Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to lower birth weight (BW) and shorter gestational age (GA) at delivery. Most research has focused on populations in high-income countries, leaving low- and middle-income countries (LMICs) understudied. We examined associations between pregnancy urinary PAH metabolites and birth outcomes in a prospective cohort in Nairobi, Kenya. The study population was drawn from women and their newborn babies enrolled in a pregnancy cohort in Nairobi, Kenya. Third-trimester urinary mono-hydroxylated PAH metabolites (OH-PAH) were measured and infant BW and GA were ascertained using medical record abstraction and self-report; BW-for-GA z-scores were computed. Linear and modified Poisson regression models were used to estimate the effects of five OH-PAHs on birth outcomes; Weighted Quantile Sum regression was used to explore OH-PAH mixture effects. Among 353 mother-infant pairs, the median infant BW was 3.2 kg and 10.7% were born preterm. All OH-PAH metabolites were present in urine of >99% of mothers. Individual OH-PAH concentrations were not associated with BW or BW-for-GA z-scores. One metabolite, 2-hydroxyphenanthrene, was associated with shortened gestation (RR = -1.6 day per doubling in concentration, 95% confidence interval: -3.1, -0.1). This association was attenuated after adjusting for self-reported exposure to household fuel and outdoor combustion and was strengthened among female infants, but not male infants, in sex-stratified analyses. Other metabolites and the OH-PAH mixture were not associated with birth outcomes. Our findings suggest that exposure to 2-hydroxyphenanthrene may have a modest adverse effect on pregnancy duration, with potential sex-specific differences in association. No associations were observed for markers of fetal growth. These results highlight need for further studies on sex-specific vulnerabilities and the role of environmental co-exposures in impacting birth outcomes in LMICs.

BackgroundPerinatal mood and anxiety disorders (PMAD) cause substantial morbidity and mortality globally. Kenya, like many low- and middle-income countries, experiences severe shortage of specialized mental healthcare workers and poor coverage of screening and management for PMAD. Provision of screening and treatment by lay and non-specialist providers in the context of routine maternal child health services may enhance access to mental health services and improve outcomes.Methods and analysisIn a hybrid type II cluster randomized clinical trial in 20 facilities in Western Kenya, we will evaluate the clinical, service delivery, and implementation outcomes of a stepped-care model integrating: 1) screening of all pregnant women for depression and anxiety symptoms, 2) Problem Management Plus (PM+) counseling delivered by trained lay providers, and 3) telepsychiatry for women with severe symptoms, suicidality, or inadequate response to PM + . The intervention package also includes a bundle of implementation strategies such as audit and feedback, process mapping, health educational health talks, and procurement of antidepressants for all sites. In addition, intervention sites will receive provider training, structured supervision and financial compensation for providers. Facilities will be randomized 1:1 to intervention and enhanced standard of care (basic screening and referral to specialist care), using restricted randomization. We will enroll a total of 2,970 women. Women will be eligible if they are pregnant and ≥20 weeks' gestation, attending antenatal care at the facility, ≥ 14 years old, and screen positive for PMAD symptoms (Patient Health Questionnaire [PHQ]-2 ≥ 3 and/or Generalized Anxiety Disorder-[GAD]-2 ≥ 3). Assessments will be conducted at enrollment (pregnancy), 6 weeks, 14 weeks, and 6 months postpartum among participants in both study arms to align with routine well-baby visits. Primary outcomes are PMAD symptoms (PHQ-9 and GAD-7 score) change at 14 weeks postpartum using an intent-to-treat analysis. Secondary outcomes include quality of life at 14 weeks postpartum, PM+ mechanism of action, and adverse pregnancy outcomes at 6 weeks postpartum. Using mixed methods, we will evaluate acceptability and fidelity of the intervention and compare service delivery and other implementation outcomes (penetration, efficiency, equity, cost) across arms and alongside multilevel drivers of implementation success.Ethics and disseminationThe study protocol was approved by Kenyatta National Hospital/University of Nairobi (P425/04/2023) and the University of Washington (STUDY00017933). All participants will provide written informed consent. Findings will be published in peer-reviewed journals and international conferences.Trial registrationTrial registration number NCT06456307.

