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The association between body mass index (BMI) and binge-eating disorder (BED) is well-established. However, data on the extent to which BMI is associated with progression from binge-eating behavior into BED among adolescents are limited, which was the aim of this investigation. Participants were 9964 U.S. adolescents from the Adolescent Brain Cognitive Development (ABCD) Study, aged 9-13 at the time of study enrollment. A computerized parent-reported assessment was used to establish adolescents' binge-eating behaviors and BED. Cox proportional hazards models adjusting for sociodemographic covariates were used to examine prospective associations between BMI and likelihood of BED onset among a) adolescents with binge-eating behavior, and b) adolescents with no binge-eating behavior. Of 975 adolescents who met the study criteria for binge-eating behavior, 89 (9.1%) subsequently met the study criteria for BED. Of 8989 adolescents with no binge-eating behavior, 82 (0.9%) subsequently met the study criteria for BED. BMI percentile was significantly associated with the likelihood of BED onset in participants with (adjusted HR = 1.03, 95% confidence interval [CI] 1.00, 1.06) and participants without (adjusted HR = 1.05, 95% CI 1.03, 1.07) binge-eating behavior. Results were also significant when examining BMI as a dichotomous predictor (above and below 85th percentile) among those with (adjusted HR = 2.60, 95% CI 1.00, 6.68) and those without (adjusted HR = 6.01, 95% CI 3.90, 11.10) binge-eating behavior. Overall, results indicate that elevated BMI is prospectively associated with a greater risk for BED onset among U.S. adolescents with or without binge-eating behavior. Adolescents with a higher BMI may benefit from screening for binge eating, and prevention/early intervention strategies to mitigate the risk for developing BED.

ObjectiveScreen time has been reported to be associated with binge-eating disorder (BED) among adolescents in the US; however, potential mediators remain unclear. This study aimed to evaluate depression symptoms as a mediator of the prospective association between screen time and BED.MethodWe utilized data from 9465 children (aged 9-11 years at baseline) from the Adolescent Brain Cognitive Development (ABCD) study (2016-2021). A generalized structural equation model was used to examine the prospective association between average daily screen time at baseline and BED at year 2, adjusting for baseline BED diagnosis, and other potential covariates (e.g., age, sex, and income). Mediation was examined using bias-corrected (BC) 95% confidence intervals for the indirect effect of baseline screen time on year 2 BED through depression symptoms (change from baseline to year 1).ResultsOne hundred and one participants (42.7% male, 49.4% racial/ethnic minority) met the criteria for BED in year 2. Participants were 9.9 years of age on average at baseline, 51.3% identified as male, and 43.1% identified as a racial/ethnic minority. Adjusting for covariates, screen time was prospectively associated with BED (OR = 1.09, 95% CI [1.03, 1.14], p = .005). Depression symptoms (B = .19, BC 95% CI [0.10, 0.28]) partially mediated (9.2%) the prospective association between screen time and BED.DiscussionAmong US adolescents, higher baseline screen time was prospectively associated with BED diagnosis at year 2, and this relationship was partially mediated by increased depression symptoms. Preventive approaches targeting high screen use may have utility for reducing BED risk among adolescents.Public significanceAmong U.S. adolescents, higher screen time was prospectively associated with the incidence of BED. This association was partially mediated by the change in depressive symptoms. Preventive approaches targeting high screen use may have utility for reducing BED risk among adolescents.

PurposeTo compare baseline mental health symptoms and gender affirmation between Black/Latine versus White transgender/nonbinary youth (BLTY vs. WTY) and examine relationships between gender affirmation and mental health symptoms, and whether associations differed by race/ethnicity subgroup.MethodsBaseline data were analyzed from the gender-affirming hormone cohort of the Trans Youth Care United States Study-a 4-clinic site, observational study. Mental health symptoms assessed included depression, suicidality, and anxiety. Gender affirmation measures included the parental acceptance subscale from the perceived Parental Attitudes of Gender Expansiveness Scale-Youth Report; non-affirmation, internalized transphobia, and community connectedness subscales from the Gender Minority Stress and Resilience Measure-Adolescent; and self-reported living full time in affirmed gender. Fisher exact tests and independent sample t tests compared mental health symptoms and gender affirmation between subgroups. Logistic regression analyses evaluated associations between gender affirmation and mental health symptoms. Interaction analyses assessed differences in associations between subgroups.ResultsThe sample (mean age 16 years, range 12-20 years) included 92 BLTY (35%) and 170 WTY (65%). Subgroups had comparable prevalence of depression and anxiety symptoms. WTY had higher prevalence of lifetime suicidality (73% vs. 59%; p = .02). There were no differences in gender affirmation. Among the whole sample, higher parental acceptance decreased odds of depression symptoms. Not living in affirmed gender increased odds of depression symptoms. Higher non-affirmation and internalized transphobia increased odds of depression and anxiety symptoms and suicidality. Associations did not vary by subgroup.DiscussionBLTY and WTY had comparable mental health symptoms. For both subgroups, gender affirmation decreased odds of those symptoms.

BackgroundMechanisms underlying persistent cardiopulmonary symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (postacute sequelae of coronavirus disease 2019 [COVID-19; PASC] or "long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity.MethodsWe conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults >1 year after SARS-CoV-2 infection, compared those with and those without symptoms, and correlated findings with previously measured biomarkers.ResultsSixty participants (median age, 53 years; 42% female; 87% nonhospitalized; median 17.6 months after infection) were studied. At CPET, 18/37 (49%) with symptoms had reduced exercise capacity (1 year after COVID-19 were associated with reduced exercise capacity, which was associated with earlier inflammatory markers. Chronotropic incompetence may explain exercise intolerance among some with "long COVID."

