CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

taken in combination with TDF/FTC or 3TC. Child ND status was assessed using the Bayley (BSID-III), BRIEF-P-SF, and CREDI (Short; Social-Emotional). ND outcomes were compared between DTG- and EFV-exposed groups, and between HEU and HUU groups, using GEE models to account for twins, and adjusting for enrollment site, child sex/age at testing, maternal age/education/marital status/income, food insecurity (and for DTG vs EFV comparisons, breastfeeding and timing of first in utero ART exposure). Children were classified "at risk" if they scored ≥1SD below the mean or were unable to complete the BSID-III. Results: A total of 564 children (202 HEU/EFV, 202 HEU/DTG, 160 HUU; Mage=25.7 months; 49% female) participated. Means were similar across ART exposure groups in unadjusted and adjusted models (Figure). Adjusted relative risk (aRR) of "at risk" classification was lower in children who were DTG-exposed than EFV-exposed on BSID-III Cognitive (4.5% vs. 8.4% aRR=0.36 (95%CI:0.16, 0.78)) and Expressive Language (10.9% vs 17.3%, 0.61 (0.38, 0.98)) domains. Children HEU (EFV+DTG) were more likely than children HUU to be classified "at risk" on BSID-III Expressive Language (14.1% vs 7.5%, aRR=1.89 (1.00, 3.60)). Children HEU were rated as having slightly better executive function skills on the BRIEF-P-SF. Inferences were similar in sensitivity analyses controlling for preterm birth status. Conclusion: Two-year ND outcomes among HEU and HUU children in Botswana were mostly comparable. However, consistent with prior studies, HEU status was associated with higher risk of adverse language outcomes. Among children HEU, those exposed in utero to EFV-ART were at higher risk of adverse cognitive and expressive language outcomes than DTG-ART-exposed. Longer-term ND follow-up is needed to examine the possibility of increased ND burden as HEU-/ ART-exposed children enter school-age. Prenatal PrEP Exposure and Neurodevelopment Among Children at 48 months Lauren A Gomez 1 , John Kinuthia 2 , Felix Abuna 2 , Sarah Benki-Nugent 1 , Julia Dettinger 1 , Anna Larsen 1 , Mary Marwa 2 , Ben Ochieng 2 , Nancy Ngumbau 2 , Salphine Watoyi 2 , Joshua Stern 1 , Barbra Richardson 1 , Grace John-Stewart 1 , Jillian Pintye 1 1 University of Washington, Seattle, WA, USA, 2 Kenyatta National Hospital, Nairobi, Kenya Background: Data on neurodevelopmental outcomes following in utero ART exposure remains scarce and most studies to date are among women living with HIV and their infants who have both ART and HIV exposure. We assessed the relationship between prenatal PrEP exposure and child neurodevelopment through 48 months among mother-child pairs without HIV. Methods: Data from women enrolled in a cluster RCT (NCT03070600) evaluating PrEP delivery strategies at 20 antenatal clinics in Western Kenya were analyzed. HIV-negative women were enrolled and offered oral tenofovir disoproxil fumarate (TDF)-based PrEP during pregnancy and followed through 9 months postpartum regardless of PrEP status. A subset were enrolled into an extension cohort at 4 sites to be followed until their children reached 5 years. Neurodevelopment was assessed by trained nurses at 36 and 48 months using the Malawi Developmental Assessment Tool (MDAT), a validated instrument that evaluates social, language, fine motor, and gross motor domains. The association between prenatal PrEP exposure and MDAT domain scores at 36-48 months was evaluated using linear regression models clustered by facility and adjusted for gestational age at birth, maternal age and education, infant sex, and partner HIV status. Results: As of September 2023, 648 mother-child pairs had children aged 36-48 months and were included in the analysis, 21% had any PrEP exposure for a median duration of 3.3 months (IQR: 2.4-4.3) during pregnancy. Compared to mothers who did not take PrEP, mothers who took PrEP in pregnancy were more likely to only have primary school education (70% vs. 56% p=0.004) and to have a partner known to be living with HIV or of unknown status (67% vs 37% p<0.001). There was no difference in mean MDAT score for any domain at 36 months (adjusted mean differences: social 0.07, 95% CI: -1.61, 1.76, p=0.92; language 0.54, 95% CI: -1.57, 2.66, p=0.58; fine motor -0.50, 95% CI: -1.49, 0.49, p=0.29; gross motor -0.17, 95% CI: -1.19, 0.85, p=0.72). Results were similar at 48-months with no differences between exposure groups.

