers were anticipated or experienced stigma, overcome through education of partners and family about PrEP. Pregnant women experienced transient side-effects, but found ways to continue, including taking PrEP at night. PrEP programs for pregnant and postpartum women should integrate strategies to assist women with realistic appraisals of risk and teach skills for disclosure and securing support from significant others.

RESUMEN: La profilaxis Pre-exposición (PrEP, siglas en inglés) es segura y eficaz, pero requiere adherencia durante una posible exposición al VIH; sin embargo, no se conocen bien los factores que facilitan la adherencia materna a largo plazo. Realizamos entrevistas semiestructuradas con 25 mujeres en posparto que informaron un alto cumplimiento (uso de PrEP> 25 días en los últimos 30 días y nunca omitieron una receta de PrEP en el embarazo y período posparto) dentro de un servicio de PrEP para mujeres embarazadas y posparto. Un enfoque temático guio un proceso iterativo de codificación y análisis. Los temas identificados como impulsores del uso óptimo de la PrEP fueron la percepción del riesgo de VIH, principalmente debido a los comportamientos de la pareja y el estado serológico desconocido, y un fuerte deseo de tener un bebé libre de VIH. La divulgación informada del uso de PrEP facilitó la adherencia a la PrEP. Las mujeres hablaron sobre el apoyo de su pareja y familia, incluidos recordatorios para tomar la PrEP cada dia. Las barreras primarias fueron el estigma anticipado o experimentado, superado a través de la educación de los socios y familiares sobre la PrEP. Las mujeres embarazadas experimentaron efectos secundarios transitorios, pero encontraron formas de continuar, incluida la toma de PrEP por la noche. Los programas de PrEP para mujeres embarazadas y posparto deben integrar estrategias para ayudar a las mujeres con evaluaciones realistas del riesgo y enseñar habilidades para la divulgación y obtener el apoyo de otras personas importantes.