High PrEP uptake and objective longitudinal adherence among HIV-exposed women with personal or partner plans for pregnancy in rural Uganda: A cohort study.

BACKGROUND: In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. METHODS AND FINDINGS: We enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure ("high" adherence when pillbox was opened ≥80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not; concentrations TFV ≥40 ng/mL and TFV-DP ≥600 fmol/punch were categorized as "high." Women who became pregnant were initially exited from the cohort by design; from March 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion who initiated PrEP); and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI: 27.8 to 29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N = 118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI: 83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% [95% CI: 43%, 62%]) and 1 HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N = 17) was 98% (95% CI: 97%, 99%). Study design limitations include lack of a control group. CONCLUSIONS: Women in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment; serial measures of TFV-DP in whole blood suggest 41% to 47% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics. Future iterations of this work should compare the outcomes to current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03832530 https://clinicaltrials.gov/ct2/show/NCT03832530?term=lynn+matthews&cond=hiv&cntry=UG&draw=2&rank=1.

Sexually Transmitted Infection Point-of-Care Testing in Resource-Limited Settings: A Narrative Review Guided by an Implementation Framework.

ABSTRACT: Most sexually transmitted infections (STIs) are acquired in resource-limited settings (RLSs) where laboratory diagnostic access is limited. Advancements in point-of-care testing (POC) technology have the potential to bring STI testing to many RLSs. We define POC as performed near the patient and with results readily available to inform clinical practice. The World Health Organization Special Programme for Research and Training in Tropical Diseases further outlines desirable POC characteristics with the REASSURED criteria.Despite advantages related to immediate test-and-treat care, integrating POC into RLS health care systems can present challenges that preclude reliance on these tests. In 2018, we incorporated molecular near-POC for chlamydia, gonorrhea, and trichomoniasis and SDBioline treponemal immunochromatographic testing confirmed by rapid plasma reagin for syphilis diagnosis at the Mbarara University of Science and Technology Research Laboratory in rural southwestern Uganda. We describe our experiences with STI POC as a case example to guide a narrative review of the field using the Consolidated Framework for Implementation Research as a conceptual framework.Although POC and near-POC are described as easy to use, the challenges of limited person-power, health care processes, limited infrastructure/resources, high costs, and quality control obstacles can impede the impact of these tests. Increased investment in operators, training, and infrastructure, restructuring health care systems to accommodate increased POC access, and optimizing costs are all crucial to the successful implementation of STI POC in RLS. Expanded STI POC in RLS will increase access to accurate diagnoses, appropriate treatment, and engagement in partner notification, treatment, and prevention efforts.

'I still desire to have a child': a qualitative analysis of intersectional HIV- and childlessness-related stigma in rural southwestern Uganda.

This study explored the intersecting forms of stigma experienced by HIV-serodifferent couples with unmet reproductive goals in rural Uganda. The parent mixed-methods study, which included 131 HIV-exposed women with plans for pregnancy, offered comprehensive HIV prevention counselling and care over a nine-month period. In-depth interviews were conducted with 37 women and seven male partners to explore care experiences and the use of safer conception strategies. This secondary analysis explored how challenges conceiving informed pregnancy plans and HIV prevention behaviours. The following themes were developed (1) partnership conflicts arise from HIV- and infertility-related forms of stigma, contributing to gender-based violence, partnership dissolution and the pursuit of new partners; (2) cultural and gender norms pressure men and women to conceive and maintain partnerships, which is complicated by the stigma directed towards serodifferent couples; (3) frustration with low partner participation in safer conception strategies led to the decreased use of these methods of HIV prevention; (4) health care provider support promotes continued hope of conception and helps overcome stigma. In HIV-affected partnerships, these intersecting forms of stigma may impact HIV prevention. Seeking to fulfil their reproductive needs, partners may increase HIV transmission opportunities as they engage in condomless sex with additional partners and decrease adherence to prevention strategies. Future research programmes should consider the integration of fertility counselling with reproductive and sexual health care.

Sexual and Relationship Benefits of a Safer Conception Intervention Among Men with HIV Who Seek to Have Children with Serodifferent Partners in Uganda.

