Clinical Sciences Oral Abstract Session #1
Tracks
*
Friday, May 2, 2025 |
11:00 - 12:30 |
Overview
Sciences cliniques séances de présentation orale d’abrégés #1
Details
HIV in women, in pregnancy and pediatrics // Le VIH chez les femmes, pendant la grossesse et pédiatrie
Speaker
Jason Brophy
Staff Physician
Cheo
Linear Growth Among Infants With In Utero Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide Exposure
Abstract
Background:
Tenofovir disoproxil fumarate (TDF) is a NRTI of choice for treating pregnant women with HIV (but not in prepubertal children due to bone toxicity concerns). Tenofovir alafenamide (TAF), a pro-drug with improved bone safety, is becoming more widely used and was recently recommended in pregnancy. Some studies among TDF-exposed infants demonstrated linear growth impairment at 12 months; limited outcomes with TAF are available. We evaluated linear growth among children with in utero TDF & TAF exposure.
Methods:
Children born to mothers with HIV treated with antiretroviral therapy (ART) from 2011-2022 were retrospectively reviewed at our centre. Height-for-corrected-age (HFA) z-scores at 12 and 18 months were compared between TDF-, TAF-, and unexposed infants using Kruskal-Wallis test. Among those on TDF/TAF, outcomes were compared for those also exposed to protease inhibitors (PI) vs no PI.
Results:
Outcomes were available for 157 children. Mean (SD) gestational age was 38.9 (2.0) weeks, with 80 (51%) females. 83 (53%) were TDF-exposed, 9 (6%) were TAF-exposed, and 65 (41%) were exposed to neither. 25 (30%) of TDF-exposed and no TAF-exposed were exposed to PI. Median (IQR) HFA z-scores at 12 months in TDF-, TAF-, and neither-exposed infants were 0.7 (-0.1, 1.3) vs 0.6 (0.3, 0.9) vs 0.5 (0.1, 1.2) (p=0.99). Among infants with TDF+PI vs TDF without PI, z-scores were 0.3 (-0.1, 1.0) vs 0.7 (-0.1, 1.5) (p=0.37). Among 128 participants with outcomes at 18 months, median z-scores in TDF- (n=70), TAF- (n=4) and neither-exposed (n=54) were 0.5 (-0.2, 1.2) vs 0.9 (0.7, 1.0) vs 0.2 (-0.3, 1.1) (p=0.54).
Conclusions:
No association was identified between HFA z-scores at 12 or 18 months and TDF exposure; small sample size of TAF-exposed infants limited ability to detect differences. With most ART-infants globally being exposed to TDF, it is essential to understand its impact on children’s health.
Tenofovir disoproxil fumarate (TDF) is a NRTI of choice for treating pregnant women with HIV (but not in prepubertal children due to bone toxicity concerns). Tenofovir alafenamide (TAF), a pro-drug with improved bone safety, is becoming more widely used and was recently recommended in pregnancy. Some studies among TDF-exposed infants demonstrated linear growth impairment at 12 months; limited outcomes with TAF are available. We evaluated linear growth among children with in utero TDF & TAF exposure.
Methods:
Children born to mothers with HIV treated with antiretroviral therapy (ART) from 2011-2022 were retrospectively reviewed at our centre. Height-for-corrected-age (HFA) z-scores at 12 and 18 months were compared between TDF-, TAF-, and unexposed infants using Kruskal-Wallis test. Among those on TDF/TAF, outcomes were compared for those also exposed to protease inhibitors (PI) vs no PI.
Results:
Outcomes were available for 157 children. Mean (SD) gestational age was 38.9 (2.0) weeks, with 80 (51%) females. 83 (53%) were TDF-exposed, 9 (6%) were TAF-exposed, and 65 (41%) were exposed to neither. 25 (30%) of TDF-exposed and no TAF-exposed were exposed to PI. Median (IQR) HFA z-scores at 12 months in TDF-, TAF-, and neither-exposed infants were 0.7 (-0.1, 1.3) vs 0.6 (0.3, 0.9) vs 0.5 (0.1, 1.2) (p=0.99). Among infants with TDF+PI vs TDF without PI, z-scores were 0.3 (-0.1, 1.0) vs 0.7 (-0.1, 1.5) (p=0.37). Among 128 participants with outcomes at 18 months, median z-scores in TDF- (n=70), TAF- (n=4) and neither-exposed (n=54) were 0.5 (-0.2, 1.2) vs 0.9 (0.7, 1.0) vs 0.2 (-0.3, 1.1) (p=0.54).
