Outcomes at the Motherhood Center: A Comparison of Virtual and On-Site Versions of a Specialized Perinatal Partial Hospitalization Program.

Objectives: Remotely administered mental health care is becoming increasingly common for treatment of a range of psychiatric disorders; however, there is a dearth of literature overviewing direct comparisons between remote and in-person interventions for treatment of Perinatal Mood and Anxiety Disorders (PMADs). The sudden advent of the Covid-19 pandemic in New York City forced an abrupt conversion for an intensive day treatment program for new mothers with PMADs, from an on-site to a remote program.

Methods: The current report compares outcomes of 81 women who completed the program in-person to those of 60 women who completed the program remotely.

Brain structural anomalies in borderline and avoidant personality disorder patients and their associations with disorder-specific symptoms.

Background: Borderline personality disorder (BPD) and avoidant personality disorder (AvPD) are characterized by hyper-reactivity to negatively-perceived interpersonal cues, yet they differ in degree of affective instability. Recent work has begun to elucidate the neural (structural and functional) and cognitive-behavioral underpinnings of BPD, although some initial studies of brain structure have reached divergent conclusions. AvPD, however, has been almost unexamined in the cognitive neuroscience literature.

Deep sequencing analysis of HIV-1 reverse transcriptase at baseline and time of failure in patients receiving rilpivirine in the phase III studies ECHO and THRIVE.

Minority variants (1.0-25.0%) were evaluated by deep sequencing (DS) at baseline and virological failure (VF) in a selection of antiretroviral treatment-naïve, HIV-1-infected patients from the rilpivirine ECHO/THRIVE phase III studies.

Elevated amygdala activity during reappraisal anticipation predicts anxiety in avoidant personality disorder.

Background: Avoidant personality disorder is characterized by pervasive anxiety, fear of criticism, disapproval, and rejection, particularly in anticipation of exposure to social situations. An important but underexplored question concerns whether anxiety in avoidant patients is associated with an impaired ability to engage emotion regulatory strategies in anticipation of and during appraisal of negative social stimuli.

Methods: We examined the use of an adaptive emotion regulation strategy, cognitive reappraisal, in avoidant patients.

White matter abnormalities in schizophrenia and schizotypal personality disorder.

Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions.

Prevalence in the USA of rilpivirine resistance-associated mutations in clinical samples and effects on phenotypic susceptibility to rilpivirine and etravirine.

Background: The prevalence of rilpivirine resistance-associated mutations (RAMs) in the USA, and their effect on phenotypic susceptibility to rilpivirine and etravirine, was evaluated in clinical samples from HIV-1-infected patients.

Methods: In total, 15,991 samples submitted to Monogram Biosciences (South San Francisco, CA, USA) for routine resistance testing between January 2010 and June 2011 were assessed for the presence of known rilpivirine RAMs K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L; non-nucleoside reverse transcriptase inhibitor (NNRTI) RAMs K103N, L100I and L100I+K103N; and the nucleoside reverse transcriptase inhibitor (NRTI) RAMs M184I/V and their combinations with rilpivirine RAMs. Phenotypic susceptibility (PhenoSenseGT(®) assay; Monogram Biosciences) was evaluated, with reduced susceptibility defined as fold change (FC) in 50% inhibitory concentration (IC50)>2.

Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve HIV-1-infected patients with HIV-1 RNA ≤100,000 copies/mL: week 96 pooled ECHO/THRIVE subanalysis.

The once daily, single-tablet regimen (STR) combining rilpivirine (RPV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) provides a simplified treatment option for antiretroviral therapy (ART)-naïve patients with baseline HIV-1 RNA (BLVL) of ≤100,000 copies/mL. The aim of this analysis is to compare long-term efficacy, safety, and tolerability of RPV+FTC/TDF vs. efavirenz (EFV)+FTC/TDF as individual components in subjects with BLVL ≤100,000 copies/mL.

The neural correlates of anomalous habituation to negative emotional pictures in borderline and avoidant personality disorder patients.

Objective: Extreme emotional reactivity is a defining feature of borderline personality disorder, yet the neural-behavioral mechanisms underlying this affective instability are poorly understood. One possible contributor is diminished ability to engage the mechanism of emotional habituation. The authors tested this hypothesis by examining behavioral and neural correlates of habituation in borderline patients, healthy comparison subjects, and a psychopathological comparison group of patients with avoidant personality disorder.

Insula-amygdala functional connectivity is correlated with habituation to repeated negative images.

Behavioral habituation during repeated exposure to aversive stimuli is an adaptive process. However, the way in which changes in self-reported emotional experience are related to the neural mechanisms supporting habituation remains unclear. We probed these mechanisms by repeatedly presenting negative images to healthy adult participants and recording behavioral and neural responses using functional magnetic resonance imaging.

