Factors associated with HIV viral load control in the early postpartum period - a Canadian prospective cohort study.

Despite success in managing HIV during pregnancy, challenges remain around sustained adherence with antiretroviral therapy (ART), and the suboptimal viral load (VL) suppression during the postpartum period. The objective of this study was to compare VL levels at delivery and during the postpartum period and assess factors associated with lack of viral suppression during the postpartum period in Canada. We combined data from two Canadian prospective cohorts, which included 286 HIV-positive women (352 pregnancies) who delivered between 2012 and 2020. Delivery VL, postpartum VL, and potential factors associated with an undetectable VL (<50 copies/mL), 2-18 weeks after delivery were assessed. To account for the correlation between multiple pregnancies from the same woman, generalized estimating equations were used to assess bivariate associations. Ninety-nine per cent of pregnant women were on ART during pregnancy compared to 93% during the postpartum period. Of those with available VL results (n = 214 pregnancies), 94% of women achieved an undetectable VL at delivery compared to 87% during the postpartum period. The postpartum period is a challenging time for ART use and VL control. Qualitative studies are needed to better understand these challenges and guide us in designing adequate interventions.

Retrospective Cohort Study on the Impact of the COVID-19 Pandemic on Pregnancy Outcomes for Women Living With HIV in British Columbia.

BACKGROUND: For pregnant women living with HIV (WLWH), engagement in care is crucial to maternal health and reducing the risk of perinatal transmission. To date, there have been no studies in Canada examining the impact of the COVID-19 pandemic on pregnant WLWH. METHODS: This was a retrospective cohort study assessing the impact of the pandemic on perinatal outcomes for pregnant WLWH using data from the Perinatal HIV Surveillance Program in British Columbia, Canada. We compared maternal characteristics, pregnancy outcomes, and clinical indicators related to engagement with care between a prepandemic (January 2017-March 2020) and pandemic cohort (March 2020-December 2022). We investigated preterm birth rates with explanatory variables using logistic regression analysis. RESULTS: The prepandemic cohort (n = 87) had a significantly (P < 0.05) lower gestational age at the first antenatal encounter (9.0 vs 11.8) and lower rates of preterm births compared with the pandemic cohort (n = 56; 15% vs 37%). Adjusted odds of preterm birth increased with the presence of substance use in pregnancy (aOR = 10.45, 95% confidence interval: 2.19 to 49.94) in WLWH. There were 2 cases of perinatal transmission of HIV in the pandemic cohort, whereas the prepandemic cohort had none. CONCLUSIONS: The pandemic had pronounced effects on pregnant WLWH and their infants in British Columbia including higher rates of preterm birth and higher gestational age at the first antenatal encounter. The nonstatistically significant increase in perinatal transmission rates is of high clinical importance.

Variations in CD4 counts during pregnancy in women living with HIV.

OBJECTIVE: Our objective was to determine the frequency at which CD4 counts drop below 200 cells/mm3 during pregnancy in women living with HIV and to identify factors associated with this. METHODS: Data from 2005 to 2020 from two prospective Canadian cohorts of pregnant women living with HIV were extracted. As per national guidelines, women received antiretroviral therapy and CD4 counts were monitored once per trimester and at delivery. RESULTS: Among 775 included cases, 72 (9.3%) had CD4 counts <200 cells/mm3 at the first pregnancy visit. Of the 703 remaining pregnancies with CD4 counts ≥200 cells/mm3 at the initial visit, 20 (2.8%) were associated with a drop to <200 cells/mm3 . In univariate analysis, factors associated with this drop were coinfection with hepatitis B virus or hepatitis C virus (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.52-10.50), lower first visit CD4 counts (OR 0.165, 95% CI 0.08-0.34), and baseline haemoglobin levels <11 g/dL (OR 2.89, 95% CI 1.04-8.00). In multivariable analysis, only CD4 count at first visit remained independently associated with this drop. A cut-off CD4 count ≤450 cells/mm3 at the first pregnancy visit had a sensitivity of 100% to detect cases of CD4 drop to <200 cells/mm3 . CONCLUSION: A drop of CD4 count to <200 cells/mm3 is uncommon during pregnancy in women living with HIV. Our results suggest that CD4 monitoring only once in pregnancy would be safe in women whose CD4 count is >450 cells/mm3 at the first pregnancy visit.

