Increasing Eligibility to Transplant Through the Selective Cytopheretic Device: A Review of Case Reports Across Multiple Clinical Conditions.

A stable, minimum physiological health status is required for patients to qualify for transplant or artificial organ support eligibility to ensure the recipient has enough reserve to survive the perioperative transplant period. Herein, we present a novel strategy to stabilize and improve patient clinical status through extracorporeal immunomodulation of systemic hyperinflammation with impact on multiple organ systems to increase eligibility and feasibility for transplant/device implantation. This involves treatment with the selective cytopheretic device (SCD), a cell-directed extracorporeal therapy shown to adhere and immunomodulate activated neutrophils and monocytes toward resolution of systemic inflammation. In this overview, we describe a case series of successful transition of pediatric and adult patients with multiorgan failure to successful transplant/device implantation procedures by treatment with the SCD in the following clinical situations: pediatric hemophagocytic lymphohistiocytosis, and adult hepatorenal and cardiorenal syndromes. Application of the SCD in these cases may represent a novel paradigm in increasing clinical eligibility of patients to successful transplant outcomes.

Neurodevelopmental delay in children exposed to maternal SARS-CoV-2 in-utero.

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.

Rationale and Design of NEUTRALIZE-AKI: A Multicenter, Randomized, Controlled, Pivotal Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device in Patients with Acute Kidney Injury Requiring Continuous Kidney Replacement Therapy.

INTRODUCTION: NEUTRALIZE-AKI is a pivotal study to evaluate the safety and effectiveness of the selective cytopheretic device (SCD) in adult patients with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT). METHODS/DESIGN: This is a two-arm, randomized, open-label, controlled multi-center pivotal US study which will enroll 200 adult patients (age 18-80 years) in the intensive care unit with acute kidney injury requiring CKRT and at least one additional organ failure across 30 clinical centers. Eligible patients will be randomized to CKRT plus SCD therapy versus CKRT alone. Therapy will be administered for up to 10 days, with the hypothesis that the CKRT plus SCD group will demonstrate a lower mortality rate or better rate of renal recovery than the CKRT alone group by day 90. The primary outcome is a composite of dialysis dependence or all-cause mortality at day 90. CONCLUSION: The SCD is a cell-directed extracorporeal therapy that targets and deactivates pro-inflammatory neutrophils and monocytes, with evidence of efficacy across a variety of critically ill patient populations. Knowledge and experience from many of those studies and other AKI trials were incorporated into the design of this pivotal study, with the aim to investigate the role of effector cell immunomodulation in the intervention of AKI.

Safety Summary of the Selective Cytopheretic Device: A Review of Safety Data Across Multiple Clinical Trials in ICU Patients With Acute Kidney Injury and Multiple Organ Failure.

OBJECTIVES: Acute kidney injury (AKI) requiring continuous kidney replacement therapy is a significant complication in ICU patients with mortality rates exceeding 50%. A dysregulated immune response can lead to systemic inflammation caused by hyperactivity of pro-inflammatory neutrophils and monocytes leading to tissue damage. The selective cytopheretic device (SCD) is an investigational medical device in a new class of cell-directed extracorporeal therapies distinct from cytokine adsorbers or filters, as it targets activated leukocytes. These leukocytes are the cellular sources driving this hyperinflammatory process. The objective of this report is to summarize the safety experience from clinical studies of the SCD in ICU patients with AKI or acute respiratory distress syndrome (ARDS) and multiple organ dysfunction (MOD). DATA SOURCES AND STUDY SELECTION: The studies included in this report represent all relevant trials of the SCD conducted in patients with AKI or ARDS and MOD. Adverse event data, clinical laboratory data and mortality rates were described and summarized in this report. DATA EXTRACTION AND DATA SYNTHESIS: Five clinical studies were included in this report, including four adult studies of AKI and/or ARDS and one pediatric AKI study, which involved 151 patients treated with the SCD in an ICU setting. Over 800 SCD sessions were deployed with an estimated 19,000 exposure hours with no device-related infections or attributable serious adverse events. Furthermore, there were no safety signals of leukopenia, thrombocytopenia, or other indications of immunodepletion or immunosuppression. CONCLUSIONS: The SCD has shown to be a promising extracorporeal therapy with promising clinical results and a favorable safety profile. These studies support that the SCD can be added as a therapeutic intervention in critically ill AKI patient populations with multiple organ failure without adding additional safety risks.

