Pharmacovigilance in Pregnancy Studies, Exposures and Outcomes Ascertainment, and Findings from Low- and Middle-Income Countries: A Scoping Review.

INTRODUCTION: Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet a high burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs. METHODS: We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources. RESULTS: We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries. CONCLUSION: The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring.

Understanding Women's Preferences for Prevention of Mother-to-Child HIV Transmission Services in Kenya.

Background and Objective: Understanding the preferences of women living with HIV (WLH) for the prevention of mother-to-child HIV transmission (PMTCT) services is important to ensure such services are person-centered. Methods: From April to December 2022, we surveyed pregnant and postpartum WLH enrolled at five health facilities in western Kenya to understand their preferences for PMTCT services. WLH were stratified based on the timing of HIV diagnosis: known HIV-positive (KHP; before antenatal clinic [ANC] enrollment), newly HIV-positive (NHP; on/after ANC enrollment). Multivariable logistic regression was used to determine associations between various service preferences and NHP (vs. KHP) status, controlling for age, facility, gravidity, retention status, and pregnancy status. Results: Among 250 participants (median age 31 years, 31% NHP, 69% KHP), 93% preferred integrated versus non-integrated HIV and maternal-child health (MCH) services; 37% preferred male partners attend at least one ANC appointment (vs. no attendance/no preference); 54% preferred support groups (vs. no groups; 96% preferred facility - over community-based groups); and, preferences for groups was lower among NHP (42%) versus KHP (60%). NHP had lower odds of preferring support groups versus KHP (aOR 0.45, 95% CI 0.25-0.82), but not the other services. Conclusion and Global Health Implications: Integrated services were highly preferred by WLH, supporting the current PMTCT service model in Kenya. Further research is needed to explore the implementation of facility-based support groups for WLH as well as the reasons underlying women's preferences.

Cost-effectiveness analysis of alternative screening strategies for the detection of cervical cancer among women in rural areas of Western Kenya.

While the incidence of cervical cancer has dropped in high-income countries due to organized cytology-based screening programs, it remains the leading cause of cancer death among women in Eastern Africa. Therefore, the World Health Organization (WHO) now urges providers to transition from widely prevalent but low-performance visual inspection with acetic acid (VIA) screening to primary human papillomavirus (HPV) DNA testing. Due to high HPV prevalence, effective triage tests are needed to identify those lesions likely to progress and so avoid over-treatment. To identify the optimal cost-effective strategy, we compared the VIA screen-and-treat approach to primary HPV DNA testing with p16/Ki67 dual-stain cytology or VIA as triage. We used a Markov model to calculate the budget impact of each strategy with incremental quality-adjusted life years and incremental cost-effectiveness ratios (ICER) as the main outcome. Deterministic cost-effectiveness analyses show that the screen-and-treat approach is highly cost-effective (ICER 2469 Int$), while screen, triage, and treat with dual staining is the most effective with favorable ICER than triage with VIA (ICER 9943 Int$ compared with 13,177 Int$). One-way sensitivity analyses show that the results are most sensitive to discounting, VIA performance, and test prices. In the probabilistic sensitivity analyses, the triage option using dual stain is the optimal choice above a willingness to pay threshold of 7115 Int$ being cost-effective as per WHO standards. The result of our analysis favors the use of dual staining over VIA as triage in HPV-positive women and portends future opportunities and necessary research to improve the coverage and acceptability of cervical cancer screening programs.

Labour pain relief practice by maternal health care providers at a tertiary facility in Kenya: An institution-based descriptive survey.

