Association of Race and Ethnicity with Initial Prescription of Antiretroviral Therapy among People with HIV in the US

Importance: Integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART) is currently the guideline-recommended first-line treatment for HIV. Delayed prescription of INSTI-containing ART may amplify differences and inequities in health outcomes. Objectives: To estimate racial and ethnic differences in the prescription of INSTI-containing ART among adults newly entering HIV care in the US and to examine variation in these differences over time in relation to changes in treatment guidelines. Design, Setting, and Participants: Retrospective observational study of 42841 adults entering HIV care from October 12, 2007, when the first INSTI was approved by the US Food and Drug Administration, to April 30, 2019, at more than 200 clinical sites contributing to the North American AIDS Cohort Collaboration on Research and Design. Exposures: Combined race and ethnicity as reported in patient medical records. Main Outcomes and Measures: Probability of initial prescription of ART within 1 month of care entry and probability of being prescribed INSTI-containing ART. Differences among non-Hispanic Black and Hispanic patients compared with non-Hispanic White patients were estimated by calendar year and time period in relation to changes in national guidelines on the timing of treatment initiation and recommended initial treatment regimens. Results: Of 41263 patients with information on race and ethnicity, 19378 (47%) as non-Hispanic Black, 6798 (16%) identified as Hispanic, and 13539 (33%) as non-Hispanic White; 36394 patients (85%) were male, and the median age was 42 years (IQR, 30 to 51). From 2007-2015, when guidelines recommended treatment initiation based on CD4+ cell count, the probability of ART initiation within 1 month of care entry was 45% among White patients, 45% among Black patients (difference, 0% [95% CI, -1% to 1%]), and 51% among Hispanic patients (difference, 5% [95% CI, 4% to 7%]). From 2016-2019, when guidelines strongly recommended treating all patients regardless of CD4+ cell count, this probability increased to 66% among White patients, 68% among Black patients (difference, 2% [95% CI, -1% to 5%]), and 71% among Hispanic patients (difference, 5% [95% CI, 1% to 9%]). INSTIs were prescribed to 22% of White patients and only 17% of Black patients (difference, -5% [95% CI, -7% to -4%]) and 17% of Hispanic patients (difference, -5% [95% CI, -7% to -3%]) from 2009-2014, when INSTIs were approved as initial therapy but were not yet guideline recommended. Significant differences persisted for Black patients (difference, -6% [95% CI, -8% to -4%]) but not for Hispanic patients (difference, -1% [95% CI, -4% to 2%]) compared with White patients from 2014-2017, when INSTI-containing ART was a guideline-recommended option for initial therapy; differences by race and ethnicity were not statistically significant from 2017-2019, when INSTI-containing ART was the single recommended initial therapy for most people with HIV. Conclusions and Relevance: Among adults entering HIV care within a large US research consortium from 2007-2019, the 1-month probability of ART prescription was not significantly different across most races and ethnicities, although Black and Hispanic patients were significantly less likely than White patients to receive INSTI-containing ART in earlier time periods but not after INSTIs became guideline-recommended initial therapy for most people with HIV. Additional research is needed to understand the underlying racial and ethnic differences and whether the differences in prescribing were associated with clinical outcomes.

Hepatitis B care cascade among people with HIV/HBV coinfection in the North American AIDS Cohort Collaboration on Research and Design, 2012-2016

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step

Complete tree subset difference broadcast encryption scheme and its analysis

The subset difference (SD) method proposed by Naor, Naor and Lotspiech is the most popular broadcast encryption (BE) scheme. It is suitable for real-time applications like Pay-TV and has been suggested for use by the AACS standard for digital rights management in Blu-Ray and HD-DVD discs. The SD method assumes the number of users to be a power of two. We propose the complete tree subset difference (CTSD) method that allows the system to support an arbitrary number of users. In particular, it subsumes the SD method and all results proved for the CTSD method also hold for the SD method. Recurrences are obtained for the CTSD scheme to count the number, N(n, r, h), of possible ways r users in the system of n users can be revoked to result in a transmission overhead or header length of h. The recurrences lead to a polynomial time dynamic programming algorithm for computing N(n, r, h). Further, they provide bounds on the maximum possible header length. A probabilistic analysis is performed to obtain an O(r log n) time algorithm to compute the expected header length in the CTSD scheme. Further, for the SD scheme we obtain an explicit limiting upper bound on the expected header length

Skin of atopic dermatitis patients shows disturbed beta-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition

Patients with Atopic Dermatitis (AD) suffer from inflamed skin and skin barrier defects. Proper formation of the outermost part of the skin, the stratum corneum (SC), is crucial for the skin barrier function. In this study we analyzed the localization and activity of lipid enzymes β-glucocerebrosidase (GBA) and acid sphingomyelinase (ASM) in the skin of AD patients and controls. Localization of both the expression and activity of GBA and ASM in the epidermis of AD patients was altered, particularly at lesional skin sites. These changes aligned with the altered SC lipid composition. More specifically, abnormal localization of GBA and ASM related to an increase in specific ceramide subclasses [AS] and [NS]. Moreover we related the localization of the enzymes to the amounts of SC ceramide subclasses and free fatty acids (FFAs). We report a correlation between altered localization of active GBA and ASM and a disturbed SC lipid composition. Localization of antimicrobial peptide beta-defensin-3 (HBD-3) and AD biomarker Thymus and Activation Regulated Chemokine (TARC) also appeared to be diverging in AD skin compared to control. This research highlights the relation between correct localization of expressed and active lipid enzymes and a normal SC lipid composition for a proper skin barrier.Medical BiochemistryBio-organic Synthesi

Direct observations of galactic cosmic rays

The mysterious “radiation ... entering our atmosphere from above” discovered by Hess in 1912 is now known to be dominated by relativistic charged particles, mostly with energies in the GeV-range, but extending to energies higher by many orders of magnitude. As none of these particles can penetrate the earth’s atmosphere without interaction, detailed studies of their composition and energy spectra require observations with high-altitude balloons or spacecraft. This became possible only towards the middle of the 20th century. The direct measurements have now revealed much detail about the Galactic cosmic rays below 1015eV, but do not yet provide much overlap with the air-shower region of energies. A historic overview of the measurements is given, beginning with the realization that the majority of the cosmic rays are protons. The discovery and astrophysical significance of the heavier nuclei, and of the ultra-heavy nuclei beyond iron and up to the actinides, are then described, and measurements of the isotopic composition are discussed. Observations of the individual energy spectra are reviewed, and finally, the detection of electrons, positrons, and anti-protons in the cosmic rays, and the searches for exotic or unusual phenomena are summarized. Emphasis is given to the fact that all of these discoveries have become possible through the evolution of increasingly sophisticated detection techniques, a process that is continuing through the present time. The precise knowledge of the abundance distributions of the elements in the cosmic rays and of their isotopic composition permits a comparison with the “universal abundance scale” and provides strong constraints on the origin of the cosmic-ray material in the interstellar medium. “Clock-isotopes” reveal the time history of the particles. The shapes of the energy spectra of the individual cosmic-ray components are related to evolving ideas about particle acceleration and propagation in the Galaxy. In conclusion, prospects for future work are briefly discussed