The Relationship Between Adverse Childhood Experiences and Weight-Related Health Behaviors in a National Sample of Children.

OBJECTIVE: To examine how adverse childhood experiences (ACEs) relate to healthy weight behaviors in children. METHODS: We examined data from the 2016 National Survey of Children's Health. ACE scores were calculated from 6 measures of household dysfunction. Outcome measures included 5 healthy weight behaviors. Logistic regression models assessed associations between ACEs and healthy weight behaviors controlling for sociodemographic variables. RESULTS: Children 6 to 17 years of age (n = 32,528) with 0 ACEs had increased odds of: watching 2 hours or less of television daily (6-12 years: odds ratio [OR] 1.46; 95% confidence interval [CI], 1.20-1.80, 13-17 years: OR 1.64; 95% CI, 1.39-1.94), using electronics for 2 hours or less daily (6-12 years: OR 1.44; 95% CI, 1.15-1.80, 13-17 years: OR 1.86; 95% CI, 1.60-2.16), sharing 4 or more family meals per week (6-12 years: OR 1.39; 95% CI, 1.17-1.66, 13-17 years: OR 1.68; 95% CI, 1.44-1.95), and getting adequate age-specific sleep (6-12 years: OR 1.50; 95% CI, 1.26-1.79, 13-17 years: OR 1.31; 95% CI, 1.11-1.55) when compared to children with one or more ACEs. Children 13 to 17 years of age with 0 ACEs had increased odds of exercising for 60 minutes daily (OR 1.27; 95% CI, 1.02-1.58) when compared to children with one or more ACEs. There was an overall gradient dose pattern; the odds of engaging in a healthy weight behavior decreased as the number of ACEs increased, with mixed significance levels. CONCLUSIONS: In children, ACE exposure is associated with decreased healthy weight behaviors and behavior counseling alone may be insufficient. Trauma-informed care to address intra-familial adversity may be necessary.

Measurement and Identification of Parenting Behaviors Associated with Social-Emotional Outcomes in Children: The Racial and Cultural Appropriateness of a Commonly Used Parenting Measure.

OBJECTIVE: The objective of this study was to examine parenting styles (observed parent-child interactions via the Two-Bag Task) associated with young children's socioemotional outcomes, comparing children from Mexican-American and African American families with children from their White counterparts. METHODS: The Early Childhood Longitudinal Study Birth Cohort data were used to examine 6 global parenting styles with socioemotional outcomes at 48 months of age while controlling for both time-independent and time-depending sociodemographic, maternal mental health, and child characteristics. Data were stratified by race and ethnicity, and weighted longitudinal linear regressions models were estimated using STATA/Xtmixed. RESULTS: The 6 global parenting scores from the Two-Bag Task measures differed across White, African American, and Mexican-American groups of parents. White parents on average scored higher on parenting styles related to sensitivity, positive regard, and cognitive stimulation, whereas Mexican-American and African American parents scored lower. These parenting styles were associated with both approach to learning and social competence outcomes among White children but were nearly nonexistent for Mexican-American and African American children when adjusting for covariates. CONCLUSION: Our results highlight the need to critically evaluate measures of parenting behaviors used in research studies with racially and ethnically diverse families. Examining the comprehensive psychometric properties and cultural appropriateness of parenting measures for diverse families is important to optimally support child development for non-White children. Furthermore, a critical lens is important to mitigate the perpetuation of inaccurate research findings for Mexican-American and African American children.

