CROI 2025 Abstract eBook

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Poster Abstracts

Results: Virome richness was lower among CHEU than CHUU (b= -130, 95% CI: -250 – -9.7, p=0.03), but there were no differences in Shannon diversity (beta= -0.3, 95% CI: -0.5–0.05, p=0.1) or Bray-Curtis distances (p=0.8) by HIV exposure. Relative abundances of 28 unique viral contigs were associated with CHEU status, of which 17 (61%) were of the family Anelloviridae . Consistent with previous studies of CHUU, older age (months; beta= 24.1, 95% CI: 4.2-43.9, p=0.02) and introduction of foods other than breast milk (beta= 343, 95% CI: 112-573, p=0.004) were also associated with higher virome richness among all infants. Conclusions: Age, feeding practices, and HIV exposure altered gut virome richness, but not Shannon or beta diversity, suggesting the presence and/ or absence of specific viruses within groups did not substantially shift overall community structure. Similarities between CHEU and CHUU suggest that HIV exposure is not a major determinant of the infant virome when mothers receive optimized ART before or in early pregnancy. Further research should assess whether lower abundance of Anelloviridae has a meaningful effect on health among CHEU. 1028 HIV Exposure Does Not Affect Cytomegalovirus Acquisition Risk in a Setting of Optimized Maternal ART Emily R. Begnel 1 , Mi-Suk Kang Dufour 2 , Kerusha Govender 2 , Jing Hu 2 , Elisabeth McClymont 3 , Ednah Ojee 4 , Prestone O. Owiti 4 , Judith Adhiambo 4 , Eliza Mabele 4 , Bhavna H. Chohan 1 , Dara A. Lehman 5 , John Kinuthia 6 , Dalton Wamalwa 4 , Soren Gantt 2 , Jennifer Slyker 1 1 University of Washington, Seattle, WA, USA, 2 University of Montreal, Montreal, Canada, 3 University of British Columbia, Vancouver, Canada, 4 University of Nairobi, Nairobi, Kenya, 5 Fred Hutchinson Cancer Center, Seattle, WA, USA, 6 Kenyatta National Hospital, Nairobi, Kenya Background: Children who are HIV-exposed, uninfected (CHEU) have had higher incidence and earlier cytomegalovirus (CMV) acquisition than children who are HIV-unexposed, uninfected (CHUU), which may contribute to the higher morbidity and mortality observed among CHEU. To determine whether this difference in CMV acquisition persists in the era of optimized, universal ART, we assessed the probability, timing, and correlates of primary CMV infection within a recent birth cohort of CHEU and CHUU. Methods: Women without HIV and women living with HIV on ART for ≥6 months were recruited in pregnancy (28-42 weeks gestation) from a maternal child health clinic in Nairobi, Kenya between December 2018-March 2020; 89% of mothers with HIV initiated ART before pregnancy. Mother-infant pairs were followed for 12 months postpartum with weekly data and sample collection. Quantitative PCR was used to measure log 10 -CMV DNA levels in infant urine/ saliva and maternal saliva/breast milk. The probability and timing of infant CMV acquisition were determined by Kaplan-Meier survival analysis. Correlates of CMV acquisition were assessed using Cox proportional hazards regression models stratified by exclusive breastfeeding (EBF) status and adjusted for infant sex, HIV exposure, and household crowding. Results: Fifty-three (74%) of 72 infants (22 CHEU, 31 CHUU) acquired CMV. Median time to infection was 2.4 months (IQR 2.0-4.7) and did not differ by HIV exposure (log-rank p=0.7). HIV exposure did not affect the hazard of CMV acquisition when infants were EBF (adjusted hazard ratio [aHR]= 1.24, 95% CI: 0.69-2.23, p=0.471) or not EBF (aHR=0.52, 95% CI: 0.10-2.68, p=0.438). However, the hazard was two times greater per log10 increase in breastmilk CMV DNA both when infants were EBF (aHR=2.09, 95% CI: 1.48-2.95, p<0.001) and received mixed feeds (aHR=1.98, 95% CI: 1.26-3.10, p=0.003); this finding did not differ by HIV exposure. Women living with HIV had higher CMV DNA levels in breast milk despite initiating ART before (89%) or in early (11%) pregnancy (Figure 1). Conclusions: Probability of CMV acquisition was similar between CHUU and CHEU whose mothers initiated optimized ART before pregnancy, and 74% of infants acquired CMV in the first 3 months of life. Breast milk remains a primary source of CMV acquisition for all infants. Though mothers with HIV had higher breast milk CMV DNA levels despite receiving optimized ART before or in early pregnancy, this did not translate to higher risk of CMV acquisition among CHEU.

