Plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio of 11.5 multiples of median predicts preeclampsia with severe features within 2 weeks of testing.

BACKGROUND: Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1) and reduced angiogenic factors (vascular endothelial growth factor and placental growth factor), contribute to the mechanisms of disease in preeclampsia. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor has been used as a biomarker for preeclampsia, but the cutoff values may vary with gestational age and assay platform. OBJECTIVE: This study aimed to compare multiples of the median of the maternal plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio, soluble fms-like tyrosine kinase 1, placental growth factor, and conventional clinical and laboratory values in their ability to predict preeclampsia with severe features. STUDY DESIGN: We conducted a cohort study across 18 United States centers involving hospitalized individuals with hypertension between 23 and 35 weeks' gestation. Receiver operating characteristic curve analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. The areas under the curve were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within 2 weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birth weight below the third percentile, very preterm birth [<32 weeks' gestation], and fetal or neonatal death). RESULTS: Of the 543 individuals included in the study, preeclampsia with severe features within 2 weeks was observed in 33.1% (n=180) of them. A receiver operating characteristic curve-derived cutoff of 11.5 multiples of the median for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio provided good sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within 2 weeks. This cutoff was used to compare test positive cases (≥ cutoff) and test negative cases (< cutoff). Preeclampsia with severe features (66.0% vs 5.7%; P<.001) and composites of severe adverse maternal (8.11% vs 2.7%; P=.006) or perinatal (41.3% vs 10.14%; P=.001) outcomes within 2 weeks were more frequent in test positive cases than in test negative cases. A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the median was independently associated with preeclampsia with severe features (adjusted incidence rate ratio, 9.08; 95% confidence interval, 6.11-14.06; P<.001) and a composite of severe adverse perinatal outcomes (adjusted incidence rate ratio, 9.42; 95% confidence interval, 6.36-14.53; P<.001) but not with a composite of severe adverse maternal outcomes (adjusted incidence rate ratio, 2.20; 95% confidence interval, 0.95-5.54; P=.08). The area under the curve for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio in multiples of the median (0.91; 95% confidence interval, 0.89-0.94) for preeclampsia with severe features within 2 weeks was significantly higher (P<.001 for all comparisons) than either plasma biomarker alone or any other parameter with the exception of absolute soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio values. CONCLUSION: A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the mean among hospitalized patients with hypertension between 23 and 35 week's gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within 2 weeks.

Age-related factors associated with intention to initiate pre-exposure prophylaxis among cisgender women in Washington D.C.

Background: Pre-exposure prophylaxis (PrEP) utilization among cisgender women (subsequently 'women') is low across age groups, relative to their risk of HIV acquisition. We hypothesize that age-related differences in psychosocial factors also influence women's intention to initiate oral PrEP in Washington, D.C. Methods: A secondary analysis of a cross-sectional survey data was performed to evaluate factors influencing intention to initiate oral PrEP among women seen at a family planning and a sexual health clinic. A bivariate analysis was performed to identify differences by age group in demographic characteristics, indications for PrEP, and attitudes toward PrEP; we then performed additional bivariate analysis to assess these variables in relation to PrEP intention. Results: Across age groups, perceived risk of HIV acquisition was not significantly different and was not associated with intention to initiate PrEP. Awareness of and attitude toward PrEP, injunctive norms, descriptive norms, and self-efficacy were not different across age, however there were significant age-associated differences in relation to PrEP intention. Specifically, among 18-24-year-olds, intention to start PrEP was associated with support from provider (p = 0.03), main sexual partner (p < 0.01), and peers (p < 0.01). For women 25-34 years old, having multiple sexual partners (p = 0.03) and support from casual sexual partners (p = 0.03) was also important. Among women 35-44 years old, prior awareness of PrEP (p = 0.02) and their children's support of PrEP uptake (p < 0.01) were associated with intention to initiate PrEP. Among 45-55 year-old women intention to initiate PrEP was positively associated with engaging in casual sex (p = 0.03) and negatively associated with stigma (p < 0.01). Conclusion: Overall, there were more similarities than differences in factors influencing intention to initiate PrEP across age groups. Observed differences offer an opportunity to tailor PrEP delivery and HIV prevention interventions to increase awareness and uptake for cisgender women.

