CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

and postpartum, respectively ( Figure 1 ). Based on established in vivo concentration-effect relationships of CYP3A inhibition by RTV 1 , at a RTV dose of 100 mg daily, CYP3A metabolic clearance is expected to be reduced to 13% of baseline in non-pregnant adults compared to 24% of baseline during pregnancy. Conclusions: RTV PK was well described by a one compartment model with first-order elimination and pregnancy significantly increased RTV CL/F and V/F. Decreased RTV exposures during pregnancy are predicted to lead to a 1.8-fold reduction in RTV-mediated CYP3A inhibition. Dosing requirements of RTV and/ or boosted CYP3A substrates may be altered during pregnancy.

PrEP exposure and language development at 60 months among mother-child pairs without HIV. Methods: Data from mother-child pairs 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-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. Language development was assessed by trained nurses using the validated Malawi Developmental Assessment Tool. The association between prenatal PrEP exposure and language development scores at 60 months was evaluated using linear regression models adjusted for gestational age at birth, maternal age and education, infant sex, and partner HIV status. We also evaluated the association between language development scores and timing of PrEP initiation (<14 weeks, 14-27 weeks, and >=27 weeks gestation) and duration on PrEP during pregnancy (<4 weeks, 4-12 weeks, and >12 weeks). Results: As of January 2025, 768 children had reached 60 months and were included in the analysis; 139 (18%) had any in-utero PrEP exposure with a median duration of 2.4 months (IQR: 1.4-3.5) 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 (69% vs. 55% p=0.004) and to have a partner known to be living with HIV or of unknown status (68% vs 38% p<0.001). Mean language development scores at 60 months were 36.8 (SD: 1.6) among exposed and 37.1 (SD: 1.6) among unexposed. There was no difference in mean language scores at 60 months (adjusted mean differences: language -0.12, 95% CI: -0.45, 0.20, p=0.47). Language development scores were similar when analyzed separately by timing of PrEP initiation and weeks of duration on PrEP in pregnancy (all p>0.05). Conclusions: Our results add to the limited data on language development in ARV-exposed children who are not exposed to HIV and suggest that exposure to ARVs without HIV exposure is not associated with adverse language development outcomes. 1021 Growth Faltering Is Partially Ameliorated by Infant Gut Bifidobacterium in Children Exposed to HIV Nicole Tobin 1 , Christine J. McGrath 2 , Fan Li 1 , Charles Mutinda 3 , Priscah Lihanda 3 , Mame M. Diakhate 2 , Grace John-Stewart 2 , Benson O. Singa 4 , Grace Aldrovandi 1 1 University of California Los Angeles, Los Angeles, CA, USA, 2 University of Washington, Seattle, WA, USA, 3 KEMRI Kenya, Nairobi, Kenya, 4 Kenya Medical Research Institute, Kilifi, Kenya Background: Children with HIV exposure (CHEU) who do not experience HIV infection are at increased risk of growth faltering compared to children unexposed to HIV (CHU). Decreased abundance of Bifidobacterium has been associated with growth faltering in CHEU. We examined the gut microbiota of CHEU versus CHU to determine if specific microbes may influence growth outcomes. Methods: 16S rRNA sequencing of the V4 region was performed on rectal swabs collected at 3 months of age as part of a prospective clinical study in Migori, Kenya. WHO Z-scores (weight-for-age [WAZ] and length-for-age [LAZ]) were calculated using weight and length measurements within 7 days of birth, at 3 and 6 weeks, and months 3, 6, 9, 12, 18 and 24. Linear mixed effects models were used to identify differentially abundant bacterial taxa between CHEU and CHU, and an interaction term was added to test whether associations between growth outcomes and bacterial abundances differed between the two groups. Results: Rectal swabs from 319 children (164 CHEU and 155 CHU) passed all filtering and quality control steps and were used for analysis. Most children were born full term (91%) and 87% were exclusively breastfed at 3 months. All CHEU began ARV prophylaxis from birth and 98% received prophylactic cotrimoxazole from 6 weeks of age. LAZ and WAZ were lower in CHEU vs CHU (t=-1.69, p=0.09 for length; t=-2.56, p=0.01 for weight) over the first two years. HIV exposure contributed minimally to overall variation in microbiome composition (0.39%, p=0.08) at 3 months of age, and no significant differences in alpha diversity or genus-level relative abundances were observed between CHEU and CHU. In an interaction model, the association between Bifidobacterium abundance and WAZ at 3 months of age was stronger among CHEU as opposed to CHU (t=1.87, p=0.06). Conclusions: Although growth trajectories differed between CHEU and CHU, there were no significant differences in the gut microbiome of CHEU versus CHU at three months. Bifidobacterium abundance was associated with growth outcomes in CHEU. Establishment and maintenance of infant gut

