CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

1045 Acceptability of a Dolutegravir Dispersible Tablet and a Novel Oral Film Formulation in Neonates Lario Viljoen 1 , Charlene Purdy 1 , Verah N. Luke 1 , Samantha du Toit 1 , Maria Groenewald 1 , Lindee Ganger 1 , Anneke C. Hesseling 1 , Anthony Garcia-Prats 2 , Tim Cressey 3 , Adrie Bekker 1 1 Stellenbosch University, Cape Town, South Africa, 2 University of Wisconsin–Madison, Madison, WI, USA, 3 Chiang Mai University, Chiang Mai, Thailand Background: Current antiretroviral (ARV) syrups used for HIV prevention and early treatment in neonates are from older, more toxic drug classes. Dolutegravir (DTG) is one of the preferred ARVs for children, but there is no pediatric formulation specifically tailored for use in neonates. We report on the mothers’ acceptability of DTG dispersible tablets (DTG-DT) and a novel oral film (DTG-OF), not yet studied in children, in neonates enrolled in the PETITE-DTG study. Methods: PETITE-DTG is an ongoing phase I/II, open-label 2-stage study evaluating the pharmacokinetics, safety and acceptability of 2 solid pediatric DTG formulations in term neonates in South Africa. In the multi-dose stage, 40 term neonates born to women receiving DTG are randomized to receive DTG-DT or DTG-OF with zidovudine (ZDV) syrup prophylaxis. The DTG-DT group receive 5 mg DTG-DT in 5mL water, administered with a syringe, followed by 2mL water from the same syringe. The DTG-OF group receive a single 5 mg dissolvable film from a sachet, folded and placed directly on the tongue. In-depth interviews were conducted in a sub-set of mothers at 3 time points and thematic analysis applied to determine acceptability. Results: 20 mother-infant pairs (10 neonates on DTG-DT and 10 on DTG-OF) were included in this analysis. Mothers reported very good acceptability to both DTG formulations. Mothers administering DTG-DT to their infants found that it dissolved easily, and was palatable (fruity smell, sweet) and appealing to babies. Challenges included technical and time-consuming preparation, and the large volume (7mL water) required. Mothers were concerned about spilling medicine and underdosing babies. For the DTG-OF, most mothers reported initial hesitancy and described the film as unfamiliar. Concerns included the inability of neonates to swallow the ‘paper’, but high levels of acceptance were reported after administering 1 to 2 doses, with DTG-OF preferred above ZDV. Convenient packaging (thin sachet), ease of administration (quick and easy to dissolve), and perceived dosing accuracy (no spilling) were reported with the film. Acceptability was further facilitated by reassurance from health workers that the ‘paper’ was indeed ‘medicine’. Conclusions: Mothers reported acceptance of pediatric DTG formulations for use in neonates. After initial hesitancy, the DTG-OF was found to be highly acceptable by mothers. Targeted peer support and engagement with mothers and health workers will be important to familiarize end-users with the novel DTG-OF.

adolescents >35kg with HIV-1 infection. IMPAACT 2036 (CRAYON) is a Phase I/II, multi-center, open-label, non-comparative study to evaluate safety, tolerability, acceptability and pharmacokinetics (PK) of oral (PO) and intramuscular (IM) CAB-LA+RPV-LA in children 2-<12 years, living with HIV-1. Here we present the first report of CAB-LA+RPV-LA in children from interim Week (W)12 data. Methods: Virologically suppressed (viral load <50 copies/mL) children living with HIV-1 on stable combination antiretroviral therapy (cART) were enrolled into weight-band (WB) 1 (35-<40kg), 2 (25-34.9kg) or 3 (20-24.9kg). After discontinuing background cART, participants received PO CAB+RPV through W4, followed by IM CAB-LA+RPV-LA injections every 4 weeks (Q4W), per WB dosing table. PK samples were drawn at W2 (to assess PO dosing) and W4, 5, 6, 8, 9 and 12 (to assess LA dosing). Results: 35 participants were enrolled: 8 in WB 1, 16 in WB 2 and 11 in WB 3; one prematurely discontinued study drug due to anxiety associated with painful procedures. The safety analysis set included 20 children who completed treatment through W12 before the safety interim analysis freeze date. Median (Q1, Q3) age and weight were 10 years (8, 10.5) and 26.2 kg (22.2, 29.9); 60% were female; 25% were Asian, 75% were Black or African American. 8 (40%) children had a Grade ≥1 adverse event (AE) through W12, all ≤Grade 3. Frequent AEs included injection site pain (n=3, all Grade 1), headache (n=3), pyrexia (n=2), oropharyngeal pain (n=2) and cough (n=2). One child (5%) had two Grade 3 AEs which resolved. Participants maintained virologic suppression through W12. 34 participants contributed to the PK analysis, with 24 completing W12 before the PK interim analysis freeze date. Median (Q1, Q3) AUCs during oral lead-in (n=34) were 109 000 (86 000, 130 000) ng*h/mL for CAB-PO and 3086 (2351 4440) ng*h/mL for RPV-PO. Median (Q1, Q3) pre-dose concentrations at W12 (n=24) were 2160 (1440, 3430) ng/mL for CAB-LA and 52 (43, 66) ng/mL for RPV-LA (Figure 1). These values met protocol-defined acceptable criteria for both drugs by PO and IM routes. Conclusions: Administration of PO CAB+RPV followed by Q4W IM CAB LA+RPV-LA in children 20-<40 kg achieved exposure concentrations comparable to adolescents and adults receiving this regimen. No new or unanticipated safety concerns were identified.

