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 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.

Data is the currency of R&D, and that currency is now generated and traded globally.

Changes in the understanding of biological science, translational research and corporate business models require a corresponding change in the approach to chemical and biological information management. The concept of operations being partitioned into discrete departments for drug discovery is beginning to be replaced by a translational approach to this process. Pharmaceutical business and organizational models are also constantly evolving. Traditional approaches to transactional systems, transferring data up to a departmental data warehouse, are no longer meeting the needs of pharmaceutical scientists and, thus, IT departments are not considered as relevant to the business. These changes and their impact on information systems, as well as some solutions to the challenges faced, are discussed in this editorial.

Classification of kinase inhibitors using a Bayesian model.

The use of Bayesian statistics to model both general (multifamily) and specific (single-target) kinase inhibitors is investigated. The approach demonstrates an alternative to current computational methods applied to heterogeneous structure/activity data sets. This approach operates rapidly and is readily modifiable as required. A generalized model generated using inhibitor data from multiple kinase classes shows meaningful enrichment for several specific kinase targets. Such an approach can be used to prioritize compounds for screening or to optimally select compounds from third-party data collections. The observed benefit of the approach is finding compounds that are not structurally related to known actives, or novel targets for which there is not enough information to build a specific kinase model. The general kinase model described was built from a basis of mostly tyrosine kinase inhibitors, with some serine/threonine inhibitors; all the test cases used in prediction were also on tyrosine kinase targets. Confirming the applicability of this technique to other kinase families will be determined once those biological assays become available.

Solubility prediction by recursive partitioning.

PURPOSE: To build and test a computational model for predicting small molecule solubility, to improve the cost-effectiveness of the selection of vendor compounds suitable for nuclear magnetic resonance (NMR) screening. METHODS: A simple recursive partitioning decision tree-based classification model was generated utilizing "off-the-shelf" commercial software from Accelrys Inc., with a training set of 1992 compounds based on a series of calculated topologic and physical properties. The predictive ability of the decision tree was then assessed by employing it to classify a test set of 2851 vendor compounds, and the classification was subsequently used to guide the purchase of 686 compounds for the purpose of NMR screening. RESULTS: When the decision tree was used to guide purchasing, the percentage of "acceptable" compounds suitable for NMR screening doubled compared with the use of a simple cLogP cutoff, improving the successful selection rate from 25% to 50%. CONCLUSIONS: A simple recursive partitioning decision tree may successfully be used to improve cost-effectiveness by reducing the wastage associated with the unnecessary purchase of vendor compounds unsuitable for NMR screening because of insolubility.