Drug concentrations in hair and dried blood spots as PrEP adherence metrics during pregnancy and postpartum.

We evaluated hair tenofovir (TFV) concentrations as an adherence metric for HIV pre-exposure prophylaxis (PrEP) during pregnancy and postpartum and compared hair levels with tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). Overall, 152 hair samples from 102 women and 36 hair-DBS paired samples from 29 women were collected from a subset of women in a cluster randomized trial. Having a partner known to be living with HIV was associated with higher hair TFV levels (p<0.001). Hair TFV concentrations were strongly correlated with DBS TFV-DP levels (r=0.76, p<0.001), indicating hair as promising cumulative adherence metric for perinatal PrEP assessment.

Cofactors of Partner HIV Self-testing and Oral PrEP Acceptance Among Pregnant Women at High Risk of HIV in Kenya.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) and male partner HIV self-testing (HIVST) is being scaled up within antenatal clinics. Few data are available on how co-distribution influences acceptance of both interventions. METHODS: We used data from the PrEP Implementation of Mothers in Antenatal Care (NCT03070600) trial in Kenya. Women included in this analysis were determined to be at high risk of HIV and offered oral PrEP and partner HIVST. Characteristics were compared between women who chose: (1) PrEP and HIVST, (2) HIVST-alone, (3) PrEP-alone, or (4) declined both (reference), excluding women who had partners known to be living with HIV. RESULTS: Among 911 women, median age was 24 years, 87.3% were married, 43.9% perceived themselves to be at high risk of HIV and 13.0% had history of intimate partner violence (IPV). Overall, 68.9% accepted HIVST and 18.4% accepted PrEP, with 54.7% accepting HIVST-alone, 4.2% PrEP-alone, and 14.3% both HIVST and PrEP. Of women accepting HIVST, partner HIV testing increased from 20% to 82% and awareness of partner HIV status increased from 4.7% to 82.0% between pregnancy and 9 months postpartum (P < 0.001). Compared with women who accepted neither, choosing: (1) HIVST-alone was associated with being married, higher level of education, and residing with partner; (2) PrEP-alone was associated with lower social support, IPV, not residing with partner, longer time living with partner, and suspicion of other partners; and (3) PrEP and HIVST was associated with being married, IPV, and suspicion that partner had other partners. CONCLUSIONS: Understanding factors associated with accepting HIVST and PrEP can inform HIV prevention programs for pregnant women. CLINICAL TRIAL NUMBER: NCT03070600.

HIV pre-exposure prophylaxis initiation, persistence, and adherence during pregnancy through the postpartum period.

OBJECTIVE: We evaluated pre-exposure prophylaxis (PrEP) initiation, persistence, and adherence measured via tenofovir-diphosphate (TFV-DP) concentrations in dried blood spots (DBS) among women offered PrEP during pregnancy. METHODS: We prospectively analyzed data from participants in the PrIMA Study (NCT03070600) who were offered PrEP during the second trimester and followed through 9 months postpartum. At follow-up visits (monthly in pregnancy; 6 weeks, 6 months, 9 months postpartum), self-reported PrEP use was assessed, and DBS were collected for quantifying TFV-DP concentrations. RESULTS: In total, 2949 participants were included in the analysis. At enrollment, median age was 24 years [interquartile range IQR) 21-29], gestational age 24 weeks (IQR 20-28), and 4% had a known partner living with HIV. Overall, 405 (14%) participants initiated PrEP in pregnancy with higher frequency among those with risk factors for HIV acquisition, including >2 lifetime sexual partners, syphilis during pregnancy, forced sex, and intimate partner violence ( P  < 0.05). At 9 months postpartum, 58% of PrEP initiators persisted with PrEP use, of which 54% self-reported not missing any PrEP pills in the last 30 days. Among DBS randomly selected from visits where participants persisted with PrEP ( n  = 427), 50% had quantifiable TFV-DP. Quantifiable TFV-DP was twice as likely in pregnancy than postpartum [adjusted risk ratio (aRR) = 1.90, 95% confidence interval (CI) 1.40-2.57, P  < 0.001]. Having a partner known to be living with HIV was the strongest predictor of PrEP initiation, persistence, and quantifiable TFV-DP ( P  < 0.001). CONCLUSIONS: PrEP persistence and adherence waned postpartum, though over half of PrEP initiators persisted through 9-months postpartum. Interventions should prioritize increasing knowledge of partner HIV status and sustaining adherence in the postpartum period.

