Objectives: To describe demographics of mother-infant pairs (MIP), antiretroviral treatment (ART) during pregnancy, and vertical transmission (VT) rates in Canada in 2024, and to examine factors associated with ART coverage during pregnancy in 2014-2024

Methods: Data are collected annually from 22 Canadian pediatric and HIV centres of the Canadian Perinatal HIV Surveillance Program. Data collected include maternal characteristics, pregnancy ART and infant outcome.

Results: There were 258 infants born in 2024 (250/year in 2014-2023); 31.8% were from Ontario, 24.4% from Quebec, 15.5% from Saskatchewan, 12.8% from Alberta, 9.7% from Manitoba; 3.5% from BC and 2.3% from the Atlantic provinces. In 2024, 62.0% were Black, 22.9% were Indigenous, and 7.0% were White. Overall, 64.7% of pregnant women/people acquired HIV heterosexually, 10.5% through injection drug use, and 4.3% perinatally. The proportion of pregnant women/people receiving <4 weeks of ART in 2024 was 6.3% (16/255). This proportion was significantly higher in 2014-2024 in Manitoba, Saskatchewan, and Alberta compared with the remainder of Canada and in women acquired HIV through injection drug use compared to heterosexual sex (OR=2.04 (95%CI: 1.50, 2.78); p<0.001 and 3.91 (2.71, 5.65); <0.001), but only the latter difference remained significant after multivariable adjustment (aOR=1.85 (1.17, 2.92); p=0.01), and the same conclusion held after excluding COVID years (2020–2021). There was one case of vertical transmission (VT) in 2024 (VT rate = 0.4%, 1/258), and this infant’s mother had no ART before delivery.

Conclusions: While Canada has reached the threshold of elimination of HIV transmission with <2 cases per 100,000 live births, suboptimal ART in pregnancy and VT events continue to occur in Canada at unacceptably high rates. Tailored interventions designed to engage pregnant women/people with HIV experiencing barriers to care are needed if further reductions in VT rates are to be achieved.

Background:
Integrase strand transfer inhibitors (INSTIs) are the recommended antiretrovirals (ARVs) for people living with HIV, including pregnant women. In utero exposure to HIV/ARVs has been associated with higher risk for neurodevelopmental deficits in HIV-exposed but uninfected children. Placental fatty acid (FA) transport, which is vital for fetal brain development, relies on several transport proteins to ensure fetal FA demands are met. We explored the effects of INSTI exposure on placental expression of FA transporter genes in a mouse pregnancy model and in pregnant persons living with HIV taking INSTIs.
Methods:
Healthy C57BL/6 mice were treated with INSTI-based ART (bictegravir, cabotegravir, dolutegravir, raltegravir) with or without a nucleoside reverse transcriptase inhibitor backbone of TDF/FTC, or water as a control, at therapeutic concentrations via oral gavage from conception until gestational day 15.5. Placental gene expression was assessed by qPCR. Term placentas were collected from Canadian individuals with or without HIV for analysis of protein expression by western blot. Individuals with HIV were taking INSTI-based regimens.
Results:
In mice, treatment with INSTIs + TDF/FTC altered placental gene expression of several FA transport proteins (Fatps), FA binding proteins (Fabps), and lipases (Lpl, Lipg) when compared to controls. Significant reductions in expression of nuclear transcription factors Pparg and Rxra were observed across INSTI + TDF/FTC regimens. INSTIs alone induced more modest changes in gene expression. Preliminary analyses of protein expression in term placental samples demonstrated alterations in the expression of LPL, FATP4, and FABP4 in HIV seropositive individuals treated with INSTIs compared to healthy controls.
Conclusion:
Our findings demonstrate that INSTI-based regimens alter gene expression of mouse placental FA transporters in healthy mice. Protein expression of several transporters in human term placentas is altered in women living with HIV taking INSTIs. Further research is required to understand how INSTIs impact placental transfer of FAs.