Daily ritonavir-boosted darunavir for viral suppression in pregnancy (DRV-P).

BACKGROUND: Ritonavir-boosted darunavir (DRV/r) is a preferred protease inhibitor in pregnant women living with HIV. Current practice at British Columbia's referral centre (the Oak Tree Clinic) is to dose DRV/r as 800/100 mg daily throughout pregnancy, although some guidelines recommend DRV/r 600/100 mg twice daily due to altered pharmacokinetics with once-daily dosing. OBJECTIVES: We describe the effect of once-daily DRV/r on viral suppression, vertical transmission, adverse drug effects and adherence in pregnant women living with HIV. METHODS: This was a retrospective analysis of pregnant women living with HIV in British Columbia. Eligible women gave birth between January 2015 and August 2021, and took DRV/r 800/100 mg daily at any time during pregnancy. RESULTS: Thirty-four women were included in this study. The mean (SD) age was 33 (5) years. Thirty (88%) women were diagnosed with HIV prior to pregnancy, with 22 (73%) having viral suppression at baseline. Four (12%) were diagnosed in pregnancy, with a median baseline viral load of 9616 copies/mL (range 8370-165 000). Viral suppression was achieved by 16 (100%), 24 (75%) and 26 (74%) women in the first, second and third trimesters, respectively. No vertical transmission occurred. This combination was well tolerated, with adverse drug effects that did not result in discontinuation or change in therapy. Most women maintained >75% adherence to once-daily DRV/r at all times during pregnancy. CONCLUSIONS: Ritonavir-boosted darunavir 800/100 mg daily appears to be an appropriate dosing strategy for pregnant women living with HIV who are able to maintain optimal adherence.

Vaccination during pregnancy: A golden opportunity to embrace.

Immunization strategies are part of routine pregnancy care to prevent infectious diseases in the mother, the fetus, and the newborn. Maternal immunization recommendations followed the recognition of the consequences of infectious diseases in pregnancy, including vertical transmission and perinatal consequences. The recent COVID-19 pandemic highlighted the issue of vaccination among pregnant individuals. Recommendations vary globally; however, Tdap, influenza, and, recently, COVID-19 vaccines are routinely recommended during pregnancy. There are several new maternal immunization products in the pipeline, including those directed against malaria, cytomegalovirus, Group B Streptococcus, herpes simplex virus, and respiratory syncytial virus. Important challenges must be addressed in all countries to guarantee that pregnant individuals and their babies receive the best care possible, including uptake of recommended immunizations by their entire target population groups. These challenges include disseminating appropriate data for vaccine recommendations and many others, such as ensuring stakeholder endorsement, achieving in-country distribution and administration, adequate vaccine supply, and a well-organized healthcare system, ideally offering the immunization free of charge. More recently, the hesitancy of pregnant women to receive immunizations highlights the relevance of cultural aspects and other contextual factors affecting vaccine uptake among pregnant individuals.

Birth Mode Does Not Determine the Presence of Shared Bacterial Strains between the Maternal Vaginal Microbiome and the Infant Stool Microbiome.