Research showing how women's age affects their decision to start pre-exposure prophylaxis to prevent HIV in Washington, DC We know that many women need pre-exposure prophylaxis (PrEP) to prevent HIV infection in Washington, DC, yet the number of women who use PrEP is lower than expected. The study was done to determine whether a woman's age affects her decision to start PrEP. This is important because providers need to know the factors affecting a woman's decision to start PrEP in order to increase PrEP use in at-risk patients. We re-analyzed a set of data that was generated from surveys given to women in a women's health clinic. The surveys asked women about their background, including risk factors for HIV infection, and their awareness of and attitudes toward PrEP. We also asked women questions that were meant to determine their belief in their own ability to make decisions as well as the degree to which other people in their life affect their own decisions. We wanted to know whether age affects the degree to which these characteristics affect women's decision to start PrEP. Overall, there were more similarities than differences between age groups when looking at how different factors affect the decision to start PrEP. Across age groups, there were no differences in how women view their risk of HIV infection. We found that 18-24-year-olds were more likely to start PrEP when they felt support from their provider, main sexual partner, and peers. 25-34-year-olds were more likely to start PrEP when they felt this same source of support and had had multiple sexual partners. 35-44-year-olds were more likely to start PREP when they already had awareness of PrEP or had their children's support of their PrEP use. 45-55-year-olds were more likely to start PrEP when they had engaged in casual sex and were less likely to start PrEP if they expected negative judgement for it. Even though there were significant similarities between age groups, the differences that we found offer an opportunity to tailor PrEP awareness and interventions to promote PrEP use among women.

Clinical trial simulation to evaluate tenofovir disoproxil fumarate/emtricitabine HIV pre-exposure prophylaxis dosing during pregnancy.

Objective: To evaluate upward-adjustment of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) pre-exposure prophylaxis (PrEP) dosing during pregnancy in order to maintain target plasma concentrations associated with HIV protection. Design: Population pharmacokinetic (PK) modeling and clinical trial simulation (CTS). Material and methods: We developed population pharmacokinetic models for TFV and FTC using data from the Partners Demonstration Project and a PK study of TDF/FTC among cisgender women by Coleman et al., and performed an in-silico simulation. Pregnancy-trimester was identified as a significant covariate on apparent clearance in the optimized final model. We simulated 1,000 pregnant individuals starting standard daily oral TDF/FTC (300 mg/200 mg) prior to pregnancy. Upon becoming pregnant, simulated patients were split into two study arms: one continuing standard-dose and the other receiving double standard-dose throughout pregnancy. Results: Standard-dose trough TFV concentrations were significantly lower in pregnancy compared to pre-pregnancy, with 34.0%, 43.8%, and 65.1% of trough plasma concentrations below the lower bound of expected trough concentrations presumed to be the protective threshold in the 1st, 2nd, and 3rd trimesters, respectively. By comparison, in the simulated double-dose group, 10.7%, 14.4%, and 27.8% of trough concentrations fell below the estimated protective thresholds in the 1st, 2nd, and 3rd trimesters, respectively. The FTC trough plasma concentration during pregnancy was also lower than pre-pregnancy, with 45.2% of the steady-state trough concentrations below the estimated protective trough concentrations of FTC. In the pregnancy-adjusted double-dose group, 24.1% of trough plasma concentrations were lower than protective levels. Conclusions: Our simulation shows >50% of research participants on standard dosing would have 3rd trimester trough plasma TFV concentrations below levels associated with protection. This simulation provides the quantitative basis for the design of prospective TDF/FTC studies during pregnancy to evaluate the safety and appropriateness of pregnancy-adjusted dosing.

Implementation of an Educational Intervention to Improve HIV Pre-Exposure Prophylaxis Services for Women in an Urban Sexual Health Clinic.

