Abacavir Dosing in Neonates from Birth to 3 Months of Life

Author:

Bekker Adrie,Capparelli Edmund V.,Violari Avy,Cotton Mark F.,Cababasay Mae,Wang Jiajia,Mathiba Ruth,Wiesner Lubbe,Wiznia Andrew,Samson Pearl,Browning Renee,Moye Jack,Nakwa Firdose,Decloedt Eric,Rabie Helena,Mirochnick Mark,Cressey Tim

Publisher

Elsevier BV

Reference41 articles.

1. PNA or chronological age is the time elapsed 210 after birth and PMA is defined as gestational age at birth plus PNA 15;The final model was 211 evaluated using the bootstrap resampling technique and a visual predictive check (VPC)

2. To determine the optimal weight-band dosing for neonates, a 218 population of virtual neonates with birth weights of 2�0, 2�5, 3�0, 3�5, 4�0 and 4�5 kg was simulated 219 during the first four weeks of life. A dose requiring no adjustment throughout the first four weeks 220 of life, i.e., independent of weight gain was considered advantageous. For both scenarios, body 221 weights were adjusted for based on the UK-WHO Growth Chart 7 contingent on their birth 222 weights;Model Simulations: Monte Carlo simulations were run in NONMEM 16 for infants receiving ABC age: 2-3 kg, 3-4 kg and 4-5 kg

3. While the WHO recommends a weight band dose for 340 children >4 weeks and ?3 kg, ABC weight-band dosing is not available for infants <4 weeks of age. 341 Based on our simulations, we propose an optimal ABC weight-band dosing strategy for term 342 neonates of 8 mg (2-3 kg), 10 mg (3-4 kg) and 12 mg (4-5 kg) twice daily. This strategy uses the 343 same dose of ABC liquid from birth to 4 weeks of life (based on birth weight) which simplify 344 treatment during this challenging period. Moreover, if we administer ABC from birth, instead of 345 ZDV, this would eliminate the switch from ZDV to ABC at age 1 month. In addition, use of ABC 346 from birth will better align with current WHO 1 st -line ART guidelines which is based on the 347 principle of using non-thymidine analogues;precise dosing of ABC liquid is not feasible and the 339 WHO weight-band dosing is preferred

4. No Grade 3 or higher AEs were deemed related to ABC 351 and no hypersensitivity reactions reported. ABC hypersensitivity reactions are uncommon in 352 children, especially in sub-Saharan Africa where the HLA*B5701 allele is rare 10 . A systematic 353 review reported a pooled incidence of 2�2% (95% CI 0�4-5�2) hypersensitivity reactions observed 354 in 1769 children (0-18 years) from Europe, North America and Africa on ART 10 . Two Grade 3 355 neutropenia adverse events in Study 2 were attributed to ZDV. A recent IMPAACT P1115 trial 356 evaluating early NVP-based ART for neonates also reported ZDV;350 ABC use across all three studies was safe

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