scholarly journals Tenofovir alafenamide plasma concentrations are reduced in pregnant women living with HIV: data from the PANNA Network

2021 ◽  
Author(s):  
Vera E Bukkems ◽  
Coca Necsoi ◽  
Carmen Hidalgo Tenorio ◽  
Coral Garcia ◽  
Irene Alba Alejandre ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Third Trimester ◽  
Safety Outcome ◽  
The Third ◽  
Women Living With Hiv ◽  
Tenofovir Alafenamide ◽  
Living With Hiv

Abstract Background Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), is included in the majority of the recommended first-line antiretroviral regimens for patients living with HIV, but there are limited data on TAF use in pregnant women. We aimed to examine the plasma pharmacokinetics of TAF and TFV in pregnant women from Europe. Methods Pregnant women living with HIV were included from treatment centers across Europe, and intensive pharmacokinetic sampling in the third trimester and postpartum was performed. Pharmacokinetic parameters of TAF and TFV were determined with noncompartmental analysis. The proportion of women with a TAF AUCtau below the target of 53.1 ng*h/mL was determined. Clinical efficacy and safety outcome parameters were reported. Results In total, 20 pregnant women living with HIV were included. At the third trimester, geometric mean TAF AUClast and Cmax were decreased by 46% and 52%, respectively, compared with postpartum. TFV AUC0-24h, Cmax, and Ctrough decreased by 33%, 30% and 34%, respectively. The proportion of women with a TAF AUClast <53.1 ng*h/mL was 6% at third trimester and 0% postpartum. One out of 20 women had a viral load >50 copies/mL at third trimester and no mother-to-child transmission occurred. Conclusions TAF plasma concentrations were reduced by about half in women living with HIV during third trimester of pregnancy, but remained above the predefined efficacy target in the majority of the pregnant women. TFV concentrations were reduced by approximately 30% during third trimester. Despite the observed exposure decrease, high virologic efficacy was observed in this study.

scholarly journals Study protocol: becoming and being a mother living with HIV - a multicentre longitudinal mixed methods study among pregnant women living with HIV, non-pregnant women living with HIV and pregnant women not living with HIV in a high-income setting (the 2B MOM study)

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e027761
Author(s):  
Ellen Moseholm ◽  
Micheal D Fetters ◽  
Inka Aho ◽  
Åsa Mellgren ◽  
Isik S Johansen ◽  
...  
Keyword(s):  
Mixed Methods ◽  
Pregnant Women ◽  
Psychosocial Outcomes ◽  
Interview Study ◽  
Mixed Methods Study ◽  
Survey Study ◽  
Third Trimester ◽  
The Third ◽  
Women Living With Hiv ◽  
Living With Hiv

IntroductionThe success of combination antiretroviral therapy has decreased the risk of perinatal HIV transmission and normalised pregnancy in women living with HIV (WLWH). Despite these advances, WLWH still face complex medical and psychosocial issues during pregnancy and postpartum, and there is a gap of knowledge on the experiences of becoming and being a mother living with HIV in today’s context. The overall aim of this study is to investigate psychosocial outcomes and experiences of WLWH in Scandinavia during pregnancy and early motherhood.Methods and analysisThis is a multicentre longitudinal convergent mixed methods study consisting of a quantitative survey study, a qualitative interview study and a mixed methods analysis. The survey study aims to examine psychosocial outcomes of WLWH across the pregnancy – postpartum trajectory. Participants are pregnant WLWH living in Scandinavia. Two control groups of HIV-negative pregnant women and non-pregnant WLWH are also included. Data is collected in the third trimester, 3 and 6 months postpartum using standardised questionnaires. Statistical analysis will assess changes over time and identify predictors of adverse outcomes. The interview study seeks to understand experiences of pregnancy and becoming a mother while living with HIV. Pregnant WLWH who are enrolled in the survey study will be asked to participate in individual interviews in the third trimester and 6 months postpartum. Data will be analysed using narrative analysis. The survey and interview results will be merged in a mixed methods analysis to assess confirmation, expansion or discordance between the data sets.Ethics and disseminationApproval from the Danish Data Protection Agency (VD-2018–253), and the Finnish and Swedish Ethics Committees have been obtained (HUS/1330/2019 and Dnr: 2019–04451, respectively). Study results will be disseminated to patient organisations, through publications in peer-reviewed journals and at scientific conferences.