Pharmacodynamic effects of the K+ binder patiromer in a novel chronic hyperkalemia model in spontaneously hypertensive rats.

Currently described hyperkalemia (HK) animal models are typically acute and cause significant distress and mortality to the animals, warranting new approaches for studying chronic HK in a more appropriate clinical setting. Using the spontaneously hypertensive rat (SHR) model as a more relevant disease template, as well as surgical (unilateral nephrectomy), dietary (3% potassium [K+ ] supplementation), and pharmacological (amiloride) interventions, we were able to stably induce HK on a chronic basis for up to 12 weeks to serum K+ elevations between 8 and 9 mmol/L, with minimal clinical stress to the animals. Short-term proof-of-concept and long-term chronic studies in hyperkalemic SHRs showed concomitant increases in serum aldosterone, consistent with the previously reported relationship between serum K+ and aldosterone. Treatment with the K+ binder patiromer demonstrated that the disease model was responsive to pharmacological intervention, with significant abrogation in serum K+ , as well as serum aldosterone to levels near baseline, and this was consistent in both short-term and long-term 12-week chronic studies. Our results demonstrate the feasibility of establishing a chronic HK disease state, and this novel HK animal model may be suitable for further evaluating the effects of long-term, K+ -lowering therapies on effects such as renal fibrosis and end-organ damage.

Network Implementation of Guideline for Early Detection Decreases Age at Cerebral Palsy Diagnosis.

BACKGROUND AND OBJECTIVES: Early diagnosis of cerebral palsy (CP) is critical in obtaining evidence-based interventions when plasticity is greatest. In 2017, international guidelines for early detection of CP were published on the basis of a systematic review of evidence. Our study aim was to reduce the age at CP diagnosis throughout a network of 5 diverse US high-risk infant follow-up programs through consistent implementation of these guidelines. METHODS: The study leveraged plan-do-study-act and Lean methodologies. The primary outcome was age at CP diagnosis. Data were acquired during the corresponding 9-month baseline and quarterly throughout study. Balancing measures were clinic no-show rates and parent perception of the diagnosis visit. Clinic teams conducted strengths, weaknesses, opportunities, and threats analyses, process flow evaluations, standardized assessments training, and parent questionnaires. Performance of a 3- to 4-month clinic visit was a critical process step because it included a Hammersmith Infant Neurologic Examination, a General Movements Assessment, and standardized assessments of motor function. RESULTS: The age at CP diagnosis decreased from a weighted average of 19.5 (95% confidence interval 16.2 to 22.8) to 9.5 months (95% confidence interval 4.5 to 14.6), with P = .008; 3- to 4-month visits per site increased from the median (interquartile range) 14 (5.2-73.7) to 54 (34.5-152.0), with P < .001; and no-show rates were not different. Parent questionnaires revealed positive provider perception with improvement opportunities for information content and understandability. CONCLUSIONS: Large-scale implementation of international guidelines for early detection of CP is feasible in diverse high-risk infant follow-up clinics. The initiative was received positively by families and without adversely affecting clinic operational flow. Additional parent support and education are necessary.

Development of a Brief Screening Tool for Early Literacy Skills in Preschool Children.

BACKGROUND: Preschool children develop early literacy skills (ELS) needed for reading acquisition. Screening for delayed ELS could trigger interventions to prevent reading problems. OBJECTIVE: To develop a brief screening test for ELS delays, the Early Literacy Skills Assessment Tool (ELSAT). METHODS: This study included 4-year-old, typically developing, English language-predominant children attending preschool. The ELSAT comprised 63 items relating to 3 main ELS domains and was piloted with 21 children. After we excluded items that were nondiscriminatory, 57 items remained and were administered to 96 children. Items were compared with reference measures of ELS (Get Ready to Read-Revised), and language (Peabody Picture Vocabulary Test-4 and Phonological Awareness from the Comprehensive Test of Phonological Processing-2). Within-domain reliability was calculated for each of the 3 ELS domains and item correlations between all ELSAT items and the reference measures were calculated. RESULTS: A final set of 10 items was retained that represented all 3 ELS domains and that maximized correlations with reference measures. Cronbach alpha for the refined 10-item ELSAT was 0.868; correlations between individual items and a composite of the reference measures ranged from 0.409 to 0.617 (all Ps < .01). In a receiver operating characteristic curve analysis, a cut-off score of ≤5 predicted a below-average score for any of the reference measures with sensitivity of 90%, specificity of 71.4%, and area under the curve of 0.872. CONCLUSIONS: The 10-item ELSAT shows strong psychometric properties and with further validation may prove valuable in screening preschool children for ELS delays.

