Clinical and neuroimaging correlates of cognition in HIV.

This study investigated whether HIV-positive participants, stable on combined antiretroviral therapy (cART), showed cognitive impairments relative to HIV-negative controls; and whether clinical and neuroimaging factors correlated with cognitive function in the HIV-positive participants. One hundred and twenty-six white men who have sex with men, of whom 78 were HIV-positive and stable on cART and 48 were HIV negative, were recruited to this cross-sectional study. The median age of HIV-positive participants in this study was 47. They underwent clinical and neuropsychological evaluation and magnetic resonance imaging of the brain, including diffusion tensor imaging (DTI). Cognitive scores for both groups were compared, and regression models were run to explore the influence of clinical, psychiatric, lifestyle, and neuroimaging variables on cognition. The prevalence of neurocognitive impairment, using the multivariate normative comparison criteria, was 28% in HIV-positive participants and 5% in HIV-negative participants. After covarying for age, years of education, and non-English speaking background, there were significant differences between the HIV group and the controls across four cognitive domains. The HIV group showed significantly higher mean diffusivity (MD) and lower fractional anisotropy (FA) than the control group on DTI. Although anxiety levels were clinically low, anxiety and DTI measures were the only variables to show significant correlations with cognitive function. In the HIV group, poorer cognitive performance was associated with higher MD and lower FA on DTI and higher (albeit clinically mild) levels of anxiety. Our findings suggest that white matter changes and subtle anxiety levels contribute independently to cognitive impairment in HIV.

United Kingdom British association for sexual health and HIV national guideline for the management of epididymo-orchitis, 2020.

The British Association for Sexual Health and HIV (BASHH) UK guideline for the management of epididymo-orchitis has been updated in 2020. It offers advice on diagnostic tests, treatment and health promotion principles in the effective management of epididymo-orchitis. Empirical treatment should be started in patients with objective swelling and tenderness on testicular examination. First-line empirical treatment for sexually acquired epididymo-orchitis has changed to ceftriaxone 1g intramuscularly and doxycycline. Higher dose of ceftriaxone in line with the BASHH 2018 gonorrhoea guideline ensures effective treatment of strains with reduced susceptibility. Ofloxacin or doxycycline is recommended in patients with epididymo-orchitis probably due to non-gonococcal organisms (e.g. negative microscopy for gram-negative intracellular diplococci or no risk factors for gonorrhoea identified). Where Mycoplasma genitalium is tested and identified, treatment should include an appropriate antibiotic (e.g. moxifloxacin). If enteric pathogens are a likely cause (e.g. older patient, not sexually active, recent instrumentation, men who practice insertive anal intercourse, men with known abnormalities of the urinary tract or a positive urine dipstick for leucocytes and nitrites), ofloxacin and levofloxacin are recommended. A clinical care pathway has been produced to simplify the management of epididymo-orchitis. A patient information leaflet has been developed.

Homelessness among an inpatient HIV-positive cohort at a tertiary care hospital in central London.

A cohort review was conducted at a central London tertiary care hospital trust on the prevalence of homelessness among human immunodeficiency virus (HIV)-positive inpatients over a year. Data were collected on the duration of inpatient stay, co-morbidities including acquired immune deficiency syndrome (AIDS)-defining illnesses, co-infections, initiation of antiretroviral therapy, CD4 cell count, HIV viral load and substance misuse. Homeless people were found to be at high risk for hepatitis C, mental health illness, substance misuse including injecting drug use, recurrent bacterial infections, AIDS-associated illnesses, lower CD4 cell counts and HIV viremia. They also had more missed HIV outpatient appointments. It was highlighted that a multidisciplinary approach in their care was necessary to address their needs and reduce the morbidity burden in this cohort.

Higher specialty training in genitourinary medicine: A curriculum competencies-based approach.

