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Pregnancy is characterized by foundational changes to the maternal anatomy and physiology in order to maintain and support the developing fetus and to protect the mother, whose survival following pregnancy is critical both to the "fourth-trimester" development of the infant and to any future offspring. While sFlt-1/PlGF imbalance is not limited to pregnancy and pre-eclampsia, in pre-eclampsia, the placenta is the main source of these factors and their imbalance. Type-II pre-eclampsia is characterized by poor maternal cardiovascular tolerance to the demands of pregnancy, with a moderately dysfunctional placenta and insufficient blood supply, often in the late stages of pregnancy. Screening for pre-eclampsia at 11-13 weeks' gestation: use of pregnancy-associated plasma protein-A, placental growth factor or both. [Extracted from the article]

A comprehensive study of unusual cases of placental pathology may provide insight into mechanisms of normal human fertilization and early embryonic development by examining the exception to the rule. A gravida three para two 39-year-old woman was monitored by ultrasound from 16 weeks of gestation for cystic placenta. A female newborn was born at 36 weeks gestation. Pathologic examination of the partially cystic placenta revealed a singleton placenta comprised of 2/3 normal placenta and 1/3 complete hydatidiform mole, largely degenerated. Immunostaining for p57 was negative in stromal cells of the molar villi. Chromogenic in-situ hybridization revealed diploidy in both normal and molar parts. A total of 16 microsatellites were studied by short tandem repeat analysis, 11 of which were informative. The analysis revealed bipaternal molar tissue of dispermic origin. The paternal monospermic contribution to the normal part was different from that in the molar part, thus resulting in tripaternal contribution to the conceptus. A chimera is a single organism composed of two or more different populations of genetically distinct cells that originated from different zygotes (tetragametic) whereas mosaic is a mixture of two cell lines in one organism originating from one zygote. The possible mechanisms leading to the formation of chimeric/mosaic placenta in our case (one of the components being complete hydatidiform mole), including twinning, fusion at an early embryonic stage and diploidization of triploids, are discussed. [ABSTRACT FROM AUTHOR]

Simplified antiretroviral treatment (ART) regimens improve quality of life and long-term medication adherence. Emtricitabine/rilpivirine/tenofovir DF (FTC/RPV/TDF) is a well-tolerated, once daily single tablet regimen (STR) treatment option. This is the first study to directly compare the safety and efficacy of the two STRs FTC/RPV/TDF and efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) in treatment-naïve adults. STaR is a randomized, open-label, multi-center, international, 96-week study to evaluate the safety and efficacy of the STR FTC/RPV/TDF compared to the STR EFV/FTC/TDF in treatment-naïve HIV-1-infected subjects. Subjects were randomized 1:1 to FTC/RPV/TDF or EFV/FTC/TDF. Eligibility criteria included screening HIV-1 RNA ≥2,500 c/mL, genotypic sensitivity to EFV, FTC, TDF, and RPV, and no prior ARV therapy. Randomization was stratified by HIV-1 RNA level (≤100,000 c/mL or >100,000 c/mL) at screening. The primary endpoint was the proportion of subjects with HIV-1 RNA <50 c/mL at Week 48 as determined by the FDA snapshot algorithm (12% pre-specified non-inferiority margin). A total of 784 subjects were randomized and received at least one dose of study drug (392 FTC/RPV/TDF; 392 EFV/FTC/TDF). Baseline characteristics were similar in both treatment arms, with a baseline mean CD4 count of 390 cells/mm3. and HIV-1 RNA of 4.8 log10 c/mL. FTC/RPV/TDF was non-inferior to EFV/FTC/TDF (86% vs 81%) at Week 48 for HIV RNA <50 c/mL (difference 4.0%, 95% CI [-1.2%, 9.2%]) per FDA snapshot analysis. Superior efficacy was demonstrated for baseline HIV-1 RNA ≤100,000 c/mL (n=508), 88% FTC/RPV/TDF vs 81% EFV/FTC/TDF (difference 7.2%, 95% CI [0.9%, 13.4%]), and non-inferior for >100,000 c/mL (n=276), 80% FTC/RPV/TDF vs 82% EFV/FTC/TDF (difference −1.8%, 95% CI [−11.2%, 7.5%]). Overall, virologic failure, defined as HIV RNA ≥50 c/mL at Week 48, discontinuation due to lack of efficacy per investigator or discontinuation of study drug for reasons other than an adverse event (AE) with HIV RNA ≥50 copies/mL was 8% for FTC/RPV/TDF vs 6% for EFV/FTC/TDF (difference 2.7%, 95% CI [−0.9%, 6.3%]). There were fewer study drug discontinuations due to AEs in the FDA snapshot analysis in FTC/RPV/TDF (2%) compared to EFV/FTC/TDF (8%). The STR FTC/RPV/TDF demonstrated overall non-inferior efficacy and improved tolerability compared to the STR EFV/FTC/TDF as well as superior efficacy for subjects with a baseline viral load ≤100,000 c/mL in treatment-naïve HIV-1-infected subjects. [ABSTRACT FROM AUTHOR]

