Antenatal depressive symptoms in Kenyan women living with HIV: contributions of recent HIV diagnosis, stigma, and partner violence.

Depression among pregnant women living with HIV (WLWH) in sub-Saharan Africa leads to poor pregnancy and HIV outcomes. This cross-sectional analysis utilized enrollment data from a randomized trial (Mobile WAChX, NCT02400671) in six Kenyan public maternal and child health clinics. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9), stigma with the Stigma Scale for Chronic Illness, and intimate partner violence (IPV) with the Abuse Assessment Screen. Correlates of moderate-to-severe depressive symptoms ("depression", PHQ-9 score ≥10) were assessed using generalized estimating equation models clustered by facility. Among 824 pregnant WLWH, 9% had depression; these women had more recent HIV diagnosis than those without depression (median 0.4 vs. 2.0 years since diagnosis, p = .008). Depression was associated with HIV-related stigma (adjusted Prevalence Ratio [aPR]:2.36, p = .025), IPV (aPR:2.93, p = .002), and lower social support score (aPR:0.99, p = .023). Using population-attributable risk percent to estimate contributors to maternal depression, 81% were attributable to stigma (27%), recent diagnosis (24%), and IPV (20%). Integrating depression screening and treatment in prevention of mother-to-child HIV transmission programs may be beneficial, particularly in women recently diagnosed or reporting stigma and IPV.

Perinatal depression and its impact on infant outcomes and maternal-nurse SMS communication in a cohort of Kenyan women.

BACKGROUND: Perinatal depression is broadly defined as depressive symptoms during pregnancy or within the 12 months following delivery, affecting approximately 20-25% of pregnant and postpartum women in low- and middle-income countries. The wide accessibility of mobile phones allows mobile health (mHealth) interventions to be considered a solution to identify perinatal depression and provide appropriate referrals for treatment. This study, nested in a larger SMS communication project, examined the prevalence and correlates of perinatal depression, determined the association between antenatal depression and infant morbidity and mortality, and compared SMS communication patterns between women with and without perinatal depression. METHODS: This was a prospective longitudinal cohort study of pregnant women seeking antenatal services at two public sector health clinics in Kenya. SMS messages were sent to participants with educational content related to their pregnancy and infant health and two-way SMS communication occurred with a nurse. Sociodemographic and obstetric characteristics, SMS messaging behaviors, infant health status, and depressive symptoms were assessed by a standardized questionnaire administered at enrollment (30-36 weeks gestation) and follow-up (14 weeks postpartum). Generalized estimating equation (GEE) with Poisson link was used to evaluate correlates of perinatal depressive symptoms, infant outcomes, and frequency of SMS messaging. RESULTS: Of the 572 women with complete follow-up information, 188 (32.9%) screened positive for elevated depressive symptoms (≥10 by EPDS scale) at some time point during pregnancy or postpartum. The strongest predictors of any depressive symptoms included interpersonal abuse during pregnancy, fewer years of schooling, and maternal unemployment. Antenatal depressive symptoms were associated with an increased risk of infant illness or hospitalization (RR = 1.12, 95% CI: 1.11, 1.13). Women with antenatal or persistent perinatal depressive symptoms sent fewer SMS messages during the study period than their counterparts without depression. CONCLUSIONS: Prevalence of elevated perinatal depressive symptoms was high in this cohort of Kenyan women. Our findings highlight the importance of screening perinatal women for experiences of symptoms of depression as well as abuse. Differences in messaging frequency between women with vs. without depressive symptoms presents an opportunity to provide more tailored support for those perinatal depression.

Chlamydia, Gonorrhea, and Incident HIV Infection During Pregnancy Predict Preterm Birth Despite Treatment.

BACKGROUND: Identifying predictors of preterm birth (PTB) in high-burden regions is important as PTB is the leading cause of global child mortality. METHODS: This analysis was nested in a longitudinal study of human immunodeficiency virus (HIV) incidence in Kenya. HIV-seronegative women enrolled in pregnancy had nucleic acid amplification tests (chlamydia and gonorrhea), rapid plasma reagin (syphilis), wet mount microscopy (Trichomonas and yeast), and Gram stain (bacterial vaginosis); sexually transmitted infection (STI) treatment was provided. PTB predictors were determined using log-binomial regression. RESULTS: Among 1244 mothers of liveborn infants, median gestational age at enrollment was 26 weeks (IQR, 22-31), and at delivery was 39.1 weeks (IQR, 37.1-40.9). PTB occurred in 302 women (24.3%). Chlamydia was associated with a 1.59-fold (P = .006), gonorrhea a 1.62-fold (P = .04), and incident HIV a 2.08-fold (P = .02) increased PTB prevalence. Vaginal discharge and cervical inflammation were associated with PTB, as were age ≤21 (prevalence ratio [PR] = 1.39, P = .001) and any STI (PR = 1.47, P = .001). Associations with chlamydia and incident HIV remained in multivariable models. CONCLUSIONS: STIs and incident HIV in pregnancy predicted PTB despite treatment, suggesting the need for earlier treatment and interventions to decrease genital inflammation.