Specialty trainees in genitourinary medicine (GUM) are required to attain competencies described in the GUM higher specialty training curriculum by the end of their training, but learning opportunities available may conflict with service delivery needs. In response to poor feedback on trainee satisfaction surveys, a four-year modular training programme was developed to achieve a curriculum competencies-based approach to training. We evaluated the clinical opportunities of the new programme to determine: (1) Whether opportunity cost of training to service delivery is justifiable; (2) Which competencies are inadequately addressed by direct clinical opportunities alone and (3) Trainee satisfaction. Local faculty and trainees assessed the 'usefulness' of the new modular programme to meet each curriculum competence. The annual General Medical Council (GMC) national training survey assessed trainee satisfaction. The clinical opportunities provided by the modular training programme were sufficiently useful for attaining many competencies. Trainee satisfaction as captured by the GMC survey improved from two reds pre- to nine greens post-intervention on a background of rising clinical activity in the department. The curriculum competencies-based approach to training offers an objective way to balance training with service provision and led to an improvement in GMC survey satisfaction.

Impact of rectal gonorrhoea and chlamydia on HIV viral load in the rectum: potential significance for onward transmission.

The aim of this study was to investigate the effect of asymptomatic rectal bacterial sexually transmitted infections (STIs) on rectal HIV viral load (VL). A prospective cohort study of HIV-positive men who have sex with men attending a tertiary centre in London, UK, for their routine HIV care was performed. Forty-two HIV-positive men who have sex with men were recruited between January and August 2014. In participants on antiretroviral therapy (ART), there was no significant difference in rectal VL in those with and without STI ( p = 0.4). All rectal HIV VLs were below the limit of detection (<100 copies/µg of total RNA) whether an STI was present or not. In those not on ART, rectal HIV VL was on average 0.6log10 lower post STI treatment. The presence of asymptomatic rectal chlamydia and gonorrhoea was not associated with increased rectal HIV VL in those fully suppressed on ART. In the context of effective ART, the presence of rectal gonorrhoea or chlamydia does not appear to increase rectal HIV VL and the risk of increased viral infectivity.

Short Communication: Lack of Effect of Maraviroc Intensification on Blood and Gut Reservoir.

We show that intensification of treatment with maraviroc in patients chronically infected with HIV-1 receiving successful long-term antiretroviral therapy was not associated with improvements in HIV-related morbidity, HIV reservoir, microbial translocation, immune activation, or immune exhaustion in either gut or peripheral blood. The measurement of reservoir in both gut and blood longitudinally contributes to a paucity of data in the area.

Pre-exposure Prophylaxis for HIV Prevention: Why, What, Who and How.

Pre-exposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. It is protective against HIV infection across populations and has few significant safety risks and little evidence of behavioural risk compensation. This article summarises the evidence behind HIV PrEP as an intervention, populations that may benefit, current guidelines and programmes, and the cost-effectiveness modelling of this strategy.

Uveitis secondary to leishmaniasis immune reconstitution syndrome in a HIV-positive patient.

We describe the case of a HIV-positive patient treated for visceral leishmaniasis who developed uveitis as part of a leishmaniasis immune reconstitution syndrome. Visceral leishmaniasis is increasingly found in HIV-positive adults. Its ophthalmic manifestations can range from relatively minor to complicated anterior uveitis, leading to secondary glaucoma and loss of vision. Clinicians caring for people living with HIV should be alert to the complications of leishmaniasis that can occur before and during treatment.

Tenofovir Disoproxil Fumarate Fails to Prevent HIV Acquisition or the Establishment of a Viral Reservoir: Two Case Reports.

The use of antiretrovirals as pre-exposure prophylaxis (PrEP) is highly efficacious in HIV prevention. The World Health Organization recently recommended Truvada(®) (Gilead Sciences, Inc.) or tenofovir disoproxil fumarate (TDF) for high-risk individuals, with limited data for single-agent TDF PrEP in men who have sex with men (MSM). We report two cases of TDF PrEP failure in MSM who had received long-term TDF for hepatitis B infection and had therapeutic levels of drug immediately after HIV acquisition. Rapid antiretroviral intensification at diagnosis of acute HIV infection failed to limit immune dysfunction or prevent the establishment of a viral reservoir.

We all need to know about HIV cure research: a case report.

A cure for HIV is not near, yet publicity surrounding the possibility of cure is high. We present the case of an individual with acute HIV who delayed antiretroviral therapy due to misinformed expectations of availability of cure treatments. Researchers and the media need to be mindful of prematurely raising hope of a cure.

Cervical screening in HIV-positive women in the East of England: recent CD4 as the predictive risk factor.