Poster Abstracts

1047 PK and Safety of Chronic Dolutegravir Administration in Neonates Exposed to HIV-1 (IMPAACT 2023) Jeremiah Momper 1 , Hardik Chandasana 2 , Jiajia Wang 3 , Benjamin Johnston 4 , Sarah Bradford 5 , Dwight E. Yin 6 , Tara Deyampert 6 , Ann M. Buchanan 7 , Edward P. Acosta 8 , Mark Mirochnick 9 , Kathleen Powis 10 , Diana F. Clarke 11 , for the IMPAACT 2023 Protocol Team 1 University of California San Diego, La Jolla, CA, USA, 2 GSK plc, Durham, NC, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 5 Family Health International 360, Durham, NC, USA, 6 National Institutes of Health, Bethesda, MD, USA, 7 ViiV Healthcare, Durham, NC, USA, 8 University of Alabama at Birmingham, Birmingham, AL, USA, 9 Boston University, Boston, MA, USA, 10 Massachusetts General Hospital, Boston, MA, USA, 11 Boston Medical Center, Boston, MA, USA Background: Dolutegravir (DTG) is approved for treatment of HIV-1 in adults and pediatric patients ≥4 weeks and ≥3 kg. We previously reported the pharmacokinetics (PK) and safety of two single doses of DTG (0.5 mg/kg) given with standard of care antiretrovirals in the first 13 days of life. Here, we describe preliminary PK and safety of 4-6 weeks DTG dosing using a 5-mg dispersible tablet (DT) formulation in neonates exposed to HIV-1. Methods: IMPAACT 2023 is a PK, safety, and tolerability study of DTG in infants during the first 4-6 weeks of life. In this cohort, DTG 5 mg DT was dosed every other day until day 13 of life, followed by once daily dosing. Intensive PK

1046 Safety and Pharmacokinetics of Long-Acting Cabotegravir and Rilpivirine in Children 20 to 40 kg

Moherndran Archary 1 , Jorge Pinto 2 , Edward P. Acosta 3 , Amy Cheung 4 , Thomas Kakuda 5 , Ellen Townley 6 , Jack Moye 7 , Ryan Milligan 8 , Rachel Scheckter 9 , Gaerolwe Masheto 10 , Pradthana Ounchanum 11 , Linda Aurpibul 12 , Lee Fairlie 13 , Edmund Capparelli 14 , for the CRAYON/IMPAACT 2036 Study Team 1 Africa Health Research Institute, Mtubatuba, South Africa, 2 Federal University of Minas Gerais, Belo Horizonte, Brazil, 3 University of Alabama at Birmingham, Birmingham, AL, USA, 4 ViiV Healthcare, Brentford, UK, 5 Janssen Research & Development, LLC, San Diego, CA, USA, 6 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 7 National Institute of Child Health and Human Development, Bethesda, MD, USA, 8 Harvard Medical School, Boston, MA, USA, 9 Family Health International 360, Durham, NC, USA, 10 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 11 Chiang Rai Prachanukroh Hospital, Chiang Rai, Thailand, 12 Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand, 13 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 14 University of California San Diego, La Jolla, CA, USA Background: Long-acting cabotegravir (CAB-LA) plus long-acting rilpivirine (RPV-LA) are approved for maintenance of viral suppression in adults and

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