CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Results: Twenty-four term neonates (14 girls) and 230 plasma ABC and 3TC concentrations were included. Median (range) body weight was 3,125 (2,270 3,995) g and postnatal age 8 (5-13) days of life at the 1st PK visit. ABC and 3TC plasma concentrations were best described by 1-comparments models. Both body weight and postnatal age influenced their oral clearance. Model-based simulations predicted the GM ABC AUC 0-24 remaining within target exposures using q48 dosing compared to q24 dosing during the first 2 weeks of life (Figure 1a). For 3TC, the GM AUC 0-24 also remained with the target with q48 dosing (Figure 1b). Conclusions: Giving 30/15 mg of ABC/3TC every 48 hours for the first 14 days of life; then daily was predicted to maintained target drug exposures comparable to young children. This dosing schedule should align with the proposed DTG regimen in term neonates during the first month of life.

sampling was performed at 7 days and 4 weeks after DTG initiation. Adverse events (AEs) were graded using the DAIDS grading table. DTG exposures were evaluated according to protocol-defined target geometric mean (GM) exposures: C trough > 0.697 µg/mL, AUC 0-tau > 37 µg*h/mL, and C max <18.35 µg/ mL. Tolerability information was collected using a questionnaire. Results: Data were available from 8 full-term infants with maternal DTG use (DTG-exposed) and 7 DTG-naïve infants with birthweights between 2.3 – 3.6 kg and postnatal age 0 – 5 days at time of DTG initiation. Participants were enrolled from South Africa (n=8), USA (n=4), and Thailand (n=3). No clinically meaningful differences were observed in DTG exposures between DTG–exposed and DTG-naïve infants and PK results for each group were combined. PK results are displayed in Figure 1 . At 7 days post-initial dose, GM (range) C trough , AUC 0-tau , and C max were 1.0 µg/mL (0.05 – 4.1), 121.1 µg*h/mL (42.0 – 321.9), and 4.9 µg/mL (2.1 – 9.1), respectively. A total of 5 of 15 participants had trough concentrations below the target at 7 days post-initial dose. At week 4, GM (range) C trough , AUC 0-tau , and C max were 2.3 µg/mL (0.1 – 5.1), 98.2 µg*h/mL (24.0 – 159.2), and 5.4 µg/mL (1.6 – 9.1), respectively. No neonates experienced ≥ grade 3 AEs related to study drug. Conclusions: Use of DTG 5-mg DT (every other day for two weeks until day 14 of life, followed by once daily dosing) for 4-6 weeks was well-tolerated with no unexpected AEs in neonates exposed to HIV-1. DTG exposures met GM protocol defined targets; however, there was considerable variability in exposures. Continued evaluation of this DTG dosing regimen including potential sources of PK variability is ongoing in IMPAACT 2023.