Many men with HIV (MWH) in Uganda desire children, yet seldom receive reproductive counseling related to HIV care. Because men are under engaged in safer conception programming, they miss opportunities to reap the benefits of these programs. The objective of this sub-analysis was to explore the relationship and intimacy benefits of integrating safer conception counseling and strategies into HIV care, an emergent theme from exit interviews with men who participated in a pilot safer conception program and their partners. Twenty interviews were conducted with MWH who desired a child in the next year with an HIV-uninfected/status unknown female partner, and separate interviews were conducted with female partners (n = 20); of the 40 interviews, 28 were completed by both members of a couple. Interviews explored experiences participating in The Healthy Families program, which offered MWH safer conception counseling and access to specific strategies. Data were analyzed using thematic analysis. Three major subthemes or "pathways" to the relationship and intimacy benefits associated with participation in the program emerged: (1) improved dyadic communication; (2) joint decision-making and power equity in the context of reproduction; and (3) increased sexual and relational intimacy, driven by reduced fear of HIV transmission and relationship dissolution. These data suggest that the intervention not only helped couples realize their reproductive goals; it also improved relationship dynamics and facilitated intimacy, strengthening partnerships and reducing fears of separation. Directly addressing these benefits with MWH and their partners may increase engagement with HIV prevention strategies for conception.

Client and Provider Experiences in Uganda Suggest Demand for and Highlight the Importance of Addressing HIV Stigma and Gender Norms Within Safer Conception Care.

Safer conception counseling supports HIV-serodifferent couples to meet reproductive goals while minimizing HIV transmission risk, but has not been integrated into routine HIV care. We piloted a novel safer conception program in an established public-sector HIV clinic in Uganda to inform future implementation. In-depth interviews and counseling observations explored experiences of program clients and healthcare providers to assess program acceptability, appropriateness, and feasibility. Fifteen index clients (8 women, 7 men), 10 pregnancy partners, and 10 providers completed interviews; 15 participants were living with HIV. Ten observations were conducted. We identified four emergent themes: (1) High demand for safer conception services integrated within routine HIV care, (2) Evolving messages of antiretroviral treatment as prevention contribute to confusion about HIV prevention options, (3) Gender and sexual relationship power inequities shape safer conception care, and (4) HIV-related stigma impacts safer conception care uptake. These findings confirm the need for safer conception care and suggest important implementation considerations.

Sexually Transmitted Infection Prevalence Among Women at Risk for HIV Exposure Initiating Safer Conception Care in Rural, Southwestern Uganda.

BACKGROUND: Knowledge of sexually transmitted infection (STI) prevalence and risk factors is important to the development of tenofovir-based preexposure prophylaxis (PrEP) and safer conception programming. We introduced STI screening among women at risk for HIV exposure who were participating in a safer conception study in southwestern Uganda. METHODS: We enrolled 131 HIV-uninfected women, planning for pregnancy with a partner living with HIV or of unknown HIV serostatus (2018-2019). Women were offered comprehensive safer conception counseling, including PrEP. Participants completed interviewer-administered questionnaires detailing sociodemographics and sexual history. We integrated laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis as a substudy to assess STI prevalence. Multivariable logistic regression was used to determine correlates. RESULTS: Ninety-four women completed STI screening (72% of enrolled). Median age was 30 (interquartile range, 26-34) years, and 94% chose PrEP as part of safer conception care. Overall, 24% had STIs: 13% chlamydia, 2% gonorrhea, 6% trichomoniasis, 6% syphilis, and 3% ≥2 STI. Sexually transmitted infection prevalence was associated with younger age (adjusted odds ratio [AOR], 0.87; 95% confidence interval [CI], 0.77-0.99), prior stillbirth (AOR, 5.04; 95% CI, 1.12-22.54), and not feeling vulnerable to HIV (AOR, 16.33; 95% CI, 1.12-237.94). CONCLUSIONS: We describe a 24% curable STI prevalence among women at risk for HIV exposure who were planning for pregnancy. These data highlight the importance of integrating laboratory-based STI screening into safer conception programs to maximize the health of HIV-affected women, children, and families.

Sexually transmitted infection (STI) knowledge and perceptions among people in HIV-sero-different partnerships in rural southwestern Uganda.

Globally, over one million people acquire curable sexually transmitted infections (STI) each day. Understanding how people think about STIs is key to building culturally appropriate STI prevention and treatment programs. We explored STI knowledge and perceptions in rural, southwestern Uganda to inform future interventions. From August 2020 to December 2020, we conducted individual in-depth interviews among adult men and women (≥18 years) with recent or current personal or partner pregnancy, a history of an STI diagnosis and treatment, and membership in an HIV-sero-different relationship. Interviews explored STI knowledge, perceptions, and barriers and facilitators to engaging in STI care. We used inductive and deductive approaches to generate a codebook guided by the healthcare literacy skills framework in a thematic analysis. Ten men with STI, five of their female partners, eighteen women with STI, and four of their male partners participated in individual in-depth interviews. The median age was 41 (range 27-50) for men and 29 (range 22-40) for women. Sixteen (43%) participants were with HIV. Significant themes include: 1) Participants obtained STI knowledge and information from the community (friends, family members, acquaintances) and medical professionals; 2) While participants knew STIs were transmitted sexually, they also believed transmission occurred via non-sexual mechanisms. 3) Participants associated different connotations and amounts of stigma with each STI, for example, participants reported that syphilis was passed down "genetically" from parent to child. 4) Participants reported uncertainty about whether STIs affected pregnancy outcomes and whether antenatal STI treatment was safe. The complicated nature of STIs has led to understandable confusion in settings without formal sexual healthcare education. Robust counseling and education prior to sexual debut will help allow men and women to understand the signs, symptoms, and treatments necessary for STI cure and to navigate often complicated and overburdened healthcare systems.