SMS messaging to improve retention and viral suppression in prevention of mother-to-child HIV transmission (PMTCT) programs in Kenya: A 3-arm randomized clinical trial.

BACKGROUND: Pregnant and postpartum women living with HIV (WLWH) need support for HIV and maternal child health (MCH) care, which could be provided using short message service (SMS). METHODS AND FINDINGS: We compared 2-way (interactive) and 1-way SMS messaging to no SMS in a 3-arm randomized trial in 6 MCH clinics in Kenya. Messages were developed using the Health Belief Model and Social Cognitive Theory; HIV messages were integrated into an existing MCH SMS platform. Intervention participants received visit reminders and prespecified weekly SMS on antiretroviral therapy (ART) adherence and MCH, tailored to their characteristics and timing. Two-way participants could message nurses as needed. Clinic attendance, viral load (VL), and infant HIV results were abstracted from program records. Primary outcomes were viral nonsuppression (VL ≥1,000 c/ml), on-time clinic attendance, loss to follow-up from clinical care, and infant HIV-free survival. Among 824 pregnant women randomized between November 2015 and May 2017, median age was 27 years, gestational age was 24.3 weeks, and time since initiation of ART was 1.0 year. During follow-up to 2 years postpartum, 9.8% of 3,150 VL assessments and 19.6% of women were ever nonsuppressed, with no significant difference in 1-way versus control (11.2% versus 9.6%, adjusted risk ratio (aRR) 1.02 [95% confidence interval (CI) 0.67 to 1.54], p = 0.94) or 2-way versus control (8.5% versus 9.6%, aRR 0.80 [95% CI 0.52 to 1.23], p = 0.31). Median ART adherence and incident ART resistance did not significantly differ by arm. Overall, 88.9% (95% CI 76.5 to 95.7) of visits were on time, with no significant differences between arms (88.2% in control versus 88.6% in 1-way and 88.8% in 2-way). Incidence of infant HIV or death was 3.01/100 person-years (py), with no significant difference between arms; risk of infant HIV infection was 0.94%. Time to postpartum contraception was significantly shorter in the 2-way arm than control. Study limitations include limited ability to detect improvement due to high viral suppression and visit attendance and imperfect synchronization of SMS reminders to clinic visits. CONCLUSIONS: Integrated HIV/MCH messaging did not improve HIV outcomes but was associated with improved initiation of postpartum contraception. In programs where most women are virally suppressed, targeted SMS informed by VL data may improve effectiveness. Rigorous evaluation remains important to optimize mobile health (mHealth) interventions. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02400671.

Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines.

OBJECTIVES: Recent studies have identified vaginal bacterial taxa associated with increased HIV risk. A possible mechanism to explain these results is that individual taxa differentially promote cervicovaginal inflammation. This study aimed to explore relationships between concentrations of bacteria previously linked to HIV acquisition and vaginal concentrations of proinflammatory cytokines and chemokines. METHODS: In this cross-sectional analysis, concentrations of 17 bacterial taxa and four proinflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-10 and tumour necrosis factor alpha (TNFα)) and two proinflammatory chemokines (IL-8 and interferon gamma-induced protein 10) were measured in vaginal swabs collected from 80 HIV-uninfected women. Cytokine and chemokine concentrations were compared between women with bacterial concentrations above or below the lower limit of detection as determined by quantitative PCR for each taxon. Principal component analysis was used to create a summary score for closely correlated bacteria, and linear regression analysis was used to evaluate associations between this score and increasing concentrations of TNFα and IL-1ß. RESULTS: Detection of Dialister micraerophilus (p=0.01), Eggerthella sp type 1 (p=0.05) or Mycoplasma hominis (p=0.03) was associated with higher TNFα concentrations, and detection of D. micraerophilus (p<0.01), Eggerthella sp type 1 (p=0.04), M. hominis (p=0.02) or Parvimonas sp type 2 (p=0.05) was associated with significantly higher IL-1ß concentrations. Seven bacterial taxa (D. micraerophilus, Eggerthella sp type 1, Gemella asaccharolytica, Sneathia sp, Megasphaera sp, M. hominis and Parvimonas sp type 2) were found to be highly correlated by principal component analysis (eigenvalue 5.24, explaining 74.92% of variability). Linear regression analysis demonstrated associations between this principal component and concentrations of TNFα (ß=0.55, 95% CI 0.01 to 1.08; p=0.048) and IL-1ß (ß=0.96, 95% CI 0.19 to 1.74; p=0.016). CONCLUSIONS: This study provides evidence that several highly correlated vaginal bacterial taxa may influence vaginal cytokine and chemokine concentrations. These results suggest a mechanism where the presence of specific bacterial taxa could influence HIV susceptibility by increasing vaginal inflammation.