To test the hypothesis that implementation of a multicomponent, educational HIV pre-exposure prophylaxis (PrEP) intervention to promote universal PrEP services for cisgender women (subsequently "women") in sexual and reproductive health centers would improve the proportion of women screened, offered, and prescribed PrEP, we implemented a multicomponent, educational intervention in a Washington D.C. Department of Health-sponsored sexual health clinic. The clinic serves a patient population with high-potential exposure to HIV. The intervention included clinic-wide PrEP trainings, an electronic health record prompt for PrEP counseling by providers, and educational videos in the waiting room. We collected preimplementation data from March 22, 2018 to July 4, 2018, including 331 clinical encounters for 329 women. Between July 5, 2018 and July 1, 2019, there were 1733 clinical encounters for 1720 HIV-negative women. We used mixed methods to systematically assess intervention implementation using the Reach Effectiveness Adoption Implementation Maintenance framework. Additionally, we assessed the interventions' acceptability and feasibility among providers through semistructured interviews. The proportion of women screened by providers for PrEP (5.6% preimplementation to a mean of 89.2% of women during the implementation period, p < 0.01), offered (6.2 to 69.8%, p < 0.01), and prescribed PrEP (2.6 to 8.1%, p < 0.01) by providers increased significantly in the implementation period. Providers and clinic staff found the intervention both highly feasible and acceptable and demonstrated increased knowledge of PrEP and HIV prevention associated with the clinic-wide trainings. Our results demonstrate the effectiveness of a low-cost educational intervention to increase provision of integrated PrEP services in an urban sexual health clinic serving women with high-potential exposure to HIV. ClinicalTrials.gov ID NCT03705663.

Intention to Initiate HIV Pre-exposure Prophylaxis Among Cisgender Women in a High HIV Prevalence U.S. City.

OBJECTIVE: Our objective was to identify the individual, interpersonal, community, health-system, and structural factors that influence HIV pre-exposure prophylaxis (PrEP) initiation among cisgender women seeking sexual and reproductive health care in a high HIV prevalence community to inform future clinic-based PrEP interventions. METHODS: We collected anonymous, tablet-based questionnaires from a convenience sample of cisgender women in family planning and sexual health clinics in the District of Columbia. The survey used the lens of the socio-ecological model to measure individual, interpersonal, community, institutional, and structural factors surrounding intention to initiate PrEP. The survey queried demographics, behavioral exposure to HIV, perceived risk of HIV acquisition, a priori awareness of PrEP, intention to initiate PrEP, and factors influencing intention to initiate PrEP. RESULTS: A total of 1437 cisgender women completed the survey. By socio-ecological level, intention to initiate PrEP was associated with positive attitudes toward PrEP (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.13-2.15) and higher self-efficacy (OR, 1.32; 95% CI, 1.02-1.72) on the individual level, perceived future utilization of PrEP among peers and low fear of shame/stigma (OR, 1.65; 95% CI, 1.33-2.04) on the community level, and having discussed PrEP with a provider (OR. 2.39; 95% CI, 1.20-4.75) on the institutional level. CONCLUSION: Our findings highlight the importance of multilevel, clinic-based interventions for cisgender women, which promote sex-positive and preventive PrEP messaging, peer navigation to destigmatize PrEP, and education and support for women's health medical providers in the provision of PrEP services for cisgender women.

Translating Clinical Pharmacology Data in Pregnancy to Evidence-Based Guideline Recommendations: Perspectives From the HIV Field.

Pharmacokinetic (PK) studies in pregnant, postpartum, and breastfeeding people are critical to informing appropriate medication use and dosing. A key component of translating PK results in these complex populations into clinical practice involves the systematic review and interpretation of data by guideline panels, composed of clinicians, scientists, and community members, to leverage available data for informed decision making by clinicians and patients and offer clinical best practices. Interpretation of PK data in pregnancy involves evaluation of multiple factors such as the study design, target population, and type of sampling performed. Assessments of fetal and infant drug exposure while in utero or during breastfeeding, respectively, are also critical for informing whether medications are safe to use during pregnancy and throughout postpartum in lactating people. This review will provide an overview of this translational process, discussion of the various factors considered by guideline panels, and practical aspects of implementing certain recommendations, using the HIV field as an example.

