NP-003 Steady-state pharmacokinetics and early safety data in HIV-infected african children weighing ≥25 kg after switching to 50 mg film-coated dolutegravir tablets in the ODYSSEY trial

Background and importance ODYSSEY is an ongoing international randomised trial evaluating dolutegravir (DTG)-based antiretroviral therapy (ART) versus standard-of-care in HIV-infected children starting first- or second-line ART. Pediatric DTG film-coated tablets (FCTs) of 10 mg and 25 mg are unavailable in low- and middle income countries (LMIC) were most HIV-infected children live. Adult DTG 50mg FTCs are produced by generic manufacturers at low-cost, are well-tolerated, and already available in many high- and LMICs. Aim and objectives Within ODYSSEY pharmacokinetic (PK) substudies were undertaken to assess PK and safety data for a simplified paediatric DTG dosing approach using WHO weight bands (WBs) 25 to Materials and methods Steady-state 24-hour PK curves were constructed from data in children (≥3 h fasted) observed taking current EMA-approved DTG doses of 25 mg and 35 mg (10 mg+25 mg FCTs)) in 25- Results 28 black-African children (52 PK profiles) from Uganda and Zimbabwe (61% male) with a median (range) age of 11.0(7.5–17.9) years old were included. For children weighing 25- Conclusions and relevance Adult 50 mg FCT once-daily dolutegravir provides appropriate PK profiles in children ≥25 kg, with no safety signal, allowing practical dosing and rapid access to dolutegravir. WHO has released new pediatric dosing guidelines in response to these results.