This study examines the relationship between CD4 count and cervical cytological abnormality in HIV-positive women attending two district general hospital genitourinary medicine clinics in the East of England. It aims to determine whether the rate of cervical cytological abnormalities differs in HIV-positive women with CD4 count >350 cells/µl and those with CD4 count ≤350 cells/µl; and to compare the rates of abnormalities with that of the general population. We retrospectively reviewed data from a cross-sectional audit undertaken between December 2010 and December 2011 and analysed them using multivariable statistics. There was a significant association between recent CD4 count ≤350 cells/µl and cervical cytological abnormality (p < 0.001). A total of 6.3% of women with recent CD4 counts >350 cells/µl had abnormal cervical smear results, compared with 6.6% of the general population in the screening period 2010-11 and 7.2% of the general population in the screening period 2009-10. In our study population of women with recent CD4 counts >350 cells/µl, the proportions of mild, moderate and severe dysplasia were also similar to national figures. This raises important questions about the cost effectiveness of blanket annual screening for HIV-positive women.

Failure of daily tenofovir to prevent HIV transmission or the establishment of a significant viral reservoir despite continued antiretroviral therapy.

INTRODUCTION: Truvada is licenced for HIV-1 prevention in the USA and is available in the private sector. Tenofovir performed as well as Truvada in the PARTNERS PrEP study and is used as HIV pre-exposure prophylaxis (PreP) in some settings. The clinical efficacy of Tenofovir for PrEP outside a clinical trial is unknown. Antiretroviral therapy (ART) at acute HIV-1 infection (AHI) limits the size of the reservoir, optimizing the chance of maintaining viral control off therapy. As such ART at acute HIV infection is proposed to offer a functional cure in a minority of subjects. We present two cases where Tenofovir PrEP failed to prevent HIV acquisition and failed to limit viral reservoir. MATERIALS AND METHODS: Two individuals receiving tenofovir monotherapy for Hepatitis B monoinfection were diagnosed with AHI as defined by a negative HIV antibody test within three months of a positive HIV test following unsafe sex with casual male partners. In-depth histories were taken. Viral genotypes and Tenofovir drug levels were measured from samples taken as close to HIV seroconversion as possible and subsequent samples were analyzed for proviral Total HIV-1 DNA by qPCR. RESULTS: Patient A had received tenofovir for the preceding six years and always maintained an undetectable Hepatitis B viral load with no concerns about adherence. Two weeks preceding the positive HIV antibody test, he experienced mild symptoms (fever, pharyngitis) of HIV seroconversion. HIV status was confirmed by a repeat fourth generation HIV antibody test and by Western Blot and an HIV viral load was undetectable. Tenofovir trough level at HIV diagnosis was within normal limits. The regimen was intensified to Eviplera and a total HIV-1 DNA was 1381 copies/million CD4 T cells. Patient B received four regimens for hepatitis B treatment before starting tenofovir monotherapy in 2011 and subsequently maintained an undetectable hepatitis B viral load. After three years of tenofovir monotherapy he developed a severe symptomatic seroconversion illness and tested HIV antibody positive. The baseline HIV viral load was 103,306 copies/mL. The regimen was intensified and total HIV-1 DNA was 2746 copies/million CD4 T cells. CONCLUSIONS: Further investigation into the efficacy of tenofovir for PrEP outside a clinical trial is required. ART at AHI does not always lead to a low viral reservoir. To explore the possibility of replication incompetent virus, viral outgrowth assays are underway.

Endovascular stent-associated infection with Staphylococcus lugdunensis.

An elderly woman presented febrile 5 days after stenting of multiple coronary arteries. Echocardiography showed a thickening of the aortic root, raising the possibility of stent infection. Four  of four blood culture bottles grew Staphylococcus lugdunensis and repeat echo showed an aortic root abscess. Despite appropriate antibiotic treatment, the patient died. A 24-year-old man with a ventricular septal defect presented febrile 4 weeks after stenting of an aortic coarctation. Initial transoesophageal echo found no vegetations around the stent or elsewhere. Four of six blood culture bottles grew S lugdunensis. Following an episode of hypoxia, the imaging was repeated and a new large vegetation was seen on the pulmonary valve with two thin-walled cavities in the lungs on a CT pulmonary angiogram. The patient was treated with a long course of appropriate antibiotic therapy and discharged from hospital 6 weeks later.