The end of Roe v. Wade: implications for Women's mental health and care.

The Supreme Court decision in Dobbs v. Jackson in June 2022 reversed precedent which had previously protected abortion prior to fetal viability as a universal right within the United States. This decision almost immediately led to abortion restrictions across 25 states. The resulting lack of access to abortion care for millions of pregnant people will have profound physical and mental health consequences, the full effects of which will not be realized for years to come. Approximately 1 in 5 women access abortions in the U.S. each year. These women are diverse and represent all American groups. The Supreme court decision, however, will affect populations that have and continue to be marginalized the most. Forcing pregnant individuals to carry unwanted pregnancies worsens health outcomes and mortality risk for both the perinatal individual and the offspring. The US has one of the highest maternal mortality rates and this rate is projected to increase with abortion bans. Abortion policies also interfere with appropriate medical care of pregnant people leading to less safe pregnancies for all. Beyond the physical morbidity, the psychological sequelae of carrying a forced pregnancy to term will lead to an even greater burden of maternal mental illness, exacerbating the already existing maternal mental health crisis. This perspective piece reviews the current evidence of abortion denial on women's mental health and care. Based on the current evidence, we discuss the clinical, educational, societal, research, and policy implications of the Dobbs v. Jackson Supreme Court decision.

Long-acting antiretrovirals and HIV treatment adherence.

Intramuscular injection of long-acting cabotegravir and rilpivirine is a novel, long-acting antiretroviral therapy (ART) combination approved for use as a fully suppressive regimen for people living with HIV. Long-acting cabotegravir with rilpivirine ART has reduced required dosing frequency from once daily to once every month or every 2 months injections. This new era of long-acting ART, which includes other antiretrovirals and formulations in various stages of clinical development, holds tremendous promise to change the standard of HIV treatment. Although long-acting ART has high potential to be revolutionary in the landscape of HIV care, prevention, and treatment cascade, more data are needed to substantiate its efficacy and cost-effectiveness among patients at risk of non-adherence and across age groups, pregnancy, and post partum. Advocacy efforts and policy changes to optimise a sustained, high-quality, equitable reach of long-acting ART, especially in low-income and middle-income countries where most people living with HIV reside, are needed to realise the full benefits of long-acting ART.

Understanding Retention in the HIV Pre-Exposure Prophylaxis Cascade Among Cisgender Women.

HIV remains a significant public health concern in the United States, with 34,800 new cases diagnosed in 2019; of those, 18% were among women. Oral pre-exposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine is effective and safe, reducing HIV transmission by up to 92% in women. Though studies demonstrate low rates of PrEP adherence among cisgender women prescribed oral PrEP, little is known about the factors that shape PrEP continuation among them. This study focuses on understanding the experiences of cisgender women who have initiated PrEP to gain insight into the factors that shape PrEP continuation. We conducted semi-structured interviews with (N = 20) women who had been prescribed oral PrEP. Interviews were guided by the social-ecological framework to identify multilevel factors affecting PrEP continuation; we specifically examined the experience of engagement and retention in the PrEP cascade. We recruited women who had been prescribed oral PrEP by a government-sponsored sexual health center or a hospital-based family planning clinic in Washington, DC. Factors facilitating PrEP continuation included a positive emotional experience associated with PrEP use, high perceived risk of HIV acquisition, and high-quality communication with health care providers. The most common reason for PrEP discontinuation was low perceived HIV risk (n = 11). Other factors influencing discontinuation were side effects, a negative emotional experience while using PrEP, and negative interactions with the health care system. This study underscores the importance of specific multi-level factors, including the provision of high-quality communication designed to resonate with women and shared decision making between women and their health care providers.

Respect Your Elders: Generativity and Life Satisfaction in Caregiving Grandparents.

