No observed bidirectional effect between tenofovir diphosphate concentrations and gender-affirming hormone concentrations among transgender persons switching from tenofovir disoproxil fumarate/emtricitabine to tenofovir alafenamide/emtricitabine for HIV pre-exposure prophylaxis.

AIMS: Many transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre-exposure prophylaxis to affect hormonal concentrations achieved from taking gender-affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT. METHODS: The study evaluated stored blood samples and dried blood spot cards from TGD adults without HIV who took ≥12 weeks of TDF/FTC and then switched to ≥12 weeks of TAF/FTC for pre-exposure prophylaxis. RESULTS: Thirty-nine individuals met the study inclusion criteria. Regardless of sex assigned at birth and the use of GAHT, there were no significant differences in hormone concentrations when individuals taking GAHT were taking TDF/FTC and then switched to TAF/FTC. Further, there was no significant difference in intraerythrocytic tenofovir diphosphate concentrations between users and nonusers of GAHT. CONCLUSION: There are no bidirectional effects between hormone and intraerythocytic tenofovir diphosphate concentrations when switching from TDF/FTC to TAF/FTC in TGD users/nonusers of GAHT.

Determinants of HIV Pre-Exposure Prophylaxis (PrEP) Retention among Transgender Women: A Sequential, Explanatory Mixed Methods Study.

Transgender women (TW) face inequities in HIV and unique barriers to PrEP, an effective biomedical intervention to prevent HIV acquisition. To improve PrEP retention among TW, we examined factors related to retention using a two-phase, sequential explanatory mixed methods approach. In Phase I, we used data from a trial of 170 TW who were provided oral PrEP to examine predictors of 24-week retention. In Phase II, we conducted 15 in-depth interviews with PrEP-experienced TW and used thematic analysis to explain Phase I findings. In Phase I, more participants who were not retained at 24 weeks reported sex work engagement (18% versus 7%) and substantial/severe drug use (18% versus 8%). In Phase II, participants reported drug use as a barrier to PrEP, often in the context of sex work, and we identified two subcategories of sex work. TW engaged in "non-survival sex work" had little difficulty staying on PrEP, while those engaged in "survival sex work" struggled to stay on PrEP. In Phase I, fewer participants not retained at 24 weeks reported gender-affirming hormone therapy (GAHT) use (56% versus 71%). In Phase II, participants prioritized medical gender affirmation services over PrEP but also described the bidirectional benefits of accessing GAHT and PrEP. TW who engaged in "survival sex work" experience barriers to PrEP retention (e.g., unstable housing, drug use) and may require additional support to stay in PrEP care.

Health Supervision for Children and Adolescents With Marfan Syndrome.

Marfan syndrome is a heritable connective tissue disorder that affects many different organ systems. In some cases, features of Marfan syndrome can be recognized at birth, but the majority will have manifestations that emerge throughout childhood and into adulthood. Significant morbidity and mortality are associated with this syndrome, and its features are best managed using a multidisciplinary approach. This clinical report is designed to assist the pediatrician in recognizing the features of Marfan syndrome as well as caring for the individual with Marfan syndrome to maximize their health and quality of life.

Impact of (recurrent) bacterial vaginosis on quality of life and the need for accessible alternative treatments.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common vaginal dysbiosis in women aged 15-44 years old. METHODS: We administered a cross-sectional, single timepoint survey to women ages 18 years or older and who have had bacterial vaginosis (BV). Women completed an anonymous online survey evaluating the impact of BV on their quality of life, how effective different types of treatments were and the amount of self-diagnosed vs. provider diagnosed BV episodes they had. RESULTS: 62 participants completed the anonymous online survey. With a self-reported median number of BV episodes in the past year was 4 (IQR 1-7). Among these women 69.8% reported BV had a negative impact on their sexual health, 67.7% on their physical health, 74.6% on their mental health. More than half of the respondents had used probiotics with oral Lactobacillus sp. (53.2%), mainly by oral route, and over a third had used vaginal boric acid (37.1%). Most women were unaware of Lactobacillus crispatus. Lactobacillus probiotics were more likely to be tried by women who were negatively impacted by BV for overall quality of life (p = 0.033), sexual health (p = 0.002), and mental health (p = 0.006) while boric acid use was more likely to be used by women who were negatively impacted by BV for their sexual health (p = 0.008). CONCLUSIONS: BV is associated with negative quality of life and the women most impacted are seeking alternative treatments such as probiotics (Lactobacillus) and boric acid. There needs to be improvements in BV treatment that include alternative therapy options that have demonstrated efficacy with standardized composition, formulation and dosage.