Dysbiosis of the neonatal gut microbiome during early life has been suggested as the missing link that may explain higher rates of certain diseases in caesarean section-delivered infants. Many studies report delivery mode-related dysbiosis in infants due to a lack of maternal vaginal microbiome exposure, prompting interventions to correct the neonatal gut microbiome by transferring these missing microbes after caesarean delivery. The maternal vaginal microbiome is among the first microbial exposures that many infants experience, yet little is known about the extent of direct transmission of maternal vaginal microbes. As part of the Maternal Microbiome Legacy Project, we aimed to determine if maternal vaginal bacteria are vertically transmitted to infants. We employed cpn60 microbiome profiling, culture-based screening, molecular strain typing, and whole-genome sequencing to determine whether identical maternal vaginal strains were present in infant stool microbiomes. We identified identical cpn60 sequence variants in both halves of maternal-infant dyads in 204 of 585 Canadian women and their newborn infants (38.9%). The same species of Bifidobacterium and Enterococcus were cultured from maternal and corresponding infant samples in 33 and 13 of these mother-infant dyads, respectively. Pulsed-field gel electrophoresis and whole-genome sequencing determined that near-identical strains were detected in these dyads irrespective of delivery mode, indicating an alternative source in cases of caesarean delivery. Overall, we demonstrated that vertical transmission of maternal vaginal microbiota is likely limited and that transmission from other maternal body sites, such as the gut and breast milk, may compensate for the lack of maternal vaginal microbiome exposure during caesarean delivery. IMPORTANCE The importance of the gut microbiome in human health and disease is widely recognized, and there has been a growing appreciation that alterations in gut microbiome composition during a "critical window" of development may impact health in later life. Attempts to correct gut microbiome dysbiosis related to birth mode are underpinned by the assumption that the lack of exposure to maternal vaginal microbes during caesarean delivery is responsible for dysbiosis. Here, we demonstrate that there is limited transmission of the maternal vaginal microbiome to the neonatal gut, even in cases of vaginal delivery. Furthermore, the presence of identical strains shared between mothers and infants in early life, even in cases of caesarean delivery, highlights compensatory microbial exposures and sources for the neonatal stool microbiome other than the maternal vagina.

Robust tobacco smoking self-report in two cohorts: pregnant women or men and women living with or without HIV.

Understanding the true burden of tobacco smoking on adverse pregnancy outcomes is critical in generating appropriate interventions to improve outcomes. Self-reporting of human behaviour that is associated with stigma is associated with underreporting in general and may bias the impact of smoking in studies; however, self-reporting is frequently the most practical method of gleaning this information. The objective of this study was to evaluate concordance between self-reported smoking and concentrations of plasma cotinine, a biomarker of smoking, among participants enrolled in two related HIV cohorts. A total of 100 pregnant women (76 living with HIV [LWH] and 24 negative controls) in their third trimester, and 100 men and non-pregnant women (43 LWH and 57 negative controls) were included. Among all participants, 43 pregnant women (49% LWH and 25% negative controls) and 50 men and non-pregnant women (58% LWH and 44% negative controls) were self-reported smokers. The odds of discordance between self-reported smoking and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others, but were significantly increased, regardless of self-reported status, among people LWH compared to negative controls. The overall concordance between plasma cotinine and self-reported data among all participants was 94% with a sensitivity and specificity of 90% and 96%, respectively. Taken together, these data demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report smoking data among both persons LWH and not, including in the context of pregnancy.

Canadian SARS-CoV-2 serological survey using antenatal serum samples: a retrospective seroprevalence study.

BACKGROUND: Insufficient data on the rate and distribution of SARS-CoV-2 infection in Canada has presented a substantial challenge to the public health response to the COVID-19 pandemic. Our objective was to assess SARS-CoV-2 seroprevalence in a representative sample of pregnant people throughout Canada, across multiple time points over 2 years of the pandemic, to describe the seroprevalence and show the ability of this process to provide prevalence estimates. METHODS: This Canadian retrospective serological surveillance study used existing serological prenatal samples across 10 provinces over multiple time periods: Feb. 3-21, 2020; Aug. 24-Sept. 11, 2020; Nov. 16-Dec. 4, 2020; Nov. 15-Dec. 3, 2021; and results from the province of British Columbia during a period in which the SARS-CoV-2 B.1.1.529 (Omicron) variant was predominant, from Nov. 15, 2021, to June 11, 2022. Age and postal code administrative data allowed for comparison with concurrent polymerase chain reactivity (PCR)-positive results collected by Statistics Canada and the Canadian Surveillance of COVID-19 in Pregnancy (CANCOVID-Preg) project. RESULTS: Seropositivity in antenatal serum as early as February 2020 indicates SARS-CoV-2 transmission before the World Health Organization's declaration of the pandemic. Seroprevalence in our sample of pregnant people was 1.84 to 8.90 times higher than the recorded concurrent PCR-positive prevalence recorded among females aged 20-49 years in November-December 2020. Overall seropositivity in our sample of pregnant people was low at the end of 2020, increasing to 15% in 1 province by the end of 2021. Seroprevalence among pregnant people in BC during the Omicron period increased from 5.8% to 43% from November 2021 to June 2022. INTERPRETATION: These results indicate widespread vulnerability to SARS-CoV-2 infection before vaccine availability in Canada. During the time periods sampled, public health tracking systems were under-reporting infections, and seroprevalence results during the Omicron period indicate extensive community spread of SARS-CoV-2 infection.

