Safety and efficacy of fixed-dose combination rilpivirine-tenofovir-emtricitabine (RPV/TDF/FTC) in treatment-experienced patients infected with HIV-1

Purpose of the study: Rilpivirine (RPV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) which has shown non-inferiority to efavirenz (EFV) in terms of efficacy and safety profiles. The vast majority of clinical data has been performed in the treatment naïve population and has not been studied in depth in treatment-experienced patients. We sought to explore the safety and efficacy of RPV/TDF/FTC in treatment-experienced patients attending our clinics. Methods: HIV-infected individuals commenced on RPV/TDF/FTC from December 2011 to June 2012 were retrospectively identified from a patient database. Patient demographics were extracted. Biochemical, virological and immunological parameters were collated. At baseline, 1 month and 3 month time points the following laboratory results were compared using the Kruskal-Wallis test: CD4 count, HIV viral load, amino transferase (ALT), cholesterol, triglyceride and HDL/cholesterol ratio. Summary of results: Sixty-five patients (4 female) were identified. Median age was 38 years (range: 25–73). Fifty-six patients were treatment experienced (2 re-start); 39 on NNRTI-based (33 on EFV), 10 on PI-based and 4 on other regimens. 9 patients were naïve to treatment. The reasons for switch are illustrated in Fig. 1. Fifty-four patients had HIV-RNA-1<40 copies/mL at the time of switch and all remained undetectable at 3 months. At baseline, the median CD4 count was 555 cells/mm3 (range: 209–1586) in the switch group, which increased significantly to 638 cells/mm3 (p<0.005) 3 months after switch. Switch to RPV/TDF/FTC had a favorable effect on lipid profile. At baseline the median cholesterol, triglyceride and HDL/cholesterol ratio levels were 4.8 mmol/L, 1.78 mmol/L and 4.37 respectively. At 1 month post-switch this decreased to 4.5 mmol/L, 1.65 mmol/L and 4.24 and at 3 months post-switch decreased to 4.1 mmol/L, 1.44 mmol/L and 4.04. Median HIV-RNA-1 in treatment-naïve patients (n=9) at baseline was 50298 copies/mL, at 1 month four patients had HIV-RNA-1<40 copies/mL and at 3 months eight patients had HIV-RNA-1<40 copies/mL. RPV/TDF/FTC had no favourable effect on lipid profile in treatment-naïve group and had no effect on ALT levels in either the switch or the treatment-naïve group. Conclusion: In this cohort, RPV/TDF/FTC has been shown to have a safe virological efficacy and safety profile as a switch therapy for patients suppressed on their current standard of care and are experiencing adverse events

Expert United Kingdom consensus on the preservation of joint health in people with moderate and severe haemophilia A: A modified Delphi panel

Aim: For people with haemophilia A (PwHA), bleeding in the joints leads to joint damage and haemophilia-related arthropathy, impacting range of motion and life expectancy. Existing guidelines for managing haemophilia A support healthcare professionals (HCPs) and PwHA in their efforts to preserve joint health. However, such guidance should be reviewed, considering emerging evidence and consensus as presented in this manuscript. Methods: Fifteen HCPs experienced in the management of PwHA in the UK participated in a three-round Delphi panel. Consensus was defined at ≥70% of panellists agreeing or disagreeing for Likert-scale questions, and ≥70% selecting the same option for multiple- or single-choice questions. Questions not reaching consensus were revised for the next round. Results: 26.8% (11/41), 44.8% (13/29) and 93.3% (14/15) of statements reached consensus in Rounds 1, 2 and 3, respectively. HCPs agreed that prophylaxis should be offered to patients with a baseline factor VIII (FVIII) level of ≤5 IU/dL and that, where there is no treatment burden, the aim of prophylaxis should be to achieve a trough FVIII level ≥15 IU/dL and maintain a longer period with FVIII levels of ≥20-30 IU/dL to provide better bleed protection. The aspirational goal for PwHA is to prevent all joint bleeds, which may be achieved by maintaining normalised (50-150 IU/dL) FVIII levels. Conclusion: The panel of experts were largely aligned on approaches to preserving joint health in PwHA, and this consensus may help guide HCPs

Expert United Kingdom consensus on the preservation of joint health in people with moderate and severe haemophilia A: A modified Delphi panel

