Methicillin-resistant Staphylococcus aureus in HIV-infected patients

Concordant with the emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community setting, colonization and infections with this pathogen have become a prevalent problem among the human immunodeficiency virus (HIV)-positive population. A variety of different host- and, possibly, pathogen-related factors may play a role in explaining the increased prevalence and incidence observed. In this article, we review pathophysiology, epidemiology, clinical manifestations, and treatment of MRSA in the HIV-infected population

Cohort Profile: The HIV Atlanta Veterans Affairs Cohort Study (HAVACS).

The originally published version of this Profile contained an error in one of the author names. Vince D. Marconi should have read Vince C. Marconi. This has now been corrected

Methicillin-resistant Staphylococcus aureus in HIV-infected patients

In this thesis, we consider the numerical solution of initial boundary value problems (IBVPs). Boundary and interface conditions are derived such that the IBVP under consideration is well-posed. We also study the dual problem and the related dual boundary/interface conditions. Once the continuous problem is analyzed, we use finite difference operators with the Summation- By-Parts property (SBP) and a weak boundary/interface treatment using the Simultaneous-Approximation-Terms (SAT) technique to construct high-order accurate numerical schemes. We focus in particular on stability, conservation and dual consistency. The energy method is used as our main analysis tool for both the continuous and numerical problems. The contributions of this thesis can be divided into two parts. The first part focuses on the coupling of different IBVPs. Interface conditions are derived such that the continuous problem satisfy an energy estimate and such that the discrete problem is stable. In the first paper, two hyperbolic systems of different size posed on two domains are considered. We derive the dual problem and dual interface conditions. It is also shown that a specific choice of penalty matrices leads to dual consistency. As an application, we study the coupling of the Euler and wave equations. In the fourth paper, we examine how to couple the compressible and incompressible Navier-Stokes equations. In order to obtain a sufficient number of interface conditions, the decoupled heat equation is added to the incompressible equations. The interface conditions include mass and momentum balance and two variants of heat transfer. The typical application in this case is the atmosphere-ocean coupling. The second part of the thesis focuses on the relation between the primal and dual problem and the relation between dual consistency and conservation. In the second and third paper, we show that dual consistency and conservation are equivalent concepts for linear hyperbolic conservation laws. We also show that these concepts are equivalent for symmetric or symmetrizable parabolic problems in the fifth contribution. The relation between the primal and dual boundary conditions for linear hyperbolic systems of equations is investigated in the sixth and last paper. It is shown that for given well-posed primal/dual boundary conditions, the corresponding well-posed dual/primal boundary conditions can be obtained by a simple scaling operation. It is also shown how one can proceed directly from the well-posed weak primal problem to the well-posed weak dual problem.  Den här avhandlingen handlar om numeriska metoder för att lösa initial och randvärdes problem. Studien fokuserar på härledningen av rand/kopplingsvillkor som garanterar välställdhet. Det duala problemet och dess duala rand/kopplingsvillkor studeras också. Dessa problem diskretiseras genom att använda noggranna finita differensscheman på SBP-form (eng. summation-by-parts), kombinerat med en svag randbehandling benämnd SAT (eng. simultaneous approximation term). Vi fokuserar särskilt på stabilitet, konservation och dualkonsistens. Det främsta analysverktyget för både det kontinuerliga och diskreta problemet är energimetoden. Den första delen av avhandlingen behandlar välställdhet och stabilitet för koppling av olika system av ekvationer. Kopplingsvillkoren är härledda så att det kontinuerliga problemet uppfyller en energiuppskattning och så att det diskreta problemet är stabilt. I den första artikeln görs analysen för koppling av två olika hyperboliska system på första ordningens form. Som tillämpning kopplar vi Euler och vågekvationerna. Koppling mellan kompressibla och inkompressibla Navier-Stokes ekvationer studeras i den fjärde artikeln. För att få rätt antal kopplingsvillkor lägger vi till värmeledningsekvationen till de inkompressibla ekvationerna. Kopplingsvillkoren innefattar massans och rörelsemängdens bevarande samt två varianter av värmeöverföring. Den typiska tillämpningen är koppling mellan atmosfär och hav. Den andra delen av avhandlingen fokuserar på relationen mellan det primära och duala problemet och relationen mellan dualkonsistens och konservation. I den andra och tredje artikeln visar vi att dualkonsistens och konservation är ekvivalenta koncept för linjära hyperboliska konserveringslagar. I den femte artikeln, visas att dessa koncept är ekvivalenta även för paraboliska problem. Relationen mellan de primära och duala randvilkoren för linjära hyperboliska system av ekvationer i två dimensioner studeras i den sista artikeln. Vi visar att primära/duala välställda randvilkor ger duala/primära välställda randvilkor genom en enkel skalningsoperation. Det visas också att man kan gå direkt från det välställda svaga primära problemet till det välställda svaga duala problemet

Retention in HIV care depends on patients’ perceptions of the clinic experience

Institutional barriers in HIV primary care settings can contribute substantially to disparities in retention in HIV treatment and HIV-related outcomes. This qualitative study compared the perceptions of clinic experiences of persons living with HIV (PLWH) in a Veterans Affairs HIV primary care clinic setting who were retained in care with the experiences of those who were not retained in care. Qualitative data from 25 in-depth interviews were analyzed to identify facilitators and barriers to retention in HIV care. Results showed that participants not retained in care experienced barriers to retention involving dissatisfaction with clinic wait times, low confidence in clinicians, and customer service concerns. For participants retained in care, patience with procedural issues, confidence in clinicians, and interpersonal connections were factors that enhanced retention despite the fact that these participants recognized the same barriers as those who were not retained in care. These findings can inform interventions aimed at improving retention in HIV care

Low Rates of Vaccination for Herpes Zoster in Older People Living With HIV.