Added Value of Early Literacy Screening in Preschool Children.

The Early Literacy Screener (ELS) is a brief screen for emergent literacy delays in 4- and 5-year-olds. Standard developmental screens may also flag these children. What is the value of adding the ELS? Parents of children aged 4 (n = 45) and 5 (n = 26) years completed the Ages and Stages Questionnaire-3 (ASQ-3), the Survey of Well-Being in Young Children (SWYC), and the ELS. Rates of positive agreement (PA), negative agreement (NA), and overall agreement (Cohen's κ) across the various screening tools were calculated. Early literacy delays were detected in 51% of those who passed the ASQ and 38% of those who passed the SWYC. For ELS versus ASQ, κ = 0.18, PA = 0.36 (95% CI = 0.23-0.51), and NA = 0.83 (95% CI = 0.66-0.92). For ELS versus SWYC, κ = 0.42, PA = 0.61 (95% CI = 0.45-0.75), and NA = 0.82 (95% CI = 0.65-0.92). The ELS adds value by flagging early literacy delays in many children who pass either the ASQ-3 or SWYC.

Inattentive Attention-Deficit/Hyperactivity Disorder, Stimulant Medication, and Weight Loss in a 15-Year-Old Girl: Are We Enabling the Development of an Eating Disorder?

CASE: Nicole is a 15-year-old girl presenting to the Developmental Behavioral Pediatrics Clinic with symptoms of the inattentive type of Attention-Deficit/Hyperactivity Disorder (ADHD) and declining school performance over the last year. She expressed frustration over her inability to concentrate on schoolwork. Assuming that her poor grades were secondary to lack of effort, her parents withdrew privileges. Nicole became increasingly depressed. She stopped participating in activities, she previously enjoyed, and her parents reported that she stopped singing in the shower. After talking to a cousin with ADHD, Nicole concluded that she had ADHD as well. She asked her parents to arrange for an evaluation.Nicole met DSM-5 criteria for the diagnosis of inattentive ADHD and was started on a stimulant medication (mixed amphetamine salts). She had symptoms of a coexisting depression, although she did not meet criteria for diagnosis of a depressive disorder. At a 3-week follow-up visit, she showed improvement in targeted ADHD symptoms; homework was now easier and her grades improved. At a 2-month follow-up, Nicole's weight dropped from 53 kg (47th percentile) prestimulant treatment to 49 kg (31st percentile). She reported appetite suppression after taking the stimulant but did not feel that her eating habits had changed significantly. Her father reported that she had a preference for junk food and snacks. Nicole did not enjoy exercising and did not participate in extracurricular sports.She weighed herself several times a day, as she was worried about losing too much weight. Nicole's mood continued to be low, despite the fact that her grades improved, and her parents were more understanding of her challenges. She was otherwise healthy and reported regular menstrual cycles. Nicole requested an increase in the dose of stimulant medication for greater improvement in concentration during homework and in school.Her pediatric clinician was concerned about the possibility of an eating disorder in addition to depression. She asked herself, "Are we treating inattentive ADHD effectively or are we enabling an eating disorder?"

Inattentive Attention-Deficit/Hyperactivity Disorder, Stimulant Medication, and Weight Loss in a 15-Year-Old Girl: Are We Enabling the Development of an Eating Disorder?