Randomized Trial of Individualized Texting for Adherence Building (iTAB) Plus Motivational Interviewing for PrEP Adherence in Transgender Individuals: The iM-PrEPT Study.

BACKGROUND: Transgender and nonbinary individuals at risk for HIV may benefit from adherence support for pre-exposure prophylaxis. METHODS: Between June 2017 and September 2020, 255 transgender and nonbinary individuals received daily oral tenofovir disoproxil fumarate/emtricitabine for 48 weeks randomized 1:1 to receive individualized Texting for Adherence Building (iTAB) or iTAB plus motivational interviewing (iTAB + MI) through phone for nonadherence. The primary end point was dried blood spot tenofovir diphosphate concentrations at weeks 12 and 48 (or last on-drug study visit) ≥1246 fmol/punch consistent with ≥7 doses/week (ie, near-perfect adherence). Secondary outcomes included dried blood spot tenofovir diphosphate concentrations ≥719 fmol/punch consistent with ≥4 doses/week (ie, adequate adherence) and self-reported adherence by daily text messages. RESULTS: Adherence for the outcome ≥1246 fmol/punch and ≥719 fmol/punch, respectively, was 49.1% and 57.9% for transgender men, 37.7% and 47.2% for nonbinary individuals, and 31.0% and 44.1% for transgender women. No difference was seen in iTAB + MI compared with iTAB alone by drug levels except where it approached significance in transgender women for the outcome of ≥719 fmol/punch in the iTAB + MI group compared with iTAB only (52% versus 35.7%, P = 0.065). There was a significant difference in self-reported daily dose adherence in the iTAB + MI group compared with iTAB alone (57.9% of days versus 46.4%, P = 0.009). In transgender women, the mean percentage of daily doses taken was 58.5% with iTAB + MI and 37.3% with iTAB alone ( P < 0.001). CONCLUSIONS: In addition to automated approaches to adherence promotion, phone-based MI triggered by repeatedly missing doses may improve pre-exposure prophylaxis adherence among transgender women.

Patient and Physician Preferences Regarding Long-Acting Pre-Exposure Prophylaxis and Antiretroviral Therapy: A Mixed-Methods Study in Southern California, USA.

Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are key strategies in ending the HIV epidemic. However, poor adherence to daily ART and PrEP increases the risk of HIV transmission and acquisition. Long-acting ART and PrEP formulations attempt to improve adherence through providing long-lasting forms of the medication delivered through different routes of administration: oral (potentially monthly), injection (1-6 months), and subdermal implant (up to annually). This study explored patient and physician preferences for long-acting ART and PrEP as well as adherence support strategies. Adult patients (n = 42) with experience taking ART or PrEP participated in individual interviews or focus groups. Physicians (n = 13) currently prescribing ART and/or PrEP completed an online questionnaire. Rapid qualitative analysis systematically synthesized qualitative data, and descriptive statistics examined survey responses. Patients supported improved adherence as a top potential advantage of long-acting ART and PrEP, and reduced internal stigma as a strong benefit specific to long-acting ART. Annual coverage offered through subdermal implants had strong appeal; however, oral was the preferred modality for long-acting ART and PrEP. Patients preferred injectable ART and PrEP if concurrently receiving hormone therapy injections. Side effects, medication cost, and treatment accessibility were potential barriers. Patients preferred calendar tracking and text messages/phone reminders for adherence supports. Physicians reported that they would reduce clinic visits and HIV testing for all patients on long-acting PrEP, except men who have sex with men who would continue to complete HIV testing every 3 months. Physicians were mixed on whether they believed long-acting ART and PrEP would improve patient adherence. Overall, findings demonstrate the potential benefits of long-acting ART and PrEP, while highlighting the need to obtain additional information to address treatment concerns.