Risks of adverse perinatal outcomes in relation to maternal depressive symptoms: A prospective cohort study in Kenya.

BACKGROUND: Evidence gaps remain regarding the influence of prenatal psychosocial factors on adverse pregnancy outcomes. OBJECTIVE: The objective of this study is to evaluate relationships between psychosocial factors and adverse perinatal outcomes among Kenyan women. METHODS: We analysed data from a prospective cohort study enrolling HIV-negative women in pregnancy (NCT03070600) in 20 antenatal clinics in Western Kenya. Study nurses assessed depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CESD-10), social support using the Medical Outcomes Survey scale (MOS-SSS), intimate partner violence (IPV) with the Hurt, Insult, Threaten, Scream scale (HITS), and pregnancy outcomes at 6 weeks postpartum. Cox proportional hazards models were used to evaluate relationships between depressive symptoms (moderate-to-severe [MSD, CESD-10 ≥10] and mild-to-severe [Mild-SD, CESD-10 ≥5]), low social support (MOS-SSS <72), and IPV (HITS ≥10) with adverse perinatal outcomes of pregnancy loss, stillbirth, preterm birth (PTB), small for gestational age, and neonatal mortality. We also estimated the population attributable risk. RESULTS: Among 4153 women, 23.9% (n = 994) had MSD, 54.7% (n = 2273) mild-SD, 37.3% (n = 1550) low social support, and 7.8% (n = 323) experienced IPV. Pregnancy loss was 5-fold higher among women with MSD (adjusted hazard ratio [HR] 5.04, 95% confidence interval [CI] 2.44, 10.42); 37.4% of losses were attributable to MSD. Mild-SD was associated with PTB (HR 1.39, 95% CI 1.03, 1.87). Stillbirth risk more than doubled among women reporting low social support (HR 2.37, 95% CI 1.14, 4.94). CONCLUSIONS: Adverse perinatal outcomes were common and associated with prenatal depressive symptoms and low social support in this large cohort of Kenyan mother-infant pairs.

COVID-19 vaccine hesitancy among pregnant and postpartum Kenyan women.

OBJECTIVE: The authors evaluated factors contributing to coronavirus disease 2019 (COVID-19) vaccine hesitancy among pregnant and postpartum women to inform vaccine scale-up strategies. METHODS: This observational study utilized data from pregnant and postpartum women attending four public maternal child health (MCH) clinics in Western Kenya. From October 2020 to July 2022, nurses assessed COVID-19 vaccine hesitancy, defined as reporting "unlikely" or "very unlikely" to the question, "If a vaccine for COVID-19 were available today, what is the likelihood that you would get vaccinated?" RESULTS: Among 1023 women (235 pregnant, 788 postpartum), 20% reported worsened MCH care during the pandemic and most (92%) perceived themselves or family members to be at risk for COVID-19, yet 54% of women reported COVID-19 vaccine hesitancy. Vaccine hesitancy was more frequent among women reporting worsened MCH care (P < 0.001) since the pandemic and those who did not trust the government as a source of COVID-19 information (P = 0.016). Over the 2-year period, willingness to receive the vaccine almost doubled (38% to 71%, P < 0.001). CONCLUSIONS: Our findings suggest that sustaining access to quality MCH services may decrease COVID-19 vaccine hesitancy. Willingness to receive the vaccine doubled over the 2-year period in our cohort, suggesting increased trust for use and acceptance in the unique context of the pregnancy/postpartum period.

