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.

An implementation strategy package (video education, HIV self-testing, and co-location) improves PrEP implementation for pregnant women in antenatal care clinics in western Kenya.

Background: Pre-exposure prophylaxis (PrEP) is recommended by the World Health Organization and the Kenyan Ministry of Health for HIV prevention in pregnancy and postpartum for women at risk for HIV. Integration of PrEP into antenatal care is promising, but delivery gaps exist in the face of healthcare provider shortages in resource-limited settings. Methods: Between May and November 2021, we conducted a difference-in-differences study (3 months pre-intervention data collection and 3 months post-intervention data collection) analyzing four intervention facilities, where the strategies were implemented, and four comparison facilities, where no strategies were implemented. We tested a combination of three implementation strategies-video-based PrEP information in the waiting bay, HIV self-testing, and dispensing of PrEP in the antenatal care rooms-to improve PrEP delivery. We compared absolute changes in the proportion of antenatal attendees screened for PrEP (PrEP penetration), the proportion receiving all PrEP-specific steps in a visit (HIV testing, risk screening, and PrEP counseling) (PrEP fidelity), and client PrEP knowledge, client satisfaction, and waiting time and service time (a priori outcomes); post hoc, we compared the proportion offered PrEP (PrEP offer) and completing HIV testing. We measured provider perceptions of the acceptability and appropriateness of the implementation strategies. Results: We observed significant improvements in PrEP penetration, PrEP offer, satisfaction, and knowledge (p < 0.05) and improvements in fidelity that trended towards significance (p = 0.057). PrEP penetration increased 5 percentage points (p = 0.008), PrEP fidelity increased 8 percentage points (p = 0.057), and PrEP offer increased 4 percentage points (p = 0.003) in intervention vs. comparison facilities. Client PrEP knowledge increased by 1.7 out of 6 total points (p < 0.001) and client satisfaction increased by 0.7 out of 24 total points (p = 0.003) in intervention vs. comparison facilities. We observed no changes in service time (0.09-min decrease; p = 0.435) and a small increase in waiting time (0.33-min increase; p = 0.005). HIV testing among those eligible did not change (1.5 percentage point decrease, p = 0.800). Providers felt the implementation strategies were acceptable and appropriate (median acceptability: 20/20; median appropriateness: 19.5/20). However, absolute levels of each step of the PrEP cascade remained suboptimal. Conclusions: An implementation strategy package with video information, HIV self-testing, and co-location of medication dispensing enhanced PrEP delivery across several implementation outcomes and client satisfaction, while not substantially increasing wait time or decreasing provider-client contact time. Clinical trial registration: ClinicalTrials.gov , identifier, NCT04712994.

Neurodevelopment of children who are HIV-exposed and uninfected in Kenya.

INTRODUCTION: Predictors of neurodevelopment among children who are HIV-exposed uninfected (CHEU) are poorly understood. METHODS: Mothers with and without HIV and their children were enrolled during 6-week postnatal care visits across seven sites in Kenya between March 2021 and June 2022. Infant neurodevelopment was assessed using the Malawi Developmental Assessment Tool, including social, language, fine motor and gross motor domains. We used multivariate linear mixed effects models to identify associations between 1-year neurodevelopment scores, HIV and antiretroviral therapy (ART) exposures, and household factors, adjusted for potential confounders and clustered by the site. RESULTS: At 1-year evaluation, CHEU (n = 709) and children who are HIV-unexposed uninfected (CHUU) (n = 715) had comparable median age (52 weeks) and sex distribution (49% vs. 52% female). Mothers living with HIV were older (31 vs. 27 years), had lower education (50% vs. 26% primary) and were more likely to be report moderate-to-severe food insecurity (26% vs. 9%) (p < 0.01 for all). Compared to CHUU, CHEU had higher language scores (adjusted coeff: 0.23, 95% CI: 0.06, 0.39) and comparable social, fine and gross motor scores. Among all children, preterm birth was associated with lower gross motor scores (adjusted coeff: -1.38, 95% CI: -2.05, -0.71), food insecurity was associated with lower social scores (adjusted coeff: -0.37, 95% CI: -0.73, -0.01) and maternal report of intimate partner violence (IPV) was associated with lower fine motor (adjusted coeff: -0.76, 95% CI: -1.40, -0.13) and gross motor scores (adjusted coeff: -1.07, 95% CI: -1.81, -0.33). Among CHEU, in utero efavirenz (EFV) exposure during pregnancy was associated with lower gross motor scores compared to dolutegravir (DTG) exposure (adjusted coeff: -0.51, 95% CI: -1.01, -0.03). Lower fine and gross motor scores were also associated with having a single or widowed mother (adjusted coeff: -0.45, 95% CI: -0.87, -0.03) or a deceased or absent father (adjusted coeff: -0.81, 95% CI: -1.58, -0.05), respectively. CONCLUSIONS: Biologic and social factors were associated with child neurodevelopment. Despite socio-demographic differences between CHEU and CHUU, 1-year neurodevelopment was similar. Addressing IPV and food insecurity may provide benefits regardless of maternal HIV status. DTG use was associated with higher neurodevelopmental scores in CHEU, compared to EFV regimens, potentially contributing to a lack of neurodevelopmental difference between CHEU and CHUU.