Plasma endothelin-1 and big endothelin-1 levels in women with pre-eclampsia

1993 ◽  
Vol 129 (2) ◽  
pp. 114-120 ◽  
Author(s):  
Norihito Sudo ◽  
Kyuzi Kamoi ◽  
Miyuki Ishibashi ◽  
Tohru Yamaji
Keyword(s):  
Pregnant Women ◽  
Vascular Endothelial Cells ◽  
Plasma Concentrations ◽  
Regulatory System ◽  
Normal Pregnancy ◽  
Molar Ratio ◽  
Chronic Hypertension ◽  
Third Trimester ◽  
Endothelin 1 ◽  
The Third

To examine a possible role for endothelin-1 (ET-1) and conversion of big ET-1 to ET-1 in the pathophysiology of pre-eclampsia, we measured plasma levels of ET-1 and big ET-1 in 16 women with pre-eclampsia in the third trimester and compared them with those in 11 age-matched normotensive pregnant women and in 10 age-matched pregnant women with chronic hypertension in the third trimester. The plasma concentrations of ET-1 and big ET-1 in the normotensive pregnant women were significantly lower than those in 16 non-pregnant women with a higher molar ratio of big ET-1 to ET-1 in the former group. The plasma concentrations of ET-1 and big ET-1 in the women with pre-eclampsia, on the other hand, were significantly higher than those in the normotensive pregnant women and the molar ratio of big ET-1 to ET-1 in the former group was less than that in the latter group. In sharp contrast, plasma ET-1 and big ET-1 levels in the pregnant women with chronic hypertension were not significantly different from those in the normotensive pregnant women. When examined after delivery, elevated plasma ET-1 and big ET-1 in the women with pre-eclampsia declined, with restoration of normal blood pressure, to the levels in the normotensive women after parturition. There were no significant differences of the levels of ET-1 and big ET-1 in umbilical venous plasma and simultaneously drawn maternal plasma at cesarean section between normotensive pregnant women and women with pre-eclampsia, respectively. These results suggest that normal pregnancy is associated with decreased plasma concentrations of ET-1 with reduced conversion of big ET-1 to ET-1 in maternal vascular endothelial cells, and the derangement of this regulatory system plays an important role in the pathophysiology of pre-eclampsia.

scholarly journals Mechanistic Modeling of Maternal Lymphoid and Fetal Plasma Antiretroviral Exposure During the Third Trimester

2021 ◽  
Vol 9 ◽  
Author(s):  
Babajide Shenkoya ◽  
Shakir Atoyebi ◽  
Ibrahim Eniayewu ◽  
Abdulafeez Akinloye ◽  
Adeniyi Olagunju
Keyword(s):  
Pregnant Women ◽  
Drug Exposure ◽  
Drug Disposition ◽  
Pharmacokinetic Parameters ◽  
Lymphoid Tissues ◽  
Third Trimester ◽  
Minimum Effective Concentration ◽  
Fetal Plasma ◽  
The Third ◽  
Pbpk Models

Pregnancy-induced changes in plasma pharmacokinetics of many antiretrovirals (ARV) are well-established. Current knowledge about the extent of ARV exposure in lymphoid tissues of pregnant women and within the fetal compartment is limited due to their inaccessibility. Subtherapeutic ARV concentrations in HIV reservoirs like lymphoid tissues during pregnancy may constitute a barrier to adequate virological suppression and increase the risk of mother-to-child transmission (MTCT). The present study describes the pharmacokinetics of three ARVs (efavirenz, dolutegravir, and rilpivirine) in lymphoid tissues and fetal plasma during pregnancy using materno-fetal physiologically-based pharmacokinetic models (m-f-PBPK). Lymphatic and fetal compartments were integrated into our previously validated adult PBPK model. Physiological and drug disposition processes were described using ordinary differential equations. For each drug, virtual pregnant women (n = 50 per simulation) received the standard dose during the third trimester. Essential pharmacokinetic parameters, including Cmax, Cmin, and AUC (0–24), were computed from the concentration-time data at steady state for lymph and fetal plasma. Models were qualified by comparison of predictions with published clinical data, the acceptance threshold being an absolute average fold-error (AAFE) within 2.0. AAFE for all model predictions was within 1.08–1.99 for all three drugs. Maternal lymph concentration 24 h after dose exceeded the reported minimum effective concentration (MEC) for efavirenz (11,514 vs. 800 ng/ml) and rilpivirine (118.8 vs. 50 ng/ml), but was substantially lower for dolutegravir (16.96 vs. 300 ng/ml). In addition, predicted maternal lymph-to-plasma AUC ratios vary considerably (6.431—efavirenz, 0.016—dolutegravir, 1.717—rilpivirine). Furthermore, fetal plasma-to-maternal plasma AUC ratios were 0.59 for efavirenz, 0.78 for dolutegravir, and 0.57 for rilpivirine. Compared with rilpivirine (0 h), longer dose forgiveness was observed for dolutegravir in fetal plasma (42 h), and for efavirenz in maternal lymph (12 h). The predicted low lymphoid tissue penetration of dolutegravir appears to be significantly offset by its extended dose forgiveness and adequate fetal compartment exposure. Hence, it is unlikely to be a predictor of maternal virological failure or MTCT risks. Predictions from our m-f-PBPK models align with recommendations of no dose adjustment despite moderate changes in exposure during pregnancy for these drugs. This is an important new application of PBPK modeling to evaluate the adequacy of drug exposure in otherwise inaccessible compartments.

