Arabidopsis thaliana SURFEIT1-like genes link mitochondrial function to early plant development and hormonal growth responses.

Mutations in SURFEIT1 (SURF1) genes affect cytochrome c oxidase (COX) levels in different prokaryotic and eukaryotic organisms. In this work, we report that Arabidopsis thaliana has two genes that potentially encode SURF1 proteins, as a result of a duplication that took place in Brassicaceae. Both genes encode mitochondrial proteins and mutation in AtSURF1a causes embryonic lethality. Mutation in AtSURF1b, instead, causes defects in hypocotyl elongation under growth-stimulating conditions, such as low light intensity, increased ambient temperature and incubation with glucose. Mutants in AtSURF1b show reduced expression of the auxin reporter DR5:GUS and increased levels of the gibberellin reporter GFP-RGA, suggesting that auxin and gibberellin homeostasis are affected. In agreement, growth defects caused by AtSURF1b mutation can be overcome by treatment with indole-3-acetic acid and gibberellin A3 , and also by increasing expression of the auxin biosynthesis gene YUC8 or the transcription factor PIF4, which shows lower abundance in AtSURF1b-deficient plants. Mutants in AtSURF1b display lower COX levels, higher alternative oxidase and superoxide levels, and increased expression of genes that respond to mitochondrial dysfunction. Decreased hypocotyl growth and DR5:GUS expression can be reversed by treatment with reduced glutathione, suggesting that redox changes, probably related to mitochondrial dysfunction, are responsible for the effect of AtSURF1b deficiency on hormone responses. The results indicate that changes in AtSURF1b affect mitochondrial function and the production of reactive oxygen species, which, in turn, impinges on a growth regulatory circuit that involves auxin, gibberellins and the transcription factor PIF4.

Effect of Number of Electrodes Used to Elicit Electrical Stapedius Reflex Thresholds in Cochlear Implants.

INTRODUCTION: When mapping cochlear implant (CI) patients with limited reporting abilities, the lowest electrical stimulus level that produces a stapedial reflex (i.e., the electrical stapedius reflex threshold [eSRT]) can be measured to estimate the upper bound of stimulation on individual or a subset of CI electrodes. However, eSRTs measured for individual electrodes or a subset of electrodes cannot be used to predict the global adjustment of electrical stimulation levels needed to achieve comfortable loudness sensations that can be readily used in a speech coding strategy. In the present study, eSRTs were measured for 1-, 4-, and 15-electrode stimulation to (1) determine changes in eSRT levels as a function of the electrode stimulation mode and (2) determine which stimulation mode eSRT levels best approximate comfortable loudness levels from patients' clinical maps. METHODS: eSRTs were measured with the 3 different electrical stimulation configurations in 9 CI patients and compared with behaviorally measured, comfortable loudness levels or M-levels from patients' clinical maps. RESULTS: A linear, mixed-effects, repeated-measures analysis revealed significant differences (p < 0.01) between eSRTs measured as a function of the stimulation mode. No significant differences (p = 0.059) were measured between 15-electrode eSRTs and M-levels from patients' clinical maps. The eSRTs measured for 1- and 4-electrode stimulation differed significantly (p < 0.05) from the M-levels on the corresponding electrodes from the patients' clinical map. CONCLUSION: eSRT profiles based on 1- or 4-electrode stimulation can be used to determine comfortable loudness level on either individual or a subset of electrodes, and 15-electrode eSRT profiles can be used to determine the upper bound of electrical stimulation that can be used in a speech coding strategy.

Depression, anxiety, and posttraumatic stress as predictors of immune functioning: differences between youth with behaviorally and perinatally acquired HIV.

Youth living with HIV (YLWH) face significant mental health problems, namely depression, anxiety, and PTSD with rates of these disorders higher than in the general population. This study explored the relationship between symptoms of depression, anxiety, and PTSD and biological markers among a sample of 145 YLWH ages 13-25 years. Participants completed the Center for Epidemiologic Studies Depression Scale (CES-D), Generalized Anxiety Disorder-7 Item Scale (GAD-7), and Primary Care-Posttraumatic Stress Disorder Screen (PC-PTSD). Biological markers included CD4 count and viral load (VL) abstracted from medical records. Findings revealed a relationship between depression and anxiety and CD4 count as well as anxiety and VL. The relationship between depression and anxiety and CD4 count and anxiety and VL was moderated by transmission mode (i.e., behavioral versus perinatal). For youth perinatally infected, greater psychological symptoms of depression and anxiety were associated with a decline in CD4 count and increase in VL, but this was not true for youth with behaviorally acquired HIV. These findings point to the need for individualized mental health prevention and intervention services for YLWH.