\ua9 2024 The Authors. Haemophilia published by John Wiley & Sons Ltd.Aim: For people with haemophilia A (PwHA), bleeding in the joints leads to joint damage and haemophilia-related arthropathy, impacting range of motion and life expectancy. Existing guidelines for managing haemophilia A support healthcare professionals (HCPs) and PwHA in their efforts to preserve joint health. However, such guidance should be reviewed, considering emerging evidence and consensus as presented in this manuscript. Methods: Fifteen HCPs experienced in the management of PwHA in the UK participated in a three-round Delphi panel. Consensus was defined at ≥70% of panellists agreeing or disagreeing for Likert-scale questions, and ≥70% selecting the same option for multiple- or single-choice questions. Questions not reaching consensus were revised for the next round. Results: 26.8% (11/41), 44.8% (13/29) and 93.3% (14/15) of statements reached consensus in Rounds 1, 2 and 3, respectively. HCPs agreed that prophylaxis should be offered to patients with a baseline factor VIII (FVIII) level of ≤5 IU/dL and that, where there is no treatment burden, the aim of prophylaxis should be to achieve a trough FVIII level ≥15 IU/dL and maintain a longer period with FVIII levels of ≥20–30 IU/dL to provide better bleed protection. The aspirational goal for PwHA is to prevent all joint bleeds, which may be achieved by maintaining normalised (50–150 IU/dL) FVIII levels. Conclusion: The panel of experts were largely aligned on approaches to preserving joint health in PwHA, and this consensus may help guide HCPs

Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial

Background: Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms. Design: The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about 1200 patients are needed to detect a 24% reduction in primary outcome. Implications: The GROUND study will provide insight into the question whether non-invasive cardiac imaging reduces the risk of cardiovascular events in patients with peripheral arterial disease, but without symptoms of coronary artery disease. Trial registration: Clinicaltrials.gov NCT0018911

An investigation into frequency and reasons why patients switch antiretroviral therapy and which antiretrovirals are commonly implicated in toxicity

Purpose of the study Previous investigation into antiretroviral (ARV) therapy switches in our HIV cohort suggested an annual switch rate of 20% in 2006 with 60% of switches being secondary to toxicity [1]. The purpose of this study was to investigate whether this switch rate has changed in recent years, determine reasons why patients change regimens, and identify which ARVs are most likely to be switched for toxicity concerns. Methods The electronic patient database was reviewed to identify all patients within our HIV cohort who switched ARV therapy between 1st December 2009 and 31st May 2011. Details of which ARVs were switched and the reasons why were recorded. Any switches due to toxicity were investigated further to identify the actual or perceived adverse effect. Summary of results Nine hundred and twenty-three regimens were switched over 18 months affecting 12% (n = 722) of patients on treatment during this time. The most common reason for switching medication was due to toxicity, occurring in 452 (49%) cases. Other reasons included simplification (15%), clinical trials (8%), virological failure (8%) and drug interactions (4%). The remaining 16% switched for various reasons including pregnancy and co-morbidities. Of 452 switches for toxicity (or perceived toxicity), 122 (27%) were due to CNS side effects (89 out of a total of 122 were related to efavirenz), 64 (14%) gastrointestinal disturbances (38/64 related to protease inhibitors), 54 (12%) actual/perceived cardiovascular risk (21/54 related to abacavir and 21/54 related to saquinavir), 54 (12%) hepatotoxicity (21/54 related to atazanavir and 14/54 related to efavirenz), 42 (9%) metabolic concerns (24/42 related to protease inhibitors) and 38 (8%) renal toxicity (28/38 related to tenofovir). Other toxicities accounted for 78 (18%) switches. An observed toxicity switch rate (OTSR) per 1000 patient years (95% CI) was calculated for each ARV. Conclusions 12% of patients switched therapy in 18 months, predicting an annual switch rate of 8%. Toxicity remained an important reason for switching. Saquinavir and lopinavir have a significantly higher OTSR than other PIs as does zidovudine compared with other NRTIs. Nevirapine has a significantly lower OTSR than other NNRTIs

FACTORS ASSOCIATED WITH MORTALITY IN PATIENTS WITH SYMPTOMATIC CAROTID STENOSIS: RESULTS FROM THE ACSRS STUDY

AIM: This study determines the factors associated with mortality in patients with asymptomatic carotid stenosis. METHODS: Patients (n=1,101) with asymptomatic internal carotid artery stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6 to 84 (median 38) months. Stenosis was graded using duplex scanning and expressed as a percentage of the carotid bulb diameter. Clinical and biochemical risk factors were recorded. The end-points were ipsilateral ischemic stroke, cardiovascular death and all cause mortality. RESULTS: In a Cox multivariate analysis 6 factors emerged as independent predictors of risk. Age, male gender, cardiac failure, left ventricular hypertrophy on electrocardiogram (ECG) and myocardial ischemia on ECG were associated with increased risk. Antiplatelet therapy was associated with decreased risk. Based on these risk factors a high-risk group consisting of one third of the population with a 40% cumulative cardiovascular death rate and a 66% all cause death rate at 7 years could be identified. The remaining 2/3 consisted of a low-risk group with a 10% cumulative cardiovascular death rate and a 21% all cause death rate at 7 years (P0.05). CONCLUSIONS: The methodology and findings from the ACSRS natural history study need to be applied to randomized controlled trials on the value of carotid endarterectomy or stenting in patients with asymptomatic carotid stenosis. They may help refine the indications for intervention in patients with carotid endarterectomy