Herpes zoster (HZ) occurs at a higher age-specific rate in people living with HIV (PLWH) than in the general population. We implemented a quality improvement study to assess herpes zoster vaccine (HZV) usage among PLWH, assess HZV usage after additional reminders/prompts, and identify barriers to HZV among older PLWH. HZV rates in PLWH were determined in six institutions with varying payment structures. For the intervention, Part 1, PLWH eligible for HZV at the University of Colorado were identified, and providers were notified of patient eligibility. In Part 2, in addition to provider notification, an order for HZV was placed in the patient's chart before a clinic appointment. HZ vaccination rates ranged from 1.5% to 42.4% at six sites. Before the intervention, 21.3% of eligible University of Colorado patients had received HZV. An additional 8.3% received HZV with Part 1 and 17.8% with Part 2 interventions. At completion, a total of 53.2% of eligible patients had received HZV through routine clinical care or the interventions. Insurance coverage concern was cited as a common reason for not receiving HZV. Minor adverse reactions occurred in 26.7% patients and did not require medical care. HZV coverage was low at a majority of sites. Clinical reminders with links to vaccination orders or preplaced vaccination orders led to improved HZV coverage in our clinic, but published guidelines for use of HZV in PLWH and improvement in logistic or insurance barriers to HZV receipt are paramount to improved HZV coverage

Low Rates of Vaccination for Herpes Zoster in Older People Living With HIV.

Herpes zoster (HZ) occurs at a higher age-specific rate in people living with HIV (PLWH) than in the general population. We implemented a quality improvement study to assess herpes zoster vaccine (HZV) usage among PLWH, assess HZV usage after additional reminders/prompts, and identify barriers to HZV among older PLWH. HZV rates in PLWH were determined in six institutions with varying payment structures. For the intervention, Part 1, PLWH eligible for HZV at the University of Colorado were identified, and providers were notified of patient eligibility. In Part 2, in addition to provider notification, an order for HZV was placed in the patient's chart before a clinic appointment. HZ vaccination rates ranged from 1.5% to 42.4% at six sites. Before the intervention, 21.3% of eligible University of Colorado patients had received HZV. An additional 8.3% received HZV with Part 1 and 17.8% with Part 2 interventions. At completion, a total of 53.2% of eligible patients had received HZV through routine clinical care or the interventions. Insurance coverage concern was cited as a common reason for not receiving HZV. Minor adverse reactions occurred in 26.7% patients and did not require medical care. HZV coverage was low at a majority of sites. Clinical reminders with links to vaccination orders or preplaced vaccination orders led to improved HZV coverage in our clinic, but published guidelines for use of HZV in PLWH and improvement in logistic or insurance barriers to HZV receipt are paramount to improved HZV coverage

The AIDS resistance of naturally SIV-infected sooty mangabeys is independent of cellular immunity to the virus

In contrast to human immunodeficiency virus (HIV)-infected humans, natural hosts for simian immunodeficiency virus (SIV) very rarely progress to acquired immunodeficiency syndrome (AIDS). While the mechanisms underlying this disease resistance are still poorly understood, a consistent feature of natural SIV infection is the absence of the generalized immune activation associated with HIV infection. To investigate the immunologic mechanisms underlying the absence of AIDS in SIV-infected sooty mangabeys (SMs), a natural host species, we performed a detailed analysis of the SIV-specific cellular immune responses in 110 SIV-infected SMs. We found that while SIV-specific T-cell responses are detectable in the majority of animals, their magnitude and breadth are, in fact, lower than what has been described in HIV-infected humans, both in terms of cytokine production (ie, IFN-γ, TNF-α, and IL-2) and degranulation (ie, CD107a expression). Of importance, SIV-specific T-cell responses were similarly low when either SIVmac239-derived peptides or autologous SIVsmm peptides were used as stimuli. No correlation was found between SIV-specific T-cell responses and either viral load or CD4+ T-cell count, or between these responses and markers of T-cell activation and proliferation. These findings indicate that the absence of AIDS in naturally SIV-infected sooty mangabeys is independent of a strong cellular immune response to the virus. (Blood. 2006;108:209-217

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial

Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 μg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87–1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3–7%) in the interferon beta-1a plus remdesivir group and 3% (2–6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69–2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. The National Institute of Allergy and Infectious Diseases (USA)