Effect of Probe-Tone Frequency on Ipsilateral and Contralateral Electrical Stapedius Reflex Measurement in Children With Cochlear Implants.

OBJECTIVES: The upper loudness limit of electrical stimulation in cochlear implant patients is sometimes set using electrically elicited stapedius reflex thresholds (eSRTs), especially in children for whom reporting skills may be limited. In unilateral cochlear implant patients, eSRT levels are measured typically in the contralateral unimplanted ear because the ability to measure eSRTs in the implanted ear is likely to be limited due to the cochlear implant surgery and consequential changes in middle ear dynamics. This practice is particularly limiting in the case of fitting bilaterally implanted pediatric cases because there is no unimplanted ear option to choose for eSRT measurement. The goal of this study was to identify an improved measurement protocol to increase the success of eSRT measurement in ipsilateral or contralateral or both implanted ears of pediatric cochlear implant recipients. This work hypothesizes that use of a higher probe frequency (e.g., 1000 Hz compared with the 226 Hz standard), which is closer to the mechanical middle ear resonant frequency, may be more effective in measuring middle ear muscle contraction in either ear. DESIGN: In the present study, eSRTs were measured using multiple probe frequencies (226, 678, and 1000 Hz) in the ipsilateral and contralateral ears of 19 children with unilateral Advanced Bionics (AB) cochlear implants (mean age = 8.6 years, SD = 2.29). An integrated middle ear analyzer designed by AB was used to elicit and detect stapedius reflexes and assign eSRT levels. In the integrated middle ear analyzer system, an Interacoustics Titan middle ear analyzer was used to perform middle ear measurements in synchrony with research software running on an AB Neptune speech processor, which controlled the delivery of electrical pulse trains at varying levels to the test subject. Changes in middle ear acoustic admittance following an electrical pulse train stimulus indicated the occurrence of an electrically elicited stapedius reflex. RESULTS: Of the 19 ears tested, ipsilateral eSRTs were successfully measured in 3 (16%), 4 (21%), and 7 (37%) ears using probe tones of 226, 678, and 1000 Hz, respectively. Contralateral eSRT levels were measured in 11 (58%), 13 (68%), and 13 (68%) ears using the three different probe frequencies, respectively. A significant difference was found in the incidence of successful eSRT measurement as a function of probe frequency in the ipsilateral ears with the greatest pair-wise difference between the 226 and 1000 Hz probe. A significant increase in contralateral eSRT measurement success as a function of probe frequency was not found. These findings are consistent with the idea that changes in middle ear mechanics, secondary to cochlear implant surgery, may interfere with the detection of stapedius muscle contraction in the ipsilateral middle ear. The best logistic, mixed-effects model of the occurrence of successful eSRT measures included ear of measurement and probe frequency as significant fixed effects. No significant differences in average eSRT levels were observed across ipsilateral and contralateral measurements or as a function of probe frequency. CONCLUSION: Typically, measurement of stapedius reflexes is less successful in the implanted ears of cochlear implant recipients compared with measurements in the contralateral, unimplanted ear. The ability to measure eSRT levels ipsilaterally can be improved by using a higher probe frequency.

Accurate PCR Detection of Influenza A/B and Respiratory Syncytial Viruses by Use of Cepheid Xpert Flu+RSV Xpress Assay in Point-of-Care Settings: Comparison to Prodesse ProFlu.

The Xpert Flu+RSV Xpress Assay is a fast, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A and B viruses and respiratory syncytial virus (RSV) performed on the Cepheid GeneXpert Xpress System. The objective of this study was to establish performance characteristics of the Xpert Flu+RSV Xpress Assay compared to those of the Prodesse ProFlu+ real-time reverse transcription-PCR (RT-PCR) assay (ProFlu+) for the detection of influenza A and B viruses as well as RSV in a Clinical Laboratory Improvement Amendments (CLIA)-waived (CW) setting. Overall, the assay, using fresh and frozen nasopharyngeal (NP) swabs, demonstrated high concordance with results of the ProFlu+ assay in the combined CW and non-CW settings with positive percent agreements (PPA) (100%, 100%, and 97.1%) and negative percent agreements (NPA) (95.2%, 99.5%, and 99.6%) for influenza A and B viruses and RSV, respectively. In conclusion, this multicenter study using the Cepheid Xpert Flu+RSV Xpress Assay demonstrated high sensitivities and specificities for influenza A and B viruses and RSV in ∼60 min for use at the point-of-care in the CW setting.