Sexually transmitted infections during pregnancy and subsequent risk of stillbirth and infant mortality in Kenya: a prospective study.

OBJECTIVES: We evaluated the relationship of sexually transmitted infections (STIs) and genital infections during pregnancy and subsequent risk for infant mortality and stillbirth. METHODS: This was a nested longitudinal analysis using data from a study of peripartum HIV acquisition in Kenya. In the parent study, HIV-uninfected women were enrolled during pregnancy and followed until 9 months postpartum. For this analysis, women who tested positive for HIV at any point, had a non-singleton pregnancy or a spontaneous abortion <20 weeks were excluded. At enrolment, laboratory methods were used to screen for bacterial vaginosis (BV), vaginal yeast, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV). Syphilis was diagnosed using rapid plasma reagin testing and genital ulcer disease (GUD) identified by clinical examination. Treatment of laboratory-confirmed STIs and syndromic management was provided per Kenyan national guidelines. Predictors of stillbirth and infant mortality were determined using logistic regression and Cox proportional hazards models. RESULTS: Overall, among 1221 women, 55% had STIs or genital infections detected: vaginal yeast (25%), BV (22%), TV (6%), CT (5%), NG (2%) and syphilis (1%). Among women with STIs/genital infections (n=592), 34% had symptoms. Overall, 19/1221 (2%) women experienced stillbirths. Among 1202 live births, 34 infant deaths occurred (incidence 4.0 deaths per 100 person-years, 95% CI 2.8 to 5.5). After adjustment for maternal age, education and study site, stillbirth was associated with maternal GUD (adjusted OR=9.19, 95% CI1.91 to 44.35, p=0.006). Maternal NG was associated with infant mortality (adjusted HR=3.83, 95% CI1.16 to 12.68, p=0.028); there was some evidence that maternal CT was associated with infant mortality. Stillbirth or infant mortality were not associated with other genital infections. CONCLUSIONS: STIs and genital infections were common, frequently asymptomatic and some associated with stillbirth or infant mortality. Expediting diagnosis and treatment of STIs in pregnancy may improve infant outcomes.

SMS messaging to improve ART adherence: perspectives of pregnant HIV-infected women in Kenya on HIV-related message content.

There is growing evidence that mobile health (mHealth) approaches including short messaging service (SMS) can improve antiretroviral therapy (ART) adherence, but consensus is lacking regarding communication of HIV-related information. Most interventions to date have delivered SMS that do not overtly refer to HIV or ART in order to avoid risk of status disclosure. In formative work for an ongoing randomized controlled trial (RCT) evaluating one-way and two-way educational SMS for prevention of mother-to-child-transmission (PMTCT) adherence in Kenya, we conducted 10 focus group discussions (FGDs) with 87 HIV-infected peripartum women to determine desirability and preferred terminology of HIV-related content. SMS for the RCT were developed based on FGD findings. Roughly half of FGD participants supported receiving SMS containing overtly HIV-related terms, such as "HIV" and "medication", citing desire for detailed educational messages about ART and PMTCT. Those opposed to overt content expressed concerns about confidentiality. Many participants argued that acceptability of HIV-related content depended on the recipient's disclosure status and others' access to her phone. Based on these findings, both covert and overt SMS were developed for the RCT and participants who owned their phone or had disclosed their HIV status to anyone with access to their phone were able to choose one of three options: (1) covert SMS only, (2) overt SMS only in response to HIV-related questions from the participant, (3) overt SMS routinely, initiated by the study. Of the 825 participants in the RCT, 94% were eligible to receive overt SMS. Of these, 66% opted to receive routine overt SMS and 10% to receive participant-initiated overt SMS. These findings show there may be interest in overt HIV-related information by SMS when risk of status disclosure is low, and support use of messaging strategies that allows participant choice in HIV-related content while protecting against undesired disclosure.