inflammatory cytokines IL10 (p=0.003, r=0.59) and IL1RA (p=0.02, r=0.48) in their newborns. Conclusion: Biomarkers in PWH are reflected at birth in their HEU infants and persist up to 6 months. Perturbed biomarkers include chemokines and cytokines involved in early germinal center development and macrophage activation markers known to play a critical role in neonatal immune responses. Maternal immune perturbations appear to be imprinted on their HEU infants, which may alter immune ontogeny and contribute to their increased morbidity. Brain Structure of South African HEU Children Exposed to Dolutegravir Versus Efavirenz Layla E Bradford 1 , Jessica E. Ringshaw 1 , Catherine J. Wedderburn 1 , Niall J. Bourke 2 , Helene Theunissen, 3 , Thokozile R. Malaba 1 , Lauren Davel 1 , Nengjie He 4 , Helen Reynolds 5 , Angela Colbers 6 , Duolao Wang 7 , Saye Khoo 3 , Landon Myer 1 , Kirsten A. Donald 1 1 University of Cape Town, Cape Town, South Africa, 2 King's College London, London, United Kingdom, 3 University of Liverpool, Liverpool, United Kingdom, 4 Liverpool School of Tropical Medicine, Liverpool, UK, 5 University of Liverpool, Liverpool, UK, 6 Radboud University Medical Center, Nijmegen, Netherlands, 7 Liverpool School of Tropical Medicine, Liverpool, United Kingdom Background: Current research suggests that children who are HIV-exposed and uninfected (CHEU) may be at risk for neurodevelopmental delay and altered structural brain development compared to children who are HIV-unexposed (CHU), however the specific factors driving this association and the potential role of specific antiretroviral regimens are poorly understood. In particular volumes of specific regions of the brain may be reduced in CHEU compared to CHU, however, there is no research published on the structural brain outcomes of children born to mothers on DTG-based ART. Methods: We collected high resolution magnetic resonance (T1-weighted) scans were from DolPHIN-2 Plus, an open-label follow-up to the DolPHIN-2 trial (NCT03249181). In this analysis, total grey matter and total subcortical volumes were compared between CHEU and CHU groups using multivariate analysis of variance (MANOVA) adjusting for age, sex and total intracranial volume. Within the CHEU group, brain volumes were compared between children who were born to mothers who received DTG and EFV-based ART. Results: Between 2021 and 2023, 24 CHEU (12 DTG, 12 EFV; mean age 45 months; 54% male) born in the DolPHIN-2 trial were enrolled and scanned at 2-4 years along with 64 CHU (mean age 43 months; 56% male). Demographic characteristics were similar for both CHEU vs CHU and DTG vs EFV groups. In unadjusted and adjusted analyses, there was no evidence for an effect of HIV exposure on total grey matter (adjusted p=0.642) or subcortical grey matter (p=0.549). Similarly, ART exposure showed no significant association with total grey matter (p=0.869), or subcortical grey matter (p=0.097), although there was a trend towards smaller subcortical volumes in the EFV compared to DTG groups (F = 3.05, partial Eta squared =0.138). Conclusion: Total grey matter brain volumes were similar in CHEU and CHU at 3-4 years of age in this sample. These are the first data comparing brain volumes in HEU children born to mothers receiving DTG- versus EFV-based ART in pregnancy. While there were no significant differences by ART regimen, the trend for larger subcortical volumes in DTG-exposed children in this small sample requires further investigation. Neurodevelopment in Children Exposed In Utero to Dolutegravir- or Efavirenz-Based ART in Botswana Adam R Cassidy 1 , Gloria K. Mayondi 2 , Kebaiphe Moabi 2 , Allison LeMahieu 1 , Paige L. Williams 3 , Naledi Kamanga 2 , Kathleen M. Powis 4 , Dinah Ramaabya 5 , Francis Banda 6 , Joseph M. Makhema 2 , Betsy Kammerer 7 , Shahin Lockman 8 1 Mayo Clinic, Rochester, MN, USA, 2 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 Massachusetts General Hospital, Boston, MA, USA, 5 Botswana Ministry of Health and Wellness, Gaborone, Botswana, 6 University of Botswana, Gaborone, Botswana, 7 Boston Children's Hospital, Boston, MA, USA, 8 Brigham and Women's Hospital, Boston, MA, USA Background: Dolutegravir (DTG)- and, to a lesser extent, efavirenz (EFV)- based antiretroviral treatment (ART) regimens are commonly used by pregnant persons living with HIV in high burden HIV settings, increasingly with initiation prior to conception. Little is known about the impact of in utero exposure to DTG- or EFV-based ART on child neurodevelopmental (ND) outcomes, although some prior data have raised concerns for EFV exposure. Methods: We prospectively enrolled 3 cohorts of 2-year-old children: HIV-exposed/uninfected (HEU)/DTG-exposed, HEU/EFV-exposed, and HIV unexposed/uninfected (HUU), from March 2021-May 2023. DTG or EFV were

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