BACKGROUND: Although pain relief is a crucial component of modern obstetric care, it remains a poorly established service in sub-Saharan countries such as Kenya. Maternal health care providers have an extensive role to play in meeting the analgesic needs of women during childbirth. This study sought to examine the practice of labour pain relief among Kenyan maternal health care providers. METHODS: This was an institution-based, cross-sectional, descriptive survey. The study included midwives, obstetricians, and anaesthesiologists (n = 120) working at the second-largest tertiary facility in Kenya. A structured, self-administered questionnaire was used. The labour pain relief practice, knowledge, attitude, and perceived barriers to labour pain management were described. RESULTS: One hundred and seventeen respondents participated in the study representing a response rate of 97.5%. More than half of maternal health care providers routinely provided the service of labour pain relief (61.5%). Sixty-four (88.9%) respondents reported providing pharmacological and non-pharmacological methods, while 11.1% provided only pharmacological ones. The most common pharmacological method prescribed was non-opioids (12.8%). The most preferred non-pharmacological method of pain management was touch and massage (93.8%). Regional analgesia was provided by 3.4% of the respondents. More than half of the respondents (53%) had poor knowledge of labour pain relief methods. Almost all (94%) of the respondents had a positive attitude towards providing labour pain relief. Non-availability of drugs and equipment (58.1%), lack of clear protocols and guidelines (56.4%), and absence of adequate skilled personnel (55.6%) were reported as the health system factors that hinder the provision of labour analgesia. CONCLUSIONS: More than half of maternal health care providers routinely relieve labour pain. Epidural analgesia is still relatively underutilized. There is a need to develop institutional labour pain management protocols to meet the analgesic needs of women during childbirth.

The use, adherence, and evaluation of interactive text-messaging among women admitted to prevention of mother-to-child transmission of HIV care in Kenya (WelTel PMTCT).

BACKGROUND: To improve future mobile health (mHealth) interventions in resource-limited settings, knowledge of participants' adherence to interactive interventions is needed, but previous studies are limited. We aimed to investigate how women in prevention of mother-to-child transmission of HIV (PMTCT) care in Kenya used, adhered to, and evaluated an interactive text-messaging intervention. METHODS: We conducted a cohort study nested within the WelTel PMTCT trial among 299 pregnant women living with HIV aged ≥ 18 years. They received weekly text messages from their first antenatal care visit until 24 months postpartum asking "How are you?". They were instructed to text within 48 h stating that they were "okay" or had a "problem". Healthcare workers phoned non-responders and problem-responders to manage any issue. We used multivariable-adjusted logistic and negative binomial regression to estimate adjusted odds ratios (aORs), rate ratios (aRRs) and 95% confidence intervals (CIs) to assess associations between baseline characteristics and text responses. Perceptions of the intervention were evaluated through interviewer-administered follow-up questionnaires at 24 months postpartum. RESULTS: The 299 participants sent 15,183 (48%) okay-responses and 438 (1%) problem-responses. There were 16,017 (51%) instances of non-response. The proportion of non-responses increased with time and exceeded 50% around 14 months from enrolment. Most reported problems were health related (84%). Having secondary education was associated with reporting a problem (aOR:1.88; 95%CI: 1.08-3.27) compared to having primary education or less. Younger age (18-24 years) was associated with responding to < 50% of messages (aOR:2.20; 95%CI: 1.03-4.72), compared to being 35-44 years. Women with higher than secondary education were less likely (aOR:0.28; 95%CI: 0.13-0.64), to respond to < 50% of messages compared to women with primary education or less. Women who had disclosed their HIV status had a lower rate of non-response (aRR:0.77; 95%CI: 0.60-0.97). In interviews with 176 women, 167 (95%) agreed or strongly agreed that the intervention had been helpful, mainly by improving access to and communication with their healthcare providers (43%). CONCLUSION: In this observational study, women of younger age, lower education, and who had not disclosed their HIV status were less likely to adhere to interactive text-messaging. The majority of those still enrolled at the end of the intervention reported that text-messaging had been helpful, mainly by improving access to healthcare providers. Future mHealth interventions aiming to improve PMTCT care need to be targeted to attract the attention of women with lower education and younger age.

Preferences of Pregnant and Postpartum Women for Differentiated Service Delivery in Kenya.