HIV Viral Load Patterns and Risk Factors Among Women in Prevention of Mother-To-Child Transmission Programs to Inform Differentiated Service Delivery.

BACKGROUND: Differentiated service delivery (DSD) approaches decrease frequency of clinic visits for individuals who are stable on antiretroviral therapy. It is unclear how to optimize DSD models for postpartum women living with HIV (PWLH). We evaluated longitudinal HIV viral load (VL) and cofactors, and modelled DSD eligibility with virologic failure (VF) among PWLH in prevention of mother-to-child transmission programs. METHODS: This analysis used programmatic data from participants in the Mobile WAChX trial (NCT02400671). Women were assessed for DSD eligibility using the World Health Organization criteria among general people living with HIV (receiving antiretroviral therapy for ≥6 months and having at least 1 suppressed VL [<1000 copies/mL] within the past 6 months). Longitudinal VL patterns were summarized using group-based trajectory modelling. VF was defined as having a subsequent VL ≥1000 copies/mL after being assessed as DSD-eligible. Predictors of VF were determined using log-binomial models among DSD-eligible PWLH. RESULTS: Among 761 women with 3359 VL results (median 5 VL per woman), a 3-trajectory model optimally summarized longitudinal VL, with most (80.8%) women having sustained low probability of unsuppressed VL. Among women who met DSD criteria at 6 months postpartum, most (83.8%) maintained viral suppression until 24 months. Residence in Western Kenya, depression, reported interpersonal abuse, unintended pregnancy, nevirapine-based antiretroviral therapy, low-level viremia (VL 200-1000 copies/mL), and drug resistance were associated with VF among DSD-eligible PWLH. CONCLUSIONS: Most postpartum women maintained viral suppression from early postpartum to 24 months and may be suitable for DSD referral. Women with depression, drug resistance, and detectable VL need enhanced services.

Mobile solutions to Empower reproductive life planning for women living with HIV in Kenya (MWACh EMPOWER): Protocol for a cluster randomized controlled trial.

BACKGROUND: Women living with HIV (WLWH) face unique reproductive health (RH) barriers which increase their risks of unmet need for contraception, contraceptive failure, unintended pregnancy, and pregnancy-related morbidity and mortality and may prevent them from achieving their reproductive goals. Patient-centered counseling interventions that support health care workers (HCWs) in providing high-quality RH counseling, tailored to the needs of WLWH, may improve reproductive health outcomes. METHODS AND DESIGN: We are conducting a non-blinded cluster randomized controlled trial (cRCT) of a digital health intervention for WLWH (clinicaltrials.gov #NCT05285670). We will enroll 3,300 WLWH seeking care in 10 HIV care and treatment centers in Nairobi and Western Kenya. WLWH at intervention sites receive the Mobile WACh Empower intervention, a tablet-based RH decision-support counseling tool administered at baseline and SMS support during two years of follow-up. WLWH at control sites receive the standard of care FP counseling. The decision-support tool is a logic-based tool for family planning (FP) counseling that uses branching logic to guide RH questions based on participants' reproductive life plans, tailoring counseling based on the responses. Follow-up SMSs are based in the Information-Motivation-Behavioral (IMB) Skills model of behavioral change and are tailored to participant characteristics and reproductive needs through separate SMS "tracks". Follow-up visits are scheduled quarterly for 2 years to assess plans for pregnancy, pregnancy prevention, and contraceptive use. The primary outcome, FP discontinuation, will be compared using an intent-to-treat analysis. We will also assess the unmet need for FP, dual method use, viral load suppression at conception and unintended pregnancy. DISCUSSION: The Mobile WACh Empower intervention is innovative as it combines a patient-centered counseling tool to support initial reproductive life decisions with longitudinal SMS for continued RH support and may help provide RH care within the context of provision of HIV care.

Programmatic Retention in Prevention of Mother-to-Child Transmission (PMTCT) Programs: Estimated Rates and Cofactors Using Different Nonretention Measures.