Erikson's theory of psychosocial development defines generativity as the drive to benefit future generations and leave a legacy. Generativity has been shown to predict life satisfaction, but generative concern and action can be impacted by factors such as perceived respect from younger generations. This study utilized caregiving grandparents aged 40 and older to assess the extent to which perceived respect mediated the relation between generativity and life satisfaction. Perceived respect from a grandchild mediated the relation between generative concern expressed by caregiving grandparents and life satisfaction after controlling for demographic variables that have been shown to influence heterogeneity and overall well-being in caregiving grandparent samples. These findings suggest that the relation between life satisfaction and generativity in grandparents may depend, in part, on perceived respect from grandchildren, intimating that the implications of generativity may be influenced by the perceived appreciation of its recipients.

Understanding Psychosocial Determinants of PrEP Uptake Among Cisgender Women Experiencing Heightened HIV Risk: Implications for Multi-Level Communication Intervention.

Pre-exposure prophylaxis (PrEP) is a highly effective daily pill that decreases the likelihood of HIV acquisition by up to 92% among individuals at risk for HIV. PrEP can be discretely used, autonomously controlled, and in place at the time of risk exposure, making it an especially promising method for HIV prevention for cisgender women (CGW). But, PrEP is underutilized by CGW relative to the demonstrable need. We apply the Integrative Model of Behavioral Prediction to identify the critical psychosocial factors that shape CGW's intentions to use PrEP and their relevant underlying beliefs. We surveyed (N = 294) community- and clinic-recruited PrEP eligible CGW to understand the relative importance of attitudes, norms, and efficacy in shaping PrEP intentions. We utilized structural equation modeling to identify the relevant paths. We inspected the summary statistics in relation to three message three selection criteria. We identified beliefs that demonstrated (1) an association with intention, (2) substantial room to move the population, (3) practicality as a target for change through communication intervention. Results show that PrEP awareness was low. When women learned about PrEP, they voiced positive intentions to use it. There were significant and positive direct effects of SE (0.316***), attitudes (0.201**), and subjective norms (0.249***) on intention to initiate PrEP. We illustrate the strategic identification of beliefs within the relevant paths using the 3 belief selection criteria. We also discuss implications for social and structural communication interventions to support women's HIV prevention.

Gabapentin as an adjunct for pain management during dilation and evacuation: A double-blind randomized controlled trial.

OBJECTIVES: To assess the analgesic efficacy of preoperative gabapentin among patients undergoing dilation and evacuation (D&E) with moderate sedation. STUDY DESIGN: We conducted a randomized, controlled, double-blind trial among patients undergoing same-day D&E at 14 to 19 weeks gestation under moderate sedation. We randomized participants 1:1 to gabapentin 600 mg or placebo after cervical preparation at least 1 hour prior to D&E. We assessed pain using a 100-mm visual analog scale before, during, and after the procedure. The primary outcome was postoperative recall of maximum procedural pain with a 13-mm a priori threshold for clinical significance. We standardized initial fentanyl and midazolam dosing. We assessed satisfaction with pain control, nausea, and vomiting via Likert scales and anxiety using a validated instrument. RESULTS: We enrolled 126 participants and randomized 61 to gabapentin and 65 to placebo, with study medication administered a mean of 211 (SD 64) minutes preoperatively. Recall of maximum pain was 41 mm for gabapentin and 49 mm for placebo (p = 0.24). Gabapentin resulted in reduced pain during uterine aspiration (56 vs 71 mm, p= 0.003) compared to placebo, but not for any other time points. The gabapentin group had higher satisfaction (78% vs 65% very or somewhat satisfied, p= 0.01). Median fentanyl dose was lower in the gabapentin group (75 vs 100 mcg, p = 0.005). Midazolam dose, nausea, vomiting, and anxiety did not differ between groups. No serious adverse events occurred in the gabapentin group. Sedation reversal was not required. CONCLUSIONS: The addition of gabapentin to moderate sedation during D&E did not result in lower maximum recalled procedural pain. Gabapentin resulted in reduced intra-operative pain during uterine aspiration and increased satisfaction with pain control. IMPLICATIONS: Gabapentin reduces intraoperative pain and improves satisfaction with pain management when administered prior to second-trimester surgical abortion and may be considered as an adjunct to intravenous sedation. Moderate sedation may impair assessment and recall of pain. Additional research is needed to identify the most effective pain management regimens for D&E.