BackgroundThe influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA level and presence of infectious virus on symptom occurrence is poorly understood, particularly among nonhospitalized individuals.MethodsThe study included 85 nonhospitalized, symptomatic adults, who were enrolled from September 2020 to November 2021. Data from a longitudinal cohort studied over 28 days was used to analyze the association of individual symptoms with SARS-CoV-2 viral RNA load, or the presence or level of infectious (culturable) virus. Presence of infectious virus and viral RNA load were assessed daily, depending on specimen availability, and amount of infectious virus was assessed on the day of maximum RNA load. Participants were surveyed for the start and end dates of 31 symptoms at enrollment and at days 9, 14, 21, and 28; daily symptom presence was determined analytically. We describe symptoms and investigate their possible association with viral determinants through a series of single or pooled (multiple days across acute period) cross-sectional analyses.ResultsThere was an association between viral RNA load and the same-day presence of many individual symptoms. Additionally, individuals with infectious virus were more than three times as likely to have a concurrent fever than individuals without infectious virus, and more than two times as likely to have concurrent myalgia, chills, headache, or sore throat.ConclusionsWe found evidence to support the association of viral RNA load and infectious virus on some, but not all symptoms. Fever was most strongly associated with the presence of infectious virus; this may support the potential for symptom-based isolation guidance for COVID-19.

BackgroundIntramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables.ObjectiveTo examine LA-ART in a population of PWH that includes those with viremia.DesignObservational cohort study.SettingUrban academic safety-net HIV clinic.PatientsPublicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use.InterventionDemonstration project of long-acting injectable CAB-RPV.MeasurementsDescriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data.ResultsBetween June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log10 reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks.LimitationSingle-site study.ConclusionThis project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed.Primary funding sourceNational Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration.

The relationship between malaria infection and malnutrition is complex. Using data from a randomized controlled trial of 450 children 0-5 years of age in Burkina Faso, we examined the effect of malaria infection on short-term changes in anthropometric measures, the effect of malnutrition on malaria infection, and whether age modified the effect of baseline anthropometric measures on malaria infection. Malaria infection, assessed by blood smear microscopy and weight, height, mid-upper arm circumference, height-for-age z-score, weight-for-age z-score, and weight-for-height z-score were measured at three time points: baseline, 2 weeks, and 6 months. We used generalized estimating equations adjusted for sex, age, breastfeeding, maternal education, and study treatment (azithromycin versus placebo) for all analyses. Interaction terms were used to assess effect modification by age. Among the 366 children with no malaria infection at baseline, 43 (11.6%) had malaria infection within 6 months. There were no important differences in anthropometric measures at 2 weeks and 6 months between those with and without malaria infection at baseline. There were no significant differences in prevalence of malaria infection by baseline anthropometric measures. Age (0-30 months versus 30-60 months) modified the effect of baseline weight and height on malaria infection. Among those aged 0-30 months, for each kilogram increase in weight, malaria infection increased by 27% (95% CI: 6-53%), and for each centimeter increase in height, it increased by 9% (95% CI: 1-17%), but there were no differences for those aged 30-60 months.

BackgroundRacial and ethnic discrimination are known stressors and are associated with negative psychological and physical health outcomes. Previous studies have found relationships between racial/ethnic discrimination and binge-eating disorder (BED), though they have mainly focused on adult populations. The aim of this study was to determine associations between racial/ethnic discrimination and BED in a large, national cohort study of early adolescents. We further sought to explore associations between the racial/ethnic discrimination perpetrator (students, teachers, or other adults) and BED.MethodsWe analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (N = 11,075, 2018-2020). Logistic regression analyses examined associations between self-reported experiences of racial or ethnic discrimination and binge-eating behaviors and diagnosis, adjusting for potential confounders. Racial/ethnic discrimination measures were assessed based on the Perceived Discrimination Scale, which measures experiences of discrimination based on race/ethnicity and frequency of ethnic discrimination by teachers, adults outside of school, and students. Binge-eating behaviors and diagnosis were based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSAD-5).ResultsIn this racially diverse sample of adolescents (N = 11,075, age range 9-12 years), 4.7% of adolescents reported racial or ethnic discrimination and 1.1% met the criteria for BED. In the adjusted models, racial/ethnic discrimination was associated with 3 times higher odds of having BED (OR 3.31, CI 1.66-7.74). Further, experiences of ethnic discrimination by students and adults outside school were associated with significantly increased odds of BED diagnosis (OR 1.36, CI 1.10-1.68 and OR 1.42 CI 1.06-1.90, respectively)., Increased odds of binge eating behaviors were only significantly associated with ethnic discrimination perpetuated by students (OR 1.12, CI 1.02-1.23).ConclusionsChildren and adolescents who have experienced racial/ethnic discrimination, particularly when discrimination was perpetuated by other students, have higher odds of having binge-eating behaviors and diagnoses. Clinicians may consider screening for racial discrimination and providing anti-racist, trauma-informed care when evaluating and treating patients for BED.

PurposeThe aim of this study is to compare substance use and school-based stressors among Black and Latinx transgender youth (trans BLY), White transgender youth (trans WY), and Black and Latinx cisgender youth (cis BLY) and identify associations between substance use and stressors among trans BLY.MethodsWe analyzed 2015-2017 Biennial California Healthy Kids Survey data with a weighted sample of the state's secondary school population. The analytic sample included 9th and 11th grade trans BLY, trans WY, and cis BLY. Past 30-day and lifetime substance use (cigarettes, e-cigarettes/vaping, marijuana, and alcohol) and school-based stressors (victimization, race-, gender-, and sexuality-based harassment) were compared between cohorts via logistic regression. For trans BLY, associations between substance use and stressors were assessed via logistic regression.ResultsThe analytic sample (n = 19,780) included 252 trans BLY, 104 trans WY, and 19,424 cis BLY. Among trans BLY, estimated prevalence of 30-day (and lifetime) use of cigarettes, e-cigarette/vaping, marijuana, and alcohol were 13% (23%), 19% (39%), 27% (42%), and 29% (48%), respectively. Trans BLY had similar odds of 30-day and lifetime use of all substances compared to trans WY but higher odds of use compared to cis BLY. For trans BLY, race- and gender-based harassment and higher victimization levels were associated with higher odds of 30-day and lifetime use of all substances. Sexuality-based harassment was associated with higher odds of 30-day and lifetime marijuana and alcohol use.DiscussionTrans BLY have high prevalence of substance use, comparable with trans WY but higher than cis BLY. Substance use among trans BLY is associated with school-based stressors.