BACKGROUND:Pregnant women are at a four times higher risk of HIV per coital act than non-pregnant women. MTN-042/DELIVER was a phase 3b randomised study of dapivirine vaginal ring (DVR) and oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine to assess safety, adherence, and acceptability when used during pregnancy. Our hypothesis was that both DVR and oral PrEP would be safe and well tolerated when started early in the second trimester and continued until delivery. METHODS:In MTN-042/DELIVER, an open-label, phase 3b randomised trial, healthy pregnant women without HIV and aged 18-40 years from Malawi, South Africa, Uganda, and Zimbabwe were enrolled and randomly allocated (4:1) to open-label monthly DVR PrEP or daily oral PrEP. Women were enrolled between 12 weeks' and 29 weeks' gestation. Product use continued until delivery or 42 weeks' gestation. The primary outcomes for safety following exposure to study product were a composite of all serious adverse events, including maternal deaths, all grade 3 or higher adverse events, and pregnancy outcomes stratified as term (≥37+0 weeks), preterm (<37+0 weeks), and pregnancy loss before 20 weeks' gestation. Pregnancy complications and adverse events were summarised with descriptive statistics. This study is registered with ClinicalTrials.gov, NCT03965923. FINDINGS:Between July 12, 2022, and Jan 12, 2023, 251 mothers were enrolled, with 202 randomly allocated to receive DVR PrEP and 49 to receive oral PrEP. The median age was 24·0 years (IQR 22·0-29·0) and the median gestational age was 23·7 weeks (19·9-26·3). 28 mothers (11%) had safety events under the composite study primary outcome (all serious adverse events plus all grade 3 or higher adverse events), none of which was related to product use. No maternal deaths or HIV seroconversions occurred. There were 247 pregnancy outcomes of which 233 (94%) were at term (≥37+0 weeks). Pregnancy complications were uncommon, and none was infectious. INTERPRETATION:Adverse pregnancy outcomes related to DVR and oral PrEP use were uncommon among women starting PrEP in the second trimester. These findings support the use of these preventive approaches during pregnancy. FUNDING:US National Institutes of Health.

BackgroundChildhood lead exposure is prevalent worldwide including low- and middle-income countries (LMICs). Structured screening and prevention programs to address pediatric lead exposure are largely absent in these settings. Adapted interventions are needed to close this implementation gap in an urban African context. This paper describes the protocol for the Lead Exposure Intervention Program (LEIP), which aims to adapt, pilot, and evaluate a pediatric lead exposure screening and risk-reduction protocol in Nairobi, Kenya.MethodsLEIP is a multi-phase, hybrid type 3 implementation-effectiveness study. Phase 1 is a formative one-arm study leveraging an existing mother-child cohort and stakeholder-led tools adaptation to pilot a program comprising blood lead level (BLL) screening with a lead risk survey and tailored caregiver risk reduction messaging. Phase 2 is a randomized trial in public sector clinics. In this phase, approximately 1,500 children will be screened to identify 100 with elevated BLL (≥5 µg/dL) for enrollment, who will then be randomized 1:1 to receive either clinic-only risk-reduction messaging or the same clinic-based messaging plus a home visit for environmental assessment and additional tailored messaging. Follow-up at 3 and 9 months will assess caregiver recall of key messages and adoption of recommended exposure-reduction behaviors, as well as changes in child BLL. Phase 3 involves qualitative interviews with caregivers and key stakeholders to identify multi-level barriers and facilitators to intervention uptake. Quantitative and qualitative findings will be integrated to inform refinements for scale-up.DiscussionThis study represents a critical opportunity to develop and evaluate an adaptive, screening-based lead exposure intervention tailored to the urban LMIC context. By incorporating implementation science principles and stakeholder-driven design, LEIP is well-positioned to inform scalable national and regional approaches. The inclusion of both quantitative and qualitative components enhances the protocol's ability to capture multilevel dynamics of uptake, fidelity, and sustainability, and generate actionable insights for future large-scale implementations.Trial registrationClinicalTrials.gov NCT07401251.