BACKGROUND: Differentiated service delivery models are implemented by HIV care programs globally, but models for pregnant and postpartum women living with HIV (PPWH) are lacking. We conducted a discrete choice experiment to determine women's preferences for differentiated service delivery. SETTING: Five public health facilities in western Kenya. METHODS: PPWH were enrolled from April to December 2022 and asked to choose between pairs of hypothetical clinics that differed across 5 attributes: clinic visit frequency during pregnancy (monthly vs. every 2 months), postpartum visit frequency (monthly vs. only with routine infant immunizations), seeing a mentor mother (each visit vs. as needed), seeing a clinician (each visit vs. as needed), and basic consultation cost (0, 50, or 100 Kenya Shillings [KSh]). We used multinomial logit modeling to determine the relative effects (ß) of each attribute on clinic choice. RESULTS: Among 250 PPWH (median age 31 years, 42% pregnant, 58% postpartum, 20% with a gap in care), preferences were for pregnancy visits every 2 months (ß = 0.15), postpartum visits with infant immunizations (ß = 0.36), seeing a mentor mother and clinician each visit (ß = 0.05 and 0.08, respectively), and 0 KSh cost (ß = 0.39). Preferences were similar when stratified by age, pregnancy, and retention status. At the same cost, predicted market choice for a clinic model with fewer pregnant/postpartum visits was 75% versus 25% for the standard of care (ie, monthly visits during pregnancy/postpartum). CONCLUSION: PPWH prefer fewer clinic visits than currently provided within the standard of care in Kenya, supporting the need for implementation of differentiated service delivery for this population.

Comparing adverse maternal and perinatal outcomes in primary caesarean delivery during first versus second-stage of labour in Kenya: An institution-based cohort study.

BACKGROUND: As caesarean delivery rates continue to increase globally, so are the number of second-stage caesarean deliveries. Second-stage caesareans may carry additional risk of complications for both the mother and fetus owing to fetal head impaction into the maternal pelvis and manipulations required for delivery. So far, data on this procedure's outcomes from low resource countries are limited. OBJECTIVES: To compare adverse maternal and perinatal outcomes between second-stage and first-stage of labour intrapartum primary caesarean deliveries over 12 months at a tertiary referral obstetric hospital in Kenya. METHODS: In a hospital-based cohort study, 222 women with singleton, cephalic presenting fetuses at term gestation who had intrapartum primary caesarean delivery during active labour were recruited post-partum. Second-stage caesarean deliveries (73) were compared to 149 first-stage caesarean deliveries. The proportion of caesarean deliveries in the second-stage of labour was estimated and the adverse maternal and perinatal outcomes were compared. The study was conducted from August 2021 to July 2022 at the Moi Teaching and Referral Hospital, Eldoret. RESULTS: The proportion of second-stage caesarean deliveries among intrapartum primary caesarean deliveries was 4.3% [95% CI: 2.9% - 4.7%]. Compared to first-stage caesarean deliveries, second-stage caesarean deliveries had a significantly higher risk of adverse maternal outcomes (RR 3.272, 95% CI 2.28-4.71, P < 0.001), including intraoperative trauma, atony, blood transfusion, and a postoperative hospital stay of more than three days. Additionally, there was a higher risk of adverse perinatal outcomes (RR 2.748, 95% CI 2.45-4.50, P < 0.001), including increased risk of a 5-min APGAR ≤3, admission to NBU, and neonatal death. CONCLUSIONS: An increased risk of adverse maternal and perinatal outcomes is associated with primary second-stage caesarean deliveries compared to primary first-stage caesarean deliveries.

Institutional capacity to prevent and manage research misconduct: perspectives from Kenyan research regulators.

BACKGROUND: Research misconduct i.e. fabrication, falsification, and plagiarism is associated with individual, institutional, national, and global factors. Researchers' perceptions of weak or non-existent institutional guidelines on the prevention and management of research misconduct can encourage these practices. Few countries in Africa have clear guidance on research misconduct. In Kenya, the capacity to prevent or manage research misconduct in academic and research institutions has not been documented. The objective of this study was to explore the perceptions of Kenyan research regulators on the occurrence of and institutional capacity to prevent or manage research misconduct. METHODS: Interviews with open-ended questions were conducted with 27 research regulators (chairs and secretaries of ethics committees, research directors of academic and research institutions, and national regulatory bodies). Among other questions, participants were asked: (1) How common is research misconduct in your view? (2) Does your institution have the capacity to prevent research misconduct? (3) Does your institution have the capacity to manage research misconduct? Their responses were audiotaped, transcribed, and coded using NVivo software. Deductive coding covered predefined themes including perceptions on occurrence, prevention detection, investigation, and management of research misconduct. Results are presented with illustrative quotes. RESULTS: Respondents perceived research misconduct to be very common among students developing thesis reports. Their responses suggested there was no dedicated capacity to prevent or manage research misconduct at the institutional and national levels. There were no specific national guidelines on research misconduct. At the institutional level, the only capacity/efforts mentioned were directed at reducing, detecting, and managing student plagiarism. There was no direct mention of the capacity to manage fabrication and falsification or misconduct by faculty researchers. We recommend the development of Kenya code of conduct or research integrity guidelines that would cover misconduct.

