Explore the vast range of titles available.

Background Chronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART). Tenofovir (TFV) in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP) have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP) such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients. Methods In a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR). Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI) or TFV and a protease-inhibitor (TFV/PI). Results Proteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 μg/mmol (343 μg/g) (p = 0.003). In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77) and eGFR <75 mL/min/1.73 m 2 (OR 3.54, 95 % CI 1.61, 7.80) were independently associated with upper quartile (UQ) RBPCR. RBPCR correlated well to CCR (r 2  = 0.71), but not to NGALCR, PCR or ACR. Conclusions In HIV positive patients, proteinuria was predominantly of tubular origin and microalbuminuria was common. RBPCR in patients without overt renal tubular disease was generally within the reference range, including those receiving TFV. RBP therefore appears a promising biomarker for monitoring renal tubular function in patients receiving TFV and for distinguishing patients with normal tubular function or mild tubular dysfunction from those with severe renal tubular disease or Fanconi syndrome.

BackgroundThe British Association of Sexual Health and HIV recommends testing for Mycoplasma genitalium (MG) in clinically indicated conditions (CIC) (non-gonococcal urethritis (NGU); epididymitis; pelvic inflammatory disease (PID); contacts of MG; test of cure (TOC)). MG testing was implemented in September 2018 in a large urban sexual health service. We aimed to assess the prevalence and antimicrobial resistance of MG in this clinic population after a 6-weeks embedding period.MethodsAll patients diagnosed with a CIC and tested for MG between 28/10/2018-18/12/2018 were included. MG testing was performed using Aptima Mycoplasma genitalium assay (AMG; Hologic); confirmatory testing and resistance testing for macrolides and fluoroquinolones was performed at the Public Health England reference laboratory.ResultsThe 371 individuals tested for MG were predominantly male (77%), heterosexual (78%) and Caucasian (46%) and 85% tested per guidance. 18% were positive for MG. 38% (25/65) were positive using AMG but had negative confirmatory test and no resistance results. 18% with MG were co-infected with another sexually transmitted infection (9 chlamydia; 2 gonorrhoea; 2 trichomonas). The prevalence of MG by testing indication was: contacts of MG (33%, 11/33), TOC (25%, 3/12), NGU/epididymitis (17%, 38/229), PID/cervicitis (11%, 5/44) and inappropriately tested (14%, 7/51). 38% of MG had resistance; 34% macrolides; 8% fluoroquinolones; 3% both. Macrolide resistance was identified on the 23SrRNA gene at loci A2058G (45%) and A209G (55%), all fluoroquinolone was on the parC gene.ConclusionWe report a high MG prevalence in this population with high rates of resistance, the majority of which is macrolide. We recommend resistance guided therapy in view of high macrolide and fluoroquinolone resistance. Positive RNA detection with negative DNA detection is concerning and may either represent very low bacterial loads, a biological false positive result of AMG or a false negative result of the confirmatory test.DisclosureNo significant relationships.

We report a case of cardiac injury in a 46-year-old man affected by COVID-19. The patient presented with shortness of breath and fever. ECG revealed sinus tachycardia with ventricular extrasystoles and T-wave inversion in anterior leads. Troponin T and N-terminal pro B-type natriuretic peptide were elevated. Transthoracic echocardiography showed severely reduced systolic function with an estimated left ventricle ejection fraction of 30%. A nasopharingeal swab was positive for SARS-CoV-2. On day 6, 11 days after onset of symptoms, the patient deteriorated clinically with new chest pain and type 1 respiratory failure. Treatment with colchicine 0.5 mg 8-hourly resulted in rapid clinical resolution. This case report highlights how cardiac injury can dominate the clinical picture in COVID-19 infection. The role of colchicine therapy should be further studied to determine its usefulness in reducing myocardial and possibly lung parenchymal inflammatory responses.