BackgroundDaily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration.MethodsParticipant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models.ResultsAround 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels.ConclusionsUsing the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.

BackgroundSARS-CoV-2 nucleocapsid antigen can be detected in plasma, but little is known about its performance as a diagnostic test for acute SARS-CoV-2 infection or infectious viral shedding among nonhospitalized individuals.MethodsWe used data generated from anterior nasal and blood samples collected in a longitudinal household cohort of SARS-CoV-2 cases and contacts. Participants were classified as true positives if polymerase chain reaction (PCR) positive for SARS-CoV-2 and as true negatives if PCR negative and seronegative. Infectious viral shedding was determined by the cytopathic effect from viral culture. Stratified by 7 days after symptom onset, we constructed receiver operating characteristic (ROC) curves to describe optimized accuracy (Youden index), optimized sensitivity, and specificity.ResultsOf 80 participants, 58 (73%) were true positives while 22 (27%) were true negatives. Using the manufacturer's cutoff of 1.25 pg/mL for evaluating infection, sensitivity was higher from 0 to 7 days (77.6% [95% confidence interval {CI}, 64%-88.2%]) than from 8 to 14 days (43.2% [95% CI, 31.1%-54.5%]) after symptom onset; specificity was unchanged at 100% (95% CI, 88.1%-100%). This test had higher sensitivity (100% [95% CI, 88.4%-100%]) and lower specificity (65% [95% CI, 40.8%-84.6%]) for infectious viral shedding as compared with infection, particularly within the first week of symptom onset. Although the presence of N-antigen correlated with infectious viral shedding (r = 0.63; P < .01), sensitivity still declined over time. Additional cutoffs from ROC curves were identified to optimize sensitivity and specificity.ConclusionsWe found that this SARS-CoV-2 N-antigen test was highly sensitive for detecting early but not late infectious viral shedding, making it a viable screening test for community-dwelling individuals to inform isolation practices.

BackgroundLimited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).MethodsWe measured SARS-CoV-2-specific humoral and cellular responses in people with and without HIV recovering from COVID-19 ( n  = 39 and n  = 43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing postacute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T-cell responses, as well as differences in the prevalence of PASC.ResultsAmong PWH, we found broadly similar SARS-CoV-2-specific antibody and T-cell responses as compared with a well matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8 + T cells ( P  = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4 + T cells ( P  = 0.007). Higher CD4 + /CD8 + ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8 + T cells (0.34-fold effect, P  = 0.02). HIV status was strongly associated with PASC (odds ratio 4.01, P  = 0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.ConclusionWe identified potentially important differences in SARS-CoV-2-specific CD4 + and CD8 + T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

Rationale: There is limited literature exploring the relationship between military exposures and idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate whether exposure to Agent Orange is associated with an increased risk of IPF among veterans. Methods: We used Veterans Health Administration data to identify patients diagnosed with IPF between 2010 and 2019. We restricted the cohort to male Vietnam veterans and performed multivariate logistic regression to examine the association between presumptive Agent Orange exposure and IPF. We conducted sensitivity analyses restricting the cohort to army veterans (highest theoretical burden of exposure, surrogate for dose response) and a more specific case definition of IPF. Fine-Gray competing risk models were used to evaluate age to IPF diagnosis. Measurements and Main Results: Among 3.6 million male Vietnam veterans, 948,103 (26%) had presumptive Agent Orange exposure. IPF occurred in 2.2% of veterans with Agent Orange exposure versus 1.9% without exposure (odds ratio, 1.14; 95% confidence interval [CI], 1.12-1.16; P

Background and objectivesThe biologic mechanisms underlying neurologic postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are incompletely understood.MethodsWe measured markers of neurologic injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and soluble markers of inflammation among a cohort of people with prior confirmed SARS-CoV-2 infection at early and late recovery after the initial illness (defined as less than and greater than 90 days, respectively). The primary clinical outcome was the presence of self-reported CNS PASC symptoms during the late recovery time point. We compared fold changes in marker values between those with and without CNS PASC symptoms using linear mixed-effects models and examined relationships between neurologic and immunologic markers using rank linear correlations.ResultsOf 121 individuals, 52 reported CNS PASC symptoms. During early recovery, those who went on to report CNS PASC symptoms had elevations in GFAP (1.3-fold higher mean ratio, 95% CI 1.04-1.63, p = 0.02), but not NfL (1.06-fold higher mean ratio, 95% CI 0.89-1.26, p = 0.54). During late recovery, neither GFAP nor NfL levels were elevated among those with CNS PASC symptoms. Although absolute levels of NfL did not differ, those who reported CNS PASC symptoms demonstrated a stronger downward trend over time in comparison with those who did not report CNS PASC symptoms (p = 0.041). Those who went on to report CNS PASC also exhibited elevations in interleukin 6 (48% higher during early recovery and 38% higher during late recovery), monocyte chemoattractant protein 1 (19% higher during early recovery), and tumor necrosis factor α (19% higher during early recovery and 13% higher during late recovery). GFAP and NfL correlated with levels of several immune activation markers during early recovery; these correlations were attenuated during late recovery.DiscussionSelf-reported neurologic symptoms present approximately 4 months after SARS-CoV-2 infection are associated with elevations in markers of neurologic injury and inflammation at earlier time points. Some inflammatory pathways seem to be involved months after acute infection. Additional work will be needed to better characterize these processes and to identify interventions to prevent or treat this condition.

Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination, people living with human immunodeficiency virus (HIV, PLWH) had lower surrogate virus neutralization test response (P = .03) and a trend toward lower immunoglobulin G (IgG) response (P = .08), particularly among those with lower CD4+ T-cell counts and who received the BNT162b2 vaccine. Study of the impact of supplemental vaccine doses among PLWH is needed.

BackgroundAfter coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline.MethodsWe assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing.ResultsData from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21-1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01-1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05-3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2-3.5).ConclusionsThe VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p < 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk.