The effect of an interactive weekly text-messaging intervention on retention in prevention of mother-to-child transmission of HIV care: a randomised controlled trial (WelTel PMTCT).

Retention in prevention of mother-to-child transmission (PMTCT) care is critical to prevent vertical HIV transmission and reduce morbidity and mortality of mother-infant pairs. We investigated whether weekly, interactive text-messaging improved 18-month postpartum retention in PMTCT care. This randomised, two-armed, parallel trial was conducted at six PMTCT clinics in western Kenya. Pregnant women with HIV at least 18 years of age with access to a mobile phone, able to text-message, or had somebody who could text on their behalf, were eligible. Participants were randomly assigned at a 1:1 ratio in block sizes of four to the intervention or control group. The intervention group received weekly text messages asking "How are you?" ("Mambo?" in Swahili) and were requested to respond within 48 h. Healthcare workers called women who indicated a problem or did not respond. The intervention was administered up to 24 months after delivery. Both groups received standard care. The primary outcome was retention in care at 18 months postpartum (i.e., clinic attendance 16-24 months after delivery based on data from patient files, patient registers and Kenya's National AIDS and STI Control Programme database), which was analysed by intention-to-treat. Researchers and data collectors were masked to group assignment, while healthcare workers were not. Between June 25th, 2015, and July 5th, 2016, we randomly assigned 299 women to the intervention and 301 to standard care only. Follow-up concluded on July 26th, 2019. The proportion of women retained in PMTCT care at 18 months postpartum was not significantly different between the intervention (n = 210/299) and control groups (n = 207/301) (risk ratio 1.02, 95% confidence interval 0.92-1.14, p = 0.697). No adverse events related to the mobile phone intervention were reported. Weekly, interactive text-messaging was not associated with improved retention in PMTCT care at 18 months postpartum or linkage to care up to 30 months postpartum in this setting. (ISRCTN No. 98818734).

Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Maternal and child health indicators in primary healthcare facilities: Findings in a health systems quasi-experimental study in western Kenya.

Background and purpose: Maternal and infant mortality are higher in low-income than in high-income countries due to weak health systems. The objective of this study was to improve access, utilization and quality of Maternal and Child Health care through a predesigned Enhanced Health Care System (EHC) that embodies the World Health Organization (WHO) pillars of the health system. Design and methodology: This study was conducted in two dispensaries in the Counties of Busia and Bungoma in Kenya as intervention sites and in four control clusters in Kakamega, Uasin Gishu, Trans Nzoia and Elgeyo Marakwet Counties. The study population was pregnant women and their children delivered over the study period in the intervention and control clusters.A quasi-experimental study design was used to conduct the study between 2015 and 2020 to compare the outcomes of the implementation of the EHC using the Find Link Treat and Retain (FLTR) strategy in one cluster, community owned initiatives in the other cluster and four control clusters at baseline and at the end of the study. A baseline survey was conducted in year one and an end line survey in the fifth year. Continuous data collection on maternal and childhood health indicators was done in all the six clusters and comparison made at the end of the study between the clusters. Results: We found a 26%, 10.3% and 0.8% increase in antenatal care (ANC) attendance in the intervention clusters of Obekai, Kabula and control clusters respectively. There was a 28.2%, 5.8% and 17.0% increase in attendance of 4+ ANC clinics of Obekai, Kabula and control clusters respectively. There was a 24% and 13% increase in Obekai and Kabula respectively in contraceptive use and a 2% decrease in contraceptive use in the control locations. There was a 38.2%, 25.6% and 34.7% increase in facility deliveries over the study period in Obekai, Kabula and control clusters respectively. There was a marked increase in immunization coverage in the intervention clusters of Obekai and Kabula compared to a significant decrease in control clusters for BCG, polio, pentavalent and measles. Conclusions and recommendations: In conclusion, use of the health systems approach in health care provision provides a holistic improvement in access and utilization of health services and in the improvement of health indicators.We do recommend that a systems approach be used in health services delivery to improve access, utilization and quality of health care provision at community and primary care levels.