Implementation of a safer conception programme for HIV-affected men and women in rural Uganda.

We integrated safer conception care into a Ugandan HIV clinic. People with HIV (PWH), or partnered with a PWH, and desiring children were eligible for the Healthy Families Clinic Program. Clients completed quarterly safer conception counselling visits and questionnaires to provide information around method preferences and outcomes (partner pregnancy, partner seroconversion). We used clinic level data to evaluate longitudinal viral suppression among PWH. Between November 2016 and January 2020, 361 clients (53% men) accessed services. 75% were PWH (51% women, 96% men): 99% were on antiretroviral therapy (ART) and most reported HIV-sero-different partnerships (97%). Frequently selected safer conception methods included ART (86%), timed condomless sex (74%), and PrEP (40%) with important differences by HIV-serostatus and gender. 22.5% reported pregnancy. Most (97%) PWH were virally suppressed at enrolment and 81% of non-virally suppressed PWH were virally suppressed at 15 months. Two HIV-negative clients (2%) had HIV seroconversion. There is demand for safer conception care in a public sector HIV-clinic in Uganda. Men and women have unique safer conception care preferences. The majority of clients engaged in safer conception care had viral suppression at follow up.

STI prevalence, incidence, and partner notification among women in a periconception HIV prevention program in Uganda.

BACKGROUND: We provided sexually transmitted infection (STI) screening and facilitated partner notification and treatment among women participating in a periconception HIV prevention program in southwestern Uganda to understand follow-up STI incidence. METHODS: Women at-risk for HIV exposure while planning for pregnancy completed laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis at enrollment and 6 months of follow-up and/or incident pregnancy; facilitated partner notification and treatment were offered for those with positive tests. We performed a logistic regression to determine correlates of follow-up STI. RESULTS: Ninety-four participants completed enrollment STI screening with a median age of 29 (IQR 26-34); 23 (24%) had ≥1 STI. Of the 23 participants with enrollment STI(s), all completed treatment and 19 (83%) returned for follow-up; 18 (78%) reported delivering partner notification cards and discussing STIs with partner(s), and 14 (61%) reported all partners received STI treatment. Of the 81 (86%) who successfully completed follow-up STI screening, 17 (21%) had ≥1 STI. The STI incidence rate was 29.0 per 100 person-years. In univariable regression analysis, enrollment STI, younger age, less education, and alcohol consumption were all significantly associated with follow-up STI. CONCLUSIONS: We demonstrated high enrollment and follow-up STI rates and moderate participant-reported partner treatment among women planning for pregnancy in Uganda despite partner notification and treatment. Novel STI partner notification and treatment interventions are needed to decrease the STI burden, especially among women planning for and with pregnancy.

A qualitative exploration to understand barriers and facilitators to daily oral PrEP uptake and sustained adherence among HIV-negative women planning for or with pregnancy in rural Southwestern Uganda.