BACKGROUND: Prevention of mother-to-child transmission programs serve women continuing and initiating antiretroviral therapy (ART) in pregnancy, and follow-up schedules align to delivery rather than ART initiation, making conventional HIV retention measures (assessed from ART initiation) challenging to apply. We evaluated 3 measures of peripartum nonretention in Kenyan women living with HIV from pregnancy to 2 years postpartum. METHODS: This longitudinal analysis used programmatic data from the Mobile WAChX trial (NCT02400671). Outcomes included loss to follow-up (LTFU) (no visit for ≥6 months), incomplete visit coverage (<80% of 3-month intervals with a visit), and late visits (>2 weeks after scheduled date). Predictors of nonretention were determined using Cox proportional hazards, log-binomial, and generalized estimating equation models. RESULTS: Among 813 women enrolled at a median of 24 weeks gestation, incidence of LTFU was 13.6/100 person-years; cumulative incidence of LTFU by 6, 12, and 24 months postpartum was 16.7%, 20.9%, and 22.5%, respectively. Overall, 35.5% of women had incomplete visit coverage. Among 794 women with 12,437 scheduled visits, a median of 11.1% of visits per woman were late (interquartile range 4.3%-23.5%). Younger age, unsuppressed viral load, unemployment, ART initiation in pregnancy, and nondisclosure were associated with nonretention by all measures. Partner involvement was associated with better visit coverage and timely attendance. Women who became LTFU had higher frequency of previous late visits (16.7% vs. 7.7%, P < 0.0001). CONCLUSIONS: Late visit attendance may be a sentinel indicator of LTFU. Identified cofactors of prevention of mother-to-child transmission programmatic retention may differ depending on retention measure assessed, highlighting the need for standardized measures.

Predictors of adverse pregnancy outcomes among Kenyan women with HIV on antiretroviral treatment in pregnancy.

OBJECTIVE: The aim of this study was to understand predictors of adverse pregnancy outcomes (APOs) among women on antiretroviral treatment (ART). DESIGN: A longitudinal cohort. METHODS: Participants from the Mobile WAChX trial were evaluated for APOs, including stillbirth (fetal death at ≥20 weeks' gestation), preterm birth (PTB, livebirth at <37 weeks' gestation,) and neonatal death (NND, ≤28 days after live birth). Predictors were determined by univariable and multivariable Cox proportional hazards and log-binomial models. RESULTS: Among 774 women included, median age was 27 years and 29.0% had unsuppressed HIV viral load (>1000 copies/ml) at enrollment. Half (55.1%) started ART prepregnancy, 89.1% on tenofovir-based regimens. Women with depression had a higher risk of stillbirth (adjusted hazard ratio [aHR] 2.93, 95% confidence interval (95% CI) 1.04-8.23), and women with lower social support score had higher risk of late stillbirth (aHR 11.74, 2.47-55.86). Among 740 livebirths, 201 (27.2%) were preterm and 22 (3.0%) experienced NND. PTB was associated with unsuppressed maternal viral load (adjusted prevalence ratio [aPR] 1.28, 95% CI 1.02-1.61), intimate partner violence (IPV) in pregnancy (aPR 1.94, 95% CI 1.28-2.94), and history of any sexually transmitted infection (STI) (aPR 1.63, 95% CI 1.06-2.51). NND was associated with PTB (aPR 2.53, 95% CI 1.10-5.78) and STI history (aPR 4.25, 95% CI 1.39-13.06). Most associations retained significance in the subgroup of women with viral suppression. CONCLUSION: Maternal viremia during pregnancy predicted PTB as did IPV, lower education, and STI history, while psychosocial stressors predicted stillbirth. Implementing mental health services, ART adherence, partner support, and routine STI screening and treatment could reduce APOs among women with HIV in sub-Saharan Africa settings.

Trajectories of Depression Symptoms From Pregnancy Through 24 months Postpartum Among Kenyan Women Living With HIV.