Psychological factors related to resilience and vulnerability among youth with HIV in an integrated care setting.

Approximately 22% of HIV diagnoses in 2015 occurred among youth aged 13-24. Much is known about the risk factors and psychopathology present in youth living with HIV (YLWH), however, relatively little is known about resiliency in this population. The current study sought to assess factors related to resilience and vulnerability among YLWH as well as the impact of psychosocial factors on these constructs using existing clinical data from an integrated care clinic serving YLWH in the southeastern United States. Data included findings from mental health screeners administered as part of the standard protocol of care for youth aged 13-24 including information about anxiety (GAD-7), post-traumatic stress disorder (PC-PTSD), depression (PHQ-A or PHQ-9), substance use (CRAFFT), and medication adherence (BEHKA-HIV Action subscale) as well as viral load and demographic variables. Hierarchical linear regression was used to determine factors related to biological (viral load) and behavioral indicators of resilience and vulnerability (BEHKA-HIV Action subscale and CRAFFT). Results showed that anxiety was a significant covariate of both biological and behavioral indicators of resilience while gender was a significant factor associated with behavioral indicators of vulnerability. None of the psychological or demographic factors examined in this study were associated with substance use, a behavioral indicator of vulnerability and resilience. Our results support the need for clinicians to screen for and monitor anxiety symptoms among YLWH in integrated care settings in an effort to promote resilience and minimize vulnerability. Practical, evidence-based strategies should be applied in clinical settings to address medication adherence and anxiety among YLWH.

Screening for depression among youth with HIV in an integrated care setting.

Youth living with HIV (YLWH) are at risk for depression. Depressive symptoms can impact treatment engagement, health outcomes, and quality of life. Early identification of symptoms can guide treatment planning. This study aimed to identify trends in depressive symptoms for YLWH in a specialty-care clinic and follow-up clinical treatment procedures. An archival review of a clinical database provided depression screening information for a sample of 130 YLWH between 11 and 25 years old in the southeastern United States. Findings indicated that approximately 24% of the sample screened positive for depression-risk. Most commonly endorsed symptoms included fatigue (54.3%) and sleep difficulties (48.5%). Depressive symptoms did not differ significantly by age, gender, race, ethnicity, or sexual orientation. Youth who acquired HIV behaviorally were more likely to endorse the critical item (i.e., self-harm and/or suicidal ideation) than youth who acquired HIV perinatally. Forty-percent of the sample (i.e., 51 youth) had a follow-up treatment plan. YLWH who endorsed the critical item were more likely to receive follow-up action when compared to those who did not endorse the item. Despite limitations of the study, findings have important implications for clinical care and future research.

Decisional capacity and medication adherence among youth with HIV.

This exploratory study examined the degree to which decisional capacity (DC) is associated with measures of self-reported medication adherence. We hypothesized that youth with higher levels of DC would report greater levels of antiretroviral medication adherence. Seventy-two (72) youth with HIV aged 13-24 participated in this study. Data collection included administration of the MacArthur Competence Tool for Treatment and measures of adherence (i.e., seven-day self-report interview, visual analog scale, and biological indicators). Data were analyzed using descriptive statistics, intercorrelations, and multiple and Poisson regression analyses. Youth with HIV who exhibited greater understanding of their disease were more likely to report fewer missed doses in the last seven days. Findings build upon literature in the areas of DC and health literacy and highlight the potential utility of enhancing HIV disease understanding among youth with HIV.

Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study.

BACKGROUND: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. METHODS: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); Ctau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. INTERPRETATION: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. FUNDING: Gilead Sciences.

Novel Application of Dot Survey Methodology at a Youth Health Clinic: A Pilot Study.

