Pharmacokinetics, Placental and Breast Milk Transfer of Antiretroviral Drugs in Pregnant and Lactating Women Living with HIV

2019 ◽  
Vol 25 (5) ◽  
pp. 556-576 ◽  
Author(s):  
E.M. Hodel ◽  
C. Marzolini ◽  
C. Waitt ◽  
N. Rakhmanina
Keyword(s):  
Breast Milk ◽  
Protease Inhibitors ◽  
Drug Class ◽  
Drug Transporters ◽  
Maternal Plasma ◽  
Antiretroviral Drugs ◽  
Physiological Changes ◽  
Women Living With Hiv ◽  
Living With Hiv ◽  
In Pregnancy

Background:Remarkable progress has been achieved in the identification of HIV infection in pregnant women and in the prevention of vertical HIV transmission through maternal antiretroviral treatment (ART) and neonatal antiretroviral drug (ARV) prophylaxis in the last two decades. Millions of women globally are receiving combination ART throughout pregnancy and breastfeeding, periods associated with significant biological and physiological changes affecting the pharmacokinetics (PK) and pharmacodynamics (PD) of ARVs. The objective of this review was to summarize currently available knowledge on the PK of ARVs during pregnancy and transport of maternal ARVs through the placenta and into the breast milk. We also summarized main safety considerations for in utero and breast milk ARVs exposures in infants.Methods:We conducted a review of the pharmacological profiles of ARVs in pregnancy and during breastfeeding obtained from published clinical studies. Selected maternal PK studies used a relatively rich sampling approach at each ante- and postnatal sampling time point. For placental and breast milk transport of ARVs, we selected the studies that provided ratios of maternal to the cord (M:C) plasma and breast milk to maternal plasma (M:P) concentrations, respectively.Results:We provide an overview of the physiological changes during pregnancy and their effect on the PK parameters of ARVs by drug class in pregnancy, which were gathered from 45 published studies. The PK changes during pregnancy affect the dosing of several protease inhibitors during pregnancy and limit the use of several ARVs, including three single tablet regimens with integrase inhibitors or protease inhibitors co-formulated with cobicistat due to suboptimal exposures. We further analysed the currently available data on the mechanism of the transport of ARVs from maternal plasma across the placenta and into the breast milk and summarized the effect of pregnancy on placental and of breastfeeding on mammal gland drug transporters, as well as physicochemical properties, C:M and M:P ratios of individual ARVs by drug class. Finally, we discussed the major safety issues of fetal and infant exposure to maternal ARVs.Conclusions:Available pharmacological data provide evidence that physiological changes during pregnancy affect maternal, and consequently, fetal ARV exposure. Limited available data suggest that the expression of drug transporters may vary throughout pregnancy and breastfeeding thereby possibly impacting the amount of ARV crossing the placenta and secreted into the breast milk. The drug transporter’s role in the fetal/child exposure to maternal ARVs needs to be better understood. Our analysis underscores the need for more pharmacological studies with innovative study design, sparse PK sampling, improved study data reporting and PK modelling in pregnant and breastfeeding women living with HIV to optimize their treatment choices and maternal and child health outcomes.

scholarly journals Drug–Drug Interactions with Antiretroviral Drugs in Pregnant Women Living with HIV: Are They Different from Non-Pregnant Individuals?

2020 ◽  
Vol 59 (10) ◽  
pp. 1217-1236
Author(s):  
Vera E. Bukkems ◽  
Angela Colbers ◽  
Catia Marzolini ◽  
Jose Molto ◽  
David M. Burger
Keyword(s):  
Drug Interactions ◽  
Pregnant Women ◽  
Antiretroviral Drugs ◽  
Women Living With Hiv ◽  
Living With Hiv

scholarly journals Breast Milk Virome and Bacterial Microbiome Resilience in Kenyan Women Living with HIV

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Rabia Maqsood ◽  
Joshua B. Reus ◽  
Lily I. Wu ◽  
LaRinda A. Holland ◽  
Ruth Nduati ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Breast Milk ◽  
Infant Mortality ◽  
Human Cytomegalovirus ◽  
Cd4 Counts ◽  
Women Living With Hiv ◽  
Bacterial Microbiome ◽  
Viral Communities ◽  
Kenyan Women ◽  
Living With Hiv