BACKGROUND:Reduced early-life interferon-γ (IFN-γ) production capacity may limit sensitivity of IFN-γ release assays to detect Mycobacterium tuberculosis (Mtb)-specific responses in young children. Measuring non-IFN-γ cytokine responses may improve detection. METHODS:Mononuclear cells isolated from peripheral blood from children exposed to HIV but uninfected and children unexposed to HIV in Western Kenya were collected at 6 to 10 weeks, and 12 and 24 months of age. Cells were incubated overnight with Mtb-specific CFP-10/ESAT-6 peptides and Staphylococcus enterotoxin B (positive control). CD4 and CD8 T-cell expression of IFN-γ and IL-2 and TNF cytokines was measured by flow cytometry. RESULTS:Among 213 children, 28.6% had CFP-10/ESAT-6-specific CD4 and/or CD8 responses through 24 months. No children with Mtb-specific responses had a reported tuberculosis exposure. Mtb-specific non-IFN-γ+ responses (IL-2+ and/or TNF+) were more common than IFN-γ+ responses (26.3% vs 10.3%, P < .001). Non-IFN-γ cytokines alone identified 18.3% of children, compared with 2.4% identified by IFN-γ+ responses alone (P < .001). Prevalence of Mtb-specific responses was similar regardless of HIV exposure (HIV exposed, 31.5%; HIV unexposed, 25.5%, P = .33). At 6 to 10 weeks, children were more likely to have non-IFN-γ+ than IFN-γ+ responses to the positive control (96.3% vs 77.8%, P = .004); by 24 months, all children mounted both IFN-γ+ and non-IFN-γ+ responses. CONCLUSIONS:Mtb-specific CD4/CD8 responses were common among Kenyan children through 24 months, despite limited reported tuberculosis exposures. Non-IFN-γ+ cytokine expression identified substantially more children than IFN-γ+ alone, suggesting current IFN-γ release assays may miss early-life Mtb-specific responses.

BACKGROUND:We evaluated the prevalence, incidence, and correlates of sexually transmitted infections among pregnant women initiating preexposure prophylaxis. METHODS:We analyzed data from an ongoing randomized control trial that enrolled pregnant women in Kenya (NCT04472884) who were ≥18 years, between 24 and 32 weeks' gestation, had high HIV risk scores, and initiated oral preexposure prophylaxis within routine antenatal care. A subset of women were sequentially offered Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing in pregnancy and at 6 and 9 months after delivery. Directly observed treatment and expedited partner therapy (EPT) were offered to women diagnosed with CT/NG. RESULTS:All pregnant women offered CT and NG testing accepted (n = 221). The median age of women was 26 years (interquartile range 22-30); median gestational age was 27 weeks (interquartile range 25-29). Prevalence of CT and/or NG during pregnancy was 19/221 (8.6%): 4.1% CT, 3.6% NG, and 1% CT and NG coinfection. Women <24 years were 3 times more likely to have prevalent CT/NG infection as older women (adjusted prevalence ratio: 3.12; 95% confidence interval [CI]: 1.24 to 7.85 P = 0.016). Overall, 21 CT/NG infections occurred in 181.2 total person-years of follow-up (incidence 11.6 per 100 person-years, 95% CI: 7.6 to 17.8). Incident CT and/or NG was 7-fold higher among women <24 years compared with older women (adjusted incidence rate ratio = 6.69, 95% CI: 2.55 to 17.54, P < 0.001). Same-day directly observed treatment and EPT acceptance was 95%; at subsequent visits, 79% reported partners accepted EPT, of whom 95% confirmed treatment completion. CONCLUSIONS:CT/NG incidence was high among women who initiated preexposure prophylaxis in pregnancy, indicating that CT/NG testing would be high yield in this population.

IntroductionVaginal washing has been associated with adverse reproductive health outcomes including pelvic inflammatory disease, reduced fecundability, and HIV acquisition. This analysis tested the hypothesis that vaginal washing is associated with increased risk of group B streptococcus (GBS) colonization.MethodWomen planning pregnancies contributed monthly visits during which vaginal fluid specimens were collected and urine pregnancy testing was performed. In women who became pregnant, additional samples were collected at 9-12 weeks gestation. Broad-range 16S rRNA gene PCR with next generation sequencing (NGS) was performed to identify vaginal bacterial species. Generalized estimating equations with a log link, Poisson family, independent correlation structure and robust errors were used to generate prevalence ratios comparing the prevalence of GBS detection at vaginal washing visits versus non-vaginal washing visits.ResultsThe 189 women who became pregnant contributed 506 samples used in this analysis. Samples were collected at periconception 196 (38.9%), early first trimester 151 (29.8%), and late first trimester visits 159 (31.4%). The prevalence of GBS during the three time periods was 20/196 (10.2%), 11/151 (7.3%) and 2/159 (1.3%) respectively. Vaginal washing was practiced by 51/196 (26.0%), 27/151 (17.9%) and 32/159 (20.1%) participants during the three time periods. Compared to visits with no vaginal washing, there was no increased prevalence of GBS detection at visits where vaginal washing with water was reported (prevalence ratio [PR] 0.51, 95% confidence interval [CI] 0.16-1.62). However, the prevalence of GBS detection was nearly five-fold higher at visits when vaginal washing using water and soap was reported (PR 4.66, 95% CI 1.51, 14.33).ConclusionVaginal washing with soap and water was associated with a nearly five-fold increase in GBS prevalence. Future studies should evaluate this association in later pregnancy and peripartum. Cessation or modification of vaginal washing practices could be a useful strategy for decreasing GBS colonization.