Selecting implementation strategies to improve implementation of integrated PrEP for pregnant and postpartum populations in Kenya: a sequential explanatory mixed methods analysis.

BACKGROUND: There is a higher risk for HIV acquisition during pregnancy and postpartum. Pre-exposure prophylaxis (PrEP) is recommended during this period for those at high risk of infection; integrated delivery in maternal and child health (MCH) clinics is feasible and acceptable but requires implementation optimization. METHODS: The PrEP in Pregnancy, Accelerating Reach and Efficiency study (PrEPARE; NCT04712994) engaged stakeholders to prioritize determinants of PrEP delivery (using Likert scores) and prioritize PrEP delivery implementation strategies. Using a sequential explanatory mixed methods design, we conducted quantitative surveys with healthcare workers at 55 facilities in Western Kenya and a stakeholder workshop (including nurses, pharmacists, counselors, and county and national policymakers), yielding visual plots of stakeholders' perceived feasibility and effectiveness of the strategies. A stepwise elimination process was used to identify seven strategies for empirical testing. Facilitator debriefing reports from the workshop were used to qualitatively assess the decision-making process. RESULTS: Among 146 healthcare workers, the strongest reported barriers to PrEP delivery were insufficient providers and inadequate training, insufficient space, and high volume of patients. Sixteen strategies were assessed, 14 of which were included in the final analysis. Among rankings from 182 healthcare workers and 44 PrEP policymakers and implementers, seven strategies were eliminated based on low post-workshop ranking scores (bottom 50th percentile) or being perceived as low feasibility or low effectiveness for at least 50% of the workshop groups. The top seven strategies included delivering PrEP within MCH clinics instead of pharmacies, fast-tracking PrEP clients to reduce waiting time, delivering PrEP-related health talks in waiting bays, task shifting PrEP counseling, task shifting PrEP risk assessments, training different providers to deliver PrEP, and retraining providers on PrEP delivery. All top seven ranked strategies were grouped into bundles for subsequent testing. Facilitator debriefing reports generally aligned with rankings but noted how stakeholders' decision-making changed when considering the impact of strategies on facility staff and non-PrEP clients. CONCLUSIONS: The most impactful barriers to integrated PrEP delivery in MCH clinics were insufficient staffing and space. Implementation strategies prioritized through multiple methods of stakeholder input focused on co-location of services and increasing clinic efficiency. Future testing of these stakeholder-prioritized strategy bundles will be conducted to assess the effectiveness and implementation outcomes.

Integrating PrEP in maternal and child health clinics in Kenya: analysis of a service availability and readiness assessment (SARA) survey.

