CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

934

First Trimester Exposure to Newer Antiretroviral Agents and Congenital Anomalies in a US Cohort Kelly Fung 1 , Sonia Hernandez-Diaz 1 , Rebecca Zash 2 , Ellen G. Chadwick 3 , Russell Van Dyke 4 , Carly Broadwell 1 , Jennifer Jao 3 , Kathleen M. Powis 5 , Lynn Yee 3 , Paige L Williams 1 , for the Pediatric HIV/AIDS Cohort Study (PHACS) 1 Harvard TH Chan School of Public Health, Boston, MA, USA, 2 Beth Israel Deaconess Medical Center, Boston, MA, USA, 3 Northwestern University, Chicago, IL, USA, 4 Tulane University, Metairie, LA, USA, 5 Massachusetts General Hospital, Boston, MA, USA Background: The teratogenicity of antiretroviral medications (ARVs) is a key consideration in clinical recommendations and prescribing decisions for HIV regimens used during pregnancy. However, in the U.S., data on the association between ARV exposures and major congenital anomalies are generally limited to older ARV agents, many of which are now rarely used. Given the timing of organogenesis, it is critical to assess the safety of first-trimester fetal exposure to newer ARVs. Methods: We evaluated the association between first trimester exposure to newer ARVs and major congenital anomalies among infants born between 2012-2022 to pregnant persons with HIV enrolled in the U.S.-based prospective Surveillance Monitoring for ART Toxicities (SMARTT) study conducted by the PHACS network. First trimester exposures to newer ARVs were abstracted from maternal medical records. Trained study site staff conducted physical exams and abstracted congenital anomalies from infant medical records, and investigators classified the anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age 1 year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation (GEE) models were used to estimate the odds ratio (OR) and confidence interval (CI) of major congenital anomalies for each ARV exposure compared to those unexposed to that ARV, adjusting for infant birth year, maternal age at delivery, pre-pregnancy BMI, pregestational diabetes, and first trimester alcohol use, and accounting for correlation among siblings and/or multifetal births. Results: Of 2034 eligible infants, major congenital anomalies occurred in 135 (6.6%; 95%CI: 5.6%-7.8%). Cardiovascular (n=43) and musculoskeletal (n=37) anomalies were most common. The adjusted odds ratios (95% CI) of congenital anomalies were 1.07 (0.64-1.78) for darunavir, 0.93 (0.47-1.85) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.25 (0.67-2.33) for elvitegravir, 0.75 (0.36-1.57) for dolutegravir, and 0.34 (0.05-2.55) for bictegravir (see Table). Findings were similar after adjustment for nucleoside backbones in the ARV regimen. Conclusion: The odds of congenital anomalies among infants with first trimester exposure to newer ARVs did not differ substantially from that among infants unexposed to these specific ARVs. However, modest effects cannot be ruled out, highlighting the need for continued evaluation of these associations in larger populations.