scholarly journals Enhanced elimination of betamethasone in dichorionic twin pregnancies

2021 ◽  
Author(s):  
Grazielle Rodrigues ◽  
Jhohann Benzi ◽  
Luísa Matos ◽  
Stella Freitas ◽  
Maria Marques ◽  
...  
Keyword(s):  
Placental Transfer ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Third Trimester ◽  
Intramuscular Dose ◽  
Cyp3a4 Enzyme ◽  
Require Dose ◽  
Twin Pregnancies

Aims: No study has evaluated the BET pharmacokinetics in twin pregnancies separated by chorionicity. The aim this study is to describe and compare the BET pharmacokinetic parameters in singleton, dichorionic (DC) and monochorionic (MC) twin pregnancies in the third trimester of pregnancy. Methods: Twenty-six pregnant women received an intramuscular dose of 6 mg of BET sodium phosphate plus 6 mg BET acetate. Serial blood samples were collected for 24 hours after the first intramuscular BET esters dose. BET plasma concentrations were quantified using a validated HPLC analytical method. BET pharmacokinetic parameters were obtained employing a non-compartment model, and were compared using ANOVA’s test with Tukey’s multiple comparisons test. Correlations between clinical features and pharmacokinetic parameters were analyzed using Pearson’s correlation. Preliminary data on the BET placental transfer were also presented. Results: The geometric mean (IC 95%) of AUC0-∞ 670.0 (504.3-805.2) vs 434.9 (311.2-539.6) ng.h/mL and the CL/F 18.38 (13.84-22.65) vs 29.40 (21.17-36.69) were significantly lower and higher, respectively, in DC twin pregnancies compared to singleton. Others pharmacokinetic parameters did not differ among the groups. Conclusions: Data from this study suggest that the presence of two fetoplacental units may increase the BET metabolism by CYP3A4 enzyme and increase its elimination. Pharmacokinetic-pharmacodynamic clinical studies are needed to investigate whether this BET pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies.

The Effect of Pregnancy on the Pharmacokinetics of Total and Unbound Dolutegravir and Its Main Metabolite in Women Living With Human Immunodeficiency Virus

2020 ◽  
Author(s):  
Pauline Bollen ◽  
Jolien Freriksen ◽  
Deborah Konopnicki ◽  
Katharina Weizsäcker ◽  
Carmen Hidalgo Tenorio ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Pregnant Women ◽  
Geometric Mean ◽  
Polymerase Chain Reaction Test ◽  
Third Trimester ◽  
Once Daily ◽  
Antiretroviral Agents ◽  
The Third ◽  
Immunodeficiency Virus ◽  
Pharmacologically Active

