CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: In this prospective observational study, we evaluated 41 young adults with PHEU and 41 young adults without HIV exposure or infection (24±5 y, 46% male per group). Young adults were matched 1:1 on ≥4 of the following: age, sex, race/ethnicity, maternal education, maternal substance use disorder, and breastfeeding. The primary outcome was BMI. Secondary outcomes were impaired glucose tolerance (HbA1c ≥5.7%, fasting glucose ≥100 mg/dL, and/ or 2-hour glucose ≥140 mg/dL on oral glucose tolerance test), hypertension (clinical diagnosis, systolic blood pressure ≥140 mmHg, and/or diastolic blood pressure ≥90 mmHg), and hepatic steatosis (controlled attenuation parameter ≥263 dB/m on transient elastography). A composite metabolic comorbidity score was devised with 1 point given for each of the latter 3 outcomes. Linear mixed effect models and chi-square tests were used to estimate differences in metabolic endpoints by PHEU status. Results: Young adults with PHEU had higher BMI (effect: 5.1 kg/m 2 ; 95% CI, 1.7, 8.5 kg/m 2 ) and prevalence of class 2-3 obesity (41% vs. 5%, P <0.0001) versus matched controls. Individuals with PHEU also had higher rates of impaired glucose tolerance (21% vs. 3%, P =0.01), hypertension (20% vs. 0%, P =0.003), and hepatic steatosis (44% vs. 15%, P =0.006), corresponding to a higher metabolic comorbidity score (effect: 0.66; 95% CI, 0.35, 0.98). PHEU remained independently associated with BMI and comorbidity score upon adjusting for young adult (e.g., adverse childhood experiences) and maternal (e.g., BMI) factors. PHEU also conferred a higher rate of at least 1 comorbidity in young adults with obesity (89% vs. 42%, P =0.004) and without obesity (31% vs. 4%, P =0.01). Conclusions: In the oldest cohort studied to date, young adults with PHEU had a higher burden of severe obesity and metabolic comorbidities versus matched unexposed peers. Though targeting BMI may partially mitigate metabolic disease risk, adverse metabolic outcomes were more common in people with PHEU irrespective of obesity.

1026 Comparing Telomere Length Between Children Who Were and Were Not Exposed to HIV in Kenya Jillian Neary 1 , Irene Njuguna 1 , Tiffany Pan 1 , Daniel Matemo 2 , Fiona McBride 1 , Alvin Onyango 3 , Maureen King'e 3 , Prestone O. Owiti 3 , Celestine Adogo 2 , Dalton Wamalwa 3 , Dan T. A. Eisenberg 1 , Grace John-Stewart 1 1 University of Washington, Seattle, WA, USA, 2 Kenyatta National Hospital, Nairobi, Kenya, 3 University of Nairobi, Nairobi, Kenya Background: Children who were HIV exposed and uninfected (CHEU) may experience higher levels of oxidative stress and inflammation compared to children who are HIV unexposed (CHU). Telomere length (TL) is an important biomarker of aging. Telomere shortening results from cellular division, inflammation, and oxidative stress and is associated with age-related diseases. We compared TL between CHEU and CHU. Methods: CHEU and CHU attending 7 public maternal and child health clinics were enrolled at their 6-week visit in the HOPE cohort from 2021-2022 in Kenya. Mothers of CHEU were on optimized antiretroviral therapy (ART). TL was measured from dried blood spots at 6 weeks of age using a modified version of the monochrome multiplex qPCR assay. We used linear mixed effects models with clinic as a random effect. Adjustment variables included infant age at DBS collection, infant sex, maternal age, paternal age, and maternal education. The statistical analysis plan was pre-registered prior to availability of TL data. Results: Between 250 CHEU and 250 CHU, there were no significant differences (p=0.05) in child sex (51% female), median age at sample collection (median: 6.6 weeks), or preterm birth (2.8%). CHEU had older mothers (median: 31 vs 26 years), older fathers (median: 37 vs 31 years), and mothers with fewer years of education (median: 8 vs 12 years) compared to CHU. The majority (88%) of mothers of CHEU started ART before pregnancy and 47% of those mothers were on dolutegravir-based regimens before pregnancy. Mean TL z-score was -0.04 (standard deviation [SD]: 0.99) among CHEU and 0.04 (SD: 1.01) among CHU. HIV exposure was not significantly associated with TL in the unadjusted (-0.08, 95% confidence intervals [CI]: -0.26, 0.09, p=0.375) or adjusted models (-0.05, 95%CI: -0.26, 0.15, p=0.604). Conclusions: In this relatively large cohort of CHEU and CHU, there was no significant difference in 6-week TL between CHEU and CHU. Future analyses will include longitudinal comparisons of the rate of TL decline between CHEU and CHU and analyses among CHEU to determine whether maternal ART regimen or viral load influence child TL. 1027 HIV Exposure Affects Gut Virome Richness but Not Diversity Among Kenyan Infants Emily R. Begnel 1 , Rabia Maqsood 2 , LaRinda A. Holland 2 , Ednah Ojee 3 , Prestone O. Owiti 3 , Judith Adhiambo 3 , Eliza Mabele 3 , Soren Gantt 4 , Bhavna H. Chohan 1 , John Kinuthia 5 , Dalton Wamalwa 3 , Efrem S. Lim 2 , Dara A. Lehman 6 , Jennifer Slyker 1 1 University of Washington, Seattle, WA, USA, 2 Arizona State University, Tempe, AZ, USA, 3 University of Nairobi, Nairobi, Kenya, 4 University of Montreal, Montreal, Canada, 5 Kenyatta National Hospital, Nairobi, Kenya, 6 Fred Hutchinson Cancer Center, Seattle, WA, USA Background: The gut virome is seeded at birth, rapidly develops in the first years of life, and is influenced by numerous behavioral and environmental factors including exposure to the maternal virome. Thus, maternal HIV infection could alter virome development and may contribute to the increased morbidity and mortality seen in children exposed to HIV. However, no study has characterized the gut virome of children who are HIV-exposed, uninfected (CHEU). To address this gap, we described and compared the gut virome of Kenyan CHEU and children who are HIV-unexposed, uninfected (CHUU) from birth-21 months. Methods: We performed metagenomic sequencing of the DNA virome on stool samples collected between January 2019-December 2020 from a birth cohort of healthy infants in Nairobi, Kenya. Data from 37 CHUU and 32 CHEU whose mothers initiated ART prior to (n=29) or in early pregnancy (n=2) were included. To compare gut virome composition by HIV exposure and breastfeeding practices, we used generalized estimating equations models adjusted for maternal age, breastfeeding, and socioeconomic status for virome richness and Shannon (alpha) diversity, principal coordinates analysis and PERMANOVA for Bray-Curtis distances (beta diversity), and MaAsLin2 to identify discriminating viral taxa.

Poster Abstracts

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1025 WITHDRAWN

CROI 2025 327