Conclusions:
No association was identified between HFA z-scores at 12 or 18 months and TDF exposure; small sample size of TAF-exposed infants limited ability to detect differences. With most ART-infants globally being exposed to TDF, it is essential to understand its impact on children’s health.
Athena McConnell
Pediatrician
University of Saskatchewan
Adequacy of Antiretroviral Treatment in Pregnancy and Vertical Transmission Rates in Canada: Data from the Canadian Perinatal HIV Surveillance Program
Abstract
Objectives: To describe demographics of mother-infant pairs (MIP), antiretroviral treatment (ART) during pregnancy, and vertical transmission (VT) rates in Canada in 2023, and to compare trends in ART coverage during pregnancy and VT rates in 2023 versus 2014-2022.
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 247 infants born in 2023 (250/year in 2014-2022); 32% were from Ontario, 24% from Quebec, 18% from Saskatchewan, 15% from Alberta, 7% from Manitoba; 4.5% from BC and 0.4% from Maritimes. 57% were Black, 25% were Indigenous, and 11% were white. Overall, 77% of pregnant women/people acquired HIV heterosexually, 17% through injection drug use and 3% perinatally. The proportion of pregnant women/people receiving <4 weeks of ART in 2023 was 7.4% (18/242). The proportion of pregnant women/people receiving <4 weeks of ART since 2014 was significantly higher in Manitoba, Saskatchewan and Alberta (8.8%, 69/786) compared with the remainder of Canada (5.3%, 65/1229; OR=1.97 (1.42, 2.72); p<0.001). However, this difference was no longer significant after accounting for mode of infection and ethnicity (aOR=0.94 (0.55, 1.59); p=0.81); the same conclusion was reached after excluding the data from the COVID years (2020-2021). There were five cases of VT in 2023 (VT rate = 2.0%, 5/247), including three infants whose mothers received <4 weeks of ART (16.7%, 3/18), and two infants whose mothers received ART for ≥4 weeks (0.9%, 2/224).
Conclusions: Suboptimal ART in pregnancy remains a major problem 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.
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 247 infants born in 2023 (250/year in 2014-2022); 32% were from Ontario, 24% from Quebec, 18% from Saskatchewan, 15% from Alberta, 7% from Manitoba; 4.5% from BC and 0.4% from Maritimes. 57% were Black, 25% were Indigenous, and 11% were white. Overall, 77% of pregnant women/people acquired HIV heterosexually, 17% through injection drug use and 3% perinatally. The proportion of pregnant women/people receiving <4 weeks of ART in 2023 was 7.4% (18/242). The proportion of pregnant women/people receiving <4 weeks of ART since 2014 was significantly higher in Manitoba, Saskatchewan and Alberta (8.8%, 69/786) compared with the remainder of Canada (5.3%, 65/1229; OR=1.97 (1.42, 2.72); p<0.001). However, this difference was no longer significant after accounting for mode of infection and ethnicity (aOR=0.94 (0.55, 1.59); p=0.81); the same conclusion was reached after excluding the data from the COVID years (2020-2021). There were five cases of VT in 2023 (VT rate = 2.0%, 5/247), including three infants whose mothers received <4 weeks of ART (16.7%, 3/18), and two infants whose mothers received ART for ≥4 weeks (0.9%, 2/224).
Conclusions: Suboptimal ART in pregnancy remains a major problem 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.
Eve A Forster
Programmer/analyst
The Hospital For Sick Children
Structural Brain Differences in School-Aged Children Who Are HIV-Exposed Uninfected
Abstract
Background:
Antiretroviral therapy (ART) has significantly lowered the rate of perinatal HIV transmission in Canada, increasing the number of children who are HIV-exposed but uninfected (CHEU). While the neuroanatomic developmental effects of in-utero HIV and ART exposure have been studied in younger children, a gap remains for those aged 6 to 12 years. This study is the first to examine impacts in this age group.
Methods:
Participants included 58 CHEU (31 female, 27 male; mean age=8.7, SD=1.5; 71% African/Caribbean/Black; 29% premature birth (< 37 weeks)) and 38 children who are HIV-unexposed, uninfected (CHUU) (15 female, 23 male; mean age=8.8, SD=1.6; 45% African/Caribbean/Black; 8% premature birth) from Ontario, Canada. T1-weighted MRI scans were processed to extract cortical and subcortical volume, cortical thickness and surface area, and grey-/white-matter tissue classification. Linear models—adjusted for sex, age, income, and total brain volume—were fit to explore the effect of exposure group on each neuroanatomic measure. Sex-stratified models were also calculated.