Objectives: Antiretroviral (ARV) therapy (ART) has been associated with increased risk for adverse birth outcomes, though the mechanisms controlling these processes are not fully understood. Variations in placental structure can result in poor function, contributing to adverse birth outcomes. We examined placental villous structure in Ugandan women living with HIV on ARVs, women without HIV on PrEP (pre-exposure prophylaxis), and women without HIV, and explored associations with mid-gestational levels of key regulating angiogenic factors and steroid hormones.
Methods: All women with placenta tissue and plasma collected between gestational weeks 20-24 were included. Formalin fixed paraffin embedded placental core tissue was randomly sectioned and stained with Masson’s Trichrome for imaging. Stereological tools were applied for quantitative analysis of villous structure (villous surface density, villous volume). Plasma, angiogenic, and hormone factors were quantified using Luminex and ELISA. Statistical assessments were performed, including ANOVA with post-hoc testing. Partial correlation networks for biomarkers and outcomes were estimated using an ensemble method, SpiderLearner.
Results: 113 Ugandan participants (44 HIV-negative, 36 HIV-negative/PrEP, 33 HIV-positive/dolutegravir (DTG) based-ART) were included. Birth weight and placental weight z-scores were similar between groups. Villous surface density and villous volume did not differ significantly between treatment groups. Vascular endothelial growth factor concentrations were significantly lower in HIV+/DTG-exposed placentas compared to HIV-negative and PrEP-exposed placentas, with all other factors being similar between groups. Using partial correlation network analysis, we observed different patterns in angiogenic and hormone networks and their relationships with villous volume and birth outcomes in each of the treatment groups.
Conclusion: These findings contribute to the larger body of research on ARV drug effects on placental morphology and development. The inclusion of PrEP in this research allows for the separation of ARV drug effects from HIV effects in the context of pregnancy.

Objective
Women living with HIV (WLWH) are 70% more likely to experience lifetime amenorrhea (no menstruation for >12 months) than HIV-negative women, placing them at higher risk for conditions linked to low sex hormone states, including dyslipidemia. While previous studies examined reproductive hormones and lipid indicators, data specific to WLWH remain limited. This study evaluated the relationship between dyslipidemia and reproductive hormone levels (estradiol and progesterone) among premenopausal women living with and without HIV.

Methods
We conducted a cross‐sectional analysis of 273 nonpregnant premenopausal female participants (116 WLWH and 157 women without HIV, ≥16y old) enrolled in BCC3 between December 2020-2024. Participants were classified as having dyslipidemia if they self-identified as having high cholesterol, took lipid medication, or had dyslipidemia diagnosis based upon interpretation of lab values with current Canadian guidelines. Hormone levels were timed for women with regular menstrual cycles, and drawn randomly for those without, and were assessed by ELISA. Univariate analysis used Wilcoxon rank-sum and Chi-squared tests for continuous and categorical variables, respectively. Multivariable logistic regression included variables with p<0.2 univariably to estimate adjusted odds ratios (AOR).

Results
In univariable analysis, lower progesterone levels were associated with dyslipidemia (p=0.04) and HIV status (p<0.01), though were not significant after controlling for covariates. A multivariable progesterone–HIV interaction term revealed opposite effects: higher progesterone was linked to increased dyslipidemia risk in WLWH but decreased risk in HIV-negative women (p=0.039). Although estradiol levels did not differ by HIV status, lower levels were associated with increased dyslipidemia risk among all women (AOR: 0.06 (0.01-0.40), p<0.001) after controlling for covariates.

Conclusion
Lower sex hormone levels may elevate dyslipidemia risk in WLWH, warranting further mechanistic research and exploration of exogenous hormone therapy to improve lipid and cardiovascular outcomes in this population.