1049 Week 24 Outcomes of F/TAF Plus Cobicistat-Boosted Protease Inhibitors in Children ≥2 y and ≥14 kg Hilda A. Mujuru 1 , Renate Strehlau 2 , Pope Kosalaraksa 3 , Jaime G. Deville 4 , Meiling Pan 5 , Vinicius Adriano Vieira 5 , Kathryn Kersey 5 , Natella Rakhmanina 6 1 University of Zimbabwe, Harare, Zimbabwe, 2 University of Witwatersrand, Johannesburg, South Africa, 3 Khon Kaen University, Khon Kaen, Thailand, 4 UCLA Mattel Children's Hospital, Los Angeles, CA, USA, 5 Gilead Sciences, Inc, Foster City, CA, USA, 6 Children's National Hospital, Washington, DC, USA Background: Nucleoside reverse transcriptase inhibitors (NRTIs) in combination with boosted protease inhibitors (PIs) are a recommended treatment for children with HIV-1 with resistance or intolerability to integrase strand transfer inhibitors. In the US, emtricitabine/tenofovir alafenamide (F/TAF) is approved in combination with boosted PIs for adults and children weighing ≥35 kg. TAF has improved renal and bone safety compared with tenofovir disoproxil fumarate. An ongoing Phase 2/3 open-label trial is evaluating F/TAF in combination with cobicistat-boosted atazanavir (ATV/co) or darunavir (DRV/co) in children with HIV-1 (NCT02016924). We present efficacy and safety outcomes through Week 24 in children aged 2-<12 y and weighing 14-<40 kg. Methods: Participants aged 6-<12 y, weighing 25-<40 kg, receive 200/25 mg F/TAF + ATV/co or DRV/co (Cohort 2); participants ≥2 y and 14-<25 kg receive 120/15 mg F/TAF + ATV/co or DRV/co (Cohort 3). Key inclusion criteria are CD4 count ≥200 cells/µL, estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m 2 , and on two NRTIs plus a third agent with no regimen changes within 3 months. Virologic suppression was assessed by FDA Snapshot algorithm; bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry of spine and total body less head (TBLH). Results: Twenty-three (Cohort 2) and 26 (Cohort 3) participants enrolled. At baseline, in Cohorts 2 and 3 respectively, 61% and 54% participants were female, 91% and 92% were Black, median age (range) was 10 (8-12) and 6 (3-10) y, median (quartile [Q] 1, Q3) CD4 counts were 876 (671, 1063) and 940 (705, 1259) cells/µL, median (Q1, Q3) CD4 % was 36 (31, 41) and 35 (30, 41), and 96% and 92% had HIV-1 RNA <50 copies/mL. At Week 24, CD4 counts were similar to baseline, and 96% in each cohort had HIV-1 RNA <50 copies/ mL. Two participants in Cohort 3 experienced Grade 3/4 study drug–related treatment-emergent adverse events (TEAEs) of increased bilirubin, considered related to ATV; one was classified as a serious TEAE. No Grade 3/4 or serious study drug–related TEAEs were reported in Cohort 2. Changes in height, weight, and body mass index Z-scores; spine and TBLH BMD; and eGFR were not clinically significant ( Table ). Conclusions: In this interim analysis, F/TAF in combination with ATV/co or DRV/ co in children aged 2-<12 y and weighing 14-<40 kg was efficacious, with an acceptable safety profile and no renal, bone, or weight concerns, supporting further evaluation in pediatric populations.

Poster Abstracts

1048 Alternative Dosing of ABC/3TC Dispersible Tablets to Align With Dolutegravir Dosing in Neonates

Navarat Panjasawatwong 1 , Adrie Bekker 2 , Helena Rabie 3 , Samantha du Toit 2 , Maria Groenewald 2 , Nicolas Salvadori 4 , Kanchana Than-in-at 4 , Edmund Capparelli 5 , Ratchada Cressey 4 , Marc Lallemant 4 , Mark Cotton 6 , Tim Cressey 4 , for the PETITE Study Team 1 Payap University, Chiang Mai, Thailand, 2 Stellenbosch University, Cape Town, South Africa, 3 Tygerberg Hospital, Cape Town, South Africa, 4 Chiang Mai University, Chiang Mai, Thailand, 5 University of California San Diego, La Jolla, CA, USA, 6 Family Clinical Research Unit, Tygerberg, South Africa Background: Rapid maturation of metabolic/elimination pathways during the first month of life complicates using pediatric fixed-dose dispersible formulations in neonates. We previously reported that once daily administration of abacavir/lamivudine dispersible tablets (ABC/3TC-DT) to neonates gave high exposure during the first week of life. Administration of 5 mg dolutegravir (DTG) every 48 hours (q48) for the first 2 weeks of life, followed by 5 mg daily (q24) until Day 28 is under investigation in the PETITE-DTG study. Hence, we performed a pharmacokinetic (PK) modeling/simulation study to determine if less frequent (q48) administration of ABC/3TC-DT during the two weeks of life would align with DTG dosing to simplify treatment delivery in neonates. Methods: The ‘PETITE’ study was a phase I/II, open-label, single arm, PK and safety trial of ABC/3TC-DT (120:60mg, double-scored) and lopinavir boosted with ritonavir (40:10 mg) granules in HIV-exposed term neonates in Tygerberg hospital, South Africa. Neonates received 30/15 mg of ABC/3TC-DT (¼ tablet) daily and 80/20 mg of LPV/r (2 sachets) twice daily through 28 days of life. PK blood samples were collected at visits during the neonatal period. Using single and multi-dose data, we developed population PK models for ABC and 3TC. Using the final models, we performed Monte Carlo simulation (n=5,600 virtual neonates) to predict plasma ABC and 3TC drug exposures using q48 dosing from birth to Day 14 and q24 from Day 15 to Day 28. Geometric mean (GM) ABC and 3TC target exposures (AUC 0-24 ) were 6.3 to 50.4 and 6.3 to 26.5 mg.hr/L for ABC and 3TC, respectively.

CROI 2025 336