Challenges with pediatric antiretroviral therapy administration: Qualitative perspectives from caregivers and HIV providers in Kenya.

BACKGROUND: Current formulations of pediatric antiretroviral therapy (ART) for children with HIV present significant barriers to adherence, leading to drug resistance, ART ineffectiveness, and preventable child morbidity and mortality. Understanding these challenges and how they contribute to suboptimal adherence is an important step in improving outcomes. This qualitative study describes how regimen-related challenges create barriers to adherence and impact families. METHODS: We conducted key informant interviews (KIIs) with 30 healthcare providers and 9 focus group discussions (FGDs) with a total of 72 caregivers, across three public hospitals in Siaya and Mombasa Kenya. The KIIs and FGDs were audio recorded, translated, and transcribed verbatim. The transcripts were hand coded based on emergent and a-priori themes. RESULTS: Caregivers discussed major regimen-related challenges to adherence included poor palatability of current formulations, complex preparation, and administration (including measuring, crushing, dissolving, mixing), complex drug storage, and frequent refill appointments and how these regimen-related challenges contributed to individual and intrapersonal barriers to adherence. Caregivers discussed how poor taste led to child anxiety, refusal of medications, and the need for caregivers to use bribes or threats during administration. Complex preparation led to concerns and challenges about maintaining privacy and confidentiality, especially during times of travel. Providers corroborated this patient experience and described how these challenges with administration led to poor infant outcomes, including high viral load and preventable morbidity. Providers discussed how the frequency of refills could range from every 2 weeks to every 3 months, depending on the patient. Caregivers discussed how these refill frequencies interrupted work and school schedules, risked unwanted disclosure to peers, required use of financial resources for travel, and ultimately were a challenge to adherence. CONCLUSION: These findings highlight the need for improved formulations for pediatric ART to ease the daily burden on caregivers and children to increase adherence, improve child health, and overall quality of life of families.

Assessing COVID-related concerns and their impact on antenatal and delivery care among pregnant women living with HIV in Kenya: a brief report.

BACKGROUND: Some studies indicate that pregnant Kenyan women were concerned about Coronavirus disease 2019 (COVID-19) exposure during maternity care. We assessed concern regarding COVID-19 exposure and any impact on antenatal care (ANC) enrollment and/or hospital delivery among pregnant women living with human immunodeficiency virus (HIV) in Kenya. METHODS: Data were collected from 1,478 pregnant women living with HIV enrolled in prevention of mother to child transmission of HIV (PMTCT) care at 12 Kenyan hospitals from October 2020 to July 2022. Surveys were conducted when women first presented for PMTCT services at the study hospital and asked demographic questions as well as items related to concerns about COVID-19. A 5-point Likert scale (strongly disagree to strongly agree) assessed concerns about COVID-19 exposure and travel challenges. Gestational age at PMTCT enrollment, number of ANC appointments attended, and delivery location were compared among women who expressed COVID-19 concerns and those who did not. RESULTS: Few women reported delaying antenatal care (4.7%), attending fewer antenatal care appointments (5.0%), or having concerns about a hospital-based delivery (7.7%) because of COVID-19. More (25.8%) reported travel challenges because of COVID-19. There were no significant differences in gestational age at enrollment, number of ANC appointments, or rates of hospital-based delivery between women with concerns about COVID-19 and those without, CONCLUSION: Few pregnant women living with HIV expressed concerns about COVID-19 exposure in the context of routine ANC or delivery care. Women with and without concerns had similar care seeking behaviors. The recognized importance of routine ANC care and facility-based deliveries may have contributed to these positive pregnancy indicators, even among women who worried about COVID-19 exposure. TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier NCT04571684.

Assessing user preferences for design characteristics of oral dissolvable strips for pediatric HIV medication: a qualitative study.