Vaccine hesitancy is a leading threat to public health, but little is known about the beliefs and mindsets that drive vaccine hesitancy, especially among people of Black ethnicities. This study aimed to understand vaccine related beliefs and their relationship with SARS-CoV-2 vaccine uptake in UK residents of Black ethnicities living with HIV. Adults of self-reported Black ethnicities with HIV were recruited at 12 clinics in England. Participants completed questionnaires in clinic, including an adapted version of the Beliefs about Medicines Questionnaire (BMQ) to assess Necessity and Concerns beliefs about the SARS-CoV-2 vaccine. SARS-CoV-2 vaccination status was ascertained through self-report and shared care records. A total of 863 participants were enrolled between June 2021 and October 2022, most of whom (92%) had received at least one dose of the SARS CoV-2 vaccine. After adjusting for age and region of birth, higher perceived need for the vaccine (OR = 2.39, 95% CI = 1.51–3.81), fewer concerns about the vaccine (OR = 0.16, 95% CI = 0.08–0.30), and weaker endorsement of COVID-19 Conspiracy Beliefs (OR = 0.31, 95% CI = 0.19–0.50) were associated with vaccination uptake. Being born outside sub-Saharan Africa was associated with reduced odds of being vaccinated. This study shows the importance of specific beliefs driving vaccine hesitancy and uptake. Further studies should explore the role of these beliefs and mindsets in influencing uptake of other vaccinations, and to work with key stakeholders to explore how to address vaccine hesitancy and improve vaccine uptake in these and other populations.

Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m²/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m²/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m²/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m²/year [95% CI, .1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided.

We conducted an observational cohort study of end-stage kidney disease (ESKD) in >7000 African and Caribbean people with HIV in the UK. Using Poisson regression and East Africans as the reference group, the adjusted incidence rate ratio (95% confidence interval) of ESKD was 3.14 (1.26-7.84) in Southern Africans, 6.35 (2.53-15.96) in West Africans, and 5.26 (1.91-14.43) in Caribbeans. Higher CD4 cell count and suppressed HIV replication were associated with reduced risk of ESKD. The risk of ESKD varied among HIV-positive people of African heritage, with the highest rates observed in those of West African descent.

Background. Human immunodeficiency virus (HIV)—associated nephropathy (HIVAN) is an important cause of end-stage renal disease among African American patients. This study was performed to study the epidemiology of HIVAN in a predominantly black African population and the impact of highly active antiretroviral therapy and other factors on the development of end-stage renal disease. Methods. We retrospectively identified all patients with HIVAN, defined by biopsy or strict clinical criteria, in 8 clinics in the United Kingdom. Baseline renal function, HIV parameters, renal pathological index of chronic damage, and responses to highly active antiretroviral therapy were analyzed, and factors associated with adverse renal outcome were identified. Results. From 1998 through 2004, we studied 16,834 patients, 61 of whom had HIVAN. HIVAN prevalence in black patients was 0.93%, and HIVAN incidence in those without renal disease at baseline was 0.61 per 1000 person-years. After a median of 4.2 years, 34 patients (56%) had developed end-stage renal disease. There were no significant differences in renal function and HIV parameters at baseline, time to initiation of highly active antiretroviral therapy, and rates of HIV RNA suppression between the 20 patients who developed end-stage renal disease >3 months after receiving the HIVAN diagnosis and the 23 patients who maintained stable renal function. However, the index of chronic damage score was significantly higher in those who developed end-stage renal disease (P<.001), and an index of chronic damage score >75 was associated with shorter renal survival (P<.001). Conclusions. Whereas overall patient survival suggested an important benefit of highly active antiretroviral therapy, no additional renal benefit of early initiation of highly active antiretroviral therapy or viral suppression could be demonstrated in this large cohort of patients with established HIVAN. Severity of chronic kidney damage, as quantified by biopsy, was the strongest predictor of renal outcome.

HIV infection is an independent risk factor for end-stage kidney disease in HIV-positive patients of black ethnicity. Highly effective antiretroviral therapy has allowed these patients to be considered for kidney transplantation (KT). We report the outcomes of KT in a national observational cohort study. We retrospectively identified HIV-positive patients who had undergone KT up to December, 2010, through all 25 UK KT centres and major HIV clinics, and included follow-up until December, 2011. Patient characteristics, treatments, and complications were described. Patient and graft survival rates and cumulative incidence of acute rejection were estimated with Kaplan-Meier and Nelson-Aalen analyses. 35 HIV-positive KT recipients (median age 40 years, 66% male, 74% black ethnicity) were identified. At the time of KT, all patients were stable on antiretroviral therapy with undetectable HIV RNA and median CD4 cell count of 366 cells per mL. Patient survival at both 1 and 3 years was 91·3%, and graft survival was 91·3% and 84·7%, respectively. In the first year after KT, blood concentrations of calcineurin inhibitors (CNI) were frequently outside the therapeutic reference range. At 1 year after KT, the cumulative incidence of acute allograft rejection was 48%, and the median estimated glomerular filtration rate 61 mL/min/1·73 m2 (IQR 46–78). Although HIV viraemia and HIV disease progression were uncommon, renal complications were relatively frequent. Our study corroborates the feasibility of KT in HIV-positive patients. Co-administration of antiretroviral therapy and CNI is challenging, and sub-therapeutic CNI concentrations may contribute to the high rate of acute allograft rejection. The optimum immune suppression strategy in this population remains to be refined. King's College London.