ABSTRACT Breast milk is nutritionally and immunologically beneficial in early life but is also a potential source of infection. Little is known about breast milk microbiota of women living with HIV (WLHIV), the impact of severe immunosuppression, and the contribution to mortality of HIV-exposed infants. Here, we performed metagenomic sequencing to characterize the bacterial microbiome and DNA virome of breast milk samples at 1 month postpartum from Kenyan WLHIV who were not receiving combination antiretroviral therapy (cART), 23 women with CD4 counts of <250 and 30 women with CD4 of >500; and additionally, 19 WLHIV with infants that lived and 26 WLHIV with infants that died during the first 2 years of life were included. We found that breast milk bacterial microbiomes in this study population were highly diverse but shared a core community composed of the Streptococcaceae, Staphylococcaceae, Moraxellaceae, and Eubacteriaceae families. The breast milk virome was dominated by human cytomegalovirus (CMV) and included the bacteriophage families Myoviridae, Siphoviridae, and Podoviridae. Bacterial microbiome and virome profiles and diversity were not significantly altered by HIV immunosuppression, as defined by a CD4 of <250. CMV viral load was not associated with maternal CD4 counts or infant mortality. In conclusion, we show that the core bacterial and viral communities are resilient in breast milk despite immunosuppression in WLHIV. IMPORTANCE Breastfeeding plays an important role in seeding the infant gut microbiome and mammary health. Although most studies focus on the diverse breast milk bacterial communities, little is known about the viral communities harbored in breast milk. We performed the first breast milk virome study of an HIV population. In this study cohort of Kenyan women living with HIV from the pre-antiretroviral therapy era, we found that breast milk harbors a core bacterial microbiome and a virome dominated by human cytomegalovirus. The virome and bacterial microbiome were not substantially altered by immunosuppression or associated with infant mortality. Together, these findings indicate resilience of the microbial community in breast milk compartmentalization. These findings advance out fundamental understanding of the breast milk core microbiome and virome interactions in the context of HIV disease.

scholarly journals MENSTRUAL PERIOD ANALISIS OF WOMEN PLWHA WITH ANTI RETROVIRAL THERAPY (ART) IN NGO LANCANG KUNING PEKANBARU CITY

1930 ◽  
Vol 8 (01) ◽  
pp. 147-154
Author(s):  
Dona Martilova ◽  
Husna Farianti Amran
Keyword(s):  
Antiretroviral Therapy ◽  
Nutritional Status ◽  
Good Condition ◽  
Sampling Technique ◽  
Antiretroviral Drugs ◽  
P Value ◽  
Cross Sectional ◽  
Women Living With Hiv ◽  
Living With Hiv ◽  
Hiv Aids

Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Virus (HIV), including infectious diseases that cause weakness of the immune system. Riau province on the 11st grade of most cases of AIDS that is 1104 cases and 53% occur in women. Treatment that can be done is to use antiretroviral therapy (ART). ARV drugs do not kill the virus but can slow the growth of the virus. The use of antiretroviral drugs can cause side effects in some women the use of antiretroviral drugs causes menstrual disorders such as prolonged bleeding, menstrual bleeding time, faster menstrual periods, longer menstrual intervals, and, periods sometimes do not occur.The research type is quantitative with cross sectional approach. The study was conducted from May to December 2017. The study population was all women living with HIV / AIDS under the guidance of NGO Lancang Kuning Pekanbaru which amounted to 96 people with a sample of 53 people taken with Simple Random Sampling technique (simple random), Instrument data collection is a questionnaire in the form of a list question and checklist list. Data were analyzed by Univariate to know the frequency distribution of respondent, and Bivariate (chi-square) to know the relation between variables. The results showed that menstrual cycle disorders in HIV-positive women were associated with age (P value 0.001), duration of use of antiretroviral therapy (P value 0.004), nutritional status of women living with HIV (P value 0,003) and environmental factor (P value 0,000). It is recommended that women living with HIV / AIDS can take Anti retroviral medication regularly and maintain their nutritional status in good condition and it is expected that the environment can provide support to PLHIV women.

scholarly journals Importance of Prospective Studies in Pregnant and Breastfeeding Women Living With Human Immunodeficiency Virus

2019 ◽  
Vol 69 (7) ◽  
pp. 1254-1258 ◽  
Author(s):  
Angela Colbers ◽  
Mark Mirochnick ◽  
Stein Schalkwijk ◽  
Martina Penazzato ◽  
Claire Townsend ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Pregnant Women ◽  
Clinical Care ◽  
Antiretroviral Drugs ◽  
New Drugs ◽  
European Medicines Agency ◽  
Controlled Clinical Trial ◽  
Women Living With Hiv ◽  
Immunodeficiency Virus ◽  
Living With Hiv