Social distancing, home confinement, economic challenges, and COVID-19-related illness and deaths during the COVID-19 pandemic can significantly affect mental health in youth. One promising approach to reduce anxiety and depression in adolescents is the neuroscience-based mindfulness intervention Training for Awareness, Resilience, and Action (TARA). The objective of this individually randomized waitlist-controlled trial (RCT) was (1) to test the feasibility of TARA, delivered partially over Zoom, and (2) to assess changes in the emotional wellbeing in healthy adolescents between the ages of 14-18 years old during the COVID-19 pandemic.MethodsTwenty-one healthy adolescents were randomized to the TARA intervention or to the waitlist control group in February 2020, just before the start of the pandemic. The TARA group intervention was delivered in person for the first five sessions and remotely over Zoom for the remaining seven sessions due to the pandemic. The participants' acceptability of TARA was assessed weekly using the Child Session Rating Scale (CSRS). The primary outcome was the emotional wellbeing measured using emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ) pre/post-TARA. We also explored weekly changes in TARA participants' wellbeing using the Child Outcome Rating Scale (CORS).ResultsThe overall session rating in TARA participants improved after the switch to Zoom (Cohen's d = 1.2, p = 0.008). The results of the two-way ANOVA showed no statistically significant difference in the change of the SDQ emotional symptoms during the 12 weeks between the TARA group and waitlist-control group (timepoint × group interaction: F = 0.77, p = 0.38). The exploratory analysis using the CORS in the TARA participants showed a significant improvement in their functioning over the weeks of training.ConclusionOur results support the feasibility of TARA delivered over Zoom. While our primary outcome did not provide support for the improvement of the emotional wellbeing with TARA compared to a passive control group, our exploratory analysis in the intervention group indicated an improved functioning over the weeks of TARA training. The important general positive impact of this study lies in the possibility of offering a neuroscience-based mindfulness intervention remotely to youth living in remote areas and for all youth during pandemic times.

BackgroundTRIUMPH (Trans Research-Informed communities United in Mobilization for the Prevention of HIV) was a community-led, transgender-specific pre-exposure prophylaxis (PrEP) demonstration project at 2 community-based clinical sites in California. TRIUMPH used peer health education, community mobilization, and clinical integration of PrEP with hormone therapy to promote PrEP knowledge and acceptability. The goal of this study was to evaluate PrEP uptake, retention, and adherence among TRIUMPH participants and examine site-based differences.MethodsEligible participants were adult transgender and gender diverse people interested in PrEP. Participants were seen at baseline and at 1, 3, 6, 9, and 12 months for PrEP provision, clinical visits, and HIV testing. PrEP uptake was defined as dispensation of PrEP, PrEP retention was defined as proportion of expected visits completed among those who initiated PrEP, and PrEP adherence was assessed by measuring tenofovir diphosphate concentrations in dried blood spots. Logistic regression models quantified the association of variables with PrEP outcomes.ResultsTRIUMPH enrolled 185 participants; the median age was 28 years (interquartile range: 23-35), 7% was Black, and 58% was Latinx. PrEP uptake was as follows: 78% in Oakland and 98% in Sacramento; 91% among trans women, 96% among trans men, and 70% among nonbinary participants. Almost half (47%) rarely/never believed about HIV, and 42% reported condomless sex act in the past 3 months. Participants who reported higher numbers of sex partners were more likely to be retained and adherent; other predictors of adherence included not having a primary partner and not experiencing violence in the past 3 months.ConclusionsThis community-led, trans-specific PrEP demonstration project documents high levels of PrEP initiation in a young transgender and gender diverse cohort at risk of HIV acquisition.

BackgroundThe biological processes associated with postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are unknown.MethodsWe measured soluble markers of inflammation in a SARS-CoV-2 recovery cohort at early (90 days) timepoints. We defined PASC as the presence of 1 or more coronavirus disease 2019 (COVID-19)-attributed symptoms beyond 90 days. We compared fold-changes in marker values between those with and without PASC using mixed-effects models with terms for PASC and early and late recovery time periods.ResultsDuring early recovery, those who went on to develop PASC generally had higher levels of cytokine biomarkers including tumor necrosis factor-α (1.14-fold higher mean ratio [95% confidence interval {CI}, 1.01-1.28]; P = .028) and interferon-γ-induced protein 10 (1.28-fold higher mean ratio [95% CI, 1.01-1.62]; P = .038). Among those with PASC, there was a trend toward higher interleukin 6 levels during early recovery (1.29-fold higher mean ratio [95% CI, .98-1.70]; P = .07), which became more pronounced in late recovery (1.44-fold higher mean ratio [95% CI, 1.11-1.86]; P

To assess SARS-CoV-2 outcomes, we matched a municipal COVID-19 registry and clinic rosters from a municipal primary care network containing a large HIV clinic and assessed clinical outcomes by HIV status. The risk of severe COVID-19 was higher among people with HIV (PWH, adjusted relative risk = 1.84, 95% confidence interval = 1.05-3.25), while SARS-CoV-2 incidence was lower despite higher testing rates. SARS-CoV-2 vaccination campaigns should prioritize PWH to prevent severe COVID-19 disease given potentially higher risk.

BackgroundUnderstanding patient-reported reasons for lapses of retention in human immunodeficiency virus (HIV) treatment can drive improvements in the care cascade. A systematic assessment of outcomes among a random sample of patients lost to follow-up (LTFU) from 32 clinics in Zambia to understand the reasons for silent transfers and disengagement from care was undertaken.MethodsWe traced a simple random sample of LTFU patients (>90 days from last scheduled visit) as determined from clinic-based electronic medical records from a probability sample of facilities. Among patients found in person, we solicited reasons for either stopping or switching care and predictors for re-engagement. We coded reasons into structural, psychosocial, and clinic-based barriers.ResultsAmong 1751 LTFU patients traced and found alive, 31% of patients starting antiretroviral therapy (ART) between 1 July 2013 and 31 July 2015 silently transferred or were disengaged (40% male; median age, 35 years; median CD4 level, 239 cells/μL); median time on ART at LTFU was 480 days (interquartile range, 110-1295). Among the 544 patients not in care, median prevalences for patient-reported structural, psychosocial, and clinic-level barriers were 27.3%, 13.9%, and 13.4%, respectively, and were highly variable across facilities. Structural reasons, including, "relocated to a new place" were mostly cited among 289 patients who silently transferred (35.5%). We found that men were less likely to re-engage in care than women (odds ratio, .39; 95% confidence interval, .22-.67; P = .001).ConclusionsEfforts to improve retention of patients on ART may need to be tailored at the facility level to address patient-reported barriers.