BACKGROUND: We examined longitudinal patterns and cofactors of depressive symptoms among pregnant and postpartum women living with HIV (WLWH). METHODS: This study used data from a randomized trial of a text messaging intervention. WLWH were serially assessed for depressive symptoms from pregnancy through 24 months postpartum at 6 time points (pregnancy, 6 weeks, and 6, 12, 18, and 24 months postpartum). Depressive symptoms were assessed using Patient Health Questionnaire-9 and longitudinal patterns using group-based trajectory modeling. Moderate-to-severe depressive symptoms (MSD) correlates were assessed using generalized estimating equations. RESULTS: Among 824 enrolled women, 14.6% ever had MSD during pregnancy or postpartum; 8.6% of WLWH had MSD in pregnancy and 9.0% any postpartum MSD. MSD was associated with abuse [RR: 3.8, 95% confidence interval (CI): 2.6 to 5.4], stigma (RR: 4.4, 95% CI: 3.1 to 6.3), and food insecurity (RR: 2.7, 95% CI: 1.9 to 3.8). Unintended pregnancy (RR: 1.6, 95% CI: 1.1 to 2.3) and recent HIV diagnosis (RR: 1.8, 95% CI: 1.2 to 2.6) were associated with higher MSD risk, whereas HIV status disclosure to partner (RR: 0.3, 95% CI: 0.2 to 0.6) and social support (RR: 0.97, 95% CI: 0.96 to 0.98) were associated with lower risk. Trajectory modeling identified 4 phenotypes of peripartum depressive symptoms: persistent no/low symptoms (38.5%), mild symptoms resolving postpartum (12.6%), low symptoms increasing slightly in postpartum (47.9%), and persistent moderate-severe symptoms throughout (1.1%). CONCLUSIONS: WLWH attending PMTCT services had varied patterns of depressive symptoms, which were associated with stressors (recent diagnosis and food insecurity) and factors reflecting low social power (abuse, stigma, and unintended pregnancy). Women experiencing concurrent abuse, stigma, and food insecurity should be prioritized for interventions to prevent persistent depression.

Risk factors for stillbirth and neonatal mortality among participants in Mobile WACh NEO pilot, a two-way SMS communication program in Kenya.

Globally, 2.5 million neonates die and 2 million more are stillborn each year; the vast majority occur where access to life-saving care is limited. High quality, feasible interventions are needed to reach, educate and empower pregnant women and new mothers to improve care-seeking behaviors. Mobile WACh (Mobile solutions for Women's and Children's health) NEO is a human-computer hybrid mobile health (mHealth) system that allows for two-way short message service (SMS) communication between women and healthcare workers during the peripartum period. We performed a secondary prospective cohort analysis of data from the Mobile WACh NEO pilot study to determine maternal characteristics associated with neonatal death and stillbirth and examine participant messaging associated with these events. Pregnant women were enrolled at two Kenyan public health clinics between 28-36 weeks gestation. They received personalized, educational, action-oriented SMS messages during pregnancy and through 14 weeks postpartum. Participants could message the study at any time and study nurses responded. Standardized questionnaires assessed participant characteristics at baseline and 14 weeks postpartum. Outcomes were ascertained at study visits or by SMS report. Among 798 pregnant women enrolled, median age was 24 years [IQR 21, 29], 37% were primiparous and 92% used SMS as a primary mode of communication. Seventeen neonatal deaths and 13 stillbirths occurred. Older maternal age was associated with increased risk of stillbirth [aRR 1.12 (CI 1.02-1.24), p <0.05]. We found no significant predictors of neonatal death. Participant messaging to study nurse about concerns in the week preceding death was less common prior to infant death after discharge home from facility birth (9%) than prior to stillbirth (23%). We found limited predictors of neonatal death and stillbirth, suggesting identifying women prenatally for targeted support may not be a feasible strategy. Scarce messaging from mothers whose neonates died may reflect difficulties identifying illness or rapid deterioration and needs to be better understood to design and test interventions for this high-risk period. Messaging prior to stillbirth, while at similar levels as other periods, does not appear to have an impact as most women do not experience identifiable signs or symptoms prior to the event.

Evaluation of a two-way SMS messaging strategy to reduce neonatal mortality: rationale, design and methods of the Mobile WACh NEO randomised controlled trial in Kenya.