BACKGROUND:Evidence gaps remain regarding the influence of perinatal depression on mother-child engagement and child social-emotional development. OBJECTIVES:We assessed relationships between perinatal depression, mother-child engagement and child social-emotional development among Kenyan mother-child pairs. METHODS:Mother-child pairs attending maternal-child health services in four sites in Western Kenya were followed from pregnancy through early childhood. Study nurses serially assessed perinatal depression (pregnancy, 6 weeks, and 9 months postpartum with the Center for Epidemiologic Studies Depression scale, CESD-10 scores ≥ 10), mother-child engagement activities (6-monthly, 24 to 60 months post-delivery with UNICEF Multiple Indicator Cluster Surveys) and child social-emotional delay (6-monthly, 30 to 60 months post-delivery with Ages and Stages Questionnaires). We estimated prevalence and correlates of low mother-child engagement and social-emotional delay. RESULTS:Among 884 mothers, the median age was 26 years (IQR 22.0, 30.3), 91.6% were married, and 36.8% had perinatal depression. High mother-child engagement (≥ 4 activities in the prior 3 days) ranged from 27.1% to 94.1% from 24 to 60 months post-delivery. The frequency of child social-emotional delay ranged from 26.6% at 30 months to 4.4% at 60 months. Low mother-child engagement at any point (< 4 activities) was more common among women with perinatal depression (adjusted relative risk [RR] 1.20, 95% confidence interval [CI] 1.08, 1.33) and was associated with twice the risk of child social-emotional delay (RR 2.22, 95% CI 1.78, 2.77). Mothers who reported adverse childhood experiences (ACES) (RR 1.08, 95% CI 1.04, 1.11) and intimate partner violence (IPV) (RR 1.28, 95% CI 1.11, 1.47) interacted less frequently with their children than women without these experiences. CONCLUSION:In this cohort of Kenyan mother-child pairs followed from pregnancy through childhood, perinatal depressive symptoms were associated with lower mother-child engagement, which was associated with double the risk of child social-emotional delay.

Early life exposure to air pollution is associated with adverse health outcomes in children however few studies have investigated children's air pollution exposures in urban settings in sub-Saharan Africa (SSA). We measured fine particulate matter (PM2.5) and carbon monoxide (CO) in homes of infants in Nairobi, Kenya and conducted exploratory analysis of exposure factors. Questionnaires captured household characteristics and self-reported air pollution exposures. Indoor and outdoor 24-hour (24 h) concentrations were measured inside and 1 m outside the house. PM2.5 was sampled using standard gravimetric procedures; CO was measured with direct-reading electrochemical sensors. Forty-eight homes were sampled at median infant age 11.5 months (range 0.8-26.2 months). During sampling, 66.7%, 18.8%, 10.4% and 10.4% of mothers, respectively, reported using liquefied petroleum gas (LPG), ethanol, electricity, and kerosene for cooking. Median indoor and outdoor 24 h PM2.5 concentrations (n = 39) were 39.9 ug/m3 (range, 12.8-519.6 ug/m3) and 23.3 ug/m3 (range, 2.6-68.2 ug/m3), respectively. Most PM2.5 concentrations (97% of indoor; 79% of outdoor) exceeded the World Health Organization (WHO) 24 h air quality guideline (AQG) of 15 ug/m3. Median indoor (n = 47) and outdoor (n = 41) 24 h mean CO concentrations were 0.7 ppm (range, 0-33.9 ppm) and 0.0 ppm (range, 0-1.0 ppm), respectively. Mean indoor CO concentrations exceeded the WHO 24 h AQG of 6.2 ppm in 9% of homes. Despite frequent use of cooking fuels considered to be clean such as LPG and ethanol, PM2.5 and CO levels in infant homes in urban SSA often exceeded the WHO AQGs. Expanded studies of children's air pollution exposures in urban SSA are needed to build awareness and inform policy.