However, the long-term health implications of these exposures for children who are HIV-exposed and uninfected (CHEU) are largely unknown. Methods: Population-based surveillance data from children born to women living with HIV in England (ISOSS) between1995 and 2022 were linked to national cancer registration and mortality data. Date of last cancer registration was used where >1 cancer event occurred. Age-and-sex standardised incidence ratios (SIR) were used to compare cancer incidence in CHEU with the general child population in England. Cancer incidence and associations with maternal, HIV/ART and child characteristics were estimated using Cox-proportional hazards models. Results: There were 19 cancer events (13 in females, 6 in males) in 17 children among 14047 CHEU records with 159,241 person-years follow-up. The cancer incidence rate was 1.07 (95% CI: 0.62-1.71). All cancer events occurred before 17 years of age and median age at last cancer event was 4 years (IQR: 7, Q1:2– Q3:9). Cancers affecting the central nervous system were most common (n=6), followed by lymphoid, haematopoietic, and related tissue cancers (n=4). There were ≤3 cancer registrations affecting the eye, kidney, thorax, bones, bronchus & lungs. Cancer events observed for males aged 0-4 years were lower than expected based on the general population (SIR: 0.14, 0.02-0.99 per 10,000 person-years) with no statistically significant differences at all other ages or among females. Univariable analyses showed weakly positive associations with cancer rate for children with a congenital anomaly (HR: 4.5, 95% CI: 1.0-20.4) and for children born small-for-gestational-age (HR: 3.2, 95% CI: 0.9-12.0) compared to children adequate for gestational age, whilst for children born to women of Black African ethnicity there was a weakly negative association with rate of cancer (HR: 0.43, 95% CI: 0.17-1.08) compared to children born to women of White ethnicity. There were no statistically significant associations between cancer rate and ART drug class used in pregnancy. Conclusion: Cancer type and incidence among CHEU in England does not differ from that in the general population, with known risk factors in the latter such as congenital anomalies also identified in the CHEU population. Further work is ongoing on mortality risk. Maternal Imprinted Immune Perturbations in HIV-Exposed Uninfected (HEU) Infants Persist for 6 Months Li Yin 1 , Bernard M. Fischer 2 , Guglielmo M. Venturi 2 , Upasana Nepal 1 , Shivangi Choudhary 2 , Jerry Shen 1 , Kai-Fen Chang 1 , Isaac D. Raplee 1 , Samiksha A. Borkar 1 , Julie J. Kim-Chang 2 , Kristina De Paris 3 , Maureen M. Goodenow 1 , John W. Sleasman 2 1 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 2 Duke University School of Medicine, Durham, NC, USA, 3 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: HEU infants exhibit higher mortality/morbidity including adverse growth, developmental, infectious, and metabolic outcomes, and perturbed immune responses. How their immune profiles are altered and influenced by maternal immunity is unknown. Methods: The study group included 46 pregnant women with HIV (PWH)/HEU infant pairs enrolled in PACTG 316, with 23 PWH virally suppressed (VS) during pregnancy by antiretroviral therapy (ART) and 23 PWH virally non-suppressed (VNS) on similar ART. Pregnant women without HIV (PWOH)/HIV unexposed uninfected (HUU) neonates (n=18) served as a reference. HEU infants were evaluated at birth and 6 months along with a longitudinal cohort of 32 HUU infants. Maternal plasma samples were obtained at or near delivery. Twenty one plasma biomarkers associated with germinal center (GC) development, immune activation, inflammation, and immune regulation were measured using Mesoscale. Results of two or multiple groups were compared by Mann Whitney or Kruskal-Wallis tests, respectively, while mother/newborn biomarker correlations were assessed by Spearman's test. Results: Compared to PWOH, biomarkers related to GC development (sCD40L, IL21), immune activation (sCD163, sCD27, IL22) and inflammation (CXCL9, CXCL10, CCL5, TNFα, IL1β) were significantly elevated in all PWH, independent of viral status. At birth, HEU compared to HUU infants had significantly higher concentrations of GC (APRIL, BAFF, sCD40L, IL21), immune activation (sCD14, IL22, IL2), inflammation (CXCL9, CCL4, CCL5, TNFα, IL1β), and immune regulation (IL1RA) that persisted for 6 months. Elevated birth levels of IL6 and IL10 normalized, while sCD27, IFNγ, and CXCL10 increased at 6 months. Correlations at birth between PWOH/HUU newborn biomarkers showed minimal relationships. In contrast, PWH/HEU pairs displayed multiple positive correlations; for example, elevation of IL6 levels in PWH correlated with increased levels of anti-

Poster Abstracts

936

935

Cancer Incidence in Children Who Are HIV-Exposed and Uninfected in England: Data Linkage Study Laurette L. Bukasa, Claire Thorne , Mario Cortina-Borja, Helen Peters, Pia Hardelid University College London, London, United Kingdom Background: Children born to women living with HIV develop in an in utero environment that includes exposure to HIV and antiretroviral therapy (ART).

CROI 2024 295