Breastfeeding Among People With Human Immunodeficiency Virus in North America: A Multisite Study.

BACKGROUND: In North American countries, national guidelines have strongly recommended formula over breastmilk for people with human immunodeficiency virus (HIV) because of concern for HIV transmission. However, data from resource-limited settings suggest the risk is <1% among virally suppressed people. Information regarding breastfeeding experience in high-resource settings is lacking. METHODS: A retrospective multisite study was performed for individuals with HIV who breastfed during 2014-2022 in the United States (8 sites) and Canada (3 sites). Descriptive statistics were used for data analysis. RESULTS: Among the 72 cases reported, most had been diagnosed with HIV and were on antiretroviral therapy prior to the index pregnancy and had undetectable viral loads at delivery. Most commonly reported reasons for choosing to breastfeed were health benefits, community expectations, and parent-child bonding. Median duration of breastfeeding was 24 weeks (range, 1 day to 72 weeks). Regimens for infant prophylaxis and protocols for testing of infants and birthing parents varied widely among institutions. No neonatal transmissions occurred among the 94% of infants for whom results were available ≥6 weeks after weaning. CONCLUSIONS: This study describes the largest cohort to date of people with HIV who breastfed in North America. Findings demonstrate high variability among institutions in policies, infant prophylaxis, and infant and parental testing practices. The study describes challenges in weighing the potential risks of transmission with personal and community factors. Finally, this study highlights the relatively small numbers of patients with HIV who chose to breastfeed at any 1 location, and the need for further multisite studies to identify best care practices.

Elevated Levels of Estradiol in Human Immunodeficiency Virus-Infected Pregnant Women on Protease Inhibitor-Based Regimens.

Background: Human immunodeficiency virus (HIV)-infected pregnant women on protease inhibitor (PI)-based combination antiretroviral therapy (cART) have a greater risk for adverse birth outcomes, and an association with steroid hormone levels has been implicated. The objective of this study was to investigate the association between PI-cART and estradiol levels in pregnancy. Methods: Fifty-five HIV-infected and 49 HIV-uninfected Canadian pregnant women were followed prospectively throughout gestation. All HIV-infected women were on a PI-based cART regimen. Maternal plasma samples were collected at 12-18 weeks, 24-28 weeks, 34-38 weeks, at delivery, and from the cord. Birth outcomes were recorded. Levels of estradiol, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), cortisol, and adrenocorticotropic hormone (ACTH) were quantified by enzyme-linked immunosorbent assay. Results: (median [interquartile range] for cord estradiol: 23.9 ng/mL [16.4-36.4] for HIV-infected exposed to PI-cART and 15.7 ng/mL [12.2-21.2] for HIV-negative; P = .0025). HIV-infected women had higher DHEAS levels in cord plasma that correlated with cord and maternal delivery estradiol levels. Cortisol and ACTH levels did not differ between groups. In the HIV-infected women, cord estradiol levels correlated negatively with birth weight centile (r = -0.47, P = .0016). Conclusions: Our data suggest that PI-cART exposure in pregnancy is associated with elevated levels of estradiol, likely driven by higher fetal DHEAS production. Cord estradiol levels were inversely correlated with birth weight centile in infants born to PI-cART-exposed women, suggesting that fetal exposure to high estradiol levels may be contributing to cART-associated fetal growth restriction.

Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor-Based Combination Antiretroviral Therapy.

BACKGROUND: It has been reported that pregnant women receiving protease inhibitor (PI)-based combination antiretroviral therapy (cART) have lower levels of progesterone, which put them at risk of adverse birth outcomes, such as low birth weight. We sought to understand the mechanisms involved in this decline in progesterone level. METHODS: We assessed plasma levels of progesterone, prolactin, and lipids and placental expression of genes involved in progesterone metabolism in 42 human immunodeficiency virus (HIV)-infected and 31 HIV-uninfected pregnant women. In vitro studies and a mouse pregnancy model were used to delineate the effect of HIV from that of PI-based cART on progesterone metabolism. RESULTS: HIV-infected pregnant women receiving PI-based cART showed a reduction in plasma progesterone levels (P= .026) and an elevation in placental expression of the progesterone inactivating enzyme 20-α-hydroxysteroid dehydrogenase (20α-HSD; median, 2.5 arbitrary units [AU]; interquartile range [IQR], 1.00-4.10 AU), compared with controls (median, 0.89 AU; IQR, 0.66-1.26 AU;P= .002). Prolactin, a key regulator of 20α-HSD, was lower (P= .012) in HIV-infected pregnant women. We observed similar data in pregnant mice exposed to PI-based cART. In vitro inhibition of 20α-HSD activity in trophoblast cells reversed PI-based cART-induced decreases in progesterone levels. CONCLUSIONS: Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women.

HIV Prophylaxis in High Risk Newborns: An Examination of Sociodemographic Factors in an Inner City Context.