Background: Risk of HIV acquisition is high during pregnancy and postpartum, and pre-exposure prophylaxis (PrEP) is recommended for peripartum populations. Integrating PrEP into maternal and child health (MCH) clinics is feasible and acceptable. Understanding clinics' service availability and readiness is essential for effective scale up. Methods: The PrEP in Pregnancy, Accelerating Reach and Efficiency study (PrEPARE; NCT04712994) engaged PrEP-experienced facilities previously linked to a programmatic or research study in Western Kenya to document available services and commodities via a modified service availability and readiness assessment (SARA) survey with 20 PrEP tracer items covering: staffing/guidelines, services/equipment, and medicines/commodities. Facilities' prior study engagement occurred between 2017 and 2019; SARA survey data was collected between April 2020 and June 2021. Descriptive statistics were stratified by prior study engagement. ANOVA tests assessed associations between facility characteristics and gaps. Fisher's tests assessed differences in commodity availability and stockouts. Results: Of the 55 facilities surveyed, 60% had received PrEP training in the last two years, 95% offered PrEP integrated into MCH, and 64% and 78% had both auditory and visual privacy in PrEP and HIV testing service (HTS) delivery spaces, respectively. Supervision frequency was heterogeneous, but 82% had received a supervision visit within 3 months. Availability of commodities was variable and the most commonly unavailable commodities were PrEP in MCH (71% available) and risk assessment screening tool (RAST) and PrEP cards (60% and 75% available, respectively). The number of service and commodity gaps per facility ranged from zero to eight (median: 3; IQR: 2, 5). The most frequent gaps were: PrEP training and risk assessment cards (40% each), lack of privacy in PrEP (36%) and HIV testing services (31%) spaces, PrEP pills in MCH (29%), and PrEP cards (25%). There were no differences in mean number of gaps by county, previous study engagement, or public vs. private status. Level 4 facilities had fewer gaps (mean 2.2) than level 2, 3, and 5 facilities (mean 5.7, 4.5, and 5.3 respectively; p < 0.001). Conclusions: PrEP service availability and readiness was generally high across MCH facilities. However, there is a need for increased frequency of provider training and supportive supervision focused on fidelity. To address key commodity stockouts such as PrEP pills, implementation of electronic logistics management information systems may be needed. Targeting these gaps is essential to effectively scale up integrated PrEP delivery, especially among facilities with limited infrastructure.

Comparison of methods to engage diverse stakeholder populations in prioritizing PrEP implementation strategies for testing in resource-limited settings: a cross-sectional study.

BACKGROUND: There is a lack of consensus about how to prioritize potential implementation strategies for HIV pre-exposure prophylaxis (PrEP) delivery. We compared several prioritization methods for their agreement and pragmatism in practice in a resource-limited setting. METHODS: We engaged diverse stakeholders with clinical PrEP delivery and PrEP decision-making experience across 55 facilities in Kenya to prioritize 16 PrEP delivery strategies. We compared four strategy prioritization methods: (1) "past experience surveys" with experienced practitioners reflecting on implementation experience (N = 182); (2 and 3) "pre- and post-small-group ranking" surveys before and after group discussion (N = 44 and 40); (4) "go-zone" quadrant plots of perceived effectiveness vs feasibility. Kendall's correlation analysis was used to compare strategy prioritization using the four methods. Additionally, participants were requested to group strategies into three bundles with up to four strategies/bundle by phone and online survey. RESULTS: The strategy ranking correlation was strongest between the pre- and post-small-group rankings (Tau: 0.648; p < 0.001). There was moderate correlation between go-zone plots and post-small-group rankings (Tau: 0.363; p = 0.079) and between past-experience surveys and post-small-group rankings (Tau: 0.385; p = 0.062). For strategy bundling, participants primarily chose bundles of strategies in the order in which they were listed, reflecting option ordering bias. Neither the phone nor online approach was effective in selecting strategy bundles. Participants agreed that the strategy ranking activities conducted during the workshop were useful in prioritizing a final set of strategies. CONCLUSIONS: Both experienced and inexperienced stakeholder participants' strategy rankings tended to prioritize strategies perceived as feasible. Small group discussions focused on feasibility and effectiveness revealed moderately different priorities than individual rankings. The strategy bundling approach, though less time- and resource-intensive, was not effective. Future research should further compare the relative effectiveness and pragmatism of methodologies to prioritize implementation strategies.

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.

Preferences and acceptability for long-acting PrEP agents among pregnant and postpartum women with experience using daily oral PrEP in South Africa and Kenya.