Integrating mental health care into well-attended health services, such as maternal-child health (MCH), offers a promising approach to increasing access to mental health care. To inform integration, we assessed the current approach to screening and treatment of perinatal mood and anxiety disorders (PMAD) in MCH facilities in Western Kenya. We conducted a cross-sectional survey among the facility managers ("in-charges") at 20 MCH facilities in Western Kenya. Trained data collectors administered questionnaires to assess facility infrastructure and human resources, perinatal mental health screening, psychological interventions, psychiatric medication availability, and level of perinatal mental health integration into standard MCH services. Across 20 MCH facilities, the majority were located in rural areas (16,80%), 2 peri-urban (10%), and 2 urban (10%). Facilities had a median of 37.5 medical staff (IQR: 31.0, 45.5); the most common cadre was nurses (median: 9.0, IQR: 6.0, 12.5). Under half of the facilities (8, 40%) screened for PMAD using a validated tool and documented results; most (19, 95%) reported diagnosing PMAD (not necessarily through a systematic approach), yet only half (10, 53%) documented the diagnosis. The most common psychotherapy reported across the sites was supportive counseling (15, 75%). Some facilities offered evidence-based psychotherapies (e.g., cognitive behavioral therapy, problem-solving therapy, etc.), but did not report on training, supervision or guidance from the evidence-based intervention manual. Across all facilities, the availability of mental health medications was limited. Only (12, 60%) had any antidepressant available, (16, 80%) had antiepileptics, (9, 45%) had antipsychotics, and (2, 10%) had mood stabilizers available. Mental health services in MCH clinics in Western Kenya are currently not offered in a structured and systematic manner to effectively alleviate PMAD. Available infrastructure and human resources offer an opportunity to integrate an evidence-based treatment model to improve perinatal mental health in the MCH clinics in Western Kenya.

Background. The association between bacterial vaginosis (BV) and increased human immunodeficiency virus (HIV) acquisition risk may be related to concentrations of HIV-susceptible immune cells in the cervix. Methods. Participants (31 with BV and 30 with normal microbiota) underwent cervical biopsy at a single visit. Immune cells were quantified and sorted using flow cytometry (n = 55), localization assessed by immunofluorescence (n = 16), and function determined by bulk RNA sequencing (RNA-seq) of live CD45(+) cells (n = 21). Results. Linear regression analyses demonstrated no differences in mean log(2) (cells/mg tissue) between women with BV versus normal microbiota for antigen-presenting cell (APC) subtypes linked to HIV risk (including CD1a(+)HLA-DR+ Langerhans cells, CD11c(+)CD14(+) dendritic cells [DCs], and CD11c(+)HLA-DR+ DCs) and CD4(+) T cells. Women with BV had a higher median proportion of CD11c(+)HLA-DR+ APCs (out of total cells) in cervical epithelium (0.1% vs 0.0%; P = .03 using Mann-Whitney test). RNA-seq identified 1032 differentially expressed genes (adjusted P < .05) in CD45(+) cells between women with BV versus normal microbiota. Women with BV demonstrated downregulation of pathways linked to translation, metabolism, cell stress, and immune signaling. Conclusions. BV alters immune cell localization and function; future studies are needed to address how these changes may mediate HIV acquisition risk.

INTRODUCTION:Adolescent girls and young women (AGYW) in Kenya have low pre-exposure prophylaxis (PrEP) initiation rates in part because of stigmatizing interactions with health care providers. Our recent randomized clinical trial of a standardized patient actor (SP) training intervention for providers found higher quality PrEP delivery at intervention sites; however, it was unclear whether improved service quality improved PrEP initiation. METHODS:This analysis used routine records from facilities participating in the randomized trial that aimed to improve provider communication and adherence to Kenyan guidelines when offering PrEP to AGYW. We used facility-level PrEP registers from May to December 2019 as the baseline period and December 2020 to June 2021 as the postintervention period. We used linear regression with percentage initiating as the outcome, intervention and baseline initiation levels as covariates, and the number eligible postintervention at each facility as frequency weights. RESULTS:Overall, 1375 AGYW presented to study sites, were eligible for PrEP, and were included in analyses (baseline: n = 706, postintervention: n = 669). Among 669 PrEP-eligible AGYW in the postintervention period (intervention: n = 360, control: n = 309), 591 (88.3%) initiated PrEP (intervention: n = 335, control: n = 256). PrEP initiation was 93.1% at intervention sites (range: 0%-100%) and 82.8% at control sites (range: 0%-100%). Adjusted for baseline initiation rates, initiation was 12.1% higher at intervention sites than at control sites ( P < 0.001, [95% CI: 0.09 to 0.15]). CONCLUSIONS:Our study found significant improvement in PrEP initiation among AGYW who presented to intervention facilities. SP training interventions that improve quality of service delivery for AGYW could lead to higher population-level PrEP coverage.

