Late diagnosis of HIV infection remains a major issue, with implications for both patient outcomes and health care costs, with around 60% of patients in the north east of England diagnosed late with CD4 counts < 350 cells/μL.1 There are national guidelines available, which advise on medical conditions that should prompt consideration of HIV testing in patients.2 However, research by Lazarus et al.3 shows that in up to 82% of patients presenting with an HIV-related symptom, testing is not carried out at the earliest opportunity. Vijeratnam et al.4 proposed that HIV testing prompts on reports containing indicator conditions could help reduce the incidence of missed HIV screening opportunities. Research on computerized reminders in general practice has shown them to have a positive effect on clinician behaviour.5 The recently published National Institute for Health and Care Excellence (NICE) guideline HIV Testing: Encouraging Uptake (quality standard 157)6 advises that ‘Young people and adults newly diagnosed with an HIV indicator condition are offered an HIV test’ as this helps to reduce late diagnosis of HIV infection, improves HIV treatment outcomes and may improve the response to treatment of the indicator condition. In 2016, we investigated the likely impact of introducing visual testing prompts on earlier diagnosis of HIV infection. We found five patients (11%) in a 17-month period who had previous laboratory requests with clinical details suggestive of an HIV indicator condition. Visual testing prompts are likely to have led to an earlier HIV diagnosis in three of these patients.4 Subsequently, over a 4-day period, in autumn 2017, we reviewed the clinical request details of all specimens received in our laboratory. Of 241 sputum samples that were processed, nine (3.7%) included clinical details suggestive of HIV indicator conditions. Only one of these patients (11%) had previously been tested for HIV. Similarly, of 227 samples sent from general practice, 12 (5.3%) included clinical details suggestive of HIV indicator conditions. Of these patients, only three had been tested for HIV (25%). Our findings suggest that implementing an automated text-based visual HIV testing prompt on reports from microbiology samples may be an effective means of reducing the incidence of late HIV diagnoses in patients with HIV indicator conditions.
Bococizumab is a humanized monoclonal antibody binding proprotein convertase subtilisin/kexin type 9, which may be a potential therapeutic option for reducing low-density lipoprotein cholesterol (LDL-C) levels in patients with hypercholesterolemia. In this 24-week, multicenter, double-blind, placebo-controlled, dose-ranging study (NCT01592240), subjects with LDL-C levels≥80 mg/dl on stable statin therapy were randomized to Q14 days subcutaneous placebo or bococizumab 50, 100, or 150 mg or Q28 days subcutaneous placebo or bococizumab 200 or 300 mg. Doses of bococizumab were reduced if LDL-C levels persistently decreased to ≤25 mg/dl. The primary end point was the absolute change in LDL-C levels from baseline to week 12 after placebo or bococizumab administration. Continuation of bococizumab administration through to week 24 enabled the collection of safety data over an extended period. Of the 354 subjects randomized, 351 received treatment (placebo [n=100] or bococizumab [n=251]). The most efficacious bococizumab doses were 150 mg Q14 days and 300 mg Q28 days. Compared with placebo, bococizumab 150 mg Q14 days reduced LDL-C at week 12 by 53.4 mg/dl and bococizumab 300 mg Q28 days reduced LDL-C by 44.9 mg/dl; this was despite dose reductions in 32.5% and 34.2% of subjects at week 10 or 8, respectively. Pharmacokinetic/pharmacodynamic model-based simulation assuming no dose reductions predicted that bococizumab would lower LDL-C levels by 72.2 and 55.4 mg/dl, respectively. Adverse events were similar across placebo and bococizumab groups. Few subjects (n=7; 2%) discontinued treatment because of treatment-related adverse events. In conclusion, bococizumab significantly reduced LDL-C across all doses despite dose reductions in many subjects. Model-based simulations predicted greater LDL-C reduction in the absence of bococizumab dose reduction. The Q14 days regimen is being evaluated in phase 3 clinical trials.
e18172 Background: Desperately ill patients who have exhausted treatment options often seek access to therapy through investigational therapies. Participation in a clinical trial may be one option. When a clinical trial is not an option, physicians and patients are left with Expanded Access (EA), and Right to Try (RTT). The 21 st Century Cures legislation requires pharmaceutical manufacturers to make information on their EA policy, contact information, and response time readily accessible. RTT became law in 2018, and this path is rarely an option. Methods: To determine best practice in the age of changing legislation of pre-approval access to investigational drugs, we compared pathways by which pharmaceutical companies are providing access to investigational medications. Data has been gathered on presentation of policy, intake of expanded access requests, and education to the public on the company’s internal pathway to access. We conducted a survey of the top 100 Pharma companies to assess compliance with regulations, policy availability, and RTT information. Results: The data has shown that companies show a range of compliance in expanded access. Many companies have published all required aspects outlined in the legislation to be fully adherent to the guidelines with additional education and guidelines for patients and physicians. Others have provided the minimum requirement to be compliant: a policy and contact information. We also see companies that have not established a stance of process in expanded access and therefore provide no public facing information on their policy and pathways toward treatment. Information on RTT remained elusive. Conclusions: While RTT is increasingly requested as a possible path, the mechanism to request RTT remains a barrier and source of confusion to physicians and patients. Companies should take the opportunity to clearly define their policy and process for Expanded Access as well as reevaluate the organization of their current procedure to ensure highest efficiency and full compliance with legislation.