BackgroundSex hormone and preexposure prophylaxis (PrEP) drug interactions among transgender women (TGW), transgender men (TGM), and cisgender men (CGM) are not fully understood.MethodsTGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral coformulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2- and 4-week samples from Directly Observed Therapy Dried Blood Spots (DOT-DBS) Study (NCT02022657).ResultsFrom May 2017 to June 2018, 24 TGM and 24 TGW were enrolled. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW, respectively. Historical controls included 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference, -6%; 95% confidence interval [CI], -21% to 12%; P = .47), comparable between TGW and CGM (mean difference, -12%; 95% CI, -27% to 7%; P = .21) and were lower among TGM compared with CGW (mean difference, -23%; 95% CI, -36% to -7%; P = .007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from human immunodeficiency virus.ConclusionsCGM, TGM, and TGW had comparable TFV-DP concentrations in dried blood spots after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use.Clinical trials registrationNCT04050371.

ObjectiveTo evaluate time trends in mortality for hospitalized adults with systemic lupus erythematosus (SLE) compared to the general hospitalized population (GHP), and to identify factors associated with increased risk of death among hospitalized SLE patients.MethodsWe used the National (Nationwide) Inpatient Sample to estimate all-cause mortality for adults discharged from community hospitals in the US between 2006 and 2016. Poisson regression models were used to estimate the risk of in-hospital death among all patients, including demographic characteristics, socioeconomic factors, comorbidity score, hospital region, SLE diagnosis, and race/ethnicity as covariates.ResultsAmong 340,467,049 hospitalizations analyzed, 1,903,279 had a discharge diagnosis of SLE. In adjusted analysis, the risk of inpatient death decreased among hospitalizations for patients with SLE from 2.2% to 1.5% (P < 0.001) between 2006 and 2016. All of the decrease in SLE mortality occurred between 2006 and 2008; after 2008, mortality stabilized at a rate statistically similar to the GHP. Hospitalizations for Black, Hispanic, and Asian/Pacific Islander patients with SLE were more likely to end in death compared to hospitalizations for either White patients with SLE or individuals of the same non-White race/ethnicity without SLE.ConclusionIn the largest study of in-hospital SLE mortality published to date, we found significant improvements in mortality for hospitalized patients with SLE in the US from 2006 until 2008, after which mortality stabilized at a level similar to that of the GHP. Our results also demonstrate a persistently high mortality burden among Black and Hispanic patients with SLE in the US and contribute new data revealing high mortality among Asian/Pacific Islander patients with SLE.

BackgroundTenofovir alafenamide (TAF) is increasingly used in HIV treatment, with or without agents that require pharmacologic boosters such as ritonavir/cobicistat. Boosters increase TAF levels, so the TAF dose is lowered in single-pill combinations. We hypothesized that individuals on dose-adjusted boosted TAF would have similar urine tenofovir (TFV) concentrations to those on unboosted TAF.Setting/methodsWe collected urine samples from patients with HIV on TAF, with evidence of virologic suppression and high self-reported adherence at 2 San Francisco clinics from June 2019 to January 2020. We measured urine TFV levels by liquid chromatography/tandem mass spectrometry and used linear regression to compare natural log-transformed urine TFV levels for patients on boosted versus unboosted TAF.ResultsOur analysis included 30 patients on unboosted TAF (25 mg daily TAF) and 15 on boosted TAF (12 on 10 mg daily TAF and 3 on 25 mg daily TAF). Patients on unboosted vs. boosted TAF had similar baseline age, weight, sex, and creatinine. In unadjusted univariate linear regression, there were no significant differences in urine TFV levels based on presence/absence of boosting after TAF dose reduction to 10 mg (geometric mean ratio 1.07; 95% confidence interval: 0.53 to 2.16). This finding was unchanged in adjusted analysis.ConclusionsNo significant differences in urine TFV levels were seen for patients on unboosted vs. boosted dose-reduced TAF. These results have important implications for our forthcoming point-of-care urine immunoassay for TAF, implying that separate adherence cutoffs will not be necessary for patients on boosters and dose-reduced TAF. A single POC TAF immunoassay will, thus, support monitoring on most TAF-based antiretroviral therapy.

Adherence to non-pharmaceutical interventions to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been highly variable across settings, particularly in the USA. In this Personal View, we review data supporting the importance of the viral inoculum (the dose of viral particles from an infected source over time) in increasing the probability of infection in respiratory, gastrointestinal, and sexually transmitted viral infections in humans. We also review the available evidence linking the relationship of the viral inoculum to disease severity. Non-pharmaceutical interventions might reduce the susceptibility to SARS-CoV-2 infection by reducing the viral inoculum when there is exposure to an infectious source. Data from physical sciences research suggest that masks protect the wearer by filtering virus from external sources, and others by reducing expulsion of virus by the wearer. Social distancing, handwashing, and improved ventilation also reduce the exposure amount of viral particles from an infectious source. Maintaining and increasing non-pharmaceutical interventions can help to quell SARS-CoV-2 as we enter the second year of the pandemic. Finally, we argue that even as safe and effective vaccines are being rolled out, non-pharmaceutical interventions will continue to play an essential role in suppressing SARS-CoV-2 transmission until equitable and widespread vaccine administration has been completed.

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

We characterized the antibody composition of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) and the immunologic responses of hospitalized COVID-19 patients after receiving CCP or nonimmune fresh frozen plasma. Despite selection of CCP with significantly higher total immunoglobulin G than recipients, neutralizing antibody levels did not differ between donor plasma and CCP recipients.