Results:
CHEU exhibited smaller total brain volumes and thinner cortices compared to CHUU. Within the male cohort, volumetric age-exposure interactions were noted in the pars opercularis, left rolandic operculum, and left precentral gyrus, suggesting delayed maturation in CHEU. Reduced cortical thickness in CHEU was noted in the frontal lobe, with pronounced effects between male CHEU and CHUU in the orbital middle frontal gyrus. Hippocampal volume was also reduced in male CHEU. An age-exposure interaction in the volume of the amygdalae suggests an altered growth trajectory or reduced growth among CHEU.
Conclusions:
These findings indicate that in-utero HIV and ART exposure may impact brain development, particularly in regions associated with motor function, expressive language, memory, and emotion. The results align with previously reported deficits in motor and language abilities, emphasizing the need for early interventions and support for CHEU.
Antiretroviral therapy (ART) has significantly lowered the rate of perinatal HIV transmission in Canada, increasing the number of children who are HIV-exposed but uninfected (CHEU). While the neuroanatomic developmental effects of in-utero HIV and ART exposure have been studied in younger children, a gap remains for those aged 6 to 12 years. This study is the first to examine impacts in this age group.
Methods:
Participants included 58 CHEU (31 female, 27 male; mean age=8.7, SD=1.5; 71% African/Caribbean/Black; 29% premature birth (< 37 weeks)) and 38 children who are HIV-unexposed, uninfected (CHUU) (15 female, 23 male; mean age=8.8, SD=1.6; 45% African/Caribbean/Black; 8% premature birth) from Ontario, Canada. T1-weighted MRI scans were processed to extract cortical and subcortical volume, cortical thickness and surface area, and grey-/white-matter tissue classification. Linear models—adjusted for sex, age, income, and total brain volume—were fit to explore the effect of exposure group on each neuroanatomic measure. Sex-stratified models were also calculated.
Results:
CHEU exhibited smaller total brain volumes and thinner cortices compared to CHUU. Within the male cohort, volumetric age-exposure interactions were noted in the pars opercularis, left rolandic operculum, and left precentral gyrus, suggesting delayed maturation in CHEU. Reduced cortical thickness in CHEU was noted in the frontal lobe, with pronounced effects between male CHEU and CHUU in the orbital middle frontal gyrus. Hippocampal volume was also reduced in male CHEU. An age-exposure interaction in the volume of the amygdalae suggests an altered growth trajectory or reduced growth among CHEU.
Conclusions:
These findings indicate that in-utero HIV and ART exposure may impact brain development, particularly in regions associated with motor function, expressive language, memory, and emotion. The results align with previously reported deficits in motor and language abilities, emphasizing the need for early interventions and support for CHEU.
Adriana Zutic
University Of Toronto
Investigating the Effects of HIV Integrase Strand Transfer Inhibitors on Expression of Fatty Acid Transporters in the Placenta of Healthy Mice
Abstract
Background:
Integrase strand transfer inhibitors (INSTIs) are part of current recommended antiretroviral regimens (ART) for people with HIV, including pregnant persons. In utero exposure to HIV/ART has been associated with higher risk for neurodevelopmental deficits in children who are HIV-exposed, uninfected. Fatty acid (FA) transport, which is vital for fetal brain development, has not been explored in the context of HIV/ART. We explored the effects of INSTI exposure on placental expression of FA transporter genes in a mouse pregnancy model.
Methods:
Healthy C57BL/6 mice (N=10-20 dams/arm) were treated with INSTI-based ART (bictegravir, cabotegravir, dolutegravir, or raltegravir administered with TDF/FTC), or water as a control, at therapeutic concentrations via oral gavage from conception until sacrifice (gestational day 15.5). Placental gene expression was assessed by qPCR. Generalized linear models assessed differences versus controls. Correlations with fetal and placental weights were analyzed using Spearman's rank correlation.
Results:
INSTI treatment altered gene expression of FA transport proteins (Fatps), FA binding proteins (Fabps), lipases (Lpl, Lipg), and fatty acid translocase (Cd36/Fat) when compared to controls, with differential results based on treatment regimen (Table 1). Significant reductions in expression of nuclear transcription factors Pparg and Rxra was observed across treatment regimens. Expression of lipases was strongly associated with placental weight but not fetal weight in the cabotegravir treatment arm.