INTRODUCTION: Antiretroviral pre-exposure prophylaxis (PrEP) may reduce periconception and pregnancy HIV incidence among women in settings, where gender power imbalances limit HIV testing, engagement in care and HIV viral suppression. We conducted qualitative interviews to understand factors influencing periconception and pregnancy PrEP uptake and use in a cohort of women (Trial registration: NCT03832530) offered safer conception counselling in rural Southwestern Uganda, where PrEP uptake was high. METHODS: Between March 2018 and January 2019, in-depth interviews informed by conceptual frameworks for periconception risk reduction and PrEP adherence were conducted with 37 women including those with ≥80% and <80% adherence to PrEP doses measured by electronic pill cap, those who never initiated PrEP, and seven of their male partners. Content and dyadic analyses were conducted to identify emergent challenges and facilitators of PrEP use within individual and couple narratives. RESULTS: The median age for women was 33 years (IQR 28, 35), 97% felt likely to acquire HIV and 89% initiated PrEP. Individual-level barriers included unwillingness to take daily pills while healthy, side effects and alcohol use. Women overcame these barriers through personal desires to have control over their HIV serostatus, produce HIV-negative children and prevent HIV transmission within partnerships. Couple-level barriers included nondisclosure, mistrust and gender-based violence; facilitators included shared goals and perceived HIV protection, which improved communication, sexual intimacy and emotional support within partnerships through a self-controlled method. Community-level barriers included multi-level stigma related to HIV, ARVs/PrEP and serodifference; facilitators included active peer, family or healthcare provider support as women aspired to safely meet socio-cultural expectations to conceive and preserve serodifferent relationships. Confidence in PrEP effectiveness was promoted by positive peer experiences with PrEP and ongoing HIV testing. CONCLUSIONS: Multi-level forms of HIV-, serodifference- and disclosure-related stigma, side effects, pill burden, alcohol use, relationship dynamics, social, professional and partnership support towards adaptation and HIV risk reduction influence PrEP uptake and adherence among HIV-negative women with plans for pregnancy in rural Southwestern Uganda. Confidence in PrEP, individually controlled HIV prevention and improved partnership communication and intimacy promoted PrEP adherence. Supporting individuals to overcome context-specific barriers to PrEP use may be an important approach to improving uptake and prolonged use.

STI prevalence among men living with HIV engaged in safer conception care in rural, southwestern Uganda.

HIV care provides an opportunity to integrate comprehensive sexual and reproductive healthcare, including sexually transmitted infection (STI) management. We describe STI prevalence and correlates among men living with HIV (MLWH) accessing safer conception care to conceive a child with an HIV-uninfected partner while minimizing HIV transmission risks. This study reflects an ongoing safer conception program embedded within a regional referral hospital HIV clinic in southwestern Uganda. We enrolled MLWH, planning for pregnancy with an HIV-uninfected partner and accessing safer conception care. Participants completed interviewer-administered questionnaires detailing socio-demographics, gender dynamics, and sexual history. Participants also completed STI laboratory screening for syphilis (immunochromatographic testing confirmed by rapid plasma reagin), and chlamydia, gonorrhea, trichomoniasis, and HIV-RNA via GeneXpert nucleic acid amplification testing. Bivariable associations of STI covariates were assessed using Fisher's exact test. Among the 50 men who completed STI screening, median age was 33 (IQR 31-37) years, 13/50 (26%) had ≥2 sexual partners in the prior three months, and 46/50 (92%) had HIV-RNA <400 copies/mL. Overall, 11/50 (22%) had STIs: 16% active syphilis, 6% chlamydia. All participants initiated STI treatment. STI prevalence was associated with the use of threats/intimidation to coerce partners into sex (27% vs 3%; p = 0.03), although absolute numbers were small. We describe a 22% curable STI prevalence among a priority population at higher risk for transmission to partners and neonates. STI screening and treatment as a part of comprehensive sexual and reproductive healthcare should be integrated into HIV care to maximize the health of men, women, and children.

"When you have no water, it means you have no peace": A mixed-methods, whole-population study of water insecurity and depression in rural Uganda.

BACKGROUND: Lack of access to clean water has well known implications for communicable disease risks, but the broader construct of water insecurity is little studied, and its mental health impacts are even less well understood. METHODS AND FINDINGS: We conducted a mixed-methods, whole-population study in rural Uganda to estimate the association between water insecurity and depression symptom severity, and to identify the mechanisms underlying the observed association. The whole-population sample included 1776 adults (response rate, 91.5%). Depression symptom severity was measured using a modified 15-item Hopkins Symptom Checklist for Depression. Water insecurity was measured with a locally validated 8-item Household Water Insecurity Access Scale. We fitted multivariable linear and Poisson regression models to the data to estimate the association between water insecurity and depression symptom severity, adjusting for age, marital status, self-reported overall health, household asset wealth, and educational attainment. These models showed that water insecurity was associated with depression symptom severity (b = 0.009; 95% confidence interval [CI], 0.004-0.15) and that the estimated association was larger among men (b = 0.012; 95% CI, 0.008-0.015) than among women (b = 0.008; 95% CI, 0.004-0.012. We conducted qualitative interviews with a sub-group of 30 participants, focusing on women given their traditional role in household water procurement in the Ugandan context. Qualitative analysis, following an inductive approach, showed that water insecurity led to "choice-less-ness" and undesirable social outcomes, which in turn led to emotional distress. These pathways were amplified by gender-unequal norms. CONCLUSIONS: Among men and women in rural Uganda, the association between water insecurity and depression symptom severity is statistically significant, substantive in magnitude, and robust to potential confounding. Data from the qualitative interviews provide key narratives that reveal the mechanisms through which women's lived experiences with water insecurity may lead to emotional distress.