Correction: A Text Messaging-Based Support Intervention to Enhance Pre-exposure Prophylaxis for HIV Prevention Adherence During Pregnancy and Breastfeeding: Protocol for a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/41170.].

Risk-based versus universal PrEP delivery during pregnancy: a cluster randomized trial in Western Kenya from 2018 to 2019.

INTRODUCTION: Integrating pre-exposure prophylaxis (PrEP) delivery for pregnant and postpartum women within maternal and child health (MCH) clinics is feasible and acceptable. It is unknown whether a risk-guided model would facilitate appropriate PrEP use among MCH attendees better than universally offering PrEP. METHODS: The PrEP Implementation for Mothers in Antenatal Care (PrIMA) study was a cluster randomized trial to assess two models for PrEP delivery among pregnant women seeking routine MCH care at 20 public clinics in Kenya between January 2018 and July 2019 (NCT03070600). In the Universal arm, all participants received PrEP counselling and self-selected whether to initiate PrEP. In the Targeted arm, participants underwent an HIV risk assessment, including an objective risk-scoring tool and an offer of HIV self-tests for at-home partner testing; those determined to be at high risk received a PrEP offer. Participants were followed through 9 months postpartum. Primary outcomes included incident HIV and appropriate PrEP use (defined as PrEP uptake among those at high risk and no PrEP uptake for those not at risk). Outcomes were compared using intention-to-treat analyses, adjusting for baseline HIV risk and marital status. RESULTS: Among 4447 women enrolled, the median age was 24.0 years (interquartile range [IQR]: 20.9, 28.3), and most were married (84.8%). The median gestational age at enrolment was 24 weeks (IQR: 20, 30). Women in the Targeted arm were more likely to be at high risk for HIV acquisition at baseline (51.6% vs. 33.3%). During 4638 person-years (p-yr) of follow-up, there were 16 maternal HIV infections with no difference in maternal HIV incidence between arms: 0.31/100 p-yr (95% CI: 0.15, 0.65) Targeted and 0.38/100p-yr (95% CI: 0.20, 0.73) Universal (adjusted relative risk [aRR]: 0.85 [CI: 0.28, 2.55]). There was no significant difference in the frequency of appropriate PrEP use between the arms (68.2% vs. 59.1% in Targeted vs. Universal, respectively) (aRR: 1.03 [CI: 0.96, 1.10]). CONCLUSIONS: Given comparable maternal HIV incidence and PrEP uptake in Universal and Targeted approaches, and the simplicity that universal PrEP offers, our findings suggest that universal PrEP counselling is optimal for integrating PrEP in MCH systems.

A Text Messaging-Based Support Intervention to Enhance Pre-exposure Prophylaxis for HIV Prevention Adherence During Pregnancy and Breastfeeding: Protocol for a Randomized Controlled Trial.