Integrating ART adherence support technologies in the care of pregnant and postpartum people with HIV: a qualitative study.

BACKGROUND: We have a limited understanding on how to best integrate technologies to support antiretroviral therapy (ART) adherence in routine HIV care. METHODS: We conducted semi-structured interviews with multidisciplinary providers caring for pregnant and postpartum people with HIV and asked providers about their perspectives on utilizing adherence support technologies such as text messages, video check-ins with providers or automated with facial recognition for directly-observed-therapy, signaling pill bottle, and signaling pill to support ART adherence. Each approach generated an adherence report. The interview instrument was guided by the Consolidated Framework for Implementation Research and included questions on the implementation climate, barriers, and facilitators to the clinical integration of the adherence approach and strategies that could be used to maximize this integration. The order of adherence support technologies was randomized to minimize bias. We used a modified grounded theory to develop the coding structure and two coders applied the codebook to the transcripts after establishing strong inter-rater reliability with 20% of interviews (kappa = 0.82). RESULTS: Between March and December 2020, we conducted 26 in-depth, semi-structured interviews with providers who weighed several factors when considering each approach, including the approach's effect on patient-provider interaction in and outside of the clinic visit, timing for and duration of the approach's utility, threat of disclosing status, and added burden to providers (e.g., needing to act on generated information) or to patients (e.g., needing to hide the signaling pills, responding to text messages). Providers' most preferred approach was text-messages, and the least preferred was the signaling pill. Barriers to acceptability varied by approach and included perceived surveillance, violation of privacy, added time demand for providers, potential inaccuracy of the adherence data generated, and negative impact on the patient-provider relationship, particularly if the approach was perceived as coercive. Payers anticipated regulatory hurdles with unfamiliar approaches, particularly the signaling pill and signaling pill bottle. Facilitators included strengthened therapeutic alliance, predictable reminder mechanisms, and options for customization according to patient preference. CONCLUSIONS: Our study elucidates barriers and facilitators to integrating technology-based adherence support approaches in clinical care to support adherence of pregnant and postpartum people with HIV.

Factors Associated with Intention to Initiate Pre-exposure Prophylaxis in Cisgender Women at High Behavioral Risk for HIV in Washington, D.C.

Pre-exposure prophylaxis (PrEP) for HIV prevention is underutilized by cisgender women at risk for HIV in the USA. Published research on PrEP initiation among cisgender women at risk for HIV focuses on identifying barriers and facilitators associated with intention to initiate, but few apply a behavioral theoretical lens to understand the relative importance of these diverse factors. This study provides a theoretically grounded view of the relative importance of factors associated with intention to initiate PrEP. We conducted an anonymous, cross-sectional survey of 1437 cisgender women seeking care at family planning and sexual health clinics to evaluate hypothesized barriers and facilitators of PrEP initiation. We categorized cisgender women with ≥ 3 behavioral risk-factors as "high-risk" for HIV acquisition; 26.9% (N = 387) met high-risk criterion. Among cisgender women in the high-risk sample, the majority were Black and single. Perceived risk of HIV acquisition was low and 13.7% reported intention to initiate PrEP. Positive attitudes toward PrEP, self-efficacy, perceived support from medical providers and social networks, and prior discussion about PrEP with medical providers were associated with intention to initiate PrEP; stigma was negatively associated. Background characteristics (other than age), risk factors for HIV acquisition, prior awareness of PrEP, and perceived risk of HIV were not associated with uptake intention. These findings support interventions that center on the role of providers in the provision of PrEP and on social networks in destigmatization of PrEP use.

Metabolomics in Placental Tissue from Women Living with HIV.