Low incidence and prevalence of hepatitis C in two cohorts of HIV pre-exposure prophylaxis adherence interventions in men who have sex with men in Southern California.

HIV pre-exposure prophylaxis (PrEP) has been associated with incident hepatitis C virus (HCV) infection in men who have sex with men (MSM) due to decreased condom use. We examined rates of HCV among MSM and transgender women at high-risk of HIV on PrEP in Southern California using data from two trials (NCT01761643 and NCT01781806). Five of 599 participants (0.84%, 95% CI, 0.27-1.93) had HCV antibodies detected at entry. Factors associated with HCV seropositivity included being older (p = .002) and lower education level (p < .001). HCV-positive participants had no reported cases of sexually transmitted infection (rectal, urethral or pharyngeal gonorrhoea and/or chlamydia) at entry while HCV-negative participants had a prevalence of 18% (95% CI, 15%-21%). There were no significant differences in substance use and sexual risk behaviour between HCV-positive and HCV-negative participants 1-3 months prior to entry. Among early PrEP adopters, incident HCV did not occur despite ongoing condomless intercourse. Screening intervals for HCV in MSM on PrEP should be led by a risk behaviour assessment.

Concurrent randomized control trials of the 1-year efficacy of two couple relationship education programs: ELEVATE and Couples Connecting Mindfully.

A long-standing university-community partnership used a longitudinal randomized control trial to implement and evaluate two couple relationship education (CRE) curricula, ELEVATE and Couples Connecting Mindfully (CCM), among an economically and racially diverse population of adult couples. Married and non-married couples (n = 929 couples) completed baseline surveys and were randomly assigned to either one of the two program groups or to the control group by implementation site. Follow-up surveys were collected at 2 months, 6 months, and 1 year after baseline. Using an intent-to-treat approach, growth curve modeling comparisons of trajectories indicated program effects at 1 year post-baseline in key outcome areas. Both the ELEVATE and the CCM group reported significant gains in couple relationship skills, couple quality, and family harmony over time compared to the control group that experienced either no change or declines. Further, the ELEVATE group also demonstrated positive program effects on measures of mental health and sleep quality. An assessment of the central premise of CRE indicated that the immediate post-program improvements in couple relationship skills predicted later couple quality for both program groups. This study indicates that both ELEVATE and CCM can be considered evidence-based CRE programs for use with a broad population of couples.

Una asociación duradera entre la universidad y la comunidad utilizó un ensayo controlado aleatorizado y longitudinal para implementar y evaluar dos currículos de educación sobre las relaciones de pareja, ELEVATE y Couples Connecting Mindfully (CCM), entre una población de parejas adultas económicamente y racialmente diversa. Parejas casadas y no casadas (n = 929 parejas) contestaron encuestas en el momento basal, y luego, en el lugar de implementación, se las distribuyó aleatoriamente a alguno de los dos grupos del programa o al grupo de referencia. Se recogieron encuestas de seguimiento dos meses, seis meses y un año después del momento basal. Utilizando un método por intención de tratar, las comparaciones de trayectorias del modelo de curva del crecimiento indicaron efectos del programa un año después del momento basal en áreas de resultado claves. Tanto el grupo de ELEVATE como el de CCM informaron beneficios significativos en las habilidades para las relaciones de pareja, la calidad de la pareja y la armonía familiar con el tiempo en comparación con el grupo de referencia, que no tuvo ningún cambio ni empeoramientos. Además, el grupo de ELEVATE también demostró efectos del programa en las medidas de salud mental y calidad del sueño. Una evaluación de la premisa fundamental de la educación sobre las relaciones de pareja indicó que las mejoras inmediatas después del programa en las habilidades para las relaciones de pareja predijeron una posterior calidad de la pareja para ambos grupos del programa. Este estudio indica que tanto ELEVATE como CCM pueden considerarse programas factuales de educación sobre las relaciones de pareja aptos para su uso con una amplia población de parejas.