Canadian Pediatric & Perinatal HIV/AIDS Research Group consensus recommendations for infant feeding in the HIV context.

Background: Providing comprehensive infant feeding guidance to families affected by HIV is complex and requires a multidisciplinary approach. While exclusive formula feeding remains the preferred recommendation for infants born to women living with HIV (WLWH) in high-income countries, a more nuanced approach that may include the option of breastfeeding under certain circumstances is emerging in many resource-rich countries. Methods: The Canadian Pediatric & Perinatal HIV/AIDS Research Group (CPARG) hosted a Canadian Institute of Health Research-funded meeting in 2016 to develop consensus among multidisciplinary providers around counselling and recommendations for infant feeding. After presentations by adult and paediatric health care providers, basic scientists, and community-based researchers, a subgroup drafted summary evidence-informed recommendations. Along with revisions among CPARG members, a community review was performed by a convenience sample of WLWH who had given birth in the past 5 years from Ontario and Quebec. A legal review was also conducted to ensure understanding of the criminalization potential and concern of HIV transmission and exposure. Results: The Canadian consensus guidelines continue to support formula feeding as the preferred method of infant feeding as it eliminates any residual risk of postnatal vertical transmission. Formula should be made available for all infants born to mothers living with HIV for their first year of life. A comprehensive approach to counselling WLWH is outlined to assist providers to effectively counsel on current evidence to ensure WLWH are fully informed in their decision making. For women meeting criteria to and elect to breastfeed, frequent maternal virologic monitoring and follow-up is required of both mother and infant. Antiretroviral prophylaxis and monitoring are recommended for breastfed infants. The community review highlighted the importance of other supports and counselling needed for implementing effective formula feeding, aside from access to formula. The legal review provided clarifying language around child protection services involvement and the need to provide referral to legal resources or information upon request. Surveillance systems to monitor for cases of breastmilk transmission should be in place to improve gaps in care and develop further knowledge in this area. Conclusion: The Canadian infant feeding consensus guideline is designed to inform and enable better care for WLWH and their babies. Ongoing evaluation of these guidelines as new evidence emerges will be important.

Historique: La transmission de conseils détaillés sur l'alimentation du nourrisson aux familles touchée par le VIH est complexe et exige une approche multidisciplinaire. Il est recommandé de recourir exclusivement aux préparations commerciales chez les nourrissons de mères vivant avec le VIH (MVIH) dans les pays à revenu élevé, mais une approche plus nuancée, qui peut inclure l'allaitement dans certaines situations, émerge dans de nombreux pays riches en ressources. Méthodologie: Le Groupe canadien de recherche pédiatrique et périnatale sur le VIH/sida (CPARG) a tenu un congrès financé par Les Instituts de recherche en santé du Canada en 2016 pour parvenir à un consensus de la part des professionnels multidisciplinaires sur le counseling et les recommandations à l'égard de l'alimentation du nourrisson. Après les présentations de professionnels de la santé pédiatrique, de chercheurs fondamentaux et de chercheurs communautaires, un sous-groupe a rédigé une synthèse des recommandations reposant sur des données probantes. En plus des révisions proposées par les membres de la CPARG, un échantillon de commodité de MVIH qui avaient accouché dans les cinq années précédentes en Ontario et au Québec a procédé à un examen communautaire. Une révision juridique a également permis de bien comprendre le potentiel de criminalisation et les inquiétudes quant à la transmission du VIH et à l'exposition à ce virus. Résultats: Les lignes directrices consensuelles canadiennes continuent de préconiser l'utilisation des préparations commerciales pour l'alimentation des nourrissons, car elles éliminent tout risque résiduel de transmission verticale après la naissance. Ces préparations doivent être mises à la disposition de tous les nourrissons nés de MVIH jusqu'à l'âge d'un an. Une approche détaillée du counseling auprès des MVIH est présentée pour aider les professionnels à leur donner des conseils efficaces sur les données probantes à jour, afin qu'elles puissent prendre une décision pleinement éclairée. Chez les femmes qui respectent les critères et qui choisissent d'allaiter, la surveillance virologique fréquente de la mère et un suivi de la mère et du nourrisson s'imposent. La prophylaxie antirétrovirale et la surveillance des nourrissons allaités sont recommandées. La révision communautaire a fait ressortir l'importance d'autres mesures de soutien et de counseling pour mettre en place une alimentation efficace à l'aide des préparations commerciales, en plus de l'accès à ces préparations. L'analyse juridique a permis de préciser les énoncés entourant la participation des services de protection de l'enfance et la nécessité de diriger les familles vers des ressources ou de l'information juridiques, sur demande. Des systèmes de surveillance visant à répertorier les cas de transmission par le lait maternel devraient être en place pour corriger les lacunes en matière de soins et accroître les connaissances dans ce domaine. Conclusion: Les lignes directrices consensuelles canadiennes sur l'alimentation des nourrissons sont conçues pour éclairer les soins aux MVIH et à leurs nourrissons et pour les améliorer. Il sera important d'assurer l'évaluation continue de ces lignes directrices à mesure que de nouvelles données probantes seront découvertes.