Abstract Background Pharmacokinetic and efficacy data on dolutegravir in pregnant women living with human immunodeficiency virus (HIV) are still limited but needed to support its use as one of the preferred antiretroviral agents. Methods Within the multicenter Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) study, pregnant women living with HIV and using dolutegravir once daily (50 mg, with food) underwent 24-hour pharmacokinetic profiling in their third trimester and postpartum. Dolutegravir exposure in the third trimester was considered adequate if geometric mean unbound, pharmacologically active, minimal plasma concentrations (Cmin, unbound) and ≥90% of individual Cmin, unbound levels were >0.85 µg/L, the proposed 90% inhibitory concentration for unbound dolutegravir. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) for comparison of total and unbound pharmacokinetic parameters in the third trimester and postpartum were calculated, including the metabolic ratio for dolutegravir-glucuronide. Safety and virological data were collected. Results Seventeen women (76% black) were enrolled (25 evaluable pharmacokinetic profiles; 15 in the third trimester, 10 in postpartum). In the third trimester, geometric mean (coefficient of variation, %) Cmin, unbound was 2.87 (87) µg/L and 93% of individual Cmin, unbound levels were >0.85 µg/L. The GMR (90% CI) in the third trimester vs postpartum was 0.86 (.68–1.10) for area under the curve (AUC0-24h), and for Cmax, 0.93 (.77–1.13). GMR (90% CI) for the trough concentrations was 0.71 (.49–1.02), based on total dolutegravir concentrations. Four serious adverse events were reported, unlikely related to dolutegravir. The HIV polymerase chain reaction test was negative in 14/17 infants (result unknown for 3 infants). Conclusions Pharmacokinetic changes for dolutegravir in late pregnancy are not clinically relevant and support the use of dolutegravir 50 mg once daily with food in pregnancy. Clinical Trials Registration NCT00825929.

Features of the course and treatment of glaucoma during pregnancy

2020 ◽  
Vol 98 (3) ◽  
pp. 178-184
Author(s):  
T. V. Chernyakova ◽  
A. Yu. Brezhnev ◽  
I. R. Gazizova ◽  
A. V. Kuroyedov ◽  
A. V. Seleznev
Keyword(s):  
Pregnant Women ◽  
Laser Treatment ◽  
Progressive Disease ◽  
Clinical Course ◽  
The Other ◽  
Third Trimester ◽  
The Third ◽  
Chronic Progressive Disease ◽  
Hypotensive Therapy ◽  
Eye Pressure

In the review we have integrated all up-to-date knowledge concerning clinical course and treatment of glaucoma among pregnant women to help specialists choose a proper policy of treatment for such a complicated group of patients. Glaucoma is a chronic progressive disease. It rarely occurs among childbearing aged women. Nevertheless the probability to manage pregnant patients having glaucoma has been recently increasing. The situation is complicated by the fact that there are no recommendations on how to treat glaucoma among pregnant women. As we know, eye pressure is progressively going down from the first to the third trimester, so we often have to correct hypotensive therapy. Besides, it is necessary to take into account the effect of applied medicines on mother health and evaluate possible teratogenic complications for a fetus. The only medicine against glaucoma which belongs to category B according to FDA classification is brimonidine. Medicines of the other groups should be prescribed with care. Laser treatment or surgery may also be a relevant decision when monitoring patients who are planning pregnancy or just bearing a child. Such treatment should be also accompanied by medicines.

scholarly journals A systematic review and meta-analysis of prevalence of insomnia in the third trimester of pregnancy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nader Salari ◽  
Niloofar Darvishi ◽  
Behnam Khaledi-Paveh ◽  
Aliakbar Vaisi-Raygani ◽  
Rostam Jalali ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Sleep Disorders ◽  
Sleep Disturbances ◽  
Meta Analysis ◽  
Physical And Mental Health ◽  
Third Trimester ◽  
Cross Sectional ◽  
The Third ◽  
Physical Problems ◽  
Meta Regression Analysis

Abstract Background Sleep disorders, which are among the foremost important medical care issues, are prevalent in pregnancy. The present study is a meta-analysis of the prevalence of insomnia in the third trimester of pregnancy. This study aims to systematically review the overall prevalence of insomnia in the third trimester of pregnancy through conducting a meta-analysis. Method The literature used in this meta-analysis for the topic discussed above were obtained through searching several databases, including SID, MagIran, IranDoc, Scopus, Embase, Web of Science (WoS), PubMed Science Direct and Google Scholar databases without time limitation until December 2020. Articles developed based on cross-sectional studies were included in the study. The heterogeneity of studies was investigated using the I2 index. Also, the possible effects of heterogeneity in the studied studies are investigated using meta-regression analysis. Result In 10 articles and 8798 participants aged between11–40, the overall prevalence of insomnia in the third trimester of pregnancy based on meta-analysis was 42.4% (95% CI: 32.9–52.5%). It was reported that as the sample size increases, the prevalence of insomnia in the third trimester of pregnancy increases. Conversely, as the year of research increases, the prevalence of insomnia in the third trimester of pregnancy decreases. Both of these differences were statistically significant (P < 0.05). Conclusion Insomnia was highly prevalent in the last trimester of pregnancy. Sleep disorders are neglected among pregnant women, and they are considered natural. While sleep disturbances can cause mental and physical problems in pregnant women, they can consequently cause problems for the fetus. As a result, maintaining the physical and mental health of pregnant mothers is very important. It is thus recommended that in addition to having regular visits during pregnancy, pregnant women should also be continuously monitored for sleep-related disorders.