BACKGROUND: Current infant antiretroviral therapy formulations pose barriers to daily adherence due to complex weight-based dosing, conspicuous preparation, and poor palatability. These adherence barriers jeopardize adherence, making patients vulnerable to virologic failure, development of drug resistance, and preventable mortality. Our team has previously established proof-of-principle for multi-drug oral dissolvable strips as alternative pediatric antiretroviral formulations with the potential to overcome these challenges and improve pediatric ART adherence and outcomes. The objective of this study was to assess caregiver and provider preferences for oral dissolvable strips and its packaging to inform its development. METHODS: Guided by concepts of user-centered design, we conducted key informant interviews with 30 HIV care providers and focus group discussions targeting caregivers of children < 10 years of age living with HIV at 3 Kenyan hospitals. Key informant interviews and focus group discussions were audio recorded, translated/transcribed verbatim, and hand coded for a-priori and emergent themes. RESULTS: A total of 30 providers and 72 caregivers (caring for 83 children, aged 5 months to 18 years) participated in the study. Caregivers and providers expressed a strong desire for an easier way to administer medication, especially among children too young to swallow tablets whole, and expressed enthusiasm around the idea of oral dissolvable strips. Key preferences included a pleasant taste; one strip per dose; small size with rapid dissolution; clear markings and instructions; and no special storage requirements. For packaging, stakeholders preferred individually wrapped strips within a dispenser. The individual packaging should be durable, waterproof, and easy to dispose of in communal spaces. They should also be easy to open, with clear indications where to open. The packaging holding the strips should be durable, re-usable, accommodating of various refill frequencies, and easy to use for children as young as 6. DISCUSSION: The concept of oral dissolvable strips was highly acceptable to caregivers of children living with HIV and HIV care providers. By engaging stakeholders in an iterative design process starting from the early phases of design and development, we will maximize the likelihood of developing a product that is acceptable to the caregiver and infant, therefore leading to sustainable adherence.

Evaluating the efficacy of the HITSystem 2.1 to improve PMTCT retention and maternal viral suppression in Kenya: Study protocol of a cluster-randomized trial.

BACKGROUND: Gaps in the provision of guideline-adherent prevention of mother-to-child transmission of HIV (PMTCT) services and maternal retention in care contribute to nearly 8000 Kenyan infants becoming infected with HIV annually. Interventions that routinize evidence-based PMTCT service delivery and foster consistent patient engagement are essential to eliminating mother-to-child transmission of HIV. The HITSystem 2.1 is an eHealth intervention that aims to improve retention in PMTCT services and viral load monitoring, using electronic alerts to providers and SMS to patients. This study will evaluate the impact, implementation, and cost-effectiveness of HITSystem 2.1. METHOD: This cluster randomized trial will be conducted at 12 study hospital (6 intervention, 6 control). Pregnant women living with HIV who have initiated PMTCT care ≤36 weeks gestation are eligible. Women enrolled at control hospitals will receive standard-of-care PMTCT services. Women enrolled at intervention hospitals will receive standard-of-care PMTCT services plus enhanced HITSystem 2.1 tracking. Mixed logistic regression models will compare the arms on two primary outcomes: (1) completed guideline-adherence PMTCT services and (2) viral suppression at both delivery and 6 months postpartum. We will assess associations between provider and patient characteristics (disclosure status, partner status, depression, partner support), PMTCT knowledge, and motivation with retention outcomes. Using the RE-AIM model, we will also assess implementation factors to guide sustainable scale-up. Finally, a cost-effectiveness analysis will be conducted. DISCUSSION: This study will provide insights regarding the development and adaptation of eHealth strategies to meet the global goal of eliminating new HIV infections in children and optimizing maternal health through PMTCT services. If efficacious, implementation and cost-effectiveness data gathered in this study will guide scale-up across Kenyan health facilities. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov (NCT04571684) on October 1, 2020.

HIV Drug Resistance in Kenyan Infants Diagnosed With HIV and Their Mothers.

The presence and type of HIV drug resistance mutations among 5 infants diagnosed with HIV were assessed and compared with their mothers' viral mutations. Mother and infant blood samples were sequenced and screened for HIV drug resistance mutations using the Stanford HIV Sequence Database. Three of 5 (60%) mother-infant pairs harbored HIV drug resistance mutations.