Maternal vaginal microbiome composition does not affect development of the infant gut microbiome in early life.

Birth mode has been implicated as a major factor influencing neonatal gut microbiome development, and it has been assumed that lack of exposure to the maternal vaginal microbiome is responsible for gut dysbiosis among caesarean-delivered infants. Consequently, practices to correct dysbiotic gut microbiomes, such as vaginal seeding, have arisen while the effect of the maternal vaginal microbiome on that of the infant gut remains unknown. We conducted a longitudinal, prospective cohort study of 621 Canadian pregnant women and their newborn infants and collected pre-delivery maternal vaginal swabs and infant stool samples at 10-days and 3-months of life. Using cpn60-based amplicon sequencing, we defined vaginal and stool microbiome profiles and evaluated the effect of maternal vaginal microbiome composition and various clinical variables on the development of the infant stool microbiome. Infant stool microbiomes showed significant differences in composition by delivery mode at 10-days postpartum; however, this effect could not be explained by maternal vaginal microbiome composition and was vastly reduced by 3 months. Vaginal microbiome clusters were distributed across infant stool clusters in proportion to their frequency in the overall maternal population, indicating independence of the two communities. Intrapartum antibiotic administration was identified as a confounder of infant stool microbiome differences and was associated with lower abundances of Escherichia coli, Bacteroides vulgatus, Bifidobacterium longum and Parabacteroides distasonis. Our findings demonstrate that maternal vaginal microbiome composition at delivery does not affect infant stool microbiome composition and development, suggesting that practices to amend infant stool microbiome composition focus factors other than maternal vaginal microbes.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

HSV-2 infection and HPV incidence, persistence, and precancerous lesions in a cohort of HPV-vaccinated women living with HIV.

BACKGROUND: Several co-factors for HPV oncogenesis have been proposed, including co-infection with HSV-2. We assessed the relationship between HSV-2 infection and HPV-related outcomes in quadrivalent HPV-vaccinated (qHPV) women living with HIV (WLWH). METHODS: In this multi-site study of immunogenicity and efficacy of the qHPV vaccine in WLWH, visits took place at months -3, 0, 2, 6, 12, 18, 24, and annually thereafter. Participants provided clinical data and cervico-vaginal swabs for HPV DNA detection; baseline serum was tested for HSV-2 type-specific antibodies. We used non-parametric statistics to compare HPV-related outcomes by HSV-2 serostatus and use of anti-HSV medication. RESULTS: 151 baseline serum samples underwent HSV-2 testing. At baseline, median age was 39 years, median CD4 count was 500 cells/mm3, and 70% had an HIV viral load of <50 copies/mL. Baseline HSV-2 seroprevalence was 76.2%. HSV-2 seropositivity was associated with increased age (p = 0.006). Controlling for age and median CD4 count, HSV-2 seropositivity was not associated with HPV incidence, persistence, and precancerous lesions. The use of anti-HSV medications was associated with higher odds of HSIL cytology (OR = 3.35, 95% CI = 1.03,11.26) and a greater number of HPV types detected (OR = 1.18, 95% CI = 1.00,1.39). Results were similar in sensitivity analyses using an index value of 3.5. The presence of HSV lesions during the study was not associated with HPV outcomes. CONCLUSIONS: HSV-2 seropositivity was common in this cohort of WLWH in Canada but was not associated with multiple measures of HPV incidence, persistence, and precancerous lesions. However, the use of anti-HSV medications was associated with HSIL cytology and number of HPV types detected.