PURPOSE: We tested a novel dot survey methodology at our clinic that provides sexual health services to youth ages 13 to 24. We conducted two interactive dot surveys to assess their feasibility and acceptability while gaining insight into patients' attitudes about mental health. METHODS: We adapted a dot survey approach to assess youths' familiarity with mental health and attitudes toward related services. We also assessed their attitudes toward participating in this survey method. All patients with scheduled appointments were eligible to participate. Participants used dot stickers to indicate their responses on survey posters displayed in the waiting room. RESULTS: Three hundred patients participated between June and September 2021 (150 participants/survey). About 95% of participants liked seeing others' responses to the dot surveys, and over 70% reported that the surveys made them think more about mental health. Over 90% would participate in future dot surveys at the clinic. Survey items with the most consensus among participants included that 74.5% "really agree" youth face barriers to accessing mental health services (n = 141, mean = 4.61, standard deviation = 0.79) and 87.1% "really agree" primary care providers should ask youth about their mental health (n = 139, mean = 4.81, standard deviation = 0.59). DISCUSSION: The dot surveys were effective at assessing patients' attitudes about mental health and feasible to conduct in our waiting room. Results confirmed that this survey method was well received among patients. Dot surveys can be adapted by other clinical settings to engage youth regarding their health-related attitudes.

Risk of COVID-19 after natural infection or vaccination.

BACKGROUND: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. METHODS: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7-15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. FINDINGS: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05-0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01-0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. INTERPRETATION: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. FUNDING: National Institutes of Health.

Adverse Childhood Experiences among a Sample of Youth Living with HIV in the Deep South.

The southern region of the United States, often referred to as the Deep South, is disproportionately affected by HIV. In fact, the highest rates of new HIV infections occur in the Deep South. Approximately one in five new HIV infections are among youth. Youth living with HIV (YLWH) have several behavioral health risks, including co-occurring mental health and substance abuse disorders, which negatively affect medication adherence, contribute to less engagement in HIV care, and result in poor health outcomes. Research suggests that adverse childhood experiences (ACEs) contribute to HIV risk behaviors and that people living with HIV may be more vulnerable to the negative health outcomes and adverse effects of stressors. Using existing program evaluation data, we examined data from 41 YLWH aged 17-24 screened for ACEs in an integrated care setting. Most participants were Black/African American young men who identified as homosexual, bisexual, or questioning, and who acquired HIV behaviorally. Approximately, one-third of YLWH screened positive or in the high-risk range on an ACEs screener. Scores fell in the intermediate range for nearly half of the sample. Results did not reveal a significant relationship between ACEs and HIV biological indicators. In this paper, we describe these findings and the importance of incorporating trauma-informed approaches into HIV prevention and treatment programs targeting youth in the Deep South.

Can the use of the CROS system provide head shadow effect contribution to unilateral Cochlear Implant Users?

PURPOSE: The aim of this study was to evaluate the contribution of the CROS system on the head shadow effect in unilateral implant users. METHODS: Prospective cross-sectional study, approved by the ethics committee under protocol 2.128.869. Eleven adults with post-lingual deafness users of unilateral Advanced Bionics CI were selected. Speech recognition was evaluated with recorded words presented at 65dBA at 0o azimuth and at 90o on the side contralateral to the CI, with noise at 55dBA, using CI alone and CI + CROS system. The results were analyzed using paired t-test with a 0.05 alpha. RESULTS: The mean speech recognition scores were significantly better with CI + CROS in relation to the condition of CI alone (p <0.05, p <0.005 and p <0.005 respectively). In the presentation at 0o azimuth, no significant differences were found. CONCLUSION: Users of unilateral CI without useful residual hearing for the use of hearing aids or unable to undergo bilateral surgery can benefit from the CROS device for speech recognition, especially when the speech is presented on the side contralateral to the CI.

Bijou: Engaging Young MSM in HIV Care Using a Mobile Health Strategy.

Young men who have sex with men (YMSM) living with HIV experience challenges with retention in care, which negatively affects viral suppression. To address this, researchers piloted Bijou, a program designed to provide health education through electronically delivered behavior and risk reduction modules. Participants were 29 YMSM aged 19-24 living with HIV from the southeastern US. Participants completed pre, post, and 3-month follow-up (3MFU) surveys assessing knowledge, intervention acceptability, satisfaction, self-efficacy, ehealth literacy, and usability. Findings revealed significant improvement in knowledge and e-health literacy from pre-test to post-test but lost significance at 3MFU. Self-efficacy scores did not show significant differences from pre-test to post-test or 3MFU. Participants who completed all modules considered Bijou usable and acceptable; however, many did not complete the program. Findings suggest a need for adaptations to promote knowledge retention, e-health literacy, engagement over time, and research with a larger, more representative sample.