Linked article: This Correspondence comments on Espinoza. Click here to view the article. [ABSTRACT FROM AUTHOR]

Study Question: Does the immune response to coronavirus disease 2019 (COVID-19) infection or the BNT162b2 mRNA vaccine involve the ovarian follicle, and does it affect its function?Summary Answer: We were able to demonstrate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG in follicular fluid (FF) from both infected and vaccinated IVF patients, with no evidence for compromised follicular function.What Is Known Already: No research data are available yet.Study Design, Size, Duration: This is a cohort study, composed of 32 consecutive IVF patients, either infected with COVID-19, vaccinated or non-exposed, conducted between 1 February and 10 March 2021 in a single university hospital-based IVF clinic.Participants/materials, Setting, Methods: A consecutive sample of female consenting patients undergoing oocyte retrieval was recruited and assigned to one of the three study groups: recovering from confirmed COVID-19 (n = 9); vaccinated (n = 9); and uninfected, non-vaccinated controls (n = 14). Serum and FF samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and heparan sulfate proteoglycan 2 concentration, as well as the number and maturity of aspirated oocytes and day of trigger estrogen and progesterone measurements. Main outcome measures were follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers.Main Results and the Role Of Chance: Both COVID-19 and the vaccine elicited anti-COVID IgG antibodies that were detected in the FF at levels proportional to the IgG serum concentration. No differences between the three groups were detected in any of the surrogate parameters for ovarian follicle quality.Limitations, Reasons For Caution: This is a small study, comprising a mixed fertile and infertile population, and its conclusions should be supported and validated by larger studies.Wider Implications Of the Findings: This is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function and these early findings suggest no measurable detrimental effect on function of the ovarian follicle.Study Funding/competing Interest(s): The study was funded out of an internal budget. There are no conflicts of interest for any of the authors.Trial Registration Number: CinicalTrials.gov registry number NCT04822012. [ABSTRACT FROM AUTHOR]

To minimise COVID-19 pandemic burden, 3rd booster dose vaccination campaigns commenced worldwide. OP02.07: Boosting maternal and neonatal anti-SARS-CoV-2 humoral immunity using a third mRNA vaccine dose We aimed to characterise the effect on anti-SARS-CoV-2 antibody titers of the 3rd, boosting dose of mRNA Pfizer BNT162b2 vaccine in pregnancy, and profile its most common side effects. [Extracted from the article]

