Assessing the adoption of lopinavir/ritonavir oral pellets for HIV‐positive children in Zimbabwe

Abstract

IntroductionHeat‐stable lopinavir/ritonavir (LPV/r) oral pellets were developed to overcome challenges with administration and storage experienced with previously available tablet and syrup forms of LPV/r prescribed to paediatric HIV patients. We report on the adoption of LPV/r pellets for infants living with HIV in the public sector antiretroviral therapy (ART) programme in Zimbabwe.MethodsInfants aged three months to three years who had been prescribed a LPV/r‐based regimen (including ART‐naïve patients) in fourteen facilities across the country were eligible to receive the pellets. Caregivers were counselled on the new formulation and provided with administration guides. A caregiver questionnaire was administered three to four months after the child initiated on pellets. Data were also extracted from patient ART records.Results and discussionOne hundred and fifty‐seven children were enrolled (median age: 21 months; interquartile range 11.8 to 29.4). Survey data from 74 caregivers were included for analysis. Eighty‐one per cent of the caregivers preferred pellets while 19% preferred the syrup formulation. Eighty‐nine per cent assessed their child's response to taking the pellets as good or very good. Overall, 46% did not report any challenges while 54% reported one or more challenges with using the pellets. Difficulties with administration included: poor taste (36%; 26 participants); swallowing pellets (16%; 12 participants); finishing the dose (14%; 10 participants); and opening the capsule (10%; seven participants). Caregivers who were not confident to instruct others on pellet administration were 5.64 (95% confidence interval 1.45 to 21.95, p = 0.013) times as likely to experience a challenge.ConclusionsA large proportion of caregivers preferred pellets to other formulations of LPV/r and reported a good response to pellets; however, they also reported challenges with administration. Counselling should focus on ensuring that caregivers can confidently administer pellets and are able to instruct others, to ensure high uptake and good adherence to treatment. LPV/r pellets may be an acceptable substitute for other available forms of LPV/r for eligible children under three years if they are currently on or in need of LPV/r‐containing regimens; however, challenges with administration still highlight the need for improved drug formulations for paediatric ART patients.

Optimising neonatal antiretroviral therapy using raltegravir: a qualitative analysis of healthcare workers’ and caregivers’ perspectives

“… 7 Caregivers in our study reported a preference for granule formulations compared with other available ART formulations for infants. This aligns with another study from Zimbabwe that found caregivers generally preferred LPV/r in the form of granules over liquid, 10 most likely due to granules masking the unpleasant medication taste. Previous research has stated that palatability is one of the main challenges with paediatric medications, leaving caregivers struggling to administer bitter-tasting medications.…”

“…The Zimbabwe LPV/r study also recommended appropriate counselling to ensure caregivers can confidently administer granules. 10 Ensuring appropriate preparation, administration and dosing of RAL granules in neonates is essential for preventing the development of HIV drug resistance to RAL, which may impact the effectiveness of the DTG-based regimens that are currently the recommended first-line regimens for infants and children ≥4 weeks of age. 4 HCWs requested that the trainings are standardised and that they are trained directly by trainers, as opposed to having previously trained HCWs teaching them how to use RAL.…”

Prioritising the most needed paediatric antiretroviral formulations: the PADO4 list

“…Of note, viral suppression rates have been somewhat lower in younger children initiating ART, for whom administration of and adherence to LPVr pellets appears to be more challenging. Sites using the formulation as part of routine care programs report similar viral suppression rates as with LPVr syrup, due to persisting administration and palatability issues 17 .…”

Drug Formulation for Pediatric Oral Antimicrobial Agents in Japan: Current Status, Prospects, and Challenges

“…55,57 In addition, attempts have been made to develop "mini-tab sprinkles" (pellets stored in capsules) as an oral solid formulation to replace syrups. 58,59 For particularly serious infections, such as soil-transmitted helminths and HIV, clinical trials are sometimes conducted during drug development to ensure pediatric acceptability of pellet capsules (sprinkle capsules) and chewable tablets. 60,61…”