CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

Oral Abstracts

121

Assessing IIT and Mortality Among CLHIV <15 yo in PEPFAR-Supported Countries, FY21 - FY24 Michelle Yang 1 , Christine Toolin 1 , Rituparna Pati 2 , Hilary Wolf 2 , Emily K. Dokubo 2 , Stephanie Hackett 1 1 US Department of State, Washington, DC, USA, 2 PEPFAR, Washington, DC, USA Background: Despite accounting for 3% of all people living with HIV, children (<15 yo) represented 12% of all AIDS-related deaths globally in 2023. Interruptions in HIV treatment (IIT) have been associated with higher mortality among children living with HIV (CLHIV). To explore this association further, we analyzed IIT and mortality data among CLHIV in PEPFAR-supported countries in the last 4 fiscal years, FY21 – FY24. Methods: We analyzed PEPFAR Monitoring, Evaluation, and Reporting data for all CLHIV <15 yo on ART with IIT between October 2020 and June 2024 (FY21 FY24) from 32 PEPFAR-supported country and regional programs. IIT was defined as having no clinical contact or ART pick-up for >28 days since the last clinical encounter. IIT data was disaggregated based on cause and included transferred out, refused treatment, unknown IIT after <3 months, 3-5 months, or 6+ months on ART, or died. Mortality data was further disaggregated by cause of death including HIV disease resulting in tuberculosis (TB), cancer, infectious or parasitic disease, or other HIV disease; other natural causes; non-natural causes; and not reported cause. Prevalence of these outcomes were calculated across quarters and by five-year age bands. Results: Among 490,000 CLHIV on ART in PEPFAR-supported countries, 22,329 experienced IIT in FY24. IIT occurred most frequently after 6+ months on ART among all CLHIV, except for those <1 (Figure 1). Among CLHIV on ART, IIT due to death was highest among children <5 yo, ranging from 0.47% to 1.88% (Figure 1). In FY24, HIV-related mortality accounted for 43% of all reported causes. This proportion remained relatively unchanged across the analysis period, but TB-related deaths increased from 6% in FY21 to 9% in FY24 (Figure 2). Data completeness improved as 80% of deaths in FY24 included an identified reported cause compared to 65% in FY21. Conclusions: CLHIV experienced notable rates of IIT and mortality, with CLHIV <5yo experiencing a disproportionate share of these outcomes, underscoring the importance of targeted interventions such as early diagnosis of HIV and differentiated service delivery models that support retention in care. Further analyses are needed to better understand the drivers of IIT and causes of mortality among CLHIV on ART. Improving pediatric data reporting is crucial to accurately determine HIV-related deaths (i.e. death audits), identify programmatic gaps and focus resources on reducing preventable deaths.

122

Multi-Dose PK/Safety of Dolutegravir Dispersible Tablets and Oral Films in Neonates: PETITE-DTG Study Adrie Bekker 1 , Nicolas Salvadori 2 , Helena Rabie 3 , Samantha du Toit 1 , Kanchana Than-in-at 2 , Maria Groenewald 1 , Edmund Capparelli 4 , Andrew Owen 5 , Ratchada Cressey 2 , Marc Lallemant 2 , Mark Cotton 6 , Tim Cressey 2 , for the PETITE-DTG Study Team 1 Stellenbosch University, Cape Town, South Africa, 2 Chiang Mai University, Chiang Mai, Thailand, 3 Tygerberg Hospital, Cape Town, South Africa, 4 University of California San Diego, La Jolla, CA, USA, 5 University of Liverpool, Liverpool, UK, 6 Family Clinical Research Unit, Tygerberg, South Africa Background: Dolutegravir (DTG) is not recommended for neonates due to absence of dosing guidelines and safety information. We are evaluating the multi-dose pharmacokinetics (PK) and safety of two pediatric DTG formulations in neonates: a dispersible scored tablet (DTG-DT, 10 mg) and a novel oral dispersible film (DTG-OF, 5 mg). Methods: PETITE-DTG is an ongoing phase I/II, open-label, single center, two stage trial in South Africa for term neonates exposed to HIV (N=56, birth weights ≥2kg). Stage 1 single dose DTG data (n=16) informed the multi-dose strategy for Stage 2: 5 mg DTG every 48 hours (q48) from Day 1 to 14 of life, followed by 5 mg daily (q24) until Day 28. In Stage 2, neonates born to mothers on DTG-based ART are randomized to receive either DTG-DT or DTG-OF with zidovudine postnatal prophylaxis. Three PK visits are performed: sparse on Day 1, intensive after ≥3 DTG doses, and sparse during week 4. Safety assessments are performed through week 6 of life. We report the interim PK/safety analysis after the first 20 neonates completed Stage 2. Target DTG criteria: geometric mean (GM) C tau >0.67 µg/mL, and C max <17.0 µg/mL in the majority of neonates; proportion of neonates with C tau <0.5 μg/mL (EC95) was also assessed. Results: Ten neonates on DTG-DT and 10 on DTG-OF were included. Overall median (range) birth weight was 3.2 (2.6-4.1) kg and 1st DTG dose given at 48 (28-60) hours of life. Median age at PK sampling visits were 3, 7, and 23 days of life. DTG GM concentrations prior to the 1st dose (placenta washout) was 0.98 μg/mL. Intensive DTG PK profiles were similar between DTG-DT and DTG-OF, with both formulations achieving a DTG GM C tau >0.67 µg/mL (Figure 1a). Two neonates, one on DTG-DT and one on DTG-ODF, had an C tau <0.5 µg/mL, but both remained >0.22 µg/mL (>3-fold higher than DTG IC 90 of 0.064 µg/mL). All neonates had a DTG C max <17.0 µg/mL across PK visits. Our prior neonatal DTG population PK model was updated with the multi-dose data and adequately predicted DTG concentrations (Figure 1b). No grade ≥3 adverse events (AEs) were related to DTG. Two grade 3 AEs unrelated to DTG were observed in one neonate with pneumonia. All neonates were HIV negative at study exit.

24

CROI 2025