Background:
Women living with HIV face persistent risks of adverse birth outcomes despite effective antiretroviral therapy. Placental System L amino acid transport, mediated by LAT1 and LAT2, is essential for fetal growth, but the effects of maternal HIV infection on placental expression remain poorly understood. We sought to examine the impact of maternal HIV infection on placental LAT1 and LAT2 expression and explored associations with birthweight outcomes.

Methods:
Placental tissues were collected between 2010-2025 from participants aged ≥18 years enrolled in the Angiogenesis and Adverse Pregnancy Outcomes in Women with HIV (AAPH) cohort in Toronto, Canada. This analysis included placentas from 60 women living with HIV (HIV+ group) and 22 women without HIV (control group). LAT1 and LAT2 protein expression was measured by Western blot and quantified using Image Lab (v6.1). Transporter expression was compared by HIV-status using Mann-Whitney test. Associations between LAT expression, birthweight, and birthweight centile were assessed using Spearman correlation.

Results:
Placental LAT1 expression was significantly higher in the HIV+ group compared to control (median [95%CI]: 0.95 [0.83-1.16]), while LAT2 expression was significantly lower (0.32 [0.26-0.37]). The LAT1:LAT2 protein expression ratio was significantly higher in the HIV+ group (2.88 [2.48-3.66]). LAT1 expression was negatively correlated with birthweight (r=-0.24, p<0.05), whereas LAT2 showed a trend towards a positive correlation (r=0.13). Increased LAT1:LAT2 ratios were negatively correlated with birthweight (r=-0.28, p<0.05), with a similar trend observed for birthweight centile.

Discussion:
Maternal HIV infection is associated with a shift toward LAT1-dominant placental System L transporter expression. This profile may act as a bottleneck, limiting amino acid transfer to fetal circulation and contributing to reduced birthweight, highlighting placental nutrient transport as a potential mechanism linking HIV exposure to adverse birth outcomes. Future studies assessing amino acid transport as well as impact of antiretrovirals on System L are merited.

Background:
With rising HCV prevalence among individuals of childbearing age, international guidelines recommend shared decision-making regarding treatment during pregnancy. Additionally, Canadian Obstetrical guidelines now recommend universal HCV screening in pregnancy, which will increase case-finding. While some clinicians have begun to offer HCV treatment in pregnancy, little is known about what influences treatment decisions among pregnant individuals.

Method:
Pregnant individuals with detectable HCV RNA were offered enrollment after discussing HCV treatment during pregnancy with their clinician. Participants ≥18 years were recruited from 7 sites in Ontario or British Columbia. Those already receiving HCV treatment or unable to consent were excluded. All, irrespective of whether they decided to be treated in pregnancy, were interviewed prior delivery. Interview guides were tailored to participants’ experiences and perspectives on living with HCV prior to, and/or during prenatal care, competing life priorities, understanding of vertical transmission, and what factors influenced decisions. Thematic analysis, informed by interpretive description, was used to identify relevant patterns and meanings.

Result(s):
Six participants were interviewed during pregnancy; one did not choose treatment. Several themes were identified: initial shock and concern regarding their diagnosis, influence of family on decision-making, further exploration through online investigation, and motivations rooted in maternal identity and external judgment. Facilitators to treatment initiation and adherence during pregnancy included maternal responsibility and motivation to protect their infant, positive clinician relationships, and structured support environments. Barriers to treatment during pregnancy included stigma, inconsistent provider messaging, competing priorities, and psychosocial stressors. Interestingly, there was a feeling of “no correct choice” balancing prevention of transmission with perinatal medication exposure.

Conclusion(s):
This study highlights the influence of identity, provider relationships and messaging, perspectives from family members, and patient-facing online resources on HCV treatment in pregnancy decision-making. As such, family-centered models of care, should include consistent messaging in stigma-free environments.