Subgroup analyses of randomized controlled trials guide resource allocation and implementation of new interventions by identifying groups of individuals who are likely to benefit most from the intervention. Unfortunately, trial populations are rarely representative of the target populations of public health or clinical interest. Unless the relevant differences between trial and target populations are accounted for, subgroup results from trials might not reflect which groups in the target population will benefit most from the intervention. Transportability provides a rigorous framework for applying results derived in potentially highly selected study populations to external target populations. The method requires that researchers measure and adjust for all variables that 1) modify the effect of interest and 2) differ between the target and trial populations. To date, applications of transportability have focused on the external validity of overall study results and understanding within-trial heterogeneity; however, this approach has not yet been used for subgroup analyses of trials. Through an example from the Iniciativa Profilaxis Pre-Exposición (iPrEx) study (multiple countries, 2007-2010) of preexposure prophylaxis for human immunodeficiency virus, we illustrate how transporting subgroup analyses can produce target-specific subgroup effect estimates and numbers needed to treat. This approach could lead to more tailored and accurate guidance for resource allocation and cost-effectiveness analyses.

From directly observed therapy studies, urine tenofovir (TFV) levels were 74% lower when taking tenofovir alafenamide (TAF) vs tenofovir disoproxil fumarate. Urine TFV remains quantifiable across a range of TAF adherence patterns, but a separate point-of-care lateral flow immunoassay with a lower TFV threshold will be needed to support TAF adherence monitoring.

BackgroundMost cohorts show similar or lower COVID-19 incidence among people living with HIV compared with the general population. However, incidence might be affected by lower testing rates among vulnerable populations. We aimed to compare SARS-CoV-2 IgG seroprevalence, disease severity, and neutralising antibody activity after infection among people with and without HIV receiving care in a county hospital system over a 3-month period.MethodsIn this matched case-control observational study, remnant serum samples were collected between Aug 1 and Oct 31, 2020, from all people living with HIV who underwent routine outpatient laboratory testing in a municipal health-care system (San Francisco General Hospital, CA, USA). Samples from people living with HIV were date of collection-matched (same day) and age-matched (±5 years) to samples from randomly selected adults (aged 18 years or older) without HIV receiving care for chronic conditions at the same hospital. We compared seroprevalence by HIV status via mixed-effects logistic regression models, accounting for the matched structure of the data (random effects for the matched group), adjusting for age, sex, race or ethnicity, and clinical factors (ie, history of cardiovascular or pulmonary disease, and type 2 diabetes). Severe COVID-19 was assessed in participants with past SARS-CoV-2 (IgG or PCR) infection by chart review and compared with multivariable mixed-effects logistic regression, adjusting for age and sex. SARS-CoV-2 IgG, neutralising antibody titres, and antibody avidity were measured in serum of participants with previous positive PCR tests and compared with multivariable mixed-effects models, adjusting for age, sex, and time since PCR-confirmed SARS-CoV-2 infection.Findings1138 samples from 955 people living with HIV and 1118 samples from 1062 people without HIV were tested. SARS-CoV-2 IgG seroprevalence was 3·7% (95% CI 2·4 to 5·0) among people with HIV compared with 7·4% (5·7 to 9·2) among people without HIV (adjusted odds ratio 0·50, 95% CI 0·30 to 0·83). Among 31 people with HIV and 70 people without HIV who had evidence of past infection, the odds of severe COVID-19 were 5·52 (95% CI 1·01 to 64·48) times higher among people living with HIV. Adjusting for time since PCR-confirmed infection, SARS-CoV-2 IgG concentrations were lower (percentage change -53%, 95% CI -4 to -76), pseudovirus neutralising antibody titres were lower (-67%, -25 to -86), and avidity was similar (7%, -73 to 87) among people living with HIV compared with those without HIV.InterpretationAlthough fewer infections were detected by SARS-CoV-2 IgG testing among people living with HIV than among those without HIV, people with HIV had more cases of severe COVID-19. Among people living with HIV with past SARS-CoV-2 infection, lower IgG concentrations and pseudovirus neutralising antibody titres might reflect a diminished serological response to infection, and the similar avidity could be driven by similar time since infection.FundingUS National Institute of Allergy and Infectious Diseases, US National Institutes of Health.

IntroductionRandomized trials of new agents for HIV pre-exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well-characterized adherence-efficacy relationship for F/TDF to back-calculate the (non-PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV).MethodsThe DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non-inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV-DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV.ResultsThere were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person-years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV-negative controls, 5% of the person-time years had low, 9% had medium and 86% had high TFV-DP levels. A non-informative prior distribution for counterfactual bHIV, combined with the prior for TFV-DP level-efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV.ConclusionsBased on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non-PrEP control group in randomized, active-controlled PrEP trials that include a F/TDF-comparator group.

Rationale: Single-center studies demonstrated that methamphetamine use is associated with pulmonary arterial hypertension (Meth-APAH). We used the Pulmonary Hypertension Association Registry to evaluate the national distribution of Meth-APAH and to compare its impact on patient-reported and clinical outcomes relative to idiopathic PAH.Objectives: To determine if patients with Meth-APAH differ from those with idiopathic PAH in demographics, regional distribution in the United States, hemodynamics, health-related quality of life, PAH-specific treatment, and health care use.Methods: The Pulmonary Hypertension Association Registry is a U.S.-based prospective cohort of patients new to care at a Pulmonary Hypertension Care Center. The registry collects baseline demographics, clinical parameters, and repeated measures of health-related quality of life, World Health Organization functional class, 6-minute walk distance, therapy, and health care use. Repeated measures of functional class, health-related quality of life, type of therapy, emergency department visits, and hospitalizations were compared using generalized estimating equations.Results: Of 541 participants included, 118 had Meth-APAH; 83% of Meth-APAH arose in the western United States. The Meth-APAH group was younger and had a poorer socioeconomic status and lower cardiac index than the idiopathic PAH group, despite no difference in mean pulmonary artery pressure or pulmonary vascular resistance. The Meth-APAH group had a more advanced functional class in longitudinal models (0.22 points greater; 95% confidence interval [CI], 0.07 to 0.37) and worse PAH-specific (emPHasis-10) health-related quality of life (-5.4; 95% CI, -8.1 to -2.8). There was no difference in dual combination therapy; however, participants with Meth-APAH were less likely to be initiated on triple therapy (odds ratio [OR], 0.43; 95% CI, 0.24 to 0.77) or parenteral therapy (OR, 0.10; 95% CI, 0.04 to 0.24). Participants with Meth-APAH were more likely to seek care in the emergency department (incidence rate ratio, 2.30; 95% CI, 1.71 to 3.11) and more likely to be hospitalized (incidence rate ratio, 1.42; 95% CI, 1.10 to 1.83).Conclusions: Meth-APAH represents a unique clinical phenotype of PAH, most common in the western United States. It accounts for a notable proportion of PAH in expert centers. Assessment for methamphetamine use is necessary in patients with PAH.