Predicting neurodevelopmental risk in children born to mothers living with HIV in Kenya: protocol for a prospective cohort study (Tabiri Study).

INTRODUCTION: For the growing number of children with in utero and postpartum exposure to HIV and/or antiretrovirals, it is unclear which exposures or risk factors play a significant role in predicting worse neurodevelopmental outcomes. This protocol describes a prospective longitudinal cohort study of infants born to mothers living with HIV and those born to mothers without HIV. We will determine which risk factors are most predictive of child neurodevelopment at 24 months. We aim to create a risk assessment tool to help predict which children are at risk for worse neurodevelopment outcomes. METHODS AND ANALYSIS: This study leverages an existing Kenyan cohort to prospectively enrol 500 children born to mothers living with HIV and 500 to those without HIV (n=1000 total) and follow them from birth to age 24 months. The following factors will be measured every 6 months: infectious morbidity and biological/sociodemographic/psychosocial risk factors. We will compare these factors between the two groups. We will then measure and compare neurodevelopment within children in both groups at 24 months of age using the Child Behaviour Checklist and the Bayley Scales of Infant and Toddler Development, third edition. Finally, we will use generalised linear mixed modelling to quantify associations with neurodevelopment and create a risk assessment tool for children ≤24 months. ETHICS AND DISSEMINATION: The study is approved by the Moi University's Institutional Research and Ethics Committee (IREC/2021/55; Approval #0003892), Kenya's National Commission for Science, Technology and Innovation (NACOSTI, Reference #700244) and Indiana University's Institutional Review Board (IRB Protocol #110990). This study carries minimal risk to the children and their mothers, and all mothers will provide written consent for participation in the study. Results will be disseminated to maternal child health clinics within Uasin Gishu County, Kenya and via papers submitted to peer-reviewed journals and presentation at international conferences.

Health related quality of life among pregnant women living with HIV in Kenya, results from comparing a patient generated index and the Euroqol 5 dimension 3 level.

BACKGROUND: Standardized tools are used to measure health-related quality of life (HRQoL) and they focus on selected physical, emotional, and social functioning. This approach may miss out on the heterogeneity of HRQoL among various sub-populations. The patient-generated index (PGI) is a tool used to measure HRQoL based on patients' expectations. Among patients living with HIV, HRQoL is an important indicator as the world moves beyond the UNAIDS 90-90-90 goals, towards the so-called fourth 90 that aims at good HRQoL. We compared the PGI and the Euroqol 5 Dimension 3-level (EQ-5D-3L) to identify areas of importance to pregnant women living with HIV affecting thier HRQoL. METHODS: Through convenience sampling, we surveyed 100 pregnant women living with HIV attending antenatal and postnatal clinics in Western Kenya, using both the PGI and the EQ-5D-3L questionnaires. A PGI score and EQ-5D-3L index were generated for each participant. Data from the PGI was also summarized into themes. The PGI scores and EQ-5D-3L index scores were correlated using Pearson correlation. RESULTS: From the PGI tool, 64% of the women reported having two to three main priority areas of their lives affected by their HIV status. These areas centered on themes of economic wellbeing (84% of the women), physical health (58%), psychological/emotional health (49%), and relationships (28%). The mean PGI score was 2.01 [SD = 1.10; median 1.10]. The majority of the women reported having no problems in any of the 5 dimensions captured in the EQ-5D-3L. The mean EQ-5D-3L score was 0.94 [SD = 1.10; median 1.00]. Both the EQ-5D-3L and the PGI showed less than perfect HRQoL. There was no correlation between the PGI and the EQ-5D-3L scores. CONCLUSION: The PGI may capture aspects of contextual social and emotional life for Kenyan pregnant women living with HIV that are not identified by generic tools. Highlighting areas of importance to patients' HRQoL is key as focus shifts towards the fourth 90 and may also inform the design of care programs aligned to patient needs.