Assessing the Attitude of Tampa Bay Youth toward HIV Self-Testing Kits.

In adults, data support the utility and acceptance of home HIV testing; however, in youth, particularly in the US, this has not been well studied. In this exploratory study, we surveyed Tampa Bay youth aged 16-27 and attending sexual health clinics between 1 June and 31 June 2018 (n = 133) regarding attitudes and perceptions towards HIV self-testing. While most indicated the clinic over home when asked for preferred testing location, study population and subgroup analysis demonstrated a positive response (agree) to Likert-scale questions regarding the use of home HIV self-testing kits and negative responses (strongly disagree) to "would not use self-testing kit". There was a significant difference between genders in testing location preference (p = 0.031) for those respondents that specified gender (n = 123), with males more likely to prefer home testing than females. This study suggests an openness of youth towards HIV home testing that could help to expand the number of youth aware of their HIV status.

Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial.

BACKGROUND: Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV. METHODS: In this single-arm, open-label trial, we enrolled virologically suppressed children and adolescents (aged 6 to <18 years) with HIV at 22 hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants had a bodyweight of at least 25 kg, were virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ART regimen for at least 6 months before screening, had a CD4 count of at least 200 cells per µL, and an estimated glomerular filtration rate of at least 90 mL/min per 1·73 m2 by the Schwartz formula at screening. All participants received the fixed-dose regimen of coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily. Pharmacokinetic analysis was used for dosing confirmation, and results compared with adult values. The primary outcomes were area under the curve at the end of the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) of bictegravir, and incidence of treatment-emergent adverse events and laboratory abnormalities at week 24. Efficacy and safety analyses included all participants who received at least one dose of study drug. We report the 48-week results. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Between Sept 29, 2016 and Feb 16, 2018, we enrolled 102 participants. 100 participants received bictegravir, emtricitabine, and tenofovir alafenamide (cohort 1 [adolescents aged 12 to <18 years], n=50; cohort 2 [children aged 6 to <12 years], n=50). The mean bictegravir AUCtau was 89 100 ng × h/mL (coefficient of variation 31·0%) in adolescents (cohort 1) and 128 000 ng × h/mL (27·8%) in children (cohort 2). Compared with adults, bictegravir Ctau was 35% lower in adolescents and 11% lower in children. The 90% CIs of both parameters were within the predefined pharmacokinetic equivalence boundary and within overall range of exposures observed in adults and deemed to be safe and efficacious (geometric least-squares mean ratio [GLSM] 86·3% [90% CI 80·0-93·0] for AUCtau and 65·4% [58·3-73·3] for Ctau in adolescents; GLSM 125% [90% CI 117-134] for AUCtau and 88·9% [80·6-98·0] for Ctau for children). Bictegravir, emtricitabine, and tenofovir alafenamide was well tolerated; most adverse events were grade 2 or less in severity and no study drug-related serious adverse events were reported. One participant discontinued study drug due to adverse events (grade 2 insomnia and anxiety). Virological suppression (HIV-1 RNA <50 copies per mL) was maintained by all 100 participants at week 24 and by 98 (98%) of 100 at week 48; no participants had treatment-emergent resistance. INTERPRETATION: In adolescents and children with HIV, the bictegravir, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen. At present, the single-tablet regimen is recommended as first-line treatment in the USA for adolescents and as an alternative regimen in children and has the potential to represent an important regimen in the paediatric population. FUNDING: Gilead Sciences.

Medical decisional capacity among children with HIV.

Medical decisional capacity (DC) refers to the ability to understand, appreciate, and make meaningful decisions about one's health. This is an important construct for children living with HIV whose involvement in their medical care has important implications for disease management. In this study, we assessed the relationship among DC, developmental stage, intellectual ability, and social-emotional functioning of children with and without HIV infection (n=50). We hypothesized a positive correlation between variables, but did not expect to find a difference in DC between groups. Results provided partial support for our hypotheses. There was a positive relationship between developmental stage and understanding, which is but one dimension of DC. Children with HIV infection obtained significantly lower scores on measures of intellectual and adaptive functioning, but there was no significant difference in DC between groups. Findings suggest that children living with HIV have the capacity to meaningfully participate in their healthcare despite lower intellectual and adaptive functioning.