CASE: Nicole is a 15-year-old girl presenting to the Developmental Behavioral Pediatrics Clinic with symptoms of the inattentive type of Attention-Deficit/Hyperactivity Disorder (ADHD) and declining school performance over the last year. She expressed frustration over her inability to concentrate on schoolwork. Assuming that her poor grades were secondary to lack of effort, her parents withdrew privileges. Nicole became increasingly depressed. She stopped participating in activities, she previously enjoyed, and her parents reported that she stopped singing in the shower. After talking to a cousin with ADHD, Nicole concluded that she had ADHD as well. She asked her parents to arrange for an evaluation.Nicole met DSM-5 criteria for the diagnosis of inattentive ADHD and was started on a stimulant medication (mixed amphetamine salts). She had symptoms of a coexisting depression, although she did not meet criteria for diagnosis of a depressive disorder. At a 3-week follow-up visit, she showed improvement in targeted ADHD symptoms; homework was now easier and her grades improved. At a 2-month follow-up, Nicole's weight dropped from 53 kg (47th percentile) prestimulant treatment to 49 kg (31st percentile). She reported appetite suppression after taking the stimulant but did not feel that her eating habits had changed significantly. Her father reported that she had a preference for junk food and snacks. Nicole did not enjoy exercising and did not participate in extracurricular sports.She weighed herself several times a day, as she was worried about losing too much weight. Nicole's mood continued to be low, despite the fact that her grades improved, and her parents were more understanding of her challenges. She was otherwise healthy and reported regular menstrual cycles. Nicole requested an increase in the dose of stimulant medication for greater improvement in concentration during homework and in school.Her pediatric clinician was concerned about the possibility of an eating disorder in addition to depression. She asked herself, "Are we treating inattentive ADHD effectively or are we enabling an eating disorder?"

Improving health care usage in a very low birth weight population.

BACKGROUND: Prematurity is the biggest contributor to admissions in the neonatal intensive care unit (NICU). The period following hospital discharge is a vital continuum for the very low birth weight (VLBW) infant. The objective of this study was to assess the impact of a unique discharge and follow-up process on the outcomes of VLBW infants leaving the NICU. METHODS: All outpatient health care usage by VLBW infants born in the study year (cases) was retrospectively tracked through 12 months of age. A cohort of healthy newborn infants were matched by birthdate to each VLBW infant (controls) and similarly tracked. RESULTS: In this study, there were 85 cases and 85 controls. The mean gestational age at birth for the cases was 29.1 ± 2.7 weeks with a mean birth weight of 1079 ± 263 g. That of the controls was 38.9 ± 1.3 weeks and 3202 ± 447 g. Over 90% of both populations had Medicaid coverage. All VLBW infants received care at the Special Care Developmental Follow-Up Clinic. When compared with the controls, VLBW infants discharged from the NICU made fewer acute, unscheduled visits to the Emergency Department or Urgent Care Clinic (2.3 ± 2.5 vs. 3.7 ± 3.5; P=0.007) despite their high-risk medical and social status. Their growth pattern showed significant "catch-up" and was similar to the matched controls at the last scheduled visit for each group. CONCLUSIONS: Outcomes including health care utilization in high-risk infants can be improved through meticulous discharge planning and follow-up measures that utilize existing hospital infrastructure to provide affordable comprehensive care.

Development of a 5-item parent questionnaire to screen preschool children for reading problems.

OBJECTIVE: To develop a brief tool for screening of emergent literacy skills in preschool children (3-5 years old) in pediatric clinics. METHODS: Parents were given an 8-item questionnaire, and the children were tested with the Get Ready to Read-Revised (GRTR-R) screener. With the GRTR-R score as gold standard, the parent questionnaire was optimized using various combinations of questions and response weights in one half of the sample. The resulting 5-item questionnaire was then validated using the other half of the sample. RESULTS: A total of 203 patients were enrolled. In the validation sample, the 5-item questionnaire had sensitivity and specificity vis-à-vis the GRTR-R of 100% and 78.6% in 5-year-olds (cutoff score of 8) and 78.6% and 68.2% in 4-year-olds (cutoff of 6). The questionnaire did not perform well in 3-year-olds. CONCLUSION: A very brief parent questionnaire may be useful as a first-line screener for early reading problems.