Abstract Recently, the US Food and Drug Administration and European Medicines Agency issued warnings on the use of dolutegravir and darunavir/cobicistat for treatment of pregnant women living with human immunodeficiency virus (HIV). It took 3–5 years to identify the risks associated with the use of these antiretroviral drugs, during which time pregnant women were exposed to these drugs in clinical care, outside of controlled clinical trial settings. Across all antiretroviral drugs, the interval between registration of new drugs and first data on pharmacokinetics and safety in pregnancy becoming available is around 6 years. In this viewpoint, we provide considerations for clinical pharmacology research to provide safe and effective treatment of pregnant and breastfeeding women living with HIV and their children. These recommendations will lead to timelier availability of safety and pharmacokinetic information needed to develop safe treatment strategies for pregnant and breastfeeding women living with HIV, and are applicable to other chronic disease areas requiring medication during pregnancy.

scholarly journals Psychosocial health in pregnancy and postpartum among women living with - and without HIV and non-pregnant women living with HIV living in the Nordic countries – Results from a longitudinal survey study

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Ellen Moseholm ◽  
Inka Aho ◽  
Åsa Mellgren ◽  
Gitte Pedersen ◽  
Terese L. Katzenstein ◽  
...  
Keyword(s):  
Social Support ◽  
Pregnant Women ◽  
Regression Models ◽  
Psychosocial Health ◽  
Survey Study ◽  
Women Living With Hiv ◽  
Pregnancy And Postpartum ◽  
Living With Hiv ◽  
Depression In Pregnancy ◽  
In Pregnancy

Abstract Background The success of antiretroviral therapy has normalized pregnancy among women living with HIV (WWH) with a very low risk of perinatal transmission of HIV. Despite these advances, WWH still face complex medical and psychosocial issues during pregnancy and postpartum. The aim of this study was to assess differences in psychosocial health outcomes between pregnant WWH, non-pregnant WWH, and pregnant women without HIV, and further identify factors associated with probable depression in the third trimester and postpartum. Methods In a longitudinal survey study, participants were included from sites in Denmark, Finland, and Sweden during 2019–2020. Data was collected in the 3rd trimester, 3 and 6 months postpartum using standardized questionnaires assessing depression, perceived stress, loneliness, and social support. Mixed regression models were used to assess changes over time within and between groups. Logistic regression models were used to identify factors associated with depression in pregnancy and postpartum. Results A total of 47 pregnant WWH, 75 non-pregnant WWH, and 147 pregnant women without HIV were included. The prevalence of depression was high among both pregnant and non-pregnant WWH. There was no significant difference between pregnant and non-pregnant WWH in depression scores, perceived stress scores, or social support scores at any time point. Compared to pregnant women without HIV, pregnant WWH reported worse outcomes on all psychosocial scales. Social support and loneliness were associated with an increased odds of depressive symptoms in the adjusted analysis. Conclusions A high burden of adverse psychosocial outcomes was observed in both pregnant and non-pregnant women living with HIV compared to pregnant women without HIV. Loneliness and inadequate social support were associated with increased odds of depression in pregnancy and should be a focus in future support interventions.

scholarly journals Prevalence and predictors for unintended pregnancy among HIV-infected pregnant women in Lira, Northern Uganda: a cross-sectional study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Agnes Napyo ◽  
Victoria Nankabirwa ◽  
David Mukunya ◽  
Josephine Tumuhamye ◽  
Grace Ndeezi ◽  
...  
Keyword(s):  
Unintended Pregnancy ◽  
Antiretroviral Drugs ◽  
Global Strategy ◽  
Northern Uganda ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Unintended Pregnancies ◽  
Women Living With Hiv ◽  
Living With Hiv ◽  
Marital Union

Abstract Prevention of unintended pregnancies is a global strategy to eliminate mother-to-child transmission of HIV. Factors surrounding unintended pregnancy among women living with HIV are not well understood. We aimed to determine the prevalence and predictors for unintended pregnancy among these women in Northern Uganda. We conducted a cross-sectional survey among 518 women using a structured questionnaire. We asked questions on socio-demographic, reproductive-related and HIV-related characteristics. We conducted multivariable logistic regression and reported adjusted odds ratios. The prevalence of unintended pregnancy was 41.1%. The predictors for unintended pregnancy were: being single (not living with a partner or being in a marital union), having five or more children and taking antiretroviral drugs for long periods of time. HIV counselling services should target women living with HIV who are not in a marital union, those having a higher parity and those who have taken ART for longer periods.