Health Knowledge and Adherence as Predictors of Viral Burden and CD4+ T-Cell Count in Youth and Young Adults Living With HIV.

Health literacy influences HIV treatment for youth and, thus, is a research priority. We explored health knowledge and self-reported adherence, as indicators of health literacy, among youth living with HIV (YLWH) and the association between health literacy and health outcomes. A total of 102 YLWH ages 13-25 years participated in the study. Participants completed the Brief Estimate of Health Knowledge and Action-HIV Version; CD4 T-cell counts and viral loads were extracted from participant medical records. Participants had a moderate amount of HIV knowledge, and most reported taking their medications under most conditions. Decreasing action scores were statistically associated with an increased likelihood of having a detectable viral load. Health literacy is an important factor that should be addressed by practitioners working with YLWH. More research is needed to determine the best way to measure and improve health literacy.

Antiretroviral therapy corrects HIV-1-induced expansion of CD8+ CD45RA+ CD2-) CD11a(bright) activated T cells.

BACKGROUND: HIV infection decreases thymic output and induces chronic T-cell activation. OBJECTIVE: To examine the reconstitution of naive and activated T cells. METHODS: Extended immune phenotyping of CD4(+) and CD8(+) T-cell subsets was combined with T-cell receptor rearrangement excision circle (TREC) levels and measures of T-cell receptor repertoire perturbations in CD8(+) T-cell subpopulation to define the global effect of HIV-1 on T-cell dynamics. Evaluations before and after therapy were performed in HIV-infected children and compared with those in healthy individuals. RESULTS: Ten HIV-infected children and adolescents with a broad range of pretherapy CD4(+) T-cell counts were compared with healthy individuals. Pretherapy late activated CD8(+) T cells (CD3(+)CD8(+)CD45RA(+)CD27(-)CD11a(bright) cells) were expanded among HIV-infected subjects. Successful antiretroviral therapy increased the proportion of naive T cells (CD3(+)CD4(+)CD45RA(+)CD27(+)CD28(+) and CD3(+)CD8(+)CD45RA(+)CD27(+)CD11a(dim) cells), with a significant decrease in late activated CD8(+) T cells. The proportion of naive CD4(+) and CD8(+) T cells significantly predicted log(10) TREC copies/10(6) PBMCs in infected children and healthy control subjects, with a negative correlation in late activated CD8(+) T cells and activated CD4(+) T cells. Treatment re-established Gaussian distributions and decreased oligoclonal expansion within the Vbeta repertoire of CD8(+)CD45RA(+) T cells, but compared with that seen in healthy children, the proportion of late activated CD8(+) T cells remained increased. CONCLUSION: HIV infection strikingly shifts the proportion of naive and late activated CD45RA(+)CD8(+) T cells. Homeostasis within this T-cell population reflects TREC levels and the extent of T-cell receptor Vbeta perturbations.

Comparison of the utility of the PHQ and CES-D for depression screening among youth with HIV in an integrated care setting.

BACKGROUND: Depressive symptoms are well documented among people living with HIV and some evidence suggests that youth living with HIV (YLWH) are more affected than their adult counterparts. Therefore, screening for depression is imperative among YLWH to ensure optimal health. The objective of this study is to compare the utility of the Center for Epidemiological Studies-Depression (CES-D) and the Patient Health Questionnaire (PHQ) as depression screeners in an integrated care setting serving YLWH in the southeastern United States. METHODS: As a part of standard care, the CES-D and the PHQ were administered to YLWH. A Retrospective review of patient records was conducted. Using receiver operating characteristic (ROC) curve analysis and reports from mental health providers, researchers compared the utility of the screeners. RESULTS: The sample consisted of 121 cases from 2017. Youth ranged in age from 12-25 (M = 20.68, SD = 2.75). Most were Black/African American (59.5%) males (56.2%) who acquired HIV behaviorally (51.2%). Sexual orientation was nearly evenly split between heterosexual (37.2%) and homosexual (34.7%). The CES-D demonstrated higher specificity and sensitivity for identifying clinical depression, yet, this was not significantly different from the PHQ, p = .09. LIMITATIONS: Generalizability of findings may be limited as the study sample included youth from a single integrated care setting. CONCLUSION: Both the PHQ and the CES-D demonstrate utility for depression screening among YLWH. However, the PHQ may be preferable for use within a clinical setting.