Coronavirus disease-2019 (COVID-19) threatens to further worsen HIV outcomes among people experiencing homelessness. We conducted an interrupted time-series analysis of care engagement and viral suppression among unhoused individuals in the 'POP-UP' low-barrier, high-intensity HIV primary care program during COVID-19. Among 85 patients, care engagement and viral suppression did not decrease in the 5 months following implementation of San Francisco's 'shelter-in-place' ordinance. Low-barrier, in-person HIV care for homeless individuals may be important for maintaining HIV outcomes during COVID-19.

ImportanceBlack and Latinx transgender youth experience stigma that may increase their susceptibility to mental health symptoms.ObjectiveTo compare past-year mental health symptoms and psychosocial factors among Black and Latinx transgender youth, White transgender youth, and Black and Latinx cisgender youth.Design, setting, and participantsThis survey study used data from the 2015-2017 Biennial California Healthy Kids Survey with a weighted sample (N = 45 269) representative of California's secondary school population. The analytic sample (n = 19 780) included Black and Latinx transgender youth, White transgender youth, and Black and Latinx cisgender youth in the 9th and 11th grades. Data analysis was conducted from July 2020 to February 2021.Main outcomes and measuresOutcomes include past-year depressive symptoms and suicidality. Psychosocial risk factors include school-based victimization, gender-based harassment, sexuality-based harassment, and race-based harassment; protective factors include school connectedness and caring adult relationships.ResultsThe analytic sample of 19 780 participants (in 9th grade: weighted percentage, 51% [95% CI, 50% to 52%]; female participants: weighted percentage, 50% [95% CI, 49% to 51%]) included 252 Black and Latinx transgender youth (weighted percentage, 1.3% [95% CI, 1.1% to 1.5%]), 104 White transgender youth (weighted percentage, 0.7% [95% CI, 0.6% to 0.8%]), and 19 424 Black and Latinx cisgender youth (weighted percentage, 98.0% [95% CI, 97.8% to 98.2%]). For Black and Latinx transgender youth, estimated prevalence of depressive symptoms and suicidality were 50% (95% CI, 44% to 57%) and 46% (95% CI, 39% to 52%), respectively. Logistic regression models adjusted for grade, living arrangement, and reported sex indicated that compared with White transgender youth, Black and Latinx transgender youth had similar odds of depressive symptoms (adjusted odds ratio, 0.6; 95% CI, 0.4 to 1.1) and suicidality (adjusted odds ratio, 1.1; 95% CI, 0.6 to 1.8) and similar odds of all forms of harassment (eg, race-based harassment: adjusted odds ratio, 1.5; 95% CI, 0.8 to 2.6). Regression models indicated that compared with White transgender youth, Black and Latinx transgender youth had similar levels of victimization (adjusted linear regression coefficient, 0.5; 95% CI, -0.3 to 1.3) and caring adult relationships (adjusted linear regression coefficient, -0.6; 95% CI, -1.4 to 0.09) but lower levels of school connectedness (adjusted linear regression coefficient, -1.6; 95% CI, -2.9 to -0.4). With similar analyses, compared with Black and Latinx cisgender youth, Black and Latinx transgender youth had higher odds of depressive symptoms (adjusted odds ratio, 2.7; 95% CI, 2.0 to 3.7) and suicidality (adjusted odds ratio, 5.9; 95% CI, 4.3 to 8.0), higher odds and levels of all forms of harassment and victimization (eg, race-based harassment: adjusted odds ratio, 3.2; 95% CI, 2.4 to 4.5), and lower levels of school connectedness (adjusted linear regression coefficient, -2.6; 95% CI -3.3 to -1.8) and caring adult relationships (adjusted linear regression coefficient, -0.9; 95% CI -1.3 to -0.5).Conclusions and relevanceIn this study, Black and Latinx transgender youth had high rates of mental health symptoms, with rates comparable with White transgender youth but higher than Black and Latinx cisgender youth. Their unique pattern of psychosocial risk and protective factors for these mental health symptoms should be factored in clinical preventive services and school-based interventions to support them.

New tools are needed to support PrEP adherence for individuals at risk for HIV, including those that enable provision of real-time feedback. In a large, completed PrEP trial, adequate urine tenofovir levels measured by a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir.

ObjectivesThe past decade has seen tremendous progress in the development of biomedical agents that are effective as pre-exposure prophylaxis (PrEP) for HIV prevention. To expand the choice of products and delivery methods, new medications and delivery methods are under development. Future trials of non-inferiority, given the high efficacy of ARV-based PrEP products as they become current or future standard of care, would require a large number of participants and long follow-up time that may not be feasible. This motivates the construction of a counterfactual estimate that approximates incidence for a randomized concurrent control group receiving no PrEP.MethodsWe propose an approach that is to enroll a cohort of prospective PrEP users and aug-ment screening for HIV with laboratory markers of duration of HIV infection to indicate recent infections. We discuss the assumptions under which these data would yield an estimate of the counterfactual HIV incidence and develop sample size and power calculations for comparisons to incidence observed on an investigational PrEP agent.ResultsWe consider two hypothetical trials for men who have sex with men (MSM) and transgender women (TGW) from different regions and young women in sub-Saharan Africa. The calculated sample sizes are reasonable and yield desirable power in simulation studies.ConclusionsFuture one-arm trials with counterfactual placebo incidence based on a recency assay can be conducted with reasonable total screening sample sizes and adequate power to determine treatment efficacy.