OBJECTIVE:Understanding alignment of contraceptive preferences and method selection among women living with HIV (WLWH) may improve contraceptive counseling. We examined whether method attribute preferences aligned with method attributes used among WLWH, and identified preference clusters. STUDY DESIGN:We used baseline survey data from WLWH enrolled in a cluster randomized controlled trial of a reproductive health counseling intervention in Kenya. Women using eligible modern contraception at baseline were included (N = 2599). We used Poisson regression models to characterize 11 relationships between method attributes preferred vs. used, and principal component analysis (PCA) to identify preferences clusters. RESULTS:Women who preferred methods that are long-acting (adjusted Prevalence Ratio [aPR]:1.63, 95% Confidence Interval [CI]:1.19-2.24), avoid daily dosing (aPR:1.11, 95% CI:1.07-1.16), permit self-discontinuation (aPR:1.32, 95% CI:1.14-1.52), and are concealable (aPR:1.06, 95% CI:1.01-1.12) were significantly more likely to use aligned methods. Attribute preferences clustered on three dimensions: (1) avoiding heavy bleeding, weight changes, libido changes, and non-hormonal; (2) long-acting, avoiding daily dosing, permitting self-discontinuation, and avoiding intermittent bleeding; and (3) concealability without an effectiveness preference. Immediate return to fertility was modeled independently due to lack of clustering. The first dimension was positively correlated with condom use and inversely with implant use. The second was also positively correlated with condom use, and use of both implants and tubal ligation, while inversely with injectable and oral contraceptive pill use. The third was correlated with injectable use. CONCLUSION:Method attribute preferences do not always align with methods used and may cluster in ways that cannot be satisfied by existing methods. IMPLICATIONS:Preferences for methods that are long-acting, avoid daily dosing, and permit self-discontinuation are widely held and related to method selection, but cannot be met by a single method when held in combination. Client-centered counseling that elicits relative strength of preferences and tailors guidance accordingly may help improve method satisfaction.

Objective: This study aimed to identify age-specific cofactors of nonretention among adolescents and young adults living with HIV (AYLHIV) ages 10–24. Design: This analysis used data from the Data-Informed Stepped Care study (DiSC; NCT05007717), a cluster randomized clinical trial in 24 health facilities in Western Kenya. Methods: During 12-month follow-up, youth-reported cofactors of missed visits and loss-to-follow-up (LTFU; did not return to clinic within study period) were assessed using generalized linear and mixed effect models and stratified by gender and age. Results: Among 1904 AYLHIV, median age was 17 years (interquartile range 14–19), and 57.9% were female. A higher proportion of missed visits was observed in older ages (10–14: 6.0%; 15–19: 7.9%; 20–24: 12.5%). Overall, higher resilience (PR = 0.93) and satisfaction with clinic (PR = 0.81) were associated with lower risk of missed visits. Among males, satisfaction with clinic was associated with lower risk (PR = 0.61) while higher stigma was associated with increased risk (PR = 1.31). Among females, resilience was associated with lower risk (PR = 0.93). Having no living parents was associated with higher LTFU risk (PR = 2.24). Among males, horizontal transmission was associated with higher risk (PR = 2.98) and resilience with lower risk (PR = 0.76). Females who came to clinic alone had lower risk of LTFU (PR = 0.27). Age-stratified analyses did not identify additional cofactors. Conclusions: In this large multisite cohort, older AYLHIV had the most retention challenges. Resilience, satisfaction with clinical care, and stigma exerted an influential role, but cofactors differed between age and gender strata, underscoring the heterogeneity of AYLHIV and suggesting need for tailored approaches.

Despite a global reduction in neonatal deaths in the last few decades, high neonatal mortality rates persist in low- to middle-income countries. Mobile health interventions offer a promising solution to promote early newborn care (ENC) practices and improve neonatal health. The Mobile WACh NEO randomized controlled trial evaluated the effect of a text messaging communication intervention on neonatal health outcomes in Kenya from 2020 to 2023. Perinatal participants received automated messages from enrollment at 28-36 weeks gestation until six weeks postpartum and could message with a study nurse. This secondary analysis aimed to characterize participant text engagement and examine associations between engagement and maternal-neonatal health outcomes. Among 2,470 intervention participants retained through follow-up, median time in the intervention was 14 weeks. Participants received a median of 58 automated messages (average 0.58 per day), sent a median of 24 messages (average 0.25 per day), and received a median of 14 nurse responses (average 0.14 per day). Younger, more educated, unmarried, unemployed, and first-time mothers sent more messages, while those who had a lower social support score at baseline messaged less. Increased participant messaging was associated with greater increase in neonatal danger sign knowledge from baseline to six-week follow-up (Adj Est: 0.39; 95% CI: 0.09-0.68) and lower odds of early initiation of breastfeeding (aOR: 0.62; 95% CI: 0.45-0.86). Our findings contribute to the understanding of who can benefit from mobile health programs and how these interventions might impact behaviors and outcomes.