Objectives The Strategic Timing of AntiRetroviral Treatment ( START) trial has recruited antiretroviral-naïve individuals with high CD4 cell counts from all regions of the world. We describe the distribution of cardiovascular disease ( CVD) risk factors, overall and by geographical region, at study baseline. Methods The distribution of CVD risk factors was assessed and compared by geographical region among START participants who had a baseline electrocardiogram ( n = 4019; North America, 11%; Europe/ Australia/ Israel, 36%; South America, 26%; Asia, 4%; Africa, 23%; median age 36 years; 26% female). Results About 58.3% ( n = 2344) of the participants had at least one CVD risk factor and 18.9% ( n = 761) had two or more. The most common CVD risk factors were current smoking (32%), hypertension (19.3%) and obesity (16.5%). There were significant differences in the prevalence of CVD risk factors among geographical regions. The prevalence of at least one risk factor across regions was as follows: North America, 70.0%; Europe/ Australia/ Israel, 65.1%; South America, 49.4%; Asia, 37.0%; Africa, 55.8% ( P-value < 0.001). Significant regional differences were also observed when risk factors were used as part of the Framingham and Data Collection on Adverse events of Anti- HIV Drugs ( D: A: D) risk scores or used to define a favourable risk profile. Conclusions CVD risk factors are common among START participants, and their distribution varies by geographical region. Better understanding of how and why CVD risk factors develop in people with HIV infection and their geographical distributions could shed light on appropriate strategies for CVD prevention and may inform the interpretation of the results of START, as CVD is expected to be a major fraction of the primary endpoints observed. [ABSTRACT FROM AUTHOR]

Background: The integrase inhibitor elvitegravir (EVG) has been co-formulated with the CYP3A4 inhibitor cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) in a single tablet given once daily. We compared the efficacy and safety of EVG/COBI/FTC/TDF with standard of care-co-formulated efavirenz (EFV)/FTC/TDF-as initial treatment for HIV infection.Methods: In this phase 3 trial, treatment-naive patients from outpatient clinics in North America were randomly assigned by computer-generated allocation sequence with a block size of four in a 1:1 ratio to receive EVG/COBI/FTC/TDF or EFV/FTC/TDF, once daily, plus matching placebo. Patients and study staff involved in giving study treatment, assessing outcomes, and collecting and analysing data were masked to treatment allocation. Eligibility criteria included screening HIV RNA concentration of 5000 copies per mL or more, and susceptibility to efavirenz, emtricitabine, and tenofovir. The primary endpoint was HIV RNA concentration of fewer than 50 copies per mL at week 48. The study is registered with ClinicalTrials.gov, number NCT01095796.Findings: 700 patients were randomly assigned and treated (348 with EVG/COBI/FTC/TDF, 352 with EFV/FTC/TDF). EVG/COBI/FTC/TDF was non-inferior to EFV/FTC/TDF; 305/348 (87·6%) versus 296/352 (84·1%) of patients had HIV RNA concentrations of fewer than 50 copies per mL at week 48 (difference 3·6%, 95% CI -1·6% to 8·8%). Proportions of patients discontinuing drugs for adverse events did not differ substantially (13/348 in the EVG/COBI/FTC/TDF group vs 18/352 in the EFV/FTC/TDF group). Nausea was more common with EVG/COBI/FTC/TDF than with EFV/FTC/TDF (72/348 vs 48/352) and dizziness (23/348 vs 86/352), abnormal dreams (53/348 vs 95/352), insomnia (30/348 vs 49/352), and rash (22/348 vs 43/352) were less common. Serum creatinine concentration increased more by week 48 in the EVG/COBI/FTC/TDF group than in the EFV/FTC/TDF group (median 13 μmol/L, IQR 5 to 20 vs 1 μmol/L, -6 to 8; p<0·001).Interpretation: If regulatory approval is given, EVG/COBI/FTC/TDF would be the only single-tablet, once-daily, integrase-inhibitor-based regimen for initial treatment of HIV infection.Funding: Gilead Sciences. [ABSTRACT FROM AUTHOR]