BACKGROUND: Cisgender women in Kenya are at elevated risk of HIV acquisition during pregnancy and post partum. Acute HIV infection during pregnancy and breastfeeding accounts for approximately one-third of all vertical HIV transmissions. The World Health Organization recommends offering oral tenofovir-based pre-exposure prophylaxis (PrEP) to pregnant and postpartum women who are HIV negative but at substantial and ongoing risk for HIV acquisition. PrEP delivery for pregnant and postpartum women is expanding within routine maternal child health clinics in Kenya. However, approximately half of pregnant women discontinue PrEP within 30 days of initiation. Therefore, it is crucial to develop PrEP adherence strategies that enhance support for adherence when peripartum events and health issues pose challenges to sustaining PrEP adherence. OBJECTIVE: We are conducting a randomized controlled trial to determine the effect of a bidirectional communication platform named Mobile Solutions for Women's and Children's Health (mWACh), which utilizes two-way SMS text messaging between patients and remote nurses to support PrEP adherence and address maternal health concerns in real time during the peripartum period. METHODS: The mWACh-PrEP study is a randomized trial designed to support PrEP adherence during the peripartum period by comparing mWACh-PrEP to the standard of care (ie, in-clinic adherence counseling) among women who are HIV negative and initiating PrEP. Purposive sampling was used to select 5 facilities offering PrEP in antenatal clinics in Kisumu and Siaya Counties, and block randomization will be used to divide participants into groups. Participants in the intervention arm will receive a customized messaging curriculum via SMS text messages targeted toward their particular perinatal stage. The primary outcome, PrEP adherence at 6 months post partum, will be evaluated using a log-binomial regression model, adjusting for imbalanced baseline characteristics. Based on a previous study of directly observed dosing conditions, we will use a hair tenofovir concentration cutoff of 0.038 ng/mg (corresponding to 7 doses/week) as the primary adherence outcome measured at 6 months post partum (binary outcome). Qualitative interviews and cost-effective analyses will be conducted to understand the feasibility, acceptability, and economic impact of the intervention. RESULTS: Enrollment began in March 2022 and is projected to continue until July 2023, with follow-up through March 2024. The study results are expected to be reported in 2025. CONCLUSIONS: This trial will provide insights into using mobile health to enhance PrEP adherence among pregnant and postpartum mothers. Additionally, the findings will have implications for the use of mobile health technology to improve adherence to other daily medications during the peripartum period. TRIAL REGISTRATION: ClinicalTrials.gov NCT04472884; https://clinicaltrials.gov/ct2/show/NCT04472884. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41170.

Comparing depression screening tools (CESD-10, EPDS, PHQ-9, and PHQ-2) for diagnostic performance and epidemiologic associations among postpartum Kenyan women: Implications for research and practice.

BACKGROUND: Identifying optimal depression screening tools for use in maternal health clinics could improve maternal and infant health. We compared four tools for diagnostic performance and epidemiologic associations. METHODS: This study was nested in a cluster-randomized trial in Kenya. Women in 20 maternal health clinics were evaluated at 6 weeks postpartum with Center for Epidemiologic Studies Depression Scale (CESD-10), Edinburgh Postnatal Depression Scale (EPDS), Patient Health Questionnaire-9 and -2 (PHQ-9, PHQ-2) for moderate-to-severe depressive symptoms (MSD) [CESD-10 ≥ 10, EPDS≥13, PHQ-9 ≥ 10, or PHQ-2 ≥ 3]. We assessed area under the curve (AUC) per scale (CESD-10, EPDS) against probable major depressive disorder (MDD) using the PHQ-9 scoring algorithm. Associations between MSD and intimate partner violence (IPV) were compared between scales. RESULTS: Among 3605 women, median age was 24 and 10 % experienced IPV. Prevalence of MSD symptoms varied by tool: 13 % CESD-10, 9 % EPDS, 5 % PHQ-2, 3 % PHQ-9. Compared to probable MDD, the CESD-10 (AUC:0.82) had higher AUC than the EPDS (AUC:0.75). IPV was associated with MSD using all scales: EPDS (RR:2.5, 95%CI:1.7-3.7), PHQ-2 (RR:2.3, 95%CI:1.6-3.4), CESD-10 (RR:1.9, 95%CI:1.2-2.9), PHQ-9 (RR:1.8, 95%CI:0.8-3.8). LIMITATIONS: Our study did not include clinical diagnosis of MDD by a specialized clinician, instead we used provisional diagnosis of probable MDD classified by the PHQ-9 algorithm as a reference standard in diagnostic performance evaluations. CONCLUSION: Depression screening tools varied in detection of postpartum MSD. The PHQ-2 would prompt fewer referrals and showed strong epidemiologic association with a cofactor.

Trajectories and predictors of perinatal depressive symptoms among Kenyan women: a prospective cohort study.