INTRODUCTION: Long-acting pre-exposure prophylaxis (PrEP) options could overcome barriers to oral PrEP persistence during pregnancy and postpartum. We evaluated long-acting PrEP preferences among oral PrEP-experienced pregnant and postpartum women in South Africa and Kenya, countries with high PrEP coverage with pending regulatory approvals for long-acting injectable cabotegravir and the dapivirine vaginal ring (approved in South Africa, under review in Kenya). METHODS: From September 2021 to February 2022, we surveyed pregnant and postpartum women enrolled in oral PrEP studies in South Africa and Kenya. We evaluated oral PrEP attitudes and preferences for long-acting PrEP methods in multivariable logistic regression models adjusting for maternal age and country. RESULTS: We surveyed 190 women in South Africa (67% postpartum; median age 27 years [IQR = 22-32]) and 204 women in Kenya (79% postpartum; median age 29 years [IQR = 25-33]). Seventy-five percent of participants reported oral PrEP use within the last 30 days. Overall, forty-nine percent of participants reported negative oral PrEP attributes, including side effects (21% South Africa, 30% Kenya) and pill burden (20% South Africa, 25% Kenya). Preferred PrEP attributes included long-acting method, effectiveness, safety while pregnant and breastfeeding, and free medication. Most participants (75%, South Africa and Kenya) preferred a potential long-acting injectable over oral PrEP, most frequently for a longer duration of effectiveness in South Africa (87% South Africa, 42% Kenya) versus discretion in Kenya (5% South Africa, 49% Kenya). Eighty-seven percent of participants preferred oral PrEP over a potential long-acting vaginal ring, mostly due to concern about possible discomfort with vaginal insertion (82% South Africa, 48% Kenya). Significant predictors of long-acting PrEP preference included past use of injectable contraceptive (aOR = 2.48, 95% CI: 1.34, 4.57), disliking at least one oral PrEP attribute (aOR = 1.72, 95% CI: 1.05, 2.80) and preferring infrequent PrEP use (aOR = 1.58, 95% CI: 0.94, 2.65). CONCLUSIONS: Oral PrEP-experienced pregnant and postpartum women expressed a theoretical preference for long-acting injectable PrEP over other modalities, demonstrating potential acceptability among a key population who must be at the forefront of injectable PrEP rollout. Reasons for PrEP preferences differed by country, emphasizing the importance of increasing context-specific options and choice of PrEP modalities for pregnant and postpartum women.

Understanding factors influencing home pregnancy test use among women in western Kenya: A qualitative analysis.

Background: There are limited data on home pregnancy test use among women in low-and-middle-income countries. A prior survey found that only 20% of women in western Kenya used a home pregnancy test to confirm their pregnancies before going to antenatal care. This qualitative study aims to understand why women do not use home pregnancy tests in early pregnancy. Methods: From April 2021 to July 2021, we interviewed women from four antenatal care clinics in Homa Bay and Siaya counties. We recruited women previously enrolled in the PrEP Implementation for Mothers in Antenatal care (PrIMA) study, a cluster-randomized trial that evaluated the best approaches to implementing PrEP in maternal and child health clinics in Western Kenya (NCT03070600). Interviews were conducted via phone, audio recorded, translated, and transcribed verbatim. We coded and analyzed the transcripts to capture factors influencing women's capability, opportunity, and motivation to use home pregnancy tests. Results: We conducted 48 semistructured interviews with women aged 21-42 years. Twenty-seven women did not use a home pregnancy test in their most recent pregnancy. Seventeen of these women reported not using a home pregnancy test before. Lack of knowledge, mistrust in the accuracy of tests, preferring to rely on signs and symptoms of pregnancy or get a test from the health facility, cost, and accessibility were key barriers to home pregnancy test use. Conclusion: Improving the uptake of home pregnancy testing during early pregnancy will require efforts to enhance community knowledge of test use and associated benefits and reduce cost burdens by making tests more affordable and accessible.

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.

Advanced Methodology for Rapid Isolation of Single Myofibers from Flexor Digitorum Brevis Muscle.

Isolated individual myofibers are valuable experimental models that can be used in various conditions to understand skeletal muscle physiology and pathophysiology at the tissue and cellular level. This report details a time- and cost-effective method for isolation of single myofibers from the flexor digitorum brevis (FDB) muscle in both young and aged mice. The FDB muscle was chosen for its documented history in single myofiber experiments. By modifying published methods for FDB myofiber isolation, we have optimized the protocol by first separating FDB muscle into individual bundles before the digestion, followed by optimizing the subsequent digestion medium conditions to ensure reproducibility. Morphological and functional assessments demonstrate a high yield of isolated FDB myofibers with sarcolemma integrity achieved in a shorter time frame than previous published procedures. This method could be also adapted to other types of skeletal muscle. Additionally, this highly reproducible method can greatly reduce the number of animals needed to yield adequate numbers of myofibers for experiments. Thus, this advanced method for myofiber isolation has the potential to accelerate research in skeletal muscle physiology and screening potential therapeutics "ex vivo" for muscle diseases and regeneration.