Background. Perinatal HIV transmission is less than 1% with antiretroviral (ARV) prophylaxis. Transmission risk appears higher in "high risk" dyads, yet this is not well defined, possibly exposing more infants to combination ARV compared with standard care. Objective. To describe characteristics of mother-infant dyads where infants received ARVs and how these characteristics relate to specific ARV regimens. Methods. Retrospective chart review of ARV-receiving newborns at St. Michael's Hospital from 2007 to 2012 (and their mothers). Numerical and categorical variables were analyzed using t-tests/ANOVA F-tests and Fisher's exact tests, respectively. Results. Maternal HIV status at delivery was as follows: 69% positive and 24% unknown. Maternal factors significantly associated with newborn-triple therapy are Canadian origin, substance abuse, unstable housing, lost custody of previous children, and sex work. Neonatal factors are child protective services involvement, NICU, and lengthier admission. Maternal factors associated with monotherapy are African origin, HIV-positive, employment, and education. Further analysis based on maternal presentation at delivery demonstrated unequal distribution of many aforementioned factors. Discussion. This cohort revealed associations between particular factors and newborn-monotherapy or triple therapy that exist, suggesting that sociodemographic factors may influence the choice of ARV regimen. Canadian perinatal HIV transmission guidelines should qualify how to risk stratify newborns and consider use of rapid HIV antibody testing.

HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

BACKGROUND: Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. METHODS: PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. RESULTS: PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. CONCLUSIONS: Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.

Key recommendations for developing a national action plan to advance the sexual and reproductive health and rights of women living with HIV in Canada.

Action on the World Health Organization Consolidated guideline on sexual and reproductive health and rights of women living with HIV requires evidence-based, equity-oriented, and regionally specific strategies centred on priorities of women living with HIV. Through community-academic partnership, we identified recommendations for developing a national action plan focused on enabling environments that shape sexual and reproductive health and rights by, with, and for women living with HIV in Canada. Between 2017 and 2019, leading Canadian women's HIV community, research, and clinical organizations partnered with the World Health Organization to convene a webinar series to describe the World Health Organization Consolidated guideline, define sexual and reproductive health and rights priorities in Canada, disseminate Canadian research and best practices in sexual and reproductive health and rights, and demonstrate the importance of community-academic partnerships and meaningful engagement of women living with HIV. Four webinar topics were pursued: (1) Trauma and Violence-Aware Care/Practice; (2) Supporting Safer HIV Disclosure; (3) Reproductive Health, Rights, and Justice; and (4) Resilience, Self-efficacy, and Peer Support. Subsequent in-person (2018) and online (2018-2021) consultation with > 130 key stakeholders further clarified priorities. Consultations yielded five cross-cutting key recommendations:1. Meaningfully engage women living with HIV across research, policy, and practice aimed at advancing sexual and reproductive health and rights by, with, and for all women.2. Centre Indigenous women's priorities, voices, and perspectives.3. Use language that is actively de-stigmatizing, inclusive, and reflective of women's strengths and experiences.4. Strengthen Knowledge Translation efforts to support access to and uptake of contemporary sexual and reproductive health and rights information for all stakeholders.5. Catalyse reciprocal relationships between evidence and action such that action is guided by research evidence, and research is guided by what is needed for effective action.Topic-specific sexual and reproductive health and rights recommendations were also identified. Guided by community engagement, recommendations for a national action plan on sexual and reproductive health and rights encourage Canada to enact global leadership by creating enabling environments for the health and healthcare of women living with HIV. Implementation is being pursued through consultations with provincial and national government representatives and policy-makers.

Exploring the impact of HIV infection and antiretroviral therapy on placenta morphology.

INTRODUCTION: Women living with HIV experience more adverse birth outcomes; the mechanisms are not fully understood. We examined placenta morphology and associations with birth outcomes in a Canadian cohort of women living with HIV (HIV+) on antiretroviral therapy (ART) from conception and HIV-uninfected (HIV-) women. METHODS: Term placentas from 94 women (40 HIV-, 54 HIV+) were studied. Trimmed placenta weight was collected. Placenta digital photos were used to compute morphometric parameters. Regression models investigated associations between log-transformed placenta parameters and birth outcomes. RESULTS: We observed a trend towards lower placenta weight and smaller placenta area in the HIV+ group, both of which were significantly associated with small for gestational age births. HIV+ serostatus was associated with 6-fold (95%CI 2-20) greater odds of having placenta area in the lowest quartile (<236 cm2). Cord marginality (distance from the edge) was significantly lower in the HIV+ group (p = 0.004), with 35% of placenta having an abnormal (marginal or velamentous) cord insertion vs. 12.5% in the HIV- group (p = 0.01). Velamentous cord insertion was seen in 13% of placentas in the HIV+ vs. 0% in HIV- group (p = 0.02). A significant correlation between cord marginality and placenta thickness was observed in the HIV- group, with a more marginal cord being associated with a thicker placenta. This correlation was not observed in the HIV+ group. HIV+ placentas exposed to protease inhibitors were significantly less circular compared to the HIV- group (p = 0.03). CONCLUSION: Our data suggest that HIV/ART exposure affects placenta morphology and is associated with higher rates of abnormal cord insertion.

