Why sexual health clinics are important in the 2020s

To make services more accessible, acceptable and affordable, sexual health service delivery models have embraced innovation, technology, outreach and decentralisation. In particular, some routine high-volume services, like asymptomatic testing for sexually transmitted infections (STIs), can be delivered in general practice, online or in non-clinical settings. On the surface, sexual health clinics, like hospitals or other primary care clinics, might appear to be operating on a model that has not changed significantly in recent times. However, globally sexual healthcare needs are rising both in volume and complexity, not all of which can be adequately met through decentralised care. Sexual health clinics themselves are the site of considerable innovation. The importance of sexual health clinics in the diagnosis and treatment of symptomatic STIs is likely to increase with the increasing burden of disease, the complexity of treatment guidelines and the emergence of new infections. Services essential to patient health such as immediate or complex clinical care, partner notification and safeguarding, and activities essential to the health system like research, training and supervision require expertise to be located where it can be accessed and maintained at reasonable cost. We do not know whether increasing some services outside existing models can safely compensate for reducing other services inside them

Acyclovir therapy reduces the CD4+ T cell response against the immunodominant pp65 protein from cytomegalovirus in immune competent individuals

Cytomegalovirus (CMV) infects the majority of the global population and leads to the development of a strong virus-specific immune response. The CMV-specific CD4+ and CD8+ T cell immune response can comprise between 10 and 50% of the T cell pool within peripheral blood and there is concern that this may impair immunity to other pathogens. Elderly individuals with the highest magnitude of CMV-specific immune response have been demonstrated to be at increased risk of mortality and there is increasing interest in interventions that may serve to moderate this. Acyclovir is an anti-viral drug with activity against a range of herpes viruses and is used as long term treatment to suppress reactivation of herpes simplex virus. We studied the immune response to CMV in patients who were taking acyclovir to assess if therapy could be used to suppress the CMV-specific immune response. The T cell reactivity against the immunodominant late viral protein pp65 was reduced by 53% in people who were taking acyclovir. This effect was seen within one year of therapy and was observed primarily within the CD4+ response. Acyclovir treatment only modestly influenced the immune response to the IE-1 target protein. These data show that low dose acyclovir treatment has the potential to modulate components of the T cell response to CMV antigen proteins and indicate that anti-viral drugs should be further investigated as a means to reduce the magnitude of CMV-specific immune response and potentially improve overall immune function

The exponent of Hölder calmness for polynomial systems

Diese Arbeit befasst sich mit Untersuchung der Hölder Calmness, eines Stabilitätskonzeptes das man als Verallgemeinerung des Begriffs der Calmness erhält. Ausgehend von Charakterisierungen dieser Eigenschaft für Niveaumengen von Funktionen, werden, unter der Voraussetzung der Hölder Calmness, Prozeduren zur Bestimmung von Elementen dieser Mengen analysiert. Ebenso werden hinreichende Bedingungen für Hölder Calmness studiert. Da Hölder Calmness (nichtleerer) Lösungsmengen endlicher Ungleichungssysteme mittels (lokaler) Fehlerabschätzungen beschrieben werden kann, werden auch Erweiterungen der lokalen zu globalen Ergebnissen diskutiert. Als Anwendung betrachten wir speziell den Fall von Niveaumengen von Polynomen bzw. allgemeine Lösungsmengen polynomialer Gleichungen und Ungleichungen. Eine konkrete Frage, die wir beantworten wollen, ist die nach dem Zusammenhang zwischen dem größten Grad der beteiligten Polynome sowie dem Typ, d.h. dem auftretenden Exponenten, der Hölder Calmness des entsprechenden Systems.This thesis is concerned with an analysis of Hölder calmness, a stability property derived from the concept of calmness. On the basis of its characterization for (sub)level sets, we will cogitate about procedures to determine points in such sets under a Hölder calmness assumption. Also sufficient conditions for Hölder calmness of (sub)level sets and of inequality systems will be given and examined. Further, since Hölder calmness of (nonempty) solution sets of finite inequality systems may be described in terms of (local) error bounds, we will as well amplify the local propositions to global ones. As an application we investigate the case of (sub)level sets of polynomials and of general solution sets of polynomial equations and inequalities. A concrete question we want to answer here is, in which way the maximal degree of the involved polynomials is connected to the exponent of Hölder calmness or of the error bound for the system in question

Frequency of pp65 and IE-1-specific CD8+ T cells detected by HLA-peptide tetramer staining in control subjects and donors taking acyclovir.

<p>PBMC were stained with HLA-peptide tetramers specific for pp65- and IE-1-derived epitopes according to the individual HLA genotype. The aggregate frequency of pp65 or IE-1-binding T cells was determined for each donor and is shown in the figure. Horizontal bars depict the mean frequencies.</p

CD4+ T cell response to control antigen in patients taking acyclovir and in control subjects.

<p>PBMC from control subjects (n = 26) and donors taking acyclovir (n = 24) were stimulated with Adenovirus 5 or PPD antigen and the proportion of IFN-γ producing T cells was determined using intracellular cytokine analysis. Horizontal bars represent means.</p

Using Climate-HIV to describe real-world clinical outcomes for people living with HIV taking dolutegravir-based regimens.