It is unknown whether antiretroviral (ARV) drugs in women living with HIV (WLHIV) are associated with mitochondrial toxicity and altered fat oxidation and branched-chain amino acid metabolism in the placenta and fetus. Immediately after delivery, we froze placental biopsies from 20 WLHIV and 20 matched uninfected women. We analyzed global biochemical profiles using high-performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We used t-tests, principle component analysis, hierarchical clustering, and random forest analysis (RFA) in our analysis. Twelve WLHIV were on protease inhibitors, six on non-nucleoside reverse inhibitors, and two on integrase strand inhibitors with optimized backbone. Mean birth weight of HIV-exposed neonates was significantly lower than unexposed neonates (3,075 g vs. 3,498 g, p = .01) at similar gestational age. RFA identified 30 of 702 analytes that differentiated the placental profiles of WLHIV from uninfected women with 72.5% predictive accuracy. Placental profiles of non-nucleoside reverse transcriptase inhibitor (NNRTI)-treated WLHIV exhibited lower levels of amino acids, including essential and branched-chain amino acids, and some medium-chain acylcarnitines. Placental metabolism may be altered in WLHIV, possibly associated with ARV exposure. The lower birth weight among neonates of WLHIV suggests the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.

Depressive Symptoms and Suicidality of Those Raised in Kincare: A Peer Comparison Study.

The rate at which children are raised in kincare has steadily been on the rise. Prior research indicates that this group of individuals are at an increased risk of mental health problems. The current study examined the suicidality and depressive symptoms of adults who were raised in kincare compared to those raised by their parents. There were a total of 1,486 participants, 171 of whom were adults raised in kincare, and 1,315 who were raised by one or both of their parents. Participants completed a measure of suicide risk and reported symptoms of depression and anhedonia.Those raised in kincare scored significantly higher on the measures of anhedonia and suicide risk. However, there were no differences in general depressive symptoms. Further analyses found that more frequent attendance of religious activities and higher levels of household income acted as protective factors. These findings suggest kincare is associated with adverse mental health outcomes.

Awareness, acceptability, and intention to initiate HIV pre-exposure prophylaxis among pregnant women.

HIV prevention is critically important during pregnancy, however, pre-exposure prophylaxis (PrEP) is underutilized. We conducted a survey of pregnant and non-pregnant women in a high HIV prevalence community in Washington D.C. to evaluate determinants of PrEP initiation during pregnancy. 201 pregnant women and a reference population of 1103 non-pregnant women completed the survey. Among pregnant women, mean age was 26.9 years; the majority were Black with household-incomes below the federal poverty level. Despite low perceived risk of HIV acquisition and low prior awareness of PrEP, 10.5% of respondents planned to initiate PrEP during pregnancy. Pregnant women identified safety, efficacy, and social network and medical provider support as key factors in PrEP uptake intention. The belief that PrEP will "protect (their) baby from HIV" was associated with PrEP uptake intention during pregnancy. Concerns regarding maternal/fetal side effects, and safety in pregnancy or while breastfeeding were not identified as deterrents to uptake intention. When compared to a nonpregnant sample, there were no significant differences in uptake intention between the two samples. These findings support the need for prenatal educational interventions to promote HIV prevention during pregnancy, as well as interventions that center on the role of providers in the provision of PrEP.

Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy.

BACKGROUND: Among women with hypertensive disorders of pregnancy, biomarkers may stratify risk for developing preeclampsia with severe features (sPE). METHODS: Across 18 U.S. centers, we prospectively measured the ratio of serum soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) in pregnant women hospitalized between 23 and 35 weeks of gestation. The primary outcome was predicting sPE, and secondary outcomes included predicting adverse outcomes within 2 weeks. The prognostic performance of the sFlt-1:PlGF ratio was assessed by using a derivation/validation design. RESULTS: A total of 1014 pregnant women were evaluated; 299 were included in the derivation cohort and 715 in the validation cohort. In the derivation cohort, the median sFlt-1:PlGF ratio was 200 (interquartile range, 53 to 458) among women who developed sPE compared with 6 (interquartile range, 3 to 26) in those who did not (P<0.001). The discriminatory ratio of ≥40 was then tested in the validation cohort and yielded a 65% positive (95% confidence interval [CI], 59 to 71) and a 96% negative (95% CI, 93 to 98) predictive value for the primary outcome. The ratio performed better than standard clinical measures (area under the receiver-operating characteristic curve, 0.92 versus <0.75 for standard-of-care tests). Compared with women with a ratio <40, women with a ratio ≥40 were at higher risk for adverse maternal outcomes (16.1% versus 2.8%; relative risk, 5.8; 95% CI, 2.8 to 12.2). CONCLUSIONS: In women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks of gestation, measurement of serum sFlt-1:PlGF provided stratification of the risk of progressing to sPE within the coming fortnight. (Funded by Cedars-Sinai Medical Center and Thermo Fisher Scientific; ClinicalTrials.gov NCT03815110.)