Birth Outcomes in Women Who Have Taken Hydroxycholoroquine During Pregnancy: A Prospective Cohort Study.

OBJECTIVE: Findings from previous small studies have been reassuring regarding the safety of treatment with hydroxychloroquine (HCQ) during pregnancy. In one recent study, it was demonstrated that the frequency of major birth defects was increased in women who had received HCQ at a dose of ≥400 mg/day during pregnancy. This study was undertaken to examine pregnancy outcomes among women following the use of HCQ. METHODS: The study cohort comprised pregnant women who were prospectively enrolled in the MotherToBaby/Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Study and were receiving treatment with HCQ. For the control groups, disease-matched women without HCQ exposure and healthy women were randomly selected from the same source, with subject matching using a 1:1 ratio. Data were collected through interviews, medical records, and dysmorphology examinations. Pregnancy outcome measures included the presence or absence of major and minor birth defects, rates of spontaneous abortion, rates of preterm delivery, and infant growth measures. RESULTS: Between 2004 and 2018, 837 pregnant women met the criteria for study inclusion, including 279 women exposed to HCQ during pregnancy and 279 women in each unexposed control group. Sixty pregnant women (7.2%) were lost to follow-up. Among the women with live births, major birth defects occurred as a pregnancy outcome in 20 (8.6%) of 232 women with HCQ exposure in the first trimester, compared to 19 (7.4%) of 256 disease-matched unexposed controls (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 0.61-2.26) and 13 (5.4%) of 239 healthy controls (adjusted OR 0.76, 95% CI 0.28-2.05). Risks did not differ in women who were receiving an HCQ dose of ≥400 mg/day. No pattern of birth defects was identified. There were no differences in the rates of spontaneous abortion or preterm delivery between groups. Occurrence of infant growth deficiencies did not differ in the HCQ-exposed group compared to the disease-matched unexposed control group, except in the infant's head circumference at birth (adjusted OR 1.85, 95% CI 1.07-3.20). CONCLUSION: In this study, there was no evidence of an increased risk of structural birth defects or other adverse outcomes among women receiving HCQ during pregnancy, with the exception of infant head circumference at birth. For pregnant women being treated with HCQ, these findings are reassuring.

Two Cases of Preaxial Polydactyly of the Foot: Important Implications for Plastic Surgeons.

Although polydactyly is quite common in general, preaxial polydactyly of the foot is rare (0.4 per 10,000 patients) and specifically associated with certain congenital abnormalities and syndromes, which can include craniosynostosis, corpus callosum agenesis, and renal malformations. We present 2 recent cases of preaxial polydactyly of the foot that highlight the importance of maintaining a high level of suspicion for associated abnormalities in these patients. The first patient, who presented with supernumerary preaxial digits on both feet, pre- and postaxial polydactyly of the hands, was also macrocephalic and hyperteloric; this presentation strongly suggested a diagnosis of Greig cephalopolysyndactyly, a GLI3-variant syndrome. The second patient, who had 2 preaxial digits on one foot, was found to also have a horseshoe kidney, a malformation that has been associated with limb defects as part of an acrorenal syndrome. These cases emphasize the importance of a thorough clinical approach to patients with preaxial polydactyly of the foot. Although many patients with this anomaly may be well known to geneticists, a child may be referred to a plastic surgeon for reconstruction of what is thought to be an isolated cosmetic or local functional issue. Plastic surgeons should be aware of the complex nature of preaxial polydactyly of the foot and potential syndromic presentation.

Glucan rich nutrition does not increase gut translocation of beta-glucan.