Poster Abstracts

1019 Neurodevelopmental Disorders in French HIV-/ARV-Exposed Uninfected Children: A National Cohort Study Pierre Frange 1 , Laurent Chouchana 2 , Mathis Collier 2 , Jeanne Sibiude 3 , Arnold Munnich 4 , Jean-Marc Treluyer 2 , Stéphane Blanche 1 1 Hôpital Necker, Paris, France, 2 Cochin Hospital, Paris, France, 3 Trousseau Hospital, Paris, France, 4 French National Institute of Health and Medical Research (Inserm), Paris, France Background: The health of uninfected children exposed to HIV requires long-term assessment, in particular, in terms of neurological and cognitive development. Numerous confounding factors have hampered such assessment, and the data are contradictory. Methods: Using data from the French National Health Data System from 2012 to 2022, we conducted a population-based matched cohort study on all live-single born children including children born to HIV-infected mothers, all prenatally exposed to antiretrovirals (ARV). The primary outcome was the diagnosis of neurodevelopmental disorders according to the 2010 International Classification of Diseases. The recourse to specialized consultations likely to indirectly reflect neurodevelopmental symptoms was also evaluated. Incidence was assessed using the Cox survival model. Results: Of 6,667 363 live-born singletons, 9,035 were born to mothers living with HIV, all exposed to ARV during pregnancy. Children were followed up to 11 years, for an average of 5.5 yrs. Overall, the incidence of neurodevelopmental disorders among exposed children was higher than in the general population, even after matching for five sociodemographic criteria (zip code, social vulnerability indicator, salary, maternal age, year of birth) and gestational age, HR [95%CI]: 1.24 [1.04 - 1.47]. It was not possible to dissect the respective role of maternal infection from that of maternal treatment, as all children were co-exposed to HIV and ARV. However, among those exposed to tenofovir emtricitabine, the r-darunavir-based combination was significantly associated with a higher combined incidence of neurodevelopmental disorders and related specialized consultations than other protease inhibitors (log rank, p<0.001). Conclusions: Children exposed in utero to ARV and HIV are at higher risk of neurodevelopmental disorders of multifactorial origin. 1020 Prenatal PrEP Exposure and Language Development Among Children at 5 Years Lauren A. Gomez 1 , John Kinuthia 2 , Felix Abuna 2 , Sarah Benki 1 , Mary Marwa 2 , Salphine Watoyi 2 , Bilhah Aomo 2 , Nancy Ngumbau 2 , Ben Ochieng 2 , Anna Larsen 1 , Joshua Stern 1 , Barbra Richardson 1 , Grace John-Stewart 1 , Jillian Pintye 1 , for the UW-KNH PrEP in Pregnancy Studies Team 1 University of Washington, Seattle, WA, USA, 2 Kenyatta National Hospital, Nairobi, Kenya Background: Data on child development following in utero antiretroviral (ARV) exposure suggest increased risk of delay in language skills, although most studies to date are among women living with HIV and their infants who have exposure to both ARVs and HIV. We assessed the relationship between prenatal

CROI 2025 325