BACKGROUND: There are gaps in understanding longitudinal patterns and predictors of perinatal depressive symptoms in sub-Saharan Africa. This study aimed to explore trajectories of depressive symptoms and associated factors from pregnancy to 9 months post partum among Kenyan women. METHODS: In this prospective cohort study, we analysed data from the PrEP Implementation for Mothers in Antenatal Care (PrIMA) study in which HIV-negative women were enrolled in pregnancy and followed up to 9 months post partum in 20 public sector maternal-child health clinics in western Kenya. Pregnant women were eligible for enrolment if they were not infected with HIV, aged 15 years or older, and were able to provide consent. Eligible participants were screened and enrolled between Jan 15, 2018, and July 31, 2019, and followed up to 9 months post partum, with the last participant study visit conducted on Jan 15, 2021. Study nurses serially assessed depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CESD-10), intimate partner violence with the Hurt, Insult, Threaten, Scream scale, and social support with the Medical Outcomes Study scale. Generalised estimating equations were used to identify correlates of moderate-to-severe depressive symptoms (CESD-10 score ≥10) and group-based trajectory modelling identified discrete trajectories of perinatal depressive symptoms. FINDINGS: Among 4447 participants in the main PrIMA study, 3555 had complete depressive symptom data in pregnancy and depressive symptom data post partum and were included in the primary analysis. Median age was 24·0 years (IQR 21·0-28·7), 1330 (38%) participants had low social support, and 278 (8%) reported intimate partner violence in pregnancy. All participants (100%) were female and all (100%) were of African Kenyan ethnicity. Prevalence of moderate-to-severe depressive symptoms was higher in pregnancy than post partum (870 [24·5%; 95% CI 23·1-25·9] vs 597 [6·8%; 15·6-18·1]; p<0·0001). Five patterns of depressive symptoms were identified; persistent moderate-to-severe depressive symptoms in pregnancy and post partum (295 [8·3%]), moderate-to-severe depressive symptoms in pregnancy that resolved post partum (139 [3·9%]), moderate-to-severe depressive symptoms that emerged post partum (40 [1·1%]), chronically mild symptoms (2709 [76·2%]), and no depressive symptoms (372 [10·5%]). Emergent moderate-to-severe depressive symptoms were associated with older age. Emergent, persistent, and resolving moderate-to-severe depressive symptoms were associated with intimate partner violence during pregnancy; and persistent and resolving moderate-to-severe depressive symptoms were associated with low social support and high HIV risk (all p<0·05). Moderate-to-severe depressive symptom risk was significantly increased with intimate partner violence (adjusted odds ratio 2·07 [95% CI 1·81-2·31]; p<0·0001), low social support (1·74 [1·56-1·95]; p<0·0001), and partner HIV-positive status (1·48 [1·22-1·78]; p<0·0001). 23·34% (95% CI 18·77-27·65) of cases of perinatal moderate-to-severe depressive symptoms were attributable to low social support. INTERPRETATION: One third of women had perinatal moderate-to-severe depressive symptoms; nearly half of these had higher severity phenotypes of resolving, persistent, and emerging moderate-to-severe depressive symptoms that might require tailored interventions. Perinatal women with comorbid psychosocial stressors such as intimate partner violence and previous pregnancy loss should be prioritised for mental health services that augment social support within routine maternal-child health care. FUNDING: National Institutes of Health. TRANSLATION: For the Kiswahili translation of the abstract see Supplementary Materials section.

Challenges of Discrepant HIV Tests in Pregnant Women in the PrEP era-to Treat or Not to Treat?

BACKGROUND: During HIV retesting in antenatal and preexposure prophylaxis (PrEP) care, discrepant results occur, but guidelines are lacking. METHODS: In a Kenyan trial implementing antenatal PrEP, if 1 test is reactive, a second is performed; if discrepant, both are repeated; if persistently discrepant, DNA polymerase chain reaction (PCR) is performed. RESULTS: Among 4451 women, 23 265 HIV retesting sessions were performed; 14 (0.06%, 95% confidence interval, 0.03%-0.10%) had discrepant results among 10 individuals; in all 10 initial cases, PCR was negative. CONCLUSIONS: Discrepant rapid tests are an expected, rare, and important challenge for antenatal care HIV retesting, with and without PrEP. CLINICAL TRIALS REGISTRATION: NCT03070600.