Background: HIV envelope glycoprotein plays a role in viral entry. Its soluble gp120 subunit (sgp120) has been associated with immune dysfunction and inflammation. sgp120 binds to uninfected bystander cells, which get eliminated by anti-cluster A antibodies (ACAA) through antibody-dependent cellular cytotoxicity. While observed in adults with undetectable viral loads, this has never been described in children with perinatal HIV (CLWH). We assessed relationships between sgp120 & ACAA and immunologic measures, HIV reservoir, and inflammatory cytokines in CLWH in the EPIC4 Cohort.

Methods: This cross-sectional sub-study used data and biosamples from CLWH with sustained viral suppression (SVS) on ART. Relationships between sgp120, ACAA and immunologic markers (CD4%, CD4:CD8 ratio), HIV reservoir size (PBMC proviral DNA quantification), and inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α) were assessed.

Results: 105 CLWH were included (49% females, median age 13.6y, ART initiation age 1.5y, ART duration 8.7y, SVS duration 6.2y, current CD4 count 750cells/µL, CD4% 37%, CD4:CD8 ratio 1.14). sgp120 was detectable in 15/105 (14%), and ACAA in 80/105 (76%). Detectable sgp120 was associated with lower CD4 count (660 vs 775cells/µL, p=0.042), CD4% (33 vs 38%, p=0.005) and CD4:CD8 ratio (0.85 vs 1.19, p<0.001); detectable ACAA was associated with lower CD4% (36 vs 40%, p=0.003), age (14.0 vs 8.4y, p=0.010), ART initiation age (2.7 vs 0.4y, p<0.001), and SVS duration (5.8 vs 7.5y, p=0.005). In regression analysis adjusted for age, sex, ART duration and CMV seropositivity, sgp120+ was associated with lower CD4:CD8 ratio, and ACAA+ with lower CD4%; sgp120/ACAA were not associated with cytokines. Proviral DNA was associated with higher IL-10 among sgp120+, lower IL-1β and TNF-α among sgp120- and lower IL-1β, IL-6, and TNF-α among ACAA+.

Conclusions: sgp120 and ACAA were inversely associated with immune function in children, and when present an association between proviral DNA and inflammatory cytokines was observed suggesting a mediating role.

Background: The Kids Imaging and Neurocognitive Development (KIND) study is an ongoing cohort recruiting school-aged children who are HIV-exposed uninfected (CHEU) and children who are HIV-unexposed uninfected (CHUU) in Toronto and Ottawa. We have previously reported intellectual difficulties in CHEU compared to CHUU KIND study participants, with greater deficits observed in boys HEU. Here we investigate behavioural difficulties in the same population and explore associations with intellectual performance.

Methods: The parent administered Strengths and Difficulties Questionnaire (SDQ) was used to collect data on behavioural difficulties. The SDQ total difficulties score, a combined score of 4 scales (emotional symptoms, conduct problems, hyperactivity/inattention, peer relationship problems) was calculated. Scores were dichotomized into those scoring >17, indicating a substantial risk of clinically significant problems, and <17. The WISC-V was used to assess intellectual abilities. Fisher’s exact was used to assess difference by HEU-status. Spearman correlation were used to assess associations between SDQ total difficulties scores and intellectual and language abilities stratified by HEU-status.

Results: Data from the parent administered SDQ were available for 99 CHEU (51 girls) and 43 CHUU (18 girls). Child median age at time of assessment was 8 years. Thirteen (13.1%) CHEU had a total difficulties score >17, scoring in the substantial risk of clinically significant problems range, compared to none of the CHUU (13.1% vs. 0%, p=0.01). Of the 13 CHEU scoring in the problem range, 11 were male. SDQ total difficulties scores correlated negatively with working memory (r= -0.37, p<0.001), processing speed (r= -0.27, p=0.009), and full-scale IQ (r= - 0.32, p=0.0014) in CHEU. No significant associations were observed in CHUU.

Conclusions: Behavioural difficulties were more prevalent in CHEU, particularly in boys. Behaviour difficulties were associated with poorer intellectual performance in CHEU. With increasing recruitment into the KIND cohort, future work will investigate associations with perinatal antiretroviral exposure.