ObjectivesThe averted infections ratio (AIR) is a novel measure for quantifying the preservation-of-effect in active-control non-inferiority clinical trials with a time-to-event outcome. In the main formulation, the AIR requires an estimate of the counterfactual placebo incidence rate. We describe two approaches for calculating confidence limits for the AIR given a point estimate of this parameter, a closed-form solution based on a Taylor series expansion (delta method) and an iterative method based on the profile-likelihood.MethodsFor each approach, exact coverage probabilities for the lower and upper confidence limits were computed over a grid of values of (1) the true value of the AIR (2) the expected number of counterfactual events (3) the effectiveness of the active-control treatment.ResultsFocussing on the lower confidence limit, which determines whether non-inferiority can be declared, the coverage achieved by the delta method is either less than or greater than the nominal coverage, depending on the true value of the AIR. In contrast, the coverage achieved by the profile-likelihood method is consistently accurate.ConclusionsThe profile-likelihood method is preferred because of better coverage properties, but the simpler delta method is valid when the experimental treatment is no less effective than the control treatment. A complementary Bayesian approach, which can be applied when the counterfactual incidence rate can be represented as a prior distribution, is also outlined.

Rationale & objectiveObservational studies have reported a U-shaped association between blood pressure (BP) before a hemodialysis session and death. In contrast, because a linear association between out-of-dialysis-unit BP and death has been reported, home BP may be a better target for treatment. To test the feasibility of this approach, we conducted a pilot trial of treating home versus predialysis BP in hemodialysis patients.Study designA 4-month, parallel, randomized, controlled trial.Settings & participants50 prevalent hemodialysis patients in San Francisco and Seattle. Participants were randomly assigned using 1:1 block randomization, stratified by site.InterventionsTo target home systolic BP (SBP) of 100-200mm Hg; 0.2% vs 0%) or low (defined as

In the United States, the efficacy and safety of convalescent plasma for treating coronavirus disease 2019 (COVID-19) is currently being tested in randomized placebo-controlled clinical trials. Treatment of individual patients with COVID-19 with convalescent plasma outside such trials is also now permitted through U.S. Food and Drug Administration Emergency Use Authorization. Here, members of the National Institutes of Health COVID-19 Treatment Guidelines Panel provide their views regarding use of convalescent plasma for treating COVID-19.

BackgroundRetention in human immunodeficiency virus (HIV) care is dynamic, with patients frequently transitioning in and out of care. Analytical approaches (eg, survival analyses) commonly used to assess HIV care cascade outcomes fail to capture such transitions and therefore incompletely represent care outcomes over time.MethodsWe analyzed antiretroviral therapy (ART)-eligible adults newly linking to care at 64 clinics in Zambia between 1 April 2014 and 31 July 2015. We used electronic medical record data and supplemented these with updated care outcomes ascertained by tracing a multistage random sample of patients lost to follow-up (LTFU, >90 days late for last appointment). We performed multistate analyses, incorporating weights from sampling, to estimate the prevalence of 9 care states over time since linkage with respect to ART initiation, retention in care, transfers, and mortality.ResultsIn sum, 23 227 patients (58% female; median age 34 years [interquartile range 28-41]) were ART-eligible at enrollment. At 1 year, 75.2% had initiated ART and were in care: 61.8% were continuously retained, 6.1% had reengaged after LTFU, and 7.3% had transferred. Also, 10.1% were LTFU within 7 days of enrollment, and 15.2% were LTFU at 1 year (6.7% prior to ART). One year after LTFU, 51.6% of those LTFU prior to ART remained out of care compared to 30.2% of those LTFU after initiating ART. Overall, 6.9% of patients had died by 1 year with 3.0% dying prior to ART.ConclusionMultistate analyses provide more complete assessments of longitudinal HIV cascade outcomes and reveal treatment gaps at distinct timepoints in care that will still need to be addressed even with universal treatment.

: The COVID-19 pandemic is expected to hinder US End the HIV Epidemic goals. We evaluated viral suppression and retention-in-care before and after telemedicine was instituted, in response to shelter-in-place mandates, in a large, urban HIV clinic. The odds of viral nonsuppression were 31% higher postshelter-in-place (95% confidence interval = 1.08-1.53) in spite of stable retention-in-care and visit volume, with disproportionate impact on homeless individuals. Measures to counteract the effect of COVID-19 on HIV outcomes are urgently needed.

Trials of candidate agents for HIV pre-exposure prophylaxis (PrEP) might randomly assign participants to be given a new PrEP agent or oral coformulated tenofovir disoproxil fumarate plus emtricitabine. This design presents unique challenges in interpretation. First, with two active arms, HIV incidence might be low. Second, the effectiveness of tenofovir disoproxil fumarate plus emtricitabine varies across populations; thus, similar HIV incidence between groups could be consistent with a wide range of effectiveness for the new PrEP. We propose a two-part approach to trial results. First, we use Bayesian methods to incorporate assumptions about the background incidence of HIV in the trial in the absence of PrEP, possibly augmented by external data. On the basis of the estimated background incidence, we estimate and compare the number of averted (or prevented) HIV infections in each of the two trial groups, calculating the averted infections ratio. We apply these methods to a completed trial of tenofovir alafenamide plus emtricitabine for PrEP. Our framework shows that leveraging external information to estimate averted infections and the averted infections ratio enhances the efficiency and interpretation of active-controlled PrEP trials.

ContextTransgender youth may initiate GnRH agonists (GnRHa) to suppress puberty, a critical period for bone-mass accrual. Low bone mineral density (BMD) has been reported in late-pubertal transgender girls before gender-affirming therapy, but little is known about BMD in early-pubertal transgender youth.ObjectiveTo describe BMD in early-pubertal transgender youth.DesignCross-sectional analysis of the prospective, observational, longitudinal Trans Youth Care Study cohort.SettingFour multidisciplinary academic pediatric gender centers in the United States.ParticipantsEarly-pubertal transgender youth initiating GnRHa.Main outcome measuresAreal and volumetric BMD Z-scores.ResultsDesignated males at birth (DMAB) had below-average BMD Z-scores when compared with male reference standards, and designated females at birth (DFAB) had below-average BMD Z-scores when compared with female reference standards except at hip sites. At least 1 BMD Z-score was