Conclusion:
Treatment with therapeutic doses of all INSTIs alters expression of placental FA transport associated genes. Changes in Pparg expression, which regulates expression of Fatps, Fabps, and lipases, suggests it is driving changes in transporter expression.
Integrase strand transfer inhibitors (INSTIs) are part of current recommended antiretroviral regimens (ART) for people with HIV, including pregnant persons. In utero exposure to HIV/ART has been associated with higher risk for neurodevelopmental deficits in children who are HIV-exposed, uninfected. Fatty acid (FA) transport, which is vital for fetal brain development, has not been explored in the context of HIV/ART. We explored the effects of INSTI exposure on placental expression of FA transporter genes in a mouse pregnancy model.
Methods:
Healthy C57BL/6 mice (N=10-20 dams/arm) were treated with INSTI-based ART (bictegravir, cabotegravir, dolutegravir, or raltegravir administered with TDF/FTC), or water as a control, at therapeutic concentrations via oral gavage from conception until sacrifice (gestational day 15.5). Placental gene expression was assessed by qPCR. Generalized linear models assessed differences versus controls. Correlations with fetal and placental weights were analyzed using Spearman's rank correlation.
Results:
INSTI treatment altered gene expression of FA transport proteins (Fatps), FA binding proteins (Fabps), lipases (Lpl, Lipg), and fatty acid translocase (Cd36/Fat) when compared to controls, with differential results based on treatment regimen (Table 1). Significant reductions in expression of nuclear transcription factors Pparg and Rxra was observed across treatment regimens. Expression of lipases was strongly associated with placental weight but not fetal weight in the cabotegravir treatment arm.
Conclusion:
Treatment with therapeutic doses of all INSTIs alters expression of placental FA transport associated genes. Changes in Pparg expression, which regulates expression of Fatps, Fabps, and lipases, suggests it is driving changes in transporter expression.
Logan Kennedy
Research Lead
Women's College Hospital
Updating the Canadian HIV Parenting (Pregnancy) Planning Guidelines
Abstract
Background: People with HIV have varied parenting planning goals. Despite improvements in HIV care and its chronic illness management, people living with HIV still encounter unique barriers and discrimination in achieving these plans, highlighting the necessity for tailored counseling and support. Parenting planning guidance should be integral to HIV care, for which the Canadian guidelines have been updated.
Methods: A multidisciplinary expert team reviewed the 2018 guidelines, identifying key questions for current revisions. A librarian also conducted updated literature reviews. A primary writing team (VLK, JH, SH, MHY, HS, EN, ML) revised the guideline text, which underwent two full drafts of review, including an in-person meeting at CAHR 2024. Community engagement has been essential for both the original development and current updates of the guidelines.
Results: The team represents diverse regions and disciplines across Canada, including infectious diseases, internal medicine, pregnancy care, fertility care, primary care, pharmacy, nursing, social science, and community. The Canadian HIV Parenting (Pregnancy) Planning Guidelines (CHPPG) aim to provide clinical information and recommendations to help healthcare providers counsel and assist individuals and couples affected by HIV in Canada. The guidelines focus on: (1) optimizing health prior to parenthood; (2) supporting reproductive rights; and (3) reducing HIV transmission risks. Given relevant advances since the 2018 publication, key updates to the forthcoming guidelines are: revised (inclusive) language conventions, including renaming ‘pregnancy’ to ‘parenting’, which also expands guidelines to be inclusive of types of parenting beyond; revised formatting to reflect current realities; expanded harm reduction and trauma-informed care principles; inclusion of pregnancy prevention and pre-exposure prophylaxis content; and reduction of recommendations from 36 to under 15 using the GRADE framework for easier integration into national HIV care.
Conclusions: The CHPPGs have been revised to maintain their relevance in 2025 and beyond, with publication and dissemination efforts planned for mid-2025.
Methods: A multidisciplinary expert team reviewed the 2018 guidelines, identifying key questions for current revisions. A librarian also conducted updated literature reviews. A primary writing team (VLK, JH, SH, MHY, HS, EN, ML) revised the guideline text, which underwent two full drafts of review, including an in-person meeting at CAHR 2024. Community engagement has been essential for both the original development and current updates of the guidelines.
