Lowered Rilpivirine Exposure During the Third Trimester of Pregnancy in Human Immunodeficiency Virus Type 1-Infected Women.

Background: The use of antiretroviral therapy during pregnancy is important for control of maternal human immunodeficiency virus (HIV) disease and the prevention of perinatal HIV transmission. Physiological changes during pregnancy can reduce antiretroviral exposure. We studied the pharmacokinetics of rilpivirine 25 mg once daily in HIV-1-infected women during late pregnancy.

Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations.

Infection with certain types of human papillomavirus (HPV) has been associated with the development of cervical and anal cancer. Worldwide, the incidence of anal cancer has increased markedly. The present study aimed to evaluate the prevalence of HPV infection of the uterine cervix and anal canal in human immunodeficiency virus (HIV)- and non-HIV-infected risk populations.

Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy.

Background: The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women.

Analysis of endoplasmic reticulum stress in placentas of HIV-infected women treated with protease inhibitors.

Combined antiretroviral therapy has proven efficacy in decreasing vertical HIV transmission. However, endoplasmic reticulum stress is a known side effect of HIV protease inhibitors. We investigated endoplasmic reticulum stress in placentas of HIV-infected and uninfected mothers by PCR-based splicing analysis of the specific endoplasmic reticulum stress marker XBP1 in post-delivery placental samples of uninfected mothers and in HIV-infected mothers taking antiretroviral therapy.

Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women.

Objectives: To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum.

Patients And Methods: This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included.

Atazanavir exposure is effective during pregnancy regardless of tenofovir use.

Background: We studied the effect of pregnancy on atazanavir pharmacokinetics in the presence and absence of tenofovir.

Methods: This was a non-randomized, open-label, multicentre Phase IV study in HIV-infected pregnant women recruited from European HIV treatment centres. HIV-infected pregnant women treated with boosted atazanavir (300/100 mg or 400/100 mg atazanavir/ritonavir) as part of their combination antiretroviral therapy (cART) were included in the study.

National Guidelines for the prevention of mother-to-child transmission of HIV across Europe - how do countries differ?

Objectives: The aim was to summarize national prevention of mother-to-child transmission (PMTCT) guidelines across Europe and to identify differences between these.

Methods: A survey was conducted using a structured questionnaire sent to experts in 25 European countries from January to March 2012, requesting a copy of the national guidelines. Responses were received from 23 countries.

Diagnostic biomarkers of pro-inflammatory immune-mediated preterm birth.

Purpose: Pro-inflammatory immunity, either infectious or sterile-derived, is one of the major causes of preterm birth and associated with enhanced maternal and fetal morbidity and mortality. Diagnosing intrauterine inflammation at an early stage is tremendously important. Amniotic fluid interleukin (IL)-6 concentration is currently the most investigated diagnostic tool for detecting intrauterine inflammation.

The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women.

Objective: To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum.

Design: A nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe.

Methods: HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were included in the study.

Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid.

Background: Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated.

Findings: Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10.

Career and Family - Are They Compatible?: Results of a Survey of Male and Female Gynaecologists in Germany.

Nowadays, most gynaecologists are female and the compatibility of job-related career and family life is an upcoming issue. The working group "Gender and Career" of the German Society for Gynaecology and Obstetrics (DGGG) designed a survey to reflect the present situation with a focus on the compatibility of career and family. A web-based 74-item survey was filled out by members of the DGGG.

The HIV reverse transcriptase inhibitor tenofovir induces cell cycle arrest in human cancer cells.

Selected HIV drugs, either of the protease inhibitor type or the nucleoside antagonist type, have been shown to exert tumoricidal effects. Here, we show that the HIV reverse transcriptase inhibitor Truvada, a combination drug of the cytidine analogue emtricitabine and the adenosine analogue tenofovir, induces DNA damage and cell cycle arrest in human cancer cells. Phosphorylation of the DNA repair enzyme H2AX by emtricitabine/tenofovir indicated that it interfered with the integrity of the DNA and replication machinery in human cancer cells.

Consultations of HIV-infected women who wish to become pregnant.

Purpose: The aim of this study was to determine the impact and outcome of consultations of HIV-infected women if a pregnancy is planned.