INTRODUCTION:The ongoing rollout of oral tenofovir-based pre-exposure prophylaxis (PrEP) has the potential to reduce HIV-1 incidence, but HIV drug resistance (HIVDR) in individuals who acquire HIV-1 on PrEP could threaten the treatment effectiveness of overlapping antiretrovirals (tenofovir/emtricitabine), contribute to development of resistance, and undermine HIV control efforts. Accordingly, the Global Evaluation of Microbicide Sensitivity (GEMS) project was established to monitor HIVDR in PrEP rollout programmes in Southern and Eastern Africa. METHODS:GEMS monitored resistance in >100,000 estimated persons who accessed PrEP through national programmes or implementation projects in Southern/Eastern Africa. Participants self-reported demographics and PrEP adherence. HIV-1 RNA and tenofovir-diphosphate levels were measured in blood samples collected at the time of study enrolment from consenting participants diagnosed with HIV who had received PrEP. HIVDR mutations were detected by population genotyping. RESULTS:Of 283 reported seroconversions on PrEP from December 2017 through September 2023, 255 (90%) individuals enrolled in GEMS, of which 81 (32%) were from Kenya, 77 (30%) from South Africa, 69 (27%) from Zimbabwe and 28 (11%) from Eswatini. Half (130; 51%) were 15-24 years of age at seroconversion, and three-quarters (193; 76%) were female. Thirty-four seroconversions occurred within 30 days of PrEP initiation. Tenofovir-diphosphate levels were consistent with moderate to high levels (≥350 femtomoles per punch) in 53% (120 of 226) individuals with drug-level data. Of 154 samples successfully genotyped, 34 (22%; 95% CI [16%, 30%]) had PrEP-associated mutations; these included 27 samples with M184I/V, one sample with K65KR, and six samples with both K65R and M184I/V. CONCLUSIONS:The frequency of HIVDR mutations associated with tenofovir or emtricitabine among individuals diagnosed with HIV who had received PrEP (22%) exceeded background levels of transmitted nucleoside reverse transcriptase inhibitor resistance in Southern and Eastern Africa (≤5%) but people with PrEP-associated mutations are likely to achieve virologic suppression with current first-line antiretroviral therapy (ART). Improved screening for acute infection before initiating PrEP, surveillance of HIVDR with the introduction of new PrEP programmes and the monitoring of longer-term ART outcomes in individuals who acquire HIV-1 on PrEP will be essential to preserve antiretroviral options for both treatment and prevention.