INTRODUCTION: Globally, approximately half of the estimated 6.3 million under-5 deaths occur in the neonatal period (within the first 28 days of life). Kenya ranks among countries with the highest number of neonatal deaths, at 20 per 1000 live births. Improved identification and management of neonates with potentially life-threatening illness is critical to meet the WHO's target of ≤12 neonatal deaths per 1000 live births by 2035. We developed an interactive (two-way) short messaging service (SMS) communication intervention, Mobile Solutions for Neonatal Health (Mobile women's and children's health (WACh) NEO), focused on the perinatal period. Mobile WACh NEO sends automated tailored SMS messages to mothers during pregnancy and up to 6 weeks post partum. Messages employ the Information-Motivation-Behaviour Skills framework to promote (1) maternal implementation of essential newborn care (ENC, including early, exclusive breast feeding, cord care and thermal care), (2) maternal identification of neonatal danger signs and care-seeking, and (3) maternal social support and self-efficacy. Participants can also send SMS to the study nurse, enabling on-demand remote support. METHODS AND ANALYSIS: We describe a two-arm unblinded randomised controlled trial of the Mobile WACh NEO intervention. We will enrol 5000 pregnant women in the third trimester of pregnancy at 4 facilities in Kenya and randomise them 1:1 to receive interactive SMS or no SMS (control), and conduct follow-up visits at 2 and 6 weeks post partum. Neonatal mortality will be compared between arms as the primary outcome. Secondary outcomes include care-seeking, practice of ENC and psychosocial health. Exploratory analysis will investigate associations between maternal mental health, practice of ENC, care-seeking and SMS engagement. ETHICS AND DISSEMINATION: This study received ethical approval from the University of Washington (STUDY00006395), Women and Infants Hospital (1755292-1) and Kenyatta National Hospital/University of Nairobi (P310/04/2019). All participants will provide written informed consent. Findings will be published in peer-reviewed journals and international conferences. TRIAL REGISTRATION NUMBER: NCT04598165.

Food insecurity, drug resistance and non-disclosure are associated with virologic non-suppression among HIV pregnant women on antiretroviral treatment.

We determined social and behavioral factors associated with virologic non-suppression among pregnant women receiving Option B+ antiretroviral treatment (ART). Baseline data was used from women in Mobile WAChX trial from 6 public maternal child health (MCH) clinics in Kenya. Virologic non-suppression was defined as HIV viral load (VL) ≥1000 copies/ml. Antiretroviral resistance testing was performed using oligonucleotide ligation (OLA) assay. ART adherence information, motivation and behavioral skills were assessed using Lifewindows IMB tool, depression using PHQ-9, and food insecurity with the Household Food Insecurity Access Scale. Correlates of virologic non-suppression were assessed using Poisson regression. Among 470 pregnant women on ART ≥4 months, 57 (12.1%) had virologic non-suppression, of whom 65% had HIV drug resistance mutations. In univariate analyses, risk of virologic non-suppression was associated with moderate-to-severe food insecurity (RR 1.80 [95% CI 1.06-3.05]), and varied significantly by clinic site (range 2%-22%, p <0.001). In contrast, disclosure (RR 0.36 [95% CI 0.17-0.78]) and having higher adherence skills (RR 0.70 [95% CI 0.58-0.85]) were associated with lower risk of virologic non-suppression. In multivariate analysis adjusting for clinic site, disclosure, depression symptoms, adherence behavior skills and food insecurity, disclosure and food insecurity remained associated with virologic non-suppression. Age, side-effects, social support, physical or emotional abuse, and distance were not associated with virologic non-suppression. Prevalence of virologic non-suppression among pregnant women on ART was appreciable and associated with food insecurity, disclosure and frequent drug resistance. HIV VL and resistance monitoring, and tailored counseling addressing food security and disclosure, may improve virologic suppression in pregnancy.

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women.

Specific causes of preterm birth remain unclear. Several recent studies have suggested that immune changes during pregnancy are associated with the timing of delivery, yet few studies have been performed in low-income country settings where the rates of preterm birth are the highest. We conducted a retrospective nested case-control evaluation within a longitudinal study among HIV-uninfected pregnant Kenyan women. To characterize immune function in these women, we evaluated unstimulated and stimulated peripheral blood mononuclear cells in vitro with the A/California/2009 strain of influenza to understand the influenza-induced immune response. We then evaluated transcript expression profiles using the Affymetrix Human GeneChip Transcriptome Array 2.0. Transcriptional profiles of sufficient quality for analysis were obtained from 54 women; 19 of these women delivered <34 weeks and were defined as preterm cases and 35 controls delivered >37 weeks. The median time to birth from sample collection was 13 weeks. No transcripts were significantly associated with preterm birth in a case-control study of matched term and preterm birth (n = 42 women). In the influenza-stimulated samples, expression of IFNL1 was associated with longer time to delivery-the amount of time between sample collection and delivery (n = 54 women). A qPCR analysis confirmed that influenza-induced IFNL expression was associated with longer time to delivery. These data indicate that during pregnancy, ex vivo influenza stimulation results in altered transcriptional response and is associated with time to delivery in cohort of women residing in an area with high preterm birth prevalence.