Implementing at-birth, point-of-care HIV testing in Kenya: a qualitative study using the Consolidated Framework for Implementation Research.

BACKGROUND: At-birth and point-of-care (POC) testing can expedite early infant diagnosis of HIV and improve infant outcomes. Guided by the Consolidated Framework for Implementation Research (CFIR), this study describes the implementation of an at-birth POC testing pilot from the perspective of implementing providers and identifies the factors that might support and hinder the scale up of these promising interventions. METHODS: We conducted 28 focus group discussions (FGDs) with 48 providers across 4 study sites throughout the course of a pilot study assessing the feasibility and impact of at-birth POC testing. FGDs were audio-recorded, transcribed, and analyzed for a priori themes related to CFIR constructs. This qualitative study was nested within a larger study to pilot and evaluate at-birth and POC HIV testing. RESULTS: Out of the 39 CFIR constructs, 30 were addressed in the FGDs. While all five domains were represented, major themes revolved around constructs related to intervention characteristics, inner setting, and outer setting. Regarding intervention characteristics, the advantages of at-birth POC (rapid turnaround time resulting in improved patient management and enhanced patient motivation) were significant enough to encourage provider uptake and enthusiasm. Challenges at the intervention level (machine breakdown, processing errors), inner settings (workload, limited leadership engagement, challenges with access to information), and outer setting (patient-level challenges, limited engagement with outer setting stakeholders) hindered implementation, frustrated providers, and resulted in missed opportunities for testing. Providers discussed how throughout the course of the study adaptations to implementation (improved channels of communication, modified implementation logistics) were made to overcome some of these challenges. To improve implementation, providers cited the need for enhanced training and for greater involvement among stakeholders outside of the implementing team (i.e., other clinicians, hospital administrators and implementing partners, county and national health officials). Despite provider enthusiasm for the intervention, providers felt that the lack of engagement from leadership within the hospital and in the outer setting would preclude sustained implementation outside of a research setting. CONCLUSION: Despite demonstrated feasibility and enthusiasm among implementing providers, the lack of outer setting support makes sustained implementation of at-birth POC testing unlikely at this time. The findings highlight the multi-dimensional aspect of implementation and the need to consider facilitators and barriers within each of the five CFIR domains. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03435887 . Retrospectively registered on 19 February 2020.

Piloting the Feasibility and Preliminary Impact of Adding Birth HIV Polymerase Chain Reaction Testing to the Early Infant Diagnosis Guidelines in Kenya.

BACKGROUND: In Kenya, standard early infant diagnosis (EID) with polymerase chain reaction (PCR) testing at 6-week postnatal achieves early treatment initiation (<12 weeks) in <20% of HIV+ infants. Kenya's new early infant diagnosis guidelines tentatively proposed adding PCR testing at birth, pending results from pilot studies. METHODS: We piloted birth testing at 4 Kenyan hospitals between November 2017 and November 2018. Eligible HIV-exposed infants were offered both point-of-care and PCR HIV testing at birth (window 0 to <4 weeks) and 6 weeks (window 4-12 weeks). We report the: proportion of infants tested at birth, 6-week, and both birth and 6-week testing; median infant age at results; seropositivity and antiretroviral therapy initiation. RESULTS: Final sample included 624 mother-infant pairs. Mean maternal age was 30.4 years, 73.2% enrolled during antenatal care and 89.9% had hospital deliveries. Among the 590 mother-infants pairs enrolled before 4 weeks postnatal, 452 (76.6%) completed birth testing before 4 weeks, with 360 (79.6%) testing within 2 weeks, and 178 (39.4%) before hospital discharge (0-2 days). Mothers were notified of birth PCR results at a median infant age of 5.4 weeks. Among all 624 enrolled infants, 575 (92.1%) were tested during the 6-week window; 417 (66.8%) received testing at both birth and 6-weeks; and 207 received incomplete testing (93.3% only 1 PCR and 6.7% no PCR). Four infants were diagnosed with HIV, and 3 infants were initiated on antiretroviral therapy early, before 12 weeks of age. CONCLUSIONS: Uptake of PCR testing at birth was high and a majority of infants received repeat testing at 6 weeks of age.