The sFlt-1 to PlGF Ratio in Pregnant Women with Rheumatoid Arthritis: Impact of Disease Activity and Sulfasalazine Use

Rheumatology ◽  
2021 ◽  
Author(s):  
Rugina I Neuman ◽  
Hieronymus T W Smeele ◽  
A H Jan Danser ◽  
Radboud J E M Dolhain ◽  
Willy Visser
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Disease Activity ◽  
Pregnant Women ◽  
Gestational Age ◽  
Third Trimester ◽  
Low Disease Activity ◽  
The Third ◽  
Observational Prospective Cohort Study ◽  
Plgf Ratio

Abstract Objectives An elevated sFlt-1/PlGF-ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with rheumatoid arthritis (RA). We explored whether the sFlt-1/PlGF-ratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since sulfasalazine has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether sulfasalazine could affect sFlt-1 or PlGF levels. Methods Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21–42 years, were included, with a median gestational age of 30 + 3 weeks. Results No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (p= 0.07 and p= 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r=-0.01 and r=-0.05, respectively). Four (2%) women with a sFlt-1/PlGF-ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio &gt; 38, corresponding to a negative predictive value of 98.1%. Sulfasalazine users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-sulfasalazine users (n = 164, p= 0.91 and p= 0.11). Conclusion Our study shows that in pregnant women with RA, the sFlt-1/PlGF-ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, sulfasalazine use did not affect sFlt-1 or PlGF levels in this population.

Social Vulnerability among Foreign-Born Pregnant Women and Maternal Virologic Control of HIV

2020 ◽  
Author(s):  
Ashish Premkumar ◽  
Lynn M. Yee ◽  
Lia Benes ◽  
Emily S. Miller
Keyword(s):  
Antiretroviral Therapy ◽  
Pregnant Women ◽  
Median Time ◽  
Social Vulnerability ◽  
Viral Suppression ◽  
Foreign Born ◽  
Women Living With Hiv ◽  
Virologic Control ◽  
Clinical Records ◽  
Living With Hiv

Objective The aim of this study was to assess whether social vulnerability among foreign-born pregnant women living with HIV is associated with maternal viremia during pregnancy. Study Design This retrospective cohort study included all foreign-born pregnant women living with HIV who received prenatal care in a multidisciplinary prenatal clinic between 2009 and 2018. A licensed clinical social worker evaluated all women and kept detailed clinical records on immigration status and social support. Social vulnerability was defined as both living in the United States for less than 5 years and reporting no family or friends for support. The primary outcome was evidence of viral non-suppression after achievement of initial suppression. Secondary outcomes were the proportion of women who required > 12 weeks after starting antiretroviral therapy to achieve viral suppression, median time to first viral suppression (in weeks) after initiation of antiretroviral therapy, and the proportion who missed ≥ 5 doses of antiretroviral therapy. Bivariable analyses were performed. Results A total of 111 foreign-born women were eligible for analysis, of whom 25 (23%) were classified as socially vulnerable. Social and clinical characteristics of women diverged by social vulnerability categorization but no differences reached statistical significance. On bivariable analysis, socially-vulnerable women were at increased risk for needing > 12 weeks to achieve viral suppression (relative risk: 1.78, 95% confidence interval: 1.18–2.67), though there was no association with missing ≥ 5 doses of antiretroviral therapy or median time to viral suppression after initiation of antiretroviral therapy. Conclusion Among foreign-born, pregnant women living with HIV, markers of virologic control during pregnancy were noted to be worse among socially-vulnerable women. Insofar as maternal viremia is the predominant driver of perinatal transmission, closer clinical surveillance and support may be indicated in this population. Key Points

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