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.

Early Antiretroviral Therapy Reduces Severity but Does Not Eliminate Neurodevelopmental Compromise in Children With HIV.

BACKGROUND: Early antiretroviral therapy (ART) during infancy reduces cognitive impairment due to HIV, but the extent of benefit is unclear. SETTING: Children were recruited from hospital and health centers providing HIV care and treatment in Nairobi, Kenya. METHODS: Cognitive, behavioral, and motor outcomes were assessed in children with HIV and early ART (<1 year), children with HIV and late ART (1.5-6 years), and children HIV-unexposed uninfected (CHUU). Domain z scores and odds neurobehavioral impairment (≤15th percentile in CHUU) were compared in adjusted analyses. RESULTS: Children with HIV initiated ART at median ages 0.4 (early ART) and 3.5 years (late ART). Children were assessed at median ages 6.9 (CHUU, N = 61), 6.9 (early ART, N = 54), and 13.5 (late ART; N = 27) years. Children with late ART vs. children with early ART had significantly lower z scores in 7 domains, specifically global cognition, short-term memory, visuospatial processing, learning, nonverbal test performance, executive function, and motor skills (adjusted mean differences, -0.42 to -0.62, P values ≤ 0.05), and had higher odds impairment in 7 domains (adjusted odds ratios [aORs], 2.87 to 16.22, P values ≤ 0.05). Children with early ART vs. CHUU had lower z scores in 5 domains (global cognition, short-term memory, delayed memory, processing speed, and behavioral regulation [adjusted mean differences, -0.32 to -0.88, P values < 0.05]) and higher impairment for 2 domains (short-term memory [aOR, 3.88] and behavioral regulation [aOR 3.46], P values < 0.05). Children with late ART vs. CHUU had lower z scores in 8 domains (adjusted mean differences, -0.57 to -1.05, P values ≤ 0.05), and higher impairment in 7 domains (aORs 1.98 to 2.32, P values ≤ 0.05). CONCLUSION: Early ART in the first year of life attenuates but does not eliminate the neurodevelopmental compromise of HIV.

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.

Lower Neurocognitive Functioning in HIV-Exposed Uninfected Children Compared With That in HIV-Unexposed Children.

BACKGROUND: Perinatal HIV and antiretroviral therapy exposure may influence neurocognitive outcomes, although evidence is mixed and most studies are limited to outcomes in the first 24 months. We compared neurocognitive outcomes in school-aged children who were HIV exposed uninfected (CHEU) with those in children who were HIV unexposed uninfected (CHUU). SETTING: Children were recruited from a health center in Nairobi, Kenya. METHODS: Key inclusion criteria were children aged 5-12 years and confirmed child and maternal HIV status; for CHEU, mothers reported knowing HIV-positive status before or at delivery of the index child. Children underwent a detailed battery of neuropsychological tests and behavioral assessment, and comparisons of scores between CHEU and CHUU were conducted using linear regression. RESULTS: Among 56 CHEU and 65 CHUU, the median age and sex distributions were 6.8 and 7.0 years (P = 0.8) and 48% and 60% girls (P = 0.2), respectively. In analyses adjusted for child's age and sex and caregiver's age, education, and household rent, CHEU had significantly lower mean z scores for global cognitive ability than CHUU [-0.35, 95% confidence interval (CI): -0.64 to -0.05; P = 0.02], short-term memory (-0.44, 95% CI: -0.76 to -0.12; P = 0.008), delayed memory (-0.43, 95% CI: -0.79 to -0.08; P = 0.02), attention (-0.41, 95% CI: -0.78 to -0.05; P = 0.03), and processing speed (-0.76, 95% CI: -1.37 to -0.16; P = 0.01). Models adjusted for child nutritional status, household food security, and orphanhood yielded similar results. CONCLUSIONS: Children exposed to HIV had poorer long-term neurocognitive outcomes than CHUU. These data suggest that long-term studies of neurocognitive and educational attainment in CHEU are warranted.