BACKGROUND: (1-3)-b-D-glucan (BDG) is a fungal cell wall component and, in the absence of invasive fungal infection, a novel biomarker for microbial translocation of endogenous fungal products from the gastrointestinal tract into systemic circulation. However, its value as a marker of fungal translocation is limited by a concern that plant BDG-rich food influences blood BDG levels. METHODS: We conducted a pilot clinical trial to evaluate the impact of a standardised oral BDG challenge on blood BDG levels in participants with and without elevated microbial translocation. We enrolled 14 participants including 8 with HIV infection, 2 with advanced liver cirrhosis, and 4 healthy controls. After obtaining a baseline blood sample, participants received a standardised milkshake containing high levels of BDG followed by serial blood samples up to 8 hours after intake. RESULTS: The standardised oral BDG challenge approach did not change the blood BDG levels over time in all participants. We found consistently elevated blood BDG levels in one participant with advanced liver cirrhosis and a single person with HIV with a low CD4 count of 201 cells/mm3 . CONCLUSION: Our findings indicate that BDG blood levels were not influenced by plant origin BDG-rich nutrition in PWH, people with advanced liver cirrhosis, or healthy controls. Future studies are needed to analyse gut mycobiota populations in individuals with elevated blood BDG levels.

Randomized Pilot Study of an Advanced Smart-Pill Bottle as an Adherence Intervention in Patients With HIV on Antiretroviral Treatment.

BACKGROUND: Adherence is critical to achieve the benefits of antiretroviral therapy. A smart-pill bottle service that transmits real-time adherence data via cellular networks to a central service and prompts nonadherent patients with phone or text messages may improve adherence. METHODS: Adults with HIV taking a tenofovir-containing regimen with suboptimal adherence were randomized to adherence counseling ± a smart-pill bottle service for 12 weeks. Tenofovir diphosphate (TFV-DP) levels by dried blood spot, HIV RNA levels, CD4 cell counts, and self-reported adherence were collected. RESULTS: Sixty-three participants (22% women; 48% black, 25% Latino) were randomized: 30 to the smart-pill bottle (2 of whom were lost to follow-up before the baseline visit), and 33 to control arms. At baseline, 49% of participants had HIV RNA ≤20 copies/mL and 61% reported 100% adherence with ART over 4 days. From baseline to week 12, median TFV-DP levels were +252 and -41 fmol/punch in the bottle and control arms, respectively (P = 0.10). Exploratory exclusion of 3 participants with known or suspected drug-drug interactions found median TFV-DP levels of +278 and -38 fmol/punch, respectively (P = 0.04). There were no differences in study discontinuations, HIV RNA suppression, CD4 cell counts, or self-reported adherence at week 12. CONCLUSIONS: In a diverse group of participants with suboptimal adherence to ART, the smart-pill bottle service was associated with higher TFV-DP levels.

EP300-related Rubinstein-Taybi syndrome: Highlighted rare phenotypic findings and a genotype-phenotype meta-analysis of 74 patients.

Pathogenic variants in the homologous and highly conserved genes-CREBBP and EP300-are causal for Rubinstein-Taybi syndrome (RSTS). CREBBP and EP300 encode histone acetyltransferases (HAT) that act as transcriptional co-activators, and their haploinsufficiency causes the pathology characteristic of RSTS by interfering with global transcriptional regulation. Though generally a well-characterized syndrome, there is a clear phenotypic spectrum; rare associations have emerged with increasing diagnosis that is critical for comprehensive understanding of this rare syndrome. We present 12 unreported patients with RSTS found to have EP300 variants discovered through gene sequencing and chromosomal microarray. Our cohort highlights rare phenotypic features associated with EP300 variants, including imperforate anus, retained fetal finger pads, and spina bifida occulta. Our findings support the previously noted prevalence of pregnancy-related hypertension/preeclampsia seen with this disease. We additionally performed a meta-analysis on our newly reported 12 patients and 62 of the 90 previously reported patients. We demonstrated no statistically significant correlation between phenotype severity (within the domains of intellectual disability and major organ involvement, as defined in our Methods section) and variant location and type; this is in contrast to the conclusions of some smaller studies and highlights the importance of large patient cohorts in characterization of this rare disease.

Utilizing RNA and outlier analysis to identify an intronic splice-altering variant in AP4S1 in a sibling pair with progressive spastic paraplegia.