Week 96 analysis of rilpivirine or efavirenz in HIV-1-infected patients with baseline viral load ≤ 100 000 copies/mL in the pooled ECHO and THRIVE phase 3, randomized, double-blind trials.

Objectives: These 96-week, ECHO/THRIVE pooled analyses evaluated data for antiretroviral treatment-naïve, HIV-1-infected adults with viral load (VL) ≤ 100 000 HIV-1 RNA copies/mL receiving rilpivirine or efavirenz.

Methods: ECHO and THRIVE were phase 3, randomized, double-blind trials. Patients received rilpivirine 25 mg once daily (qd) or efavirenz 600 mg qd, with a fixed (ECHO) or investigator-chosen (THRIVE) nucleoside/tide reverse transcriptase inhibitor (N[t]RTI) background regimen.

96-Week resistance analyses of rilpivirine in treatment-naive, HIV-1-infected adults from the ECHO and THRIVE Phase III trials.

Background: In the ECHO/THRIVE 96-week efficacy analysis, the response rate was 78% with rilpivirine (RPV) and efavirenz (EFV) plus two nucleoside/nucleotide reverse transcriptase inhibitors.

Methods: For resistance analyses, virological failures (VFs) were genotyped and/or phenotyped at baseline and failure.

Results: In the overall 96-week resistance analyses, the proportion of VFs was higher with RPV (96/686, 14%) versus EFV (52/682, 8%), but similar within weeks 48-96 (22/686, 3% versus 16/682, 2%).

Rilpivirine vs. efavirenz in HIV-1 patients with baseline viral load 100,000 copies/ml or less: week 48 phase III analysis.

Objectives: To compare efficacy, resistance development, and safety between rilpivirine and efavirenz in treatment-naive, HIV-1-infected adults with baseline viral load 100,000 copies/ml or less in the pooled 48-week dataset of the ECHO (Efficacy Comparison in treatment-naive HIV-infected subjects Of TMC278 and EFV) and THRIVE (TMC278 against HIV, in a once-daily RegImen Vs. Efavirenz) trials.

Design: Phase III, double-blind, double-dummy, randomized trials.

Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials.

Background: In the week 48 primary analysis of ECHO and THRIVE, rilpivirine demonstrated noninferior efficacy and more favourable tolerability versus efavirenz in treatment-naive, HIV-1-infected adults. Pooled 96-week results are presented.

Methods: Patients (N = 1368) received rilpivirine 25 mg once-daily (q.

Pre-existing mutations in the rilpivirine Phase III trials ECHO and THRIVE: prevalence and impact on virological response.

Background: Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), was approved for HIV-1 infected, antiretroviral treatment-naive adults based on data from two Phase III trials. In the screening population, the prevalence of 49 NNRTI resistance-associated mutations (RAMs) and the impact of allowed NNRTI RAMs on virological response to an RPV- or efavirenz (EFV)-containing regimen were analysed.

Methods: ECHO and THRIVE were global, Phase III, doubleblind, double-dummy, randomized trials in antiretroviral treatment-naive, HIV-1-infected adults to determine whether RPV 25 mg once daily had non-inferior efficacy versus EFV 600 mg once daily, both given with tenofovir/emtricitabine (ECHO) or tenofovir/emtricitabine, zidovudine/lamivudine or abacavir/lamivudine (THRIVE).

Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE Trials.

Background: Pooled analysis of phase 3, double-blind, double-dummy ECHO and THRIVE trials comparing rilpivirine (TMC278) and efavirenz.

Methods: Treatment-naive HIV-1-infected adults were randomized 1:1 to rilpivirine 25 mg once daily or efavirenz 600 mg once daily, with background tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (ECHO) or TDF/FTC, zidovudine/lamivudine, or abacavir/lamivudine (THRIVE). The primary endpoint was confirmed response [viral load <50 copies per milliliter; intent-to-treat time-to-loss-of-virologic-response (ITT-TLOVR) algorithm] at week 48.

Genotypic and phenotypic characterization of HIV-1 isolates obtained from patients on rilpivirine therapy experiencing virologic failure in the phase 3 ECHO and THRIVE studies: 48-week analysis.

Genotypic and phenotypic characterization was performed of HIV-1 isolates from treatment-naive HIV-1-infected patients experiencing virologic failure (VF) during treatment with the nonnucleoside reverse transcriptase inhibitor (NNRTIs) rilpivirine or efavirenz in the pooled phase 3 studies ECHO and THRIVE. Among 686 patients receiving rilpivirine, 72 (10%) experienced VF versus 39 of 682 (6%) receiving efavirenz. In patients with low baseline viral load (VL) ≤100,000 copies per milliliter, the proportions of rilpivirine VFs (19 of 368) and efavirenz VFs (16 of 330) were the same (5%).