Type and timing of antiretroviral therapy during pregnancy: Impact on risk of preterm delivery and small-for-gestational age births in Canada, a retrospective cohort study.

OBJECTIVE: To evaluate the impact of type and timing of antiretroviral therapy (ART) on the risk of preterm delivery (PTD) and small-for-gestational age (SGA) birth among pregnant women and people living with HIV in Canada. METHODS: Data for this retrospective cohort study were analyzed from the Canadian Perinatal HIV Surveillance Program from 1990 to 2020. The association between ART and risk of PTD (<37 weeks) and SGA birth (<10th percentile) was explored using mixed effects logistic regression and time-dependent Cox proportional hazards models. RESULTS: Overall, there were 14.9% (654 of 4379) PTD and 18.5% (732 of 3947) SGA cases. A higher risk of PTD was observed with nonnucleoside reverse transcriptase inhibitor-(adjusted hazard ratio [aHR], 1.73; P = 0.019) and boosted protease inhibitor- (aHR, 186; P = 0.007) based regimens compared with integrase strand transfer inhibitor (INSTI)-based regimens. ART initiation prior to conception was associated with a lower risk of SGA birth compared with ART initiation after conception at 1 to 14 weeks (adjusted odds ratio [aOR], 0.69; P = 0.024) and > 14 weeks (aOR, 0.70; P = 0.005). CONCLUSION: INSTI-based ART regimens were associated with lower risk of PTD compared with other regimens, and ART initiation before conception was associated with a lower risk of SGA birth. These findings, with overall safety data, should be considered when providing pregnancy counseling to people living with HIV.

Prescribing patterns of antiretroviral treatments during pregnancy for women living with HIV in Canada 2004-2020: A surveillance study.

BACKGROUND: While treatment guidelines for HIV in adults have evolved rapidly with the advent of new antiretroviral (ARV) treatment, those for the prevention of vertical HIV transmission in pregnancy have evolved more slowly due to safety and efficacy concerns. Here we describe Canadian prescribing patterns for ARV treatments during pregnancy and compare them to perinatal HIV prescribing guidelines of the United States Department of Health and Human Services (HHS), that are commonly used in Canada and include recommendations for newly commercialized therapies. METHODS: The Canadian Perinatal HIV Surveillance Program (CPHSP) captures annual medical data on mothers living with HIV and their infants from 23 sites across Canada. Women from this cohort who received an ARV treatment during pregnancy and who gave birth between 2004 and 2020 were included in the study. ARV treatments were designated as 'preferred/alternative' as per HHS HIV perinatal guidelines, or 'other than preferred/alternative'. RESULTS: We identified 3673 pregnancies from 2720 women. The proportion of women that conceived while on ARV treatment increased from 29% in 2003 to 90% in 2020. Other than preferred/alternative ARV treatments were received in 1112 (30%) of pregnancies and this was significantly associated with having initiated ARV treatment before conception. CONCLUSION: In Canada during the study period, a high number of women were prescribed an other than preferred/alternative ARV treatment during pregnancy. Further optimization of ARV treatment in women of childbearing age living with HIV is warranted.

Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen.

Introduction: The use of antiretroviral therapy (ART) during pregnancy, particularly protease-inhibitor-based regimens (PI), has been linked to adverse outcomes including preterm delivery. As this outcome may be related to systemic inflammation, we sought to characterize inflammatory profiles of pregnant people living with HIV (PLWH) by comparing their levels of inflammatory mediators at two timepoints during pregnancy according to ART regimen, and to HIV-negative controls. Methods: Second and third trimester samples from 144 pregnant PLWH treated with ART and 24 HIV-uninfected controls were retrieved from the CARMA-PREG cohort. Peripheral plasma levels of 12 inflammatory mediators previously linked to HIV infection and/or poor pregnancy outcomes were quantified by multiplex assay: HMGB1, GM-CSF, IFNα, IFNß, IFNγ, IL-10, IL-17, IL-1ß, IL-6, TNFα, AGP, and CRP. Levels were compared by ART regimen and HIV status. Results: Adjusted analyses showed that PLWH have higher levels of AGP throughout pregnancy and lower levels of IFNγ and IL-1ß during the second trimester. PI-based regimens are associated with significantly higher levels of IFNα and IL-17 during the second trimester and IFNα, CRP, HMGB1, and IFNß during the third trimester compared to InSTI-based regimens. The PI-subgroup was associated with preterm delivery and higher HIV-1 viral load. Discussion: Our results suggest that PI-based regimens are associated with a pro-inflammatory and antiviral immunological response and a high viral load, which may be a mechanism through which PI-based regimens increase the risk of preterm delivery. Further investigations into cellular mechanisms and pro-inflammatory cascades leading to preterm delivery are necessary to support this association.