Results: The team represents diverse regions and disciplines across Canada, including infectious diseases, internal medicine, pregnancy care, fertility care, primary care, pharmacy, nursing, social science, and community. The Canadian HIV Parenting (Pregnancy) Planning Guidelines (CHPPG) aim to provide clinical information and recommendations to help healthcare providers counsel and assist individuals and couples affected by HIV in Canada. The guidelines focus on: (1) optimizing health prior to parenthood; (2) supporting reproductive rights; and (3) reducing HIV transmission risks. Given relevant advances since the 2018 publication, key updates to the forthcoming guidelines are: revised (inclusive) language conventions, including renaming ‘pregnancy’ to ‘parenting’, which also expands guidelines to be inclusive of types of parenting beyond; revised formatting to reflect current realities; expanded harm reduction and trauma-informed care principles; inclusion of pregnancy prevention and pre-exposure prophylaxis content; and reduction of recommendations from 36 to under 15 using the GRADE framework for easier integration into national HIV care.
Conclusions: The CHPPGs have been revised to maintain their relevance in 2025 and beyond, with publication and dissemination efforts planned for mid-2025.
Cara Spence
Assistant Professor
University Of Saskatchewan
Demographic and Clinical Outcomes of Pregnant Women Living with HIV in Saskatchewan – A Retrospective Study
Abstract
Background
Saskatchewan (SK) continues to record the highest HIV incidence rates in Canada. Epidemiological trends shifted in 2020 from intravenous drug use to heterosexual transmission as a primary risk factor. In 2023, women of childbearing years represented an estimated 62% of new HIV diagnoses. This study reports the HIV, HCV, syphilis, and associated health outcome prevalence among women living with HIV (WLWH) in central and northern SK.
Methods
A dataset of 184 pregnant WLWH was created by retrospective chart review of the Canadian Paediatric & Perinatal HIV/AIDS Research Group (CPARG) database and clinical electronic medical records from January 1, 2018, to December 31, 2023. 180 live infants born to WLWH receiving care in Saskatoon, SK, accounting for all infants born to WLWH in Saskatoon, central and northern regions, representing 68% of all cases in SK. Three time periods were analyzed and compared: T1=Jan.1, 2018–Dec. 31, 2019; T2=Jan.1, 2020–Dec. 31, 2021; T3=Jan.1, 2022–Dec. 31, 2023. Descriptive variables, testing, treatment, and laboratory trends across periods were extracted.
Results
Table 1: HIV Maternal Outcomes January 1, 2018 – December 31, 2023 (attached)
Conclusions
The use of ARVs at conception is remarkably low. However, data indicates that adherence can be supported when pregnant women are engaged in care. Although injection drug use continues to increase among pregnant women, utilization of opiate substitution therapy has declined. The rapid and significant rising rates of HIV co-infection with syphilis and hepatitis C among women of childbearing age in SK underscores the necessity for research and targeted strategies to eliminate new infections, support better access to care, and reduce vertical transmission risk for infants.
Saskatchewan (SK) continues to record the highest HIV incidence rates in Canada. Epidemiological trends shifted in 2020 from intravenous drug use to heterosexual transmission as a primary risk factor. In 2023, women of childbearing years represented an estimated 62% of new HIV diagnoses. This study reports the HIV, HCV, syphilis, and associated health outcome prevalence among women living with HIV (WLWH) in central and northern SK.
Methods
A dataset of 184 pregnant WLWH was created by retrospective chart review of the Canadian Paediatric & Perinatal HIV/AIDS Research Group (CPARG) database and clinical electronic medical records from January 1, 2018, to December 31, 2023. 180 live infants born to WLWH receiving care in Saskatoon, SK, accounting for all infants born to WLWH in Saskatoon, central and northern regions, representing 68% of all cases in SK. Three time periods were analyzed and compared: T1=Jan.1, 2018–Dec. 31, 2019; T2=Jan.1, 2020–Dec. 31, 2021; T3=Jan.1, 2022–Dec. 31, 2023. Descriptive variables, testing, treatment, and laboratory trends across periods were extracted.
Results
Table 1: HIV Maternal Outcomes January 1, 2018 – December 31, 2023 (attached)
Conclusions
The use of ARVs at conception is remarkably low. However, data indicates that adherence can be supported when pregnant women are engaged in care. Although injection drug use continues to increase among pregnant women, utilization of opiate substitution therapy has declined. The rapid and significant rising rates of HIV co-infection with syphilis and hepatitis C among women of childbearing age in SK underscores the necessity for research and targeted strategies to eliminate new infections, support better access to care, and reduce vertical transmission risk for infants.
