Dolutegravir (DTG), a second-generation integrase strand-transfer inhibitor (INSTI), is equivalent or superior to current non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and first-generation INSTI-based antiretroviral regimens (ARVs). It has the potential to make big improvements in HIV control globally and within patients. This is perhaps the most “precious” HIV drug available. The integrase mutation R263K has been observed in tissue culture experiments and in patients treated with dolutegravir monotherapy in clinical trials. Globally, adherence and monitoring may be less than optimal and therefore DTG resistance more common. This is particularly important in low–middle-income countries, where patients may remain on failing regimens for longer periods of time and accumulate drug resistance. Data on this mutation in non–subtype B infections do not exist. We describe the first report of the R263K integrase mutation in a dolutegravir-exposed subtype D–infected individual with vertically acquired HIV. We have used deep sequencing of longitudinal samples to highlight the change in resistance over time while on a failing regimen. The case highlights that poorly adherent patients should not be offered dolutegravir even as part of a combination regimen and that protease inhibitors should be used preferentially.
Background New consultants consistently feel better prepared for the clinical rather than non-clinical aspects of their role. However, deficiencies in generic competencies have been linked to burnout and patient complaints. This study explored how higher specialty training prepares doctors for the transition to consultant in genitourinary medicine. Results New consultants felt less prepared for non-clinical aspects of their role. Prior practical experience was the greatest influencing factor in levels of preparedness, with increased responsibility and leadership driving deeper learning. Observation of others helped individuals develop a professional identity but also learn about the wider processes within their service. The learning environment positively influenced preparedness but highlighted a need for dedicated time to learn non-clinical aspects. Conclusion To ensure future trainees feel prepared for the non-clinical aspects of the consultant role, practical experience of nonclinical areas with high levels of leadership and responsibility within a supportive learning environment is essential.
A 69-year-old man, previously independent and with a pre-existing metallic aortic valve, presented with a history of fevers, confusion and malaise and was diagnosed with prosthetic valve endocarditis. Blood cultures taken on presentation grewStreptococcus sanguinisand vegetations were confirmed on transoesophageal echocardiogram. He had had a dental procedure 10 days before presentation but had not received prophylactic antibiotics; he had been receiving antibiotic prophylaxis for dental treatment up until the change in NICE guidelines in 2008. He was treated with high dose antibiotics and was referred for cardiothoracic surgery, but developed a cerebrovascular event, thought to be embolic, and deteriorated and died. Given that the patient had a metallic aortic valve and poor dentition, and therefore was at increased risk of infective endocarditis, should the new guidelines have been followed so rigidly, particularly as American and European guidelines still recommend the use of antibiotic prophylaxis in this patient group?
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