We report a likely pathogenic splice-altering AP4S1 intronic variant in two sisters with progressive spastic paraplegia, global developmental delay, shy character, and foot deformities. Sequencing was completed on whole-blood messenger RNA (mRNA) and analyzed for gene expression outliers after exome sequencing analysis failed to identify a causative variant. AP4S1 was identified as an outlier and contained a rare homozygous variant located three bases upstream of exon 5 (NC_000014.8(NM_007077.4):c.295-3C>A). Confirmed by additional RNA-seq, reverse-transcription polymerase chain reaction, and Sanger sequencing, this variant corresponded with exon 5, including skipping, altered isoform usage, and loss of expression from the canonical isoform 2 (NM_001128126.3). Previously, loss-of-function variants within AP4S1 were associated with a quadriplegic cerebral palsy-6 phenotype, AP-4 Deficiency Syndrome. In this study, the inclusion of mRNA-seq allowed for the identification of a previously missed splice-altering variant, and thereby expands the mutational spectrum of AP-4 Deficiency Syndrome to include impacts to some tissue-dependent isoforms.

Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation.

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Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation.

PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. METHODS: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. RESULTS: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_2972del. CONCLUSION: We demonstrate that individuals with the NF1 p.Met992del pathogenic variant have a mild NF1 phenotype lacking clinically suspected plexiform, cutaneous, or subcutaneous neurofibromas. However, learning difficulties are clearly part of the phenotypic presentation in these individuals and will require specialized care.

Tissue Specificity in Trisomy 22 Mosaicism: A Tale of Caution for Interpretation of Chromosomal Microarray Results.

OBJECTIVES: While the complete form of trisomy 22 is seemingly incompatible with life, the mosaic form is a rare syndrome associated with developmental delays, intellectual disability, and dysmorphic features. Due in part to the difficulty of analyzing chromosomal mosaicism, many instances either go undiagnosed or have their diagnosis delayed. We report a case of mosaic trisomy 22 in a diamnionic-dichorionic twin with marked growth discordance and intra-uterine growth restriction, diagnosed in a 2-year-old with developmental delays, sensorineural hearing loss, cardiac and gastrointestinal abnormalities, and osteopenia of prematurity. Evaluation with a chromosomal oligonucleotide microarray with SNP analysis did not detect any copy number variants. Fibroblast metaphase karyotype analysis from a skin biopsy, however, showed trisomy 22 which was confirmed by FISH. Follow-up peripheral blood karyotype analysis and FISH studies revealed a normal male karyotype. This case highlights an instance where classical cytogenetics from two separate tissue types can provide a diagnosis that is more cost-effective than microarray analysis in assessing pediatric developmental delay. Trisomy 22 is the second most common aneuploidy in spontaneous miscarriages and has a nondescript and variable phenotype, especially in cases of mosaicism. As such, this condition may be underdiagnosed using the current recommended testing algorithm. Chromosomal microarray is considered first tier testing in an unrecognized phenotype with whole exome or whole genome sequencing, often performed on peripheral blood, as second tier testing. Diagnoses such as mosaic trisomy 22 suggest the second tier of testing in undiagnosed cases should also include a recommendation to look at alternative tissue types.

Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117.

A clinical trial was performed to evaluate 3BNC117, a potent anti-HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative viral outgrowth assay (Q2VOA) at entry and after 6 mo. There were no significant quantitative changes in the size of the reservoir before ATI, and the composition of circulating reservoir clones varied in a manner that did not correlate with 3BNC117 sensitivity. 3BNC117 binding site amino acid variants found in rebound viruses preexisted in the latent reservoir. However, only 3 of 217 rebound viruses were identical to 868 latent viruses isolated by Q2VOA and near full-length sequencing. Instead, 63% of the rebound viruses appeared to be recombinants, even in individuals with 3BNC117-resistant reservoir viruses. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating latent reservoir, but frequently appear to represent recombinants of latent viruses.

The Undergraduate Training in Genomics (UTRIG) Initiative: early & active training for physicians in the genomic medicine era.

Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIG's collaborative goal is building medical student genomic literacy through development of a ready-to-use genomics curriculum. Key elements to the UTRIG curriculum are expert consensus-driven objectives, active learning methods, rigorous assessment and integration.