OBJECTIVES The objective of this study was to describe the real-world use and effectiveness of dolutegravir-based regimens (DBRs) in routine clinical practice in the United Kingdom. METHODS Retrospective analysis was conducted using data from four National Health Service trusts using Climate-HIV, an electronic case record system. Eligible patients were aged ≥18 years with HIV-1 infection who were prescribed a DBR from December 2012 to March 2018. Outcome measurements were accessed at DBR initiation and at weeks 24, 48 and 96 and the last recorded visit up to the extraction date (last measurement). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at Week 48. RESULTS The study cohort included 934 patients; 337 (36%) were female, 414 (47%) were white and 717 (77%) were treatment experienced (TE). The Kaplan-Meier estimated probability of achieving HIV-1 RNA <50 copies/mL at 48 weeks was 96% for treatment-naive (TN) patients and 86% for TE patients. Median times to viral suppression (<50 copies/mL) were 49 and 57 days for TN and TE patients with detectable baseline viral load, respectively, according to Kaplan-Meier analysis. Median follow-up time was 377 days (interquartile range: 131-683). At last measurement, 87% (809/934) of patients remained on a DBR; among those patients, 681 (84%) had HIV-1 RNA <50 copies/mL. CONCLUSIONS High levels of virologic suppression and low rates of discontinuation of DBRs were seen in a large, diverse, UK-based population with HIV-1 infection. These findings are broadly consistent with efficacy data from phase III studies

Hepmarc: a 96 week randomised controlled feasibility trial of add-on maraviroc in people with HIV and non-alcoholic fatty liver disease

Objectives Maraviroc may reduce hepatic inflammation in people with HIV and non-alcoholic fatty liver disease (HIV-NAFLD) through CCR5-receptor antagonism, which warrants further exploration. Methods We performed an open-label 96-week randomised-controlled feasibility trial of maraviroc plus optimised background therapy (OBT) versus OBT alone, in a 1:1 ratio, for people with virologically-suppressed HIV-1 and NAFLD without cirrhosis. Dosing followed recommendations for HIV therapy in the Summary of Product Characteristics for maraviroc. The primary outcomes were safety, recruitment and retention rates, adherence and data completeness. Secondary outcomes included the change in Fibroscan-assessed liver stiffness measurements (LSM), controlled attenuation parameter (CAP) and Enhanced Liver Fibrosis (ELF) scores. Results Fifty-three participants (53/60, 88% of target) were recruited; 23 received maraviroc plus OBT; 89% were male; 19% had type 2 diabetes mellitus. The median baseline LSM, CAP & ELF scores were 6.2 (IQR 4.6–7.8) kPa, 325 (IQR 279–351) dB/m and 9.1 (IQR 8.6–9.6) respectively. Primary outcomes: all individuals eligible after screening were randomised; there was 92% (SD 6.6%) adherence to maraviroc [target >90%]; 83% (95%CI 70%-92%) participant retention [target >65%]; 5.5% of data were missing [target Conclusions This feasibility study provides preliminary evidence of maraviroc safety amongst people with HIV-NAFLD, and acceptable recruitment, retention, and adherence rates. These data support a definitive randomised-controlled trial assessing maraviroc impact on hepatic steatosis and fibrosis. Trial registration Clinical trial registry: ISCRTN, registration number 31461655.</p

Dataset for Hepmarc: a 96 week randomised controlled feasibility trial of add-on maraviroc in people with HIV and non-alcoholic fatty liver disease

Data for paper published in PLOS ONE 14.07.2023 These files were used for the statistical analysis of the hemparc feasibility trial using Stata software verson 17, and are as follows, both Stata format and .csv format as appropriate.  The .do file is a simple text file. hepmarc_data minimum dataset: .csv, .dta: See doi:10.1136/bmjopen-2019-035596 for study protocol describing all data collected hepmarc Data dictionary .xls, .dta; description of each data fields in minimum dataset hepmarc AE listing: Adverse events listing .csv, .dta hepmarc SAP v1.0 240322_.xls .dta; description of each data fields in minimum dataset hepmarc data.do Stata .do file used to perform the analysis Notes: Each particpant's age has been altered by a random amount to preserve anonymity.  There are two rows for two of the participants who each reported two adverse reactions. Abstract Objectives  Maraviroc may reduce hepatic inflammation in people with HIV and non-alcoholic fatty liver disease (HIV-NAFLD) through CCR5-receptor antagonism, which warrants further exploration.  Methods We performed an open-label 96-week randomised-controlled feasibility trial of maraviroc plus optimised background therapy (OBT) versus OBT alone, in a 1:1 ratio, for people with virologically-suppressed HIV-1 and NAFLD without cirrhosis. Dosing followed recommendations for HIV therapy in the Summary of Product Characteristics for maraviroc. The primary outcomes were safety, recruitment and retention rates, adherence and data completeness. Secondary outcomes included the change in Fibroscan-assessed liver stiffness measurements (LSM), controlled attenuation parameter (CAP) and Enhanced Liver Fibrosis (ELF) scores.  Results Fifty-three participants (53/60, 88% of target) were recruited; 23 received maraviroc plus OBT; 89% were male; 19% had type 2 diabetes mellitus. The median baseline LSM, CAP & ELF scores were 6.2 (IQR 4.6-7.8) kPa, 325 (IQR 279-351) dB/m and 9.1 (IQR 8.6-9.6) respectively. Primary outcomes: all individuals eligible after screening were randomised; there was 92% (SD 6.6%) adherence to maraviroc [target >90%]; 83% (95%CI 70%-92%) participant retention [target >65%]; 5.5% of data were missing [target Secondary outcomes: no important differences were seen by treatment group for the change from baseline in LSM, CAP or ELF scores Conclusions This feasibility study provides preliminary evidence of maraviroc safety amongst people with HIV-NAFLD, and acceptable recruitment, retention, and adherence rates. These data support a definitive randomised-controlled trial assessing maraviroc impact on hepatic steatosis and fibrosis. Clinical trial registry: ISCRTN, registration number 31461655.</p