scholarly journals Nelfinavir and Its Active Metabolite, Hydroxy-t-Butylamidenelfinavir (M8), Are Transferred in Small Quantities to Breast Milk and Do Not Reach Biologically Significant Concentrations in Breast-Feeding Infants Whose Mothers Are Taking Nelfinavir

2011 ◽  
Vol 55 (11) ◽  
pp. 5168-5171 ◽  
Author(s):  
Paul J. Weidle ◽  
Clement Zeh ◽  
Amy Martin ◽  
Richard Lando ◽  
Frank Angira ◽  
...  
Keyword(s):  
Breast Milk ◽  
Breast Feeding ◽  
Active Metabolite ◽  
Hiv Transmission ◽  
Dried Blood Spots ◽  
Maternal Plasma ◽  
Antiretroviral Drugs ◽  
Blood Spots ◽  
Mother To Child

ABSTRACTAntiretroviral drugs cross from maternal plasma to breast milk and from breast milk to the infant in different concentrations. We measured concentrations of nelfinavir and its active metabolite (M8) in maternal plasma and breast milk from women and in dried blood spots collected from their infants at delivery and postnatal weeks 2, 6, 14, and 24 in the Kisumu Breastfeeding Study, Kisumu, Kenya. Nelfinavir-based antiretroviral regimens given to mothers as prevention of mother-to-child HIV transmission (PMTCT) do not expose the breast-feeding infant to biologically significant concentrations of nelfinavir or M8.

Human papillomavirus (HPV) shedding in breast milk from African women living with HIV

2018 ◽  
Vol 106 ◽  
pp. 41-43 ◽  
Author(s):  
Sophie Diaz ◽  
Nathalie Boulle ◽  
Jean-Pierre Molès ◽  
Marianne Peries ◽  
David Rutagwera ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Breast Milk ◽  
African Women ◽  
Women Living With Hiv ◽  
Living With Hiv

scholarly journals 935. Repeat Pregnancies Among Women Living With HIV: Evaluating Temporal Changes in HIV Disease Status and Exploring the Association Between Preterm Birth and Protease Inhibitor Use in Pregnancy

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S32-S33
Author(s):  
Brigid O’Brien ◽  
Paige Williams ◽  
Deborah Kacanek ◽  
Ellen Chadwick ◽  
Kathleen Powis ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Maternal Age ◽  
Regression Models ◽  
First Trimester ◽  
Mixed Effect ◽  
Cd4 Counts ◽  
Women Living With Hiv ◽  
Stock Dividends ◽  
Living With Hiv ◽  
In Pregnancy

Abstract Background With improved treatment, women living with HIV (WLHIV) are increasingly becoming pregnant. Studies have shown suboptimal viral suppression following pregnancy. In addition, protease inhibitors (PI) have been associated with preterm birth (PTB). Methods We studied WLHIV with at least 2 live births while on the PHACS SMARTT study. We first compared CD4 counts and viral loads (VL) between the first and second pregnancies using Wilcoxon rank-sum tests. We then examined trends in these measures over all reported pregnancies using mixed-effect linear regression models adjusting for maternal age and birth year, with a random effect to account for repeated measures in the same woman over time. Finally, we evaluated the association of PI or non-PI use during pregnancy with PTB, using GEE logistic regression models to adjust for pregnancy number, maternal age, and birth year. Results Between 2007 and 2018, 699 women had &gt;1 pregnancy while on study, with a total of 1642 children. Their mean CD4 counts remained stable over repeat pregnancies. Their mean log10 VL decreased between the first and second pregnancies, both early and late in pregnancy (–0.42 cp/mL and –0.16 cp/mL respectively, P &lt; 0.001 for each), but increased by 0.61 cp/mL (P &lt; 0.001) between the end of the first pregnancy and early in the next pregnancy. Most women had VL suppression during pregnancy with VL rebound by the next pregnancy (figure). A majority of women (55%) received a PI in both their first and second pregnancies, with an increase in PTB rate of 4.3%, whereas those who changed from a PI to a non-PI had a decrease of 4.7% (table). Changing to a PI resulted in a stable rate, whereas remaining on a non-PI resulted in a drop of 2%. In adjusted models including all pregnancies, first trimester PI use was associated with an increased rate of PTB (adjusted OR 1.35; 95% CI 1.02, 1.97). Conclusion Most WLHIV achieved VL suppression during pregnancy, but many had a VL rebound after pregnancy. First trimester PI use was associated with higher risk of PTB. Disclosures E. Chadwick, Abbott Labs: Shareholder, stock dividends. AbbVie: Shareholder, stock dividends. R. B. Van Dyke, Giliad Sciences: Grant Investigator, Research grant.

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