Elevation of cervical C-X-C motif chemokine ligand 10 levels is associated with HIV-1 acquisition in pregnant and postpartum women.

OBJECTIVE: To evaluate the relationship between cervical cytokine/chemokine concentrations and HIV-1 acquisition in peripartum Kenyan women. DESIGN: Nested case-control study. METHODS: Women participating in a prospective study of peripartum HIV acquisition in Kenya (the Mama Salama Study), were tested for HIV-1 at 1-3 month intervals during pregnancy and through 9 months postpartum. Cases positive for HIV-1 RNA during follow-up (N = 14), were matched 3 : 1 with HIV-negative controls (N = 42) based on age, marital status, partner HIV-1 status, transactional sex, and timing of cervical swab collection. Concentrations of five cytokines (IL-1ß, IL-6, IL-10, IFNγ, and TNFα) and four chemokines (IL-8, C-X-C motif chemokine ligand 10 (CXCL10), macrophage inflammatory protein-1 α, and macrophage inflammatory protein-1 ß) were measured from cervical swabs collected at the visit prior to HIV-1 diagnosis (cases) or matched gestational/postpartum time (controls). Cytokine/chemokine concentrations were compared between cases and controls using Wilcoxon rank-sum tests. Principal component analysis was used to create a summary score for closely correlated cytokines/chemokines. Associations with HIV-1 acquisition were analyzed using conditional logistic regression. Path analysis was used to evaluate hypothesized relationships between CXCL10, vaginal washing, Nugent score, and HIV-1 acquisition. RESULTS: Conditional logistic regression analysis demonstrated an association between increased concentrations of CXCL10 and HIV-1 acquisition (odds ratio = 1.74, 95% confidence interval 1.04, 2.93; P = 0.034). Path analysis confirmed a positive independent association between higher concentrations of CXCL10 and HIV-1 acquisition (path coefficient = 0.37, 95% confidence interval 0.15, 0.59; P < 0.001). CONCLUSION: HIV-1 acquisition was associated with increased cervical concentrations of CXCL10 in pregnant and postpartum women.

HIV acquisition during pregnancy and postpartum is associated with genital infections and partnership characteristics.

OBJECTIVE: The objective of this study is to determine the risk and cofactors for HIV acquisition during pregnancy and postpartum. DESIGN: A prospective cohort study METHODS: : Pregnant women in western Kenya were enrolled if HIV seronegative at that visit or within 3 months. Serial HIV nucleic acid amplification tests (NAATs) were conducted at 1 to 3-month intervals to 9 months postpartum. Genital swabs were collected for detection of chlamydia and gonorrhoea at baseline, and for trichomonas, bacterial vaginosis and yeast at baseline and follow-up. RESULTS: Among 1304 pregnant women, median age was 22 years, 78% were married for a median of 4 years, 66% reported knowing partner HIV status and 8% reported using condoms. Study retention was 98%. During 1235 person-years of follow-up, HIV incidence was 2.31/100 person-years [95% confidence interval (95% CI) 0.71-4.10]. Incident HIV was associated with syphilis (hazard ratio 9.18, 95% CI 2.15-39.3), chlamydia (hazard ratio 4.49, 95% CI 1.34-15.0), bacterial vaginosis (hazard ratio 2.91, 95% CI 1.25-6.76), yeast (hazard ratio 3.46, 95% CI 1.46-8.19), sexually transmitted infection (STI) history (hazard ratio 3.48, 95% CI 1.31-9.27), lifetime number of sex partners (hazard ratio 1.19, 95% CI 1.03-1.37), partner age discordance (hazard ratio 1.07 per year, 95% CI 1.02-1.13) and shorter marriage (hazard ratio 1.19 per year, 95% CI 1.03-1.38). No women with incident HIV reported an HIV-infected partner. In multivariate analyses, chlamydia, older partners and yeast infection remained significant; however, power was limited. CONCLUSION: Pregnant and lactating women may not perceive HIV risk and rarely used condoms. Prevention and treatment of genital infections and risk stratification to identify women for pre-exposure prophylaxis (PrEP) could decrease HIV acquisition in pregnant/lactating women.