Understanding acceptance of and adherence to a new formulation of paediatric antiretroviral treatment in the form of pellets (LPV/r)—A realist evaluation

Abstract

Background Improving access to paediatric HIV treatment requires large-scale antiretroviral treatment programmes and medication adapted to infants and children’s needs. The World Health Organisation recommends lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors as first-line treatment for all HIV-infected children younger than three years, usually given as a syrup. A pellet formulation (i.e. tiny cylinders of compressed medication put in capsules) was developed to overcome the syrup formulation’s disadvantages such as bitterness, toxicity and cold storage. This study assessed multi-level factors influencing caregivers’ acceptance of and adherence to lopinavir/ritonavir pellets as well as their underlying mechanisms. Methods A realist evaluation (a theory-driven evaluation method considering the social context and mechanisms of change), embedded in a clinical trial was carried out in three hospital settings in Kenya. Data were collected through document review, observations (n = 34) in home and clinic settings and semi-structured interviews (n = 44) with caregivers and providers. Data analysis was based on realist principles. Results High levels of treatment initiation and adherence were observed. Taste masking, neutral packaging and easy storage made the new formulation highly acceptable. Caregivers developed individual strategies to deliver the treatment, particularly to overcome specific problems e.g. in case of just-weaned babies or food shortage. A refined program theory emerged from the triangulated findings showing that ease of administration combined with increased self-efficacy and competences of the caregivers, and effective provider support contributed to high levels of adherence. Conclusions Formulating combined antiretroviral treatment in the form of pellets is clearly a more acceptable solution for infants and children and their caregivers compared to the syrup. Further research in non-trial settings may shed light on factors related to providers, services and the health system that contribute to better adherence of such formulations.

An Adaptable Framework for Factors Contributing to Medication Adherence: Results from a Systematic Review of 102 Conceptual Frameworks

“…lack of resources, living circumstances) (n=3); Lifestyle factors (i.e. substance abuse) (n=2) Pediatrics patients ( n = 9) 112 – 120 n = 9 112 – 120 n = 5 113 , 114 , 117 , 118 , 120 n = 6 112 , 113 , 115 , 117 , 118 , 120 n = 5 113 , 116 , 118 – 120 n = 8 112 – 116 , 118 – 120 Personal characteristics (i.e., family, caregiver and child characteristics, child’s relationship with caregiver, adult support, child’s personal responsibility) ( n = 6); Cognitive and psychological factors (i.e., beliefs, perception, information, emotion, caregiver acceptance, trust, autonomy, self-efficacy, motivation, plans for future, illness representation, appraisal) ( n = 6); Behavioral factors (i.e., skills – administration routine, coping strategy, rewarding adherence, physical and psychological capability) ( n = 5) Disease control (i.e., number, severity of symptoms, Lazarus effect, prognosis, functional remission) ( n = 3); Patient-specific factors (i.e., time since diagnosis, history of declining health, concrete thinking) ( n = 3); Disease characteristics (i.e., identity, timeline, consequences) ( n = 1) Medication effects (i.e., side effects, effectiveness, experience) ( n = 4); Medication properties (i.e., physical properties, formulation, cost) ( n = 4); Medication regimen (i.e., dosing, duration, frequency, count, type, administration, complexity) ( n = 3) Healthcare system factors (i.e., access, delay, hospitalization, access to health insurance, drug supply adequacy, medical facility) ( n = 5); HCP factors (i.e., relationship, skills, supportive presence, communication, treatment decision) ( n = 3) Social/environmental factors (i.e., social, community, institutional support, stigma, media portraya...…”

Acceptability of a new 4-in-1 Abacavir/Lamivudine/Lopinavir/Ritonavir paediatric fixed-dose combination: the caregiver–child dyads’ perspective

“…This is in line with the results of a detailed realist evaluation of paediatric HIV treatment in the form of pellets. 24 Tailored support has to be specific and practical, to overcome individual problems and initial struggle by caregivers to administer a new formulation. Research has shown that adherence support often suffers from poor communication and a lack of clear instructions on how to take medication or what to take journals.sagepub.com/home/tai TherapeuTic advances in infectious disease the medication with to make it palatable for children.…”

An Evaluation of US Food and Drug Administration’s Program to Register HIV Drugs for Use in Resource-Constrained Settings

“…1 Many of the currently available HIV medicines for children are either tablets or bitter-tasting syrups, which make them difficult to give to children; furthermore, syrups that require refrigeration pose procurement and storage challenges in resource-limited settings. 28,29 Although FDA has registered many pediatric-specific ARTs, such as 2-drug combination pellets that can be sprinkled on food for ease of administration, more are needed, in particular 4-drug combinations to further simplify pediatric therapy, as well as tablets for oral suspension, ideally with masked taste. 28,30 The FDA recently issued a guidance to help manufacturers develop drugs to treat pediatric HIV and the agency stands ready to work with drug companies and the HIV community to advance the availability of pediatric drugs for global use.…”

“…In 2018, there were 160 000 new pediatric infections of HIV and 1.7 million children living with HIV globally, of whom only 54% were receiving therapy . Many of the currently available HIV medicines for children are either tablets or bitter-tasting syrups, which make them difficult to give to children; furthermore, syrups that require refrigeration pose procurement and storage challenges in resource-limited settings . Although FDA has registered many pediatric-specific ARTs, such as 2-drug combination pellets that can be sprinkled on food for ease of administration, more are needed, in particular 4-drug combinations to further simplify pediatric therapy, as well as tablets for oral suspension, ideally with masked taste .…”