Providers PrEP: Identifying Primary Health care Providers' Biases as Barriers to Provision of Equitable PrEP Services.

BACKGROUND: Despite their disparately high HIV incidence and voiced willingness to use pre-exposure prophylaxis (PrEP), Black cisgender women's knowledge and uptake of PrEP are low, especially relative to White cisgender women and men who have sex with men. Mounting evidence demonstrates that health care provider recommendations are a critical factor in women's awareness, willingness, and ability to uptake PrEP. Health care providers may make clinical judgments about who is (not) a good candidate for PrEP based on unconscious and conscious stereotypes and prejudice. SETTING: We conducted an online experiment among N = 160 health care providers with prescribing privileges in the 48 HIV hotspot counties. METHOD: Providers received 1 of 4 vignettes about a PrEP eligible woman. Vignettes varied by patient race and substance use status. Then, providers reported their willingness to discuss PrEP with the patient and willingness to prescribe PrEP to her. RESULTS: We tested 2 models predicting providers (1) willingness to discuss and (2) willingness to prescribe PrEP, contingent on their racial attitudes. Providers who scored high on a modern racism measure were less willing to discuss and prescribe PrEP to the Black patient. These effects were mediated by provider perceptions of patients' abilities to adhere to PrEP, but not their expectations of risk compensatory behaviors. CONCLUSIONS: Our findings highlight the importance of applying an intersectional lens in documenting the processes that exacerbate inequities in PrEP use. This study provides evidence to support the development of interventions that address the mechanisms that work to thwart optimal care.

Understanding Women's Vaginal Douching Behaviors and Practices for Consideration in the Development of a Potential Future Vaginal Microbicide Douche for HIV Prevention: A Systematic Review of the Literature.

Despite clinicians consistently advising against vaginal douching, 29-92% of women worldwide report douching. This review documents women's douching practices, motivations for douching, and specific associations (or absence of associations) between vaginal douche use and vaginal outcomes thought to be associated with douching. Understanding women's existing douching behaviors and vaginal health outcomes is critical for developing a safe vaginal microbicide douche that can be used as HIV pre-exposure prophylaxis (PrEP). A vaginal douche as PrEP could help prevent new HIV infections, since emerging evidence shows some women discontinue oral PrEP. We performed a systematic review of the literature using the guidelines for Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). Articles included in the analysis (N = 48) were published 2009-2019 in English and focused on women's experiences with douching. Two trained independent reviewers assessed these articles for content on vaginal douching, including racial/ethnic focus of studies, study design, sampling, women's reasons for douching, contents of douche solutions, and associations between vaginal douching and vaginal health outcomes. Several studies focused on Black women (N = 12 studies) or had no racial/ethnic focus (N = 12). Just over half of all studies (N = 24) were cross-sectional and involved a self-reported questionnaire and lab samples. Studies sampled women from health clinics where they were (N = 13) or were not (N = 14) presenting for vaginal health complaints. Women's primary motivation for douching was for "general cleanliness" (N = 13), and most douche solutions contained water (N = 12). There was little empirical agreement between vaginal douche use and most vaginal health outcomes. Future studies of PrEP vaginal douches should be well controlled and prioritize safety to ensure positive vaginal health outcomes.