Improving maternal and child health outcomes through a community involvement strategy in Kabula location, Bungoma County, Kenya.

Background: Maternal, fetal and neonatal mortality are higher in low-income compared to high-income countries due to weak health systems including poor access and utilization of health services. Despite enormous recent improvements in maternal, neonatal and under five children health indicators, more rapid progress is needed to meet the targets including the Sustainable Development Goal 3(SDG). In Kenya these indicators are still high and comprehensive systems are needed to attain these goals. Objective: To facilitate innovative partnerships in health care provision and to assess trends in access, utilization and quality of Maternal and Child Health care through the health systems approach using community owned initiatives including use of community owned resourse persons (CORPs), establishment of Community Based Organisations (CBOs) and Income Generating Activities(IGAs). Study site: This was implemented in Kabula location, Bungoma County, Kenya between January 2016 and April 2019. Study population: Pregnant women, newborns and under-five children living in Kabula location identified by Community Owned Resource Persons (CORPs). Methods: A prospective study to show trends in maternal, neonatal and infant outcomes through the implementation of community owned initiatives. Findings: General, under five and antenatal clinic attendance increased four fold in 2016,2017 and 2018. There was a 76% full immunization coverage with 97% BCG and 84% Polio coverage respectively among children studied. There was an 87% facility delivery rate among the pregnant women enrolled in the study. Conclusions: Trends in Maternal and under-five health indicators in Kabula showed improvements over the study period following the implementation of the community owned initiatives and community participation. Recommendations: The community owned initiatives as implemented in this study is useful in primary care and universal health coverage programs in health care delivery systems in LMICs.

The effect of weekly interactive text-messaging on early infant HIV testing in Kenya: a randomised controlled trial (WelTel PMTCT).

Mother-to-child transmission of HIV remains a significant concern in Africa despite earlier progress. Early infant diagnosis (EID) of HIV is crucial to reduce mortality among infected infants through early treatment initiation. However, a large proportion of HIV-exposed infants are still not tested in Kenya. Our objective was to investigate whether weekly interactive text-messages improved prevention of mother-to-child transmission (PMTCT) of HIV care outcomes including EID HIV testing. This multicentre, parallel-group, randomised, open-label trial included six antenatal care clinics across western Kenya. Pregnant women living with HIV, aged 18 years or older, with mobile phone access, were randomised in a 1:1 ratio to weekly text messages that continued until 24 months postpartum, asking "How are you?" ("Mambo?") to which they were asked to respond within 48 h, or a control group. Healthcare workers contacted participants reporting problems and non-responders by phone. Participants in both groups received routine PMTCT care. The prespecified secondary outcome reported in this paper is EID HIV testing by eight weeks of age (blinded outcome assessment). Final 24-months trial results will be published separately. We estimated risk ratios using Poisson regression with robust standard errors. Between June 2015-July 2016, we screened 735 pregnant women, of whom 600 were enrolled: 299 were allocated to the intervention and 301 to the control group. By eight weeks of age, the uptake of EID HIV testing out of recorded live births was 85.5% in the intervention and 84.7% in the control group (71.2% vs. 71.8% of participants randomised, including miscarriages, stillbirths, etc.). The intention-to-treat risk ratio was 0.99; 95% CI: 0.90-1.10; p = 0.89. The proportion of infants diagnosed with HIV was 0.8% in the intervention and 1.2% in the control group. No adverse events were reported. We found no evidence to support that the WelTel intervention improved EID HIV testing. A higher uptake of EID testing than expected in both groups may be a result of lower barriers to EID testing and improved PMTCT care in western Kenya, including the broader standard use of mobile phone communication between healthcare workers and patients. (ISRCTN No. 98818734. Funded by the European-Developing Countries Clinical Trial Partnership and others).

Integrating Prevention of Mother-to-Child Transmission of HIV Care into General Maternal Child Health Care in Western Kenya.