1029 Rapid Waning in Hepatitis B Virus Vaccine Immunity Among Children HIV-Exposed Uninfected in Botswana Lynette Bhebhe 1 , Bonolo B. Phinius 1 , Tsholofelo K. Ratsoma 1 , Gorata Mpebe 1 , Chanana Tsayang 1 , Kabo Baruti 1 , Basetsana K. S. Phakedi 1 , Linda D. T. Mpofu Dobo 1 , Patience Motshosi 1 , Justine Legbedze 2 , Jennifer Jao 3 , Kathleen Powis 4 , Sikhulile Moyo 1 , Motswedi Anderson 1 , Simani Gaseitsiwe 1 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA, 3 Northwestern University, Chicago, IL, USA, 4 Massachusetts General Hospital, Boston, MA, USA Background: The impact of perinatal HIV exposure on children’s immune response to the hepatitis B virus (HBV) vaccine over time has yet to be fully understood. We determined the HBV prevalence in mother-child pairs and HBV vaccine response in children HIV-exposed uninfected (cHEU) and those unexposed uninfected (cHUU) over time in Botswana. Methods: Mother-child specimens from pregnant women with and without HIV enrolled in the Botswana-based Tshilo Dikotla study (2016–2022) and followed up for three years were utilised. Baseline maternal samples were tested for HBV surface antigen (HBsAg) and HBV core antibodies (anti-HBc) using an enzyme linked immunosorbent assay. Plasma samples from children were screened for HBsAg, anti-HBc and HBV surface antibodies (anti-HBs) using a chemiluminescent assay at 2 and 3 years of age. Anti-HBs levels ≥10 mIU/ mL were considered protective. Wilcoxon Rank-sum test and Chi-square tests were used to compare characteristics and vaccine responses by child HIV status. Paired t-tests were used to compare anti-HBs titers at two timepoints (year 2 and 3). Results: Women with HIV (WWH) were older, median age 30 years (interquartile range (IQR):25–35) compared to those without (24 years (IQR:21– 29)) (p<0.001). Among 248 maternal plasma samples tested (>24 weeks gestation), HBV prevalence was 2.0% (95% CI:0.74–4.9). WWH had a higher HBV exposure (anti-HBc positivity) 29.0% (95% CI:22.5–36.4) compared to mothers without HIV, 13.9% (95% CI:7.2–24.5, p=0.02). HBV prevalence among 3-year olds was 0.56% (1/179) (95% CI: 0.03–3.5) with no observed differences by HIV exposure (0.74% cHEU vs 0% in cHUU, p=0.53). None had prior HBV exposure. 18.4% (25/136) of cHEU and 9.3% (4/43) of cHUU had non-protective HBV immunity at the age of 3 (Figure 1). Vaccine response was assessed in 89 paired plasma samples available at 2 and 3 years. A significant decline in anti-HBs titers within a year was observed in both cHEU (coefficient=0.76, p<0.001) and cHUU (coefficient=0.80, p<0.01). Of the 17 (19.1%) non-responders (<10mIU/mL), 14 (83.2%) were cHEU, and a significant decline in immune response was observed among cHEU within 12 months (p<0.05), with no difference in cHUU (p=0.08). Conclusions: We report rapid waning of HBV vaccine immunity within the first 3 years of life, which was more pronounced in cHEU than those cHUU. This increases the risk of HBV infection hence longer-term studies are needed to determine if HBV vaccine booster doses are required for these children.

Poster Abstracts

CROI 2025 328