Methods: This study was performed retrospectively based on patient's records of HIV-infected women with the desire to become pregnant between 2000 and 2008. Relevant data regarding HIV infection, obstetrical history, diagnostic procedures and medical interventions related to conception, as well as pregnancy outcomes, were evaluated.

HIV testing in pregnancy: are we testing enough?

Objective: The crucial first step in the prevention of mother-to-child transmission of HIV is awareness of pregnant women of their HIV status. The aim of this study was to define the percentage of patients who received HIV tests between 2001 and 2007 in a German city hospital.

Materials And Methods: In this retrospective cohort analysis at a University hospital in a German urban area, 12,873 deliveries were retrospectively analysed to determine whether an HIV test had been performed during prenatal counselling.

Anal cytology as a screening tool for early detection of anal dysplasia in HIV-infected women.

Background And Aim: HIV-infected patients show a high rate of anal dysplasia and anal carcinoma but there is no gold standard for early detection. Therefore, the objectives of this prospective study were: a) evaluation of an anal screening using anal/perianal cytology; b) in case of a positive result to investigate its relation to immune status, clinical symptoms of HIV infection and antiretroviral therapy.

Patients And Methods: In every HIV-infected woman visiting our gynaecological outpatient clinic, an anal and perianal swab for anal cytology was taken.

Immunohistochemical labeling of the inhibin/activin betaC subunit in normal human placental tissue and chorionic carcinoma cell lines.

Inhibins and activins are important regulators of the female reproductive system. A novel inhibin subunit, named betaC, has been identified and demonstrated to be expressed in several human tissues. We demonstrate here that inhibin betaC is expressed in human placenta.

New prospects for nelfinavir in non-HIV-related diseases.

Nelfinavir (Viracept) was originally designed as a specific HIV protease inhibitor and, since its introduction in 1997, has served as an effective, reliable, and well-tolerated HIV drug. Although nelfinavir is being increasingly displaced by second generation HIV protease inhibitors that allow better combination treatments, it has again become a focus of interest due to an interesting paradoxical effect: nelfinavir inhibits experimentally-induced tissue degeneration or cell damage by preventing loss of the mitochondrial membrane potential, and even protects mitochondria in cancer cells but, conversely, it selectively induces a mitochondria-independent cell death mechanism in cancer cells by the so-called endoplasmic reticulum/unfolded protein stress response, allowing nelfinavir to act on otherwise chemo-resistant cancer cells. Furthermore, anti-microbial effects of nelfinavir have been described, including an efficacy against malaria, tuberculosis, and SARS.

Protease inhibitor-based antiretroviral prophylaxis during pregnancy and the development of drug resistance.

Background: The aim of this study was to determine the development of drug resistance among pregnant women receiving a protease inhibitor-based antiretroviral prophylaxis for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV).

Methods: HIV-infected pregnant women without maternal indication for antiretroviral therapy were enrolled prospectively. Genotypic resistance testing was performed prior to initiation of antiretroviral prophylaxis and was repeated 4-8 weeks after cessation of antiretroviral therapy at the time of delivery.

The mitochondria-independent cytotoxic effect of nelfinavir on leukemia cells can be enhanced by sorafenib-mediated mcl-1 downregulation and mitochondrial membrane destabilization.

Background: Nelfinavir is an HIV protease inhibitor that has been used for a long period of time to treat HIV-infected individuals. It has recently emerged that nelfinavir could represent a prospective new anti-cancer drug, prompting us to test the effect of nelfinavir on leukemia cells.

Methods: By combining in vitro and ex vivo studies, the effect of nelfinavir on leukemia cells and non-malignant, bone marrow-derived tissue cells was analyzed.

Inhibin/activin-betaE subunit is expressed in normal and pathological human placental tissue including chorionic carcinoma cell lines.

Background: Inhibins and activins are important regulators of the female reproductive system. Recently, a novel inhibin subunit, named betaE, has been identified and shown to be expressed in several human tissues. However, only limited data on the expression of this novel inhibin-betaE subunit in normal and pathological human placenta as well as and human chorionic carcinoma cell lines exist.