ART Initiation for Infants Diagnosed With HIV Through Point of Care and Conventional Polymerase Chain Reaction Testing in Kenya: A Case Series.

We sought to understand the sequence of testing and treatment among nine infants offered both conventional and point-of-care testing and diagnosed as HIV-positive by 6 months of age in Kenya. One infant received per protocol testing and treatment. Patient-level (late presentation and disengagement), provider-level (reluctance and error/oversight) and system-level (stock outs, errors) challenges delayed diagnosis and treatment. Early point-of-care testing can streamline testing; however, challenges mitigate benefits.

Programmatic evaluation of feasibility and efficiency of at birth and 6-week, point of care HIV testing in Kenyan infant.

BACKGROUND: Testing infants at birth and with more efficient point of care (POC) HIV diagnostic can streamline EID and expedite infant ART initiation. We evaluated the implementation of at birth and 6-week POC testing to assess the effectiveness and feasibility when implemented by existing hospital staff in Kenya. METHODS: Four government hospitals were randomly assigned to receive a GeneXpert HIV-1 Qual (n = 2) or Alere m-PIMA (n = 2) machine for POC testing. All HIV-exposed infants enrolled were eligible to receive POC testing at birth and 6-weeks of age. The primary outcome was repeat POC testing, defined as testing both at birth and 6-weeks of age. Secondary outcomes included predictors of repeat POC testing, POC efficiency (turnaround times of key services), and operations (failed POC results, missed opportunities). RESULTS: Of 626 enrolled infants, 309 (49.4%) received repeat POC testing, 115 (18.4%) were lost to follow up after an at-birth test, 120 (19.2%) received POC testing at 6-weeks only, 80 (12.8%) received no POC testing, and 2 (0.3%) received delayed POC testing (>12 weeks of age). Three (0.4%) were identified as HIV-positive. Of the total 853 POC tests run at birth (n = 424) or 6-weeks (n = 429), 806 (94.5%) had a valid result documented and 792 (98.3%) results had documented maternal notification. Mean time from sample collection to notification was 1.08 days, with 751 (94.8%) notifications on the same day as sample collection. Machine error rates at birth and 6-weeks were 8.5% and 2.5%, respectively. A total of 198 infants presented for care (48 at birth; 150 at 6-weeks) without receiving a POC test, representing missed opportunities for testing. DISCUSSION: At birth POC testing can streamline infant HIV diagnosis, expedite ART initiation and can be implemented by existing hospital staff. However, maternal disengagement and missed opportunities for testing must be addressed to realize the full benefits of at birth POC testing.

Maternal viral load monitoring: Coverage and clinical action at 4 Kenyan hospitals.

BACKGROUND: Kenya's guidelines for prevention of mother-to-child transmission of HIV (PMTCT) recommend routine viral load (VL) monitoring for pregnant and breastfeeding women. METHOD: We assessed PMTCT VL monitoring and clinical action occurring between last menstrual period (LMP) and 6 months postpartum at 4 Kenyan government hospitals. Pregnant women enrolled in the HIV Infant Tracking System from May 2016-March 2018 were included. We computed proportions who received VL testing within recommended timeframes and who received clinical action after unsuppressed VL result. RESULTS: Of 424 participants, any VL testing was documented for 305 (72%) women and repeat VL testing was documented for 79 (19%). Only 115 women (27%) received a guideline-adherent baseline VL test and 27 (6%) received a guideline-adherent baseline and repeat VL test sequence. Return of baseline and repeat VL test results to the facility was high (average 96%), but patient notification of VL results was low (36% baseline and 49% repeat). Clinical action for unsuppressed VL results was even lower: 11 of 38 (29%) unsuppressed baseline results and 2 of 14 (14%) unsuppressed repeat results triggered clinical action. DISCUSSION: Guideline-adherent VL testing and clinical intervention during PMTCT must be prioritized to improve maternal care and reduce the risk of HIV transmission to infants.