BACKGROUND: Health systems integration is becoming increasingly important as the global health community transitions from acute, disease-specific health programming to models of care built for chronic diseases, primarily designed to strengthen public-sector health systems. In many countries across sub-Saharan Africa, including Kenya, prevention of mother-to-child transmission of HIV (pMTCT) services are being integrated into the general maternal child health (MCH) clinics. The objective of this study was to evaluate the benefits and challenges for integration of care within a developing health system, through the lens of an evaluative framework. METHODS: A framework adapted from the World Health Organization's six critical health systems functions was used to evaluate the integration of pMTCT services with general MCH clinics in western Kenya. Perspectives were collected from key stakeholders, including pMTCT and MCH program leadership and local health providers. The benefits and challenges of integration across each of the health system functions were evaluated to better understand this approach. RESULTS: Key informants in leadership positions and MCH staff shared similar perspectives regarding benefits and challenges of integration. Benefits of integration included convenience for families through streamlining of services and reduced HIV stigma. Concerns and challenges included confidentiality issues related to HIV status, particularly in the context of high-volume, crowded clinical spaces. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: The results from this study highlight areas that need to be addressed to maximize the effectiveness and clinical flow of the pMTCT-MCH integration model. The lessons learned from this integration may be applied to other settings in sub-Saharan Africa attempting to integrate HIV care into the broader public-sector health system.

Novel concepts in cervical cancer screening: a comparison of VIA, HPV DNA test and p16INK4a/Ki-67 dual stain cytology in Western Kenya.

BACKGROUND: Screening of unvaccinated women remains essential to mitigate the high morbidity/mortality of cervical cancer. Here, we compared visual inspection with acetic acid (VIA), recommended by WHO as the most cost-effective screening approach in LMICs, with HPV-based screening, and usage of p16INK4a/Ki-67 dual stain cytology. METHODS: We prospectively enrolled women participating in a VIA-based cervical cancer screening program in two peri-urban health centers of Kenya. Consenting women had a VIA examination preceded by collection of a liquid-based cytology sample from the cervix stored in PreservCyt medium (Hologic®). Analysis of all samples included a hrHPV DNA test and evaluation of a p16INK4a /Ki-67 (CINtecPLUS®) dual stained slide that was prepared using the ThinPrep® 2000 Processor and evaluated by a pathologist trained in the methodology. RESULTS: In 701 of a total of 800 women aged 18-64 years, all three investigations were performed and data could be analyzed. The HPV, VIA and dual stain cytology positivity were 33%, 7%, and 2% respectively. The HPV positivity rate of VIA positive cases was 32%. The five most common HPV types were HPV16, 52, 68, 58 and 35. The OR among HIV infected women of an HPV infection, VIA positivity and positive dual stain cytology were 2.6 (95%CI 1.5-4.3), 1.9 (95%CI 0.89-4.4) and 3.4 (95%CI 1.07-10.9) respectively. The sensitivity of VIA to detect a p16INK4a/Ki-67 positive transforming infection was 13% (95%CI 2-38). CONCLUSIONS: Primary HPV testing appears feasible and should be considered as a primary screening test also in LMICs. The poor sensitivity of VIA renders it unsuitable as a triage test for HPV positive women. The utility of p16INK4a/Ki-67 dual stain cytology as a triage test for HPV positive women in LMICs should be further studied.

Perceptions of occurrence of research misconduct and related factors among Kenyan investigators engaged in HIV research.

We report on occurrence and correlates of self-reported research misconduct (RM) by 100 Kenyan researchers who had received ethics approval for an HIV research in the 5 years preceding the survey. The survey used the Scientific Misconduct Questionnaire-Revised tool uploaded on a Research Electronic Data Capture (REDCAP) platform. The response rate was low at 17.3% (100 out of 577) with 53.9% reporting awareness of an incident of RM in the preceding 5 years. Awareness was associated with being in academia, perception of vulnerability to being caught, and the severity of possible punishment, if discovered. Two-thirds (68.3%) reported ever-involvement in any misconduct. Self-report of involvement in misconduct was associated with knowledge of rules and procedures on RM and a disposition to support such rules and regulations. Nearly 36% reported ever-involvement infabrication, falsification and/or plagiarism (FFP). Self-report of ever-involvement in FFP was associated with number of years in the academic position, perceived likelihood of being caught, and the perceived severity of the sanctions, if caught. We conclude that the occurrence of RM is not uncommon, and efforts to create awareness about RM as well as to establish institutional structures and policies on RM are needed.