Development of the Canadian Women-Centred HIV Care Model Using the Knowledge-to-Action Framework.

In Canada, women make up 25% of the prevalent HIV cases and represent an important population of those living with HIV, as a high proportion are racialized and systemically marginalized; furthermore, many have unmet healthcare needs. Using the knowledge-to-action framework as an implementation science methodology, we developed the "Women-Centred HIV Care" (WCHC) Model to address the needs of women living with HIV. The WCHC Model is depicted in the shape of a house with trauma- and violence-aware care as the "foundation". Person-centred care with attention with attention to social determinants of health and family make up the "first" floor. Women's health (including sexual and reproductive health and rights) and mental and addiction health care are integrated with HIV care, forming the "second" floor. Peer support, leadership, and capacity building make up the "roof". To address the priorities of women living with HIV in all their diversity and across their life course, the WCHC Model should be flexible in its delivery (e.g., single provider, interdisciplinary clinic or multiple providers) and implementation settings (e.g., urban, rural).

Prevalence and Correlates of Forced Sex as a Self-Reported Mode of HIV Acquisition Among a Cohort of Women Living With HIV in Canada.

Gender-based violence (GBV) is a global epidemic associated with increased HIV exposure. We assessed the prevalence and correlates of HIV acquisition via forced sex among women living with HIV (WLWH) in Canada. Baseline questionnaire data were analyzed for WLWH (≥16 years) with data on self-reported mode of HIV acquisition, enrolled in a community-based cohort study in British Columbia, Ontario, and Québec. We assessed forced sex (childhood, adulthood) as a self-reported mode of HIV acquisition. Of 1,330 participants, the median age was 42 (interquartile range [IQR] = 35-50) years; 23.5% were Indigenous, 26.3% African/Caribbean/Black, 43% White, and 7.2% of Other ethnicities. Forced sex was the third dominant mode of HIV transmission at 16.5% (n = 219; vs. 51.6% consensual sex, 19.7% sharing needles, 5.3% blood transfusion, 3.8% perinatal, 1.3% contaminated needles, 0.4% other, 1.6% do not know/prefer not to answer). In multivariable analyses, significant correlates of HIV acquisition from forced versus consensual sex included legal status as a landed immigrant (adjusted odds ratio [aOR] = 1.99; 95% confidence interval [CI] = [1.12, 3.54]) or refugee (aOR = 3.62; 95% CI = [1.63, 8.04]) versus Canadian citizen; African/Caribbean/Black ethnicity versus Caucasian (aOR = 2.49; 95% CI = [1.43, 4.35]), posttraumatic stress disorder symptoms (aOR = 3.00; 95% CI = [1.68, 5.38]), histories of group home residence (aOR = 2.40; 95% CI = [1.10, 5.23]), foster care (aOR = 2.18; 95% CI = [1.10, 4.34]), and having one child relative to having three or more children (aOR = 0.52; 95% CI = [0.31, 0.89]). GBV must be considered a distinct HIV risk factor; forced sex is a significant underrecognized risk factor and mode of women's HIV acquistion. Public health reporting systems can separate consensual and forced sex in reporting modes of HIV acquisition. Practitioners can engage in screening practices to meet client needs.

Antiretroviral therapy during pregnancy and risk of preterm birth.

BACKGROUND: Antiretroviral therapy use in pregnancy, and specifically regimens containing protease inhibitors (PIs), has been associated with adverse infant outcomes including preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) infants. However, there are conflicting results in the literature with respect to the degree of risk. These results may be related to demographic factors and confounding of maternal HIV infection and degree of immune suppression. OBJECTIVE: The primary objective of our study was to assess the risk of PTB in HIV-positive pregnant women on ART compared to HIV-negative pregnant women. Secondary objectives included: comparing the risks of LBW and SGA infants in HIV-positive women on ART to HIV-negative pregnant women; comparing the risks of PTB, LBW and SGA in HIV-positive women on PI-based regimens compared to HIV-negative women. METHODS: A retrospective matched cohort study of 384 women was conducted between 2007 and 2012 comparing outcomes of HIV-positive women on ART to HIV-negative women. Univariate and multivariable logistic regression models were used, adjusting for potential confounding factors, to compare the two groups on adverse infant outcomes. RESULTS: Unadjusted odds ratios revealed a >2-fold increase in rates: PTB OR 2.6 [95% CI 1.3-5.1]; LBW OR 2.9 [95% CI 1.4-6.3]; SGA OR 2.5 [95% CI 1.3-4.7]. Once odds ratios were adjusted to account for race (p<0.01), our results were no longer statistically significant as this study was underpowered to detect smaller differences: PTB aOR 1.4 [95% CI 0.5-3.6]; LBW OR 1.9 [95% CI 0.6-5.5]; SGA OR 1.8 [95% CI 0.8-4.6]. CONCLUSION: Our preliminary results show an increase in PTB, LBW and SGA but due to lack of power, our adjusted results are not statistically significant. A larger prospective follow-up study is needed to further explore these findings in this population.