The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness.

Background: The registrational phase III clinical trials of the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) rilpivirine (RPV) in combination with two nucleoside/nucleotide RT inhibitors (NRTIs) found a unique genotypic resistance pattern involving the NNRTI mutation E138K with the NRTI mutation M184I. Eighty percent of subjects used emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF); a single tablet regimen of FTC/RPV/TDF is in development.

Methods: HIV-1 with E138K and/or M184V or I mutations were constructed and phenotyped in MT-2 cells and the PhenoSense and Antivirogram assays.

Long-term efficacy, safety, and tolerability of rilpivirine (RPV, TMC278) in HIV type 1-infected antiretroviral-naive patients: week 192 results from a phase IIb randomized trial.

TMC278-C204 (NCT00110305), a 96-week trial of the nonnucleoside reverse transcription inhibitor (NNRTI) rilpivirine (RPV, TMC278) in 368 HIV-1-infected, treatment-naive patients, was extended to investigate long-term safety and efficacy. Week 192 analysis results are presented. This was a long-term follow-up of a Phase IIb, randomized trial.

Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial.

Background: Efavirenz with tenofovir-disoproxil-fumarate and emtricitabine is a preferred antiretroviral regimen for treatment-naive patients infected with HIV-1. Rilpivirine, a new non-nucleoside reverse transcriptase inhibitor, has shown similar antiviral efficacy to efavirenz in a phase 2b trial with two nucleoside/nucleotide reverse transcriptase inhibitors. We aimed to assess the efficacy, safety, and tolerability of rilpivirine versus efavirenz, each combined with tenofovir-disoproxil-fumarate and emtricitabine.

Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial.

Background: The non-nucleoside reverse transcriptase inhibitor (NNRTI), rilpivirine (TMC278; Tibotec Pharmaceuticals, County Cork, Ireland), had equivalent sustained efficacy to efavirenz in a phase 2b trial in treatment-naive patients infected with HIV-1, but fewer adverse events. We aimed to assess non-inferiority of rilpivirine to efavirenz in a phase 3 trial with common background nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs).

Methods: We undertook a 96-week, phase 3, randomised, double-blind, double-dummy, non-inferiority trial in 98 hospitals or medical centres in 21 countries.

Short communication: activity of etravirine on different HIV type 1 subtypes: in vitro susceptibility in treatment-naive patients and week 48 pooled DUET study data.

Etravirine (ETR) has previously shown potent in vitro activity against different primary HIV-1 isolates and demonstrated durable efficacy in treatment-experienced, HIV-1-infected patients in the Phase III DUET studies. The antiviral activity and efficacy of ETR against HIV-1 subtypes B and non-B were further investigated. The effect of HIV-1 subtype on ETR fold change in EC(50) value (FC) was analyzed in HIV-1 recombinant clinical isolates from 673 treatment-naive patients enrolled in other Tibotec studies.

TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) have proven efficacy against human immunodeficiency virus type 1 (HIV-1). However, in the setting of incomplete viral suppression, efavirenz and nevirapine select for resistant viruses. The diarylpyrimidine etravirine has demonstrated durable efficacy for patients infected with NNRTI-resistant HIV-1.

Efficacy and safety of TMC278 in antiretroviral-naive HIV-1 patients: week 96 results of a phase IIb randomized trial.

Objective: TMC278 is a next-generation nonnucleoside reverse transcriptase inhibitor highly active against wild-type and nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 in vitro. The week 96 analysis of TMC278-C204, a large dose-ranging study of TMC278 in treatment-naive HIV-1-infected patients, is presented.

Design: Phase IIb randomized trial.

Compilation and prevalence of mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors.

Background: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are an important component of antiretroviral therapy for HIV type-1 (HIV-1)-infected patients. Development of NNRTI resistance can lead to treatment failure and is conferred by the presence of specific resistance-associated mutations (RAMs) in the reverse transcriptase. In addition to the widely used list of NNRTI RAMs provided by the International AIDS Society-USA HIV-1 Drug Resistance Mutation Group, which were identified on the basis of clinical experience with the approved NNRTIs, a more comprehensive list of NNRTI RAMs is needed to guide the study of baseline and emerging resistance to new NNRTIs.

tSNP-based identification of allelic loss of gene expression in a patient with a balanced chromosomal rearrangement.

Identification of genes affected by disease-associated rare chromosomal rearrangements has led to the cloning of several disease genes. Here we have used a simple approach involving allele-specific RT-PCR-based detection of gene expression to identify a gene affected by a balanced autosome;autosome translocation. We identified a transcribed SNP (tSNP), c.