Structural and immunogenicity studies of a cleaved, stabilized envelope trimer derived from subtype A HIV-1.

SOSIP gp140 trimers represent a soluble, stabilized, proteolytically cleaved form of the HIV-1 envelope (Env) glycoproteins. SOSIP gp140 derived from a subtype A HIV-1 isolate, KNH1144, forms exceptionally stable trimers that resemble virion-associated Env in antigenicity and topology. Here, we used electron microscopy to demonstrate that KNH1144 SOSIP gp140 trimers bound three soluble CD4 molecules in a symmetrical orientation similar to that seen for native Env. We compared the immunogenicities of KNH1144 SOSIP gp140 trimers and gp120 monomers in rabbits and found that the trimers were superior at eliciting neutralizing antibodies (NAbs) to homologous virus as well as neutralization-sensitive subtype B and C viruses. The NAb specificities for SOSIP antisera mapped in part to the CD4 binding site on gp120. We also observed adjuvant-dependent induction of antibodies to the residual levels of host cell proteins (HCPs) contained in the purified Env preparations. When present, HCP antibodies enhanced pseudovirus infection. Our findings are relevant for the further development of Env-based vaccines for HIV-1.

HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is a vaccine immunogen that can signal via several cell surface receptors. To investigate whether receptor biology could influence immune responses to gp120, we studied its interaction with human, monocyte-derived dendritic cells (MDDCs) in vitro. Gp120 from the HIV-1 strain JR-FL induced IL-10 expression in MDDCs from 62% of donors, via a mannose C-type lectin receptor(s) (MCLR). Gp120 from the strain LAI was also an IL-10 inducer, but gp120 from the strain KNH1144 was not. The mannose-binding protein cyanovirin-N, the 2G12 mAb to a mannose-dependent gp120 epitope, and MCLR-specific mAbs inhibited IL-10 expression, as did enzymatic removal of gp120 mannose moieties, whereas inhibitors of signaling via CD4, CCR5, or CXCR4 were ineffective. Gp120-stimulated IL-10 production correlated with DC-SIGN expression on the cells, and involved the ERK signaling pathway. Gp120-treated MDDCs also responded poorly to maturation stimuli by up-regulating activation markers inefficiently and stimulating allogeneic T cell proliferation only weakly. These adverse reactions to gp120 were MCLR-dependent but independent of IL-10 production. Since such mechanisms might suppress immune responses to Env-containing vaccines, demannosylation may be a way to improve the immunogenicity of gp120 or gp140 proteins.

Purified, proteolytically mature HIV type 1 SOSIP gp140 envelope trimers.

HIV type 1 (HIV-1) envelope is a noncovalent trimer of gp120-gp41 heterodimers, and its lability has hindered structural studies. SOSIP gp140 is a soluble, proteolytically mature form of the HIV-1 envelope wherein gp120-gp41 interactions are stabilized via a disulfide bond and gp41 contains an additional trimer-stabilizing point mutation. We describe the isolation of a substantially pure preparation of SOSIP gp140 trimers derived from KNH1144, a subtype A isolate. Following initial purification, the only significant contaminant was higher-order gp140 aggregates; however, 0.05% Tween 20 quantitatively converted these aggregates into trimers. The surfactant effect was rapid, dose dependent, and similarly effective for a subtype B SOSIP gp140. Surfactant-treated SOSIP gp140 retained favorable antigenicity and formed compact trimers 12-13 nm in size as determined by electron microscopy. This report provides the first description of homogeneous, cleaved HIV-1 envelope trimers. These proteins may be useful as vaccine immunogens and for studying structure-function relationships within the HIV-1 envelope glycoproteins.