In the USA, women, racial/ethnic minorities and persons who acquire HIV infection through heterosexual intercourse represent an increasing proportion of HIV-infected persons, and yet are frequently underrepresented in clinical trials. We assessed the demographic predictors of trial participation in antiretroviral-naïve patients. Methods Patients were characterized as trial participants if highly active antiretroviral therapy (HAART) was initiated within a clinical trial. Prevalence ratios (PRs) were obtained using binomial regression. Results Between 1996 and 2006, 30% of 738 treatment-naïve patients initiated HAART in a clinical trial. Trial participation rates for men who have sex with men (MSM), heterosexual men, and women were respectively 36.5, 29.6 and 24.3%. After adjustment for other factors, heterosexual men appeared less likely to participate in trials compared with MSM [PR 0.79, 95% confidence interval (CI) 0.57, 1.11], while women were as likely to participate as MSM (PR 0.97, 95% CI 0.68, 1.39). The participation rate in Black patients (25.9%) was lower compared with non-Black patients (37.5%) (adjusted PR 0.80, 95% CI 0.60, 1.06). Conclusions In our clinical setting, gender did not appear to impact participation in HIV treatment trials, but Black patients were slightly less likely to participate in these trials. Considering the substantial proportion of HIV-infected patients who are Black, future trials need to consider strategies to incorporate such underrepresented populations. [ABSTRACT FROM AUTHOR]

Purpose of the study The primary Week 48 analysis of this ongoing, randomized, double-blind, double-dummy, active-controlled Phase 3 trial of elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) in treatment-naïve patients demonstrated that Quad was non-inferior to efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) with a differentiated safety profile. We report the Week 96 interim data. Methods Key eligibility criteria included HIV-1 RNA ≥5,000 c/mL and eGFR ≥70 mL/min. Virologic success (HIV-1 RNA <50 c/mL) at Week 96 was assessed per snapshot algorithm. Adverse events and laboratory data were collected prospectively. Results 700 patients (89% male, 63% white, 33% with HIV-1 RNA >100,000 c/mL) were randomized and treated. At Week 48, Quad was non-inferior to EFV/FTC/TDF (88% vs 84%, difference +3.6%, 95% CI -1.6% to 8.8%). High rates of virologic success were maintained at Week 96 (84% vs 82%, difference 2.7%, 95% CI -2.9% to 8.3%). Subgroup analysis revealed similar rates of virologic success in patients with baseline HIV-1 RNA >100,000 c/mL (81% vs 83%). Mean CD4 cell increase (cells/mm3) was 295 vs 273. Emergent resistance was infrequent (3% vs 3%). Rates of study drug discontinuation due to adverse events (AEs) were low and comparable (5% vs 7%). Rates of neuropsychiatric AEs were lower in Quad than in EFV/FTC/TDF (47% vs 66%, P<0.001), as were rates of rash (21% vs 31%, P=0.006). Drug discontinuation due to renal reasons occurred in 7 (2%) vs 0 patients through Week 96; only two patients discontinued Quad since Week 48 due to serum creatinine (Cr) increase without features of proximal renal tubulopathy. Median changes in serum Cr (µmol/L [mg/dL]) at Week 96 in Quad vs EFV/FTC/TDF (11.5 vs 0.9 [0.13 vs 0.01]) were similar to those at Week 48 (12.4 vs 0.9 [0.14 vs 0.01]). Quad had smaller median increases (mmol/L [mg/dL]) in total (0.23 vs 0.47 [9 vs 18], P<0.001) and LDL cholesterol (0.23 vs 0.41 [9 vs16], P=0.011), and similar increase in triglycerides (0.05 vs 0.09 [4 vs 8], P=0.41). Conclusions At Week 96, Quad demonstrated high rates of virologic suppression with low rates of resistance and a differentiated safety and tolerability profile relative to EFV/FTC/TDF. These results support the durable efficacy and long-term safety of Quad in HIV-1 infected patients. [ABSTRACT FROM AUTHOR]