Infants Born to Mothers Who Were SARS-CoV-2 Positive during Pregnancy and Admitted to Neonatal Intensive Care Unit.

INTRODUCTION: Our objective was to compare neonatal outcomes and resource use of neonates born to mothers with SARS-CoV-2 positivity during pregnancy with neonates born to mothers without SARS-CoV-2 positivity. METHODS: We conducted a two-country cohort study of neonates admitted between January 1, 2020, and September 15, 2021, to tertiary neonatal intensive care unit (NICU) in Canada and Sweden. Neonates from mothers who were SARS-CoV-2 positive during pregnancy were compared with three randomly selected NICU neonates of mothers who were not test-positive, matched on gestational age, sex, and birth weight (±0.25 SD). Subgroup analyses were conducted for neonates born <33 weeks' gestation and mothers who were SARS-CoV-2 positive ≤10 days prior to birth. Primary outcome was duration of respiratory support. Secondary outcomes were in-hospital mortality, neonatal morbidity, late-onset sepsis, receipt of breast milk at discharge, and length of stay. RESULTS: There were 163 exposed and 468 matched neonates in Canada, and 303 exposed and 903 matched neonates in Sweden. There was no statistically significant difference in invasive or noninvasive respiratory support durations, mortality, respiratory and other neonatal morbidities, or resource utilizations between two groups in both countries in entire cohort and in subgroup analyses. Receipt of breast milk at discharge was lower in the Canadian neonates of mothers who were SARS-CoV-2 positive ≤10 days before birth (risk ratio 0.68, 95% CI: 0.57-0.82). CONCLUSION: Maternal SARS-CoV-2 positivity was not associated with increased durations of respiratory support, morbidities, mortality, or length of hospital stay in Canada and Sweden among neonates admitted to tertiary NICU.

Vaginal microbiota associated with oncogenic HPV in a cohort of HPV-vaccinated women living with HIV.

BACKGROUND: Women living with HIV (WLWH) experience higher rates of human papillomavirus (HPV) infection and cervical cancer than women without HIV. Changes in the vaginal microbiome have been implicated in HPV-related disease processes such as persistence of high-risk HPV infection but this has not been well defined in a population living with HIV. METHODS: Four hundred and 20 girls and WLWH, age ≥9, across 14 clinical sites in Canada were enrolled to receive three doses of quadrivalent HPV vaccine for assessment of vaccine immunogenicity. Blood, cervical cytology, and cervico-vaginal swabs were collected. Cervico-vaginal samples were tested for HPV DNA and underwent microbiota sequencing. RESULTS: Principal component analysis (PCA) and hierarchical clustering generated community state types (CSTs). Relationships between taxa and CSTs with HPV infection were examined using mixed-effects logistic regressions, Poisson regressions, or generalized linear mixed-effects models, as appropriate. Three hundred and fifty-six cervico-vaginal microbiota samples from 172 women were sequenced. Human papillomavirus DNA was detected in 211 (59%) samples; 110 (31%) contained oncogenic HPV. Sixty-five samples (18%) were taken concurrently with incident oncogenic HPV infection and 56 (16%) were collected from women with concurrent persistent oncogenic HPV infection. CONCLUSIONS: No significant associations between taxa, CST, or microbial diversity and HPV-related outcomes were found. However, we observed weak associations between a dysbiotic microbiome and specific species, including Gardnerella, Porphyromonas, and Prevotella species, with incident HPV infection.