Social concerns related to HIV status disclosure and participation in the prevention of mother-to-child transmission of HIV care among pregnant women in Kenya.

BACKGROUND: Social concerns about unintentional HIV status disclosure and HIV-related stigma are barriers to pregnant women's access to prevention of mother-to-child transmission of HIV (PMTCT) care. There is limited quantitative evidence of women's social and emotional barriers to PMTCT care and HIV disclosure. We aimed to investigate how social concerns related to participation in PMTCT care are associated with HIV status disclosure to partners and relatives among pregnant women living with HIV in western Kenya. METHODS: A cross-sectional study, including 437 pregnant women living with HIV, was carried out at enrolment in a multicentre mobile phone intervention trial (WelTel PMTCT) in western Kenya. Women diagnosed with HIV on the day of enrolment were excluded. To investigate social concerns and their association with HIV disclosure we used multivariable-adjusted logistic regression, adjusted for sociodemographic and HIV-related characteristics, to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The majority (80%) had disclosed their HIV status to a current partner and 46% to a relative. Older women (35-44 years) had lower odds of disclosure to a partner (OR = 0.15; 95% CI: 0.05-0.44) compared to women 18-24 years. The most common social concern was involuntary HIV status disclosure (reported by 21%). Concern about isolation or lack of support from family or friends was reported by 9%, and was associated with lower odds of disclosure to partners (OR = 0.33; 95% CI: 0.12-0.85) and relatives (OR = 0.37; 95% CI: 0.16-0.85). Concern about separation (reported by 5%; OR = 0.17; 95% CI: 0.05-0.57), and concern about conflict with a partner (reported by 5%; OR = 0.18; 95% CI: 0.05-0.67), was associated with lower odds of disclosure to a partner. CONCLUSIONS: Compared to previous reports from Kenya, our estimated disclosure rate to a partner is higher, suggesting a possible improvement over time in disclosure. Younger pregnant women appear to be more likely to disclose, suggesting a possible decreased stigma and more openness about HIV among younger couples. Healthcare providers and future interventional studies seeking to increase partner disclosure should consider supporting women regarding their concerns about isolation, lack of support, separation, and conflict with a partner. PMTCT care should be organized to ensure women's privacy and confidentiality.

Effects of social health insurance on access and utilization of obstetric health services: results from HIV+ pregnant women in Kenya.

BACKGROUND: Reducing maternal morbidity and mortality remains a top global health agenda especially in high HIV/AIDS endemic locations where there is increased likelihood of mother to child transmission (MTCT) of HIV. Social health insurance (SHI) has emerged as a viable option to improve population access to health services, while improving outcomes for disenfranchised populations, particularly HIV+ women. However, the effect of SHI on healthcare access for HIV+ persons in limited resource settings is yet to undergo rigorous empirical evaluation. This study analyzes the effect of health insurance on obstetric healthcare access including institutional delivery and skilled birth attendants for HIV+ pregnant women in Kenya. METHODS: We analyzed cross-sectional data from HIV+ pregnant women (ages 15-49 years) who had a delivery (full term, preterm, miscarriage) between 2008 and 2013 with their insurance enrollment status available in the electronic medical records database of a HIV healthcare system in Kenya. We estimated linear and logistic regression models and implemented matching and inverse probability weighting (IPW) to improve balance on observable individual characteristics. Additionally, we estimated heterogeneous effects stratified by HIV disease severity (CD4 < 350 as "Severe HIV disease", and CD4 > 350 otherwise). FINDINGS: Health Insurance enrollment is associated with improved obstetric health services utilization among HIV+ pregnant women in Kenya. Specifically, HIV+ pregnant women covered by NHIF have greater access to institutional delivery (12.5-percentage points difference) and skilled birth attendants (19-percentage points difference) compared to uninsured. Notably, the effect of NHIF on obstetric health service use is much greater for those who are sicker (CD4 < 350) - 20 percentage points difference. CONCLUSION: This study confirms conceptual and practical considerations around health insurance and healthcare access for HIV+ persons. Further, it helps to inform relevant policy development for health insurance and HIV financing and delivery in Kenya and in similar countries in sub-Saharan Africa in the universal health coverage (UHC) era.