Background Retinoblastoma (Rb) is the most common childhood intraocular cancer, with heritable forms caused by pathogenic germline variants in the RB1 (or retinoblastoma 1) gene, which necessitate intensive and costly lifelong surveillance. Genetic testing enables precise risk prediction and individualized clinical management, yet data on the RB1 variant spectrum in African populations remains scarce. This study investigated the molecular landscape of clinically presumed heritable Rb in a Southern African cohort and evaluated the potential healthcare and economic benefits of implementing genetic testing. Methods Fifty-eight patients with clinically presumed heritable Rb were recruited from two tertiary hospitals in South Africa. Comprehensive RB1 gene analysis was performed using next-generation sequencing (NGS) to detect single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variants (CNVs), and was supplemented by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). A cost comparison model was developed to evaluate conventional clinical screening versus a genetically guided approach. Results RB1 pathogenic and/or likely pathogenic variants were identified in 84.5% (49/58) of patients, including eleven novel variants. The variant spectrum included frameshift, nonsense, splicing, intronic, and missense changes, with a notable concentration in the pocket domain region of the Rb associated protein (pRb). CNVs were detected in 10.3% of probands. Our cost analysis demonstrated significant savings associated with genetic testing, reducing surveillance-related expenses by up to US$228,989 across extended family generations in the private sector and US$166,489 in the public sector. Implementing genetic testing would also minimize unnecessary examinations and promote more efficient allocation of healthcare resources. Conclusions Comprehensive RB1 genetic testing in this Southern African cohort revealed a diverse variant landscape, including novel pathogenic changes, and demonstrated the clinical and economic value of integrating genetic testing into Rb management. These findings contribute to the global understanding of genetic variation within the RB1 gene and support tailored care strategies that can reduce the surveillance burden, optimize healthcare resources, and improve outcomes for affected families.

Objectives Age‐related vocal atrophy (ARVA) has a significant impact on voice, communication, and quality of life. Vocal folds are bowed with incomplete glottic closure during phonation. Efficient quantification of vocal fold atrophy and collection of voice recordings in clinic remains challenging. The primary focus of this study is to describe a novel method for quantifying vocal atrophy and obtaining voice recordings in clinic among patients with ARVA. Methods Patients with ARVA were included. Voice recordings were collected during the clinic visit, and acoustic analysis was subsequently performed. A novel mobile application was used to quantify the bowing index (BI). Results The study included 10 patients with ARVA, with a mean age of 72.7 ± 6.8 years and body mass index (BMI) of 24.9 ± 2.4 kg/m2. Calculation of BI was feasible with a mean of 9.9 ± 1.8 units. On average, the audio recording took 2.6 ± 0.4 min, and subsequent analysis required 7.1 ± 1.8 min. Mean continuous speech f0 was 212.1 ± 10.1 and 134.2 ± 31.5 Hz for male and female patients, respectively. Smoothed cepstral peak prominence was 8.9 ± 1.5 dB (male) and 8.5 ± 0.3 dB (female), and maximum phonation time between male and female patients was 16.7 ± 9.8 and 13.8 ± 1.9 s, respectively. Conclusion We present a feasible and streamlined method for quantification of vocal fold atrophy in the clinic among patients with ARVA. The accuracy and reliability of this new method are areas of ongoing investigation. Quantification of vocal atrophy may help with clinical decisions, including diagnosing vocal atrophy and tracking treatment progress. Moreover, this method may improve research data acquisition without burdening patients and clinicians with additional time‐consuming tasks. Level of evidence: 4. Quantification of age‐related vocal atrophy is difficult in clinic. This study presents a novel and practical method for quantifying endoscopic and acoustic data in patients with this condition.