Background In 2021, WHO recommended dapivirine vaginal rings (DVRs) for HIV prevention, but noted evidence gaps for breastfeeding populations. This trial aimed to describe safety profiles associated with DVRs and oral pre- exposure prophylaxis (PrEP) use during breastfeeding and to summarise study-drug quantification and concentrations for mothers and infants. Methods Microbicide Trials Network (MTN)-043 was a phase 3b, open-label, randomised trial in which mother-infant pairs were recruited from local health facilities and enrolled at four HIV clinical trial sites in Malawi, South Africa, Uganda, and Zimbabwe. Eligible mothers (aged >= 18 years) were HIV-negative, exclusively breastfeeding one infant (aged 6-12 weeks, birthweight >= 2000 g), and had not been exposed to HIV post-exposure prophylaxis in the previous 6 months. Mother-infant pairs were randomly assigned (3:1) via a computer-generated sequence to 12 weeks of 25 mg monthly DVR or daily oral PrEP (200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate), with stratification by site using a permuted block design. Participants and staff were aware of study product assignment. Primary outcomes were maternal and infant safety (all serious adverse events and grade 3 or worse adverse events) and drug concentrations, which were measured in maternal plasma, maternal blood, breastmilk, infant plasma, and infant blood. All mother-infant pairs who received at least one dose of study product were included in the primary safety analysis, and those with at least one post-enrolment drug concentration result were included in the drug quantification analysis. The trial was registered at ClinicalTrials.gov (NCT04140266). Findings Between Sept 24, 2020, and July 29, 2021, 197 mother-infant pairs enrolled (148 on DVR and 49 on PrEP), all of whom received at least one dose of study product and were included in the primary safety analysis. Two (1%) of 148 mothers in the DVR group had serious adverse events, and three (2%) in the DVR group and two (4%) in the oral PrEP group had a grade 3 or worse adverse event; four (3%) of 148 infants in the DVR group had a serious adverse event, and ten (7%) in the DVR group and one (2%) in the oral PrEP group had a grade 3 or worse adverse event. No mother or infant in the oral PrEP group had a serious adverse event. No HIV infections were detected. 144 participants in the DVR group and 48 in the oral PrEP group had at least one post-enrolment drug concentration result. Quantifiable median dapivirine concentrations ranged from 6560 (IQR 4070-8780) pg/mL at week 1 to 5585 (2820-7780) pg/mL at month 3, but were observed infrequently (5-15%) in specimens from infants, with median concentrations below the limit of quantification at all visits. Median tenofovir diphosphate concentrations ranged from 2630 (1930-3630) fmol/punch at week 1 to 7770 (3810-12410) fmol/punch at month 3, but were not observed in specimens from infants, with all concentrations below the limit of quantification at all visits. Interpretation Increased risk of HIV acquisition in the postnatal period, favourable product safety profile, and low drug exposures among infants support the recommendation for DVRs as an additional HIV prevention choice during breastfeeding. Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Increasing HIV testing and counselling (HTC) is a first step to reducing HIV transmission. Implementing HTC in family planning (FP) clinics has been proposed to increase HIV testing coverage in at-risk populations. The Systems Analysis and Improvement Approach (SAIA) was used to improve HTC rates in FP clinics in Mombasa, Kenya. This hypothesis-generating exploratory analysis evaluated the associations between organizational climate characteristics, organizational readiness for implementing change, and successful implementation of HTC. Surveys were conducted with clinic managers and staff from FP clinics implementing SAIA to increase HTC. Likert-style questions were used to characterize organizational climate metrics and organizational readiness for implementing change (ORIC). Linear regression was performed to examine the association between organizational climate metrics, ORIC domains, and two FP client outcomes: 1) percentage of clients receiving pre-HIV test counseling, and 2) percentage of clients tested for HIV. Eleven clinic staff and 10 clinic managers completed the surveys. For clinic staff, higher innovation and flexibility scores were associated with higher change commitment (β = 0.20, CI 0.09-0.31, p = 0.001) and change efficacy (β = 0.17, CI 0.07-0.26, p = 0.002). Higher clinic manager scores for innovation and flexibility were associated with a higher change commitment (β = 0.44, CI 0.04-0.84, p = 0.03). Additionally, clinic managers' scores for management support (β = 0.25, CI 0.06-0.45, p = 0.01), commitment to facility (β = 0.78, CI 0.60-0.96, p = 0.001), and relative priority (β = 0.24, CI 0.08-0.39, p = 0.004) were positively associated with higher change commitment and change efficacy. In contrast, clinic managers' scores for tradition were negatively associated with change commitment (β = -0.38, CI -0.75-0.01, p = 0.05). Clinic staff perceptions of management support were positively associated with the proportion of clients counseled for HIV testing (β = 1.20, CI 0.08-2.32, p = 0.04). Support from leadership and innovation/flexibility are important predictors of change commitment and change efficacy. Strong management support may increase the likelihood of successful implementation of SAIA to improve HTC.

End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only). Self-reports of vaginal bleeding and adherence (ring removals, expulsions) were collected via daily short message service. Acceptability data were recorded in face-to-face interviews at study exit. We assessed differences in acceptability by product characteristics and adherence; and associations between baseline characteristics/demographics, number of bleeding days, adherence, and overall acceptability. Most (21/23) women in the 14-day MTN-030 study and about half (13/25) in the 90-day MTN-044 study liked their assigned rings. In MTN-030 there were no significant associations between any variables and overall acceptability of either ring. In MTN-044, women who disliked the DPV-LNG ring had a significantly higher incidence of unanticipated vaginal bleeding, and reporting that vaginal bleeding changes were unacceptable than those who liked it. Although we found no overall association between adherence and acceptability, significantly more women who disliked (versus liked) the DPV-LNG ring reported expulsions during toileting. The DPV-LNG ring could meet the needs of women seeking simultaneous protection from HIV and unintended pregnancy. Addressing issues related to vaginal bleeding and expulsions early in product development will likely enhance acceptability of the DPV-LNG ring. Trial registration: Clinical Trial Registration: MTN-030/IPM 041: ClinicalTrials.gov NCT02855346; MTN-044/IPM 053/CCN019: ClinicalTrials.gov NCT03467347.