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Objectives: The objective of the paper is to present the outcomes of the HepHIV 2019 conference, held in Bucharest under the Romanian EU Presidency and focusing on challenges of timely and integrated testing and care. Methods: The conference programme was put together by the organizing committee. It consisted of invited talks and peer‐reviewed abstracts. Results: In all, 65 abstracts from 20 countries were presented during the conference, which had nearly 250 delegates, including high‐profile political representation. The conference highlighted the need to shift towards further disease integration because of the epidemiological characteristics of the hepatitis B (HBV), hepatitis C (HCV), HIV, sexually transmitted infection (STIs) and tuberculosis (TB) epidemics in the WHO European region. Integration should be a priority in the response to the epidemics to better reach key populations and to ensure better testing coverage. This relates to both the integration of services in shared care models and the integration of different settings and stakeholders in national strategies. Conclusions: The conference demonstrated the need for greater political support for the policy changes required to implement integration. Testing normalization efforts are key to maximizing the impact of integration efforts. The conference call to action can help to guide developments in testing and linkage‐to‐care interventions across the European region. [ABSTRACT FROM AUTHOR]

Objectives: Despite the availability of HIV testing guidelines to facilitate prompt diagnosis, late HIV diagnosis remains high across Europe. The study synthesizes recent evidence on HIV testing strategies adopted in health care settings in the European Union/European Economic Area (EU/EEA). Methods: Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed and systematic searches were run in five databases (2010–2017) to identify studies describing HIV testing interventions in health care settings in the EU/EEA. The grey literature was searched for unpublished studies (2014–2017). Two reviewers independently performed study selection, data extraction and critical appraisal. Results: One hundred and thirty intervention and/or feasibility studies on HIV testing in health care settings were identified. Interventions included testing provision (n = 94), campaigns (n = 14) and education and training for staff and patients (n = 20). HIV test coverage achieved through testing provision varied: 2.9–94% in primary care compared to 3.9–66% in emergency departments. HIV test positivity was lower in emergency departments (0–1.3%) and antenatal services (0–0.05%) than in other hospital departments (e.g. inpatients: 0–5.3%). Indicator condition testing programmes increased HIV test coverage from 3.9–72% before to 12–85% after their implementation, with most studies reporting a 10–20% increase. There were 51 feasibility and/or acceptability studies that demonstrated that HIV testing interventions were generally acceptable to patients and providers in health care settings (e.g. general practitioner testing acceptable: 77–93%). Conclusions: This review has identified several strategies that could be adopted to achieve high HIV testing coverage across a variety of health care settings and populations in the EU/EEA. Very few studies compared the intervention under investigation to a baseline, but, where this was assessed, data suggested increases in testing. [ABSTRACT FROM AUTHOR]

Objectives: In recent years, new technologies and new approaches to scale up HIV testing have emerged. The objective of this paper was to synthesize the body of recent evidence on strategies aimed at increasing the uptake and coverage of HIV testing outside of health care settings in the European Union (EU)/European Economic Area (EEA). Methods: Systematic searches to identify studies describing effective HIV testing interventions and barriers to testing were run in five databases (2010–2017) with no language restrictions; the grey literature was searched for similar unpublished studies (2014–2017). Study selection, data extraction and critical appraisal were performed by two independent reviewers following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Results: Eighty studies on HIV testing in non‐health care settings were identified, the majority set in Northern Europe. Testing was implemented in 65 studies, with men who have sex with men the risk group most often targeted. Testing coverage and positivity/reactivity rates varied widely by setting and population group. However, testing in community and outreach settings was effective at reaching people who had never previously been tested and acceptability of HIV testing, particularly rapid testing, outside of health care settings was found to be high. Other interventions aimed to increase HIV testing identified were: campaigns (n = 8), communication technologies (n = 2), education (n = 3) and community networking (n = 1). Conclusions: This review has identified several strategies with potential to achieve high HIV testing coverage outside of health care settings. However, the geographical spread of studies was limited, and few intervention studies reported before and after data, making it difficult to evaluate the impact of interventions on test coverage. [ABSTRACT FROM AUTHOR]

Objectives: Since 2013, the London HIV Mortality Review Group has conducted annual reviews of deaths among people with HIV to reduce avoidable mortality. Methods: All London HIV care Trusts reported data on 2016 patient deaths in 2017. Deaths were submitted using a modified Causes of Death in HIV reporting form and categorized by a specialist HIV pathologist and two HIV clinicians. Results: There were 206 deaths reported; 77% were among men. Median age at death was 56 years. Cause was established for 82% of deaths, with non‐AIDS‐related malignancies and AIDS‐defining illnesses being the most common causes reported. Risk factors in the year before death included: tobacco smoking (37%), excessive alcohol consumption (19%), non‐injecting drug use (10%), injecting drug use (7%) and opioid substitution therapy (6%). Thirty‐nine per cent of patients had a history of depression, 33% chronic hypertension, 27% dyslipidaemia, 17% coinfection with hepatitis B virus and/or hepatitis C virus and 14% diabetes mellitus. At the time of death, 81% of patients were on antiretroviral therapy (ART), 61% had a CD4 count < 350 cells/μL, and 24% had a viral load ≥ 200 HIV‐1 RNA copies/mL. Thirty‐six per cent of deaths were unexpected; 61% of expected deaths were in hospital. Two‐thirds of expected deaths had a prior end‐of‐life care discussion documented. Conclusions: In 2016, most deaths were attributable to non‐AIDS‐related conditions and the majority of patients were on ART and virally suppressed. However, several potentially preventable deaths were identified and underlying risk factors were common. As London HIV patients are not representative of people with HIV in the UK, a national mortality review is warranted. [ABSTRACT FROM AUTHOR]

Objectives: People living with HIV (PLWH) have multidimensional concerns requiring person‐centred care. Routine use of patient‐reported outcome measures (PROMs) improves outcomes. No brief PROM currently reflects the breadth of concerns for PLWH. This study sought to identify priority outcomes for PLWH, model current practice, explore views on introducing PROMs into routine care, and devise a model for person‐centred care incorporating the PROM. Methods: A cross‐national multi‐centre study (London, Brighton and Dublin) was carried out. Semi‐structured qualitative interviews with adult PLWH, HIV health care professionals and HIV commissioners (responsible for planning and commissioning services) were performed. Interviews were analysed using thematic and framework analysis. Results: PLWH (n = 28), professionals (n = 21) and commissioners (n = 8) described concerns related to living with HIV across six domains: physical (e.g. pain and gastrointestinal symptoms), cognitive (e.g. memory and sleep), psychological (e.g. anxiety and depression), social (e.g. isolation and intimacy), welfare (e.g. finances and fears regarding change of immigration status), and information (e.g. long‐term outcomes) needs. Themes were highly inter‐related, impacting across domains of need (e.g. physical and cognitive problems impacting on psychological and social wellbeing). Perceived benefits of using PROMs in routine HIV care included improved person‐centredness, patient empowerment, fewer missed concerns, increased engagement with services, and informed planning of services. Potential challenges included heterogeneity of PLWH, literacy, and utility for those who struggle to engage with care. Conclusions: This study presents a novel model of person‐centred care incorporating an HIV‐specific PROM. The model reflects priorities of key stakeholders. Explicit use of PROMs in routine HIV care could afford benefits for PLWH, clinical teams and commissioners. [ABSTRACT FROM AUTHOR]

Objectives European guidelines recommend HIV testing for individuals presenting with indicator conditions ( ICs) including AIDS-defining conditions ( ADCs). The extent to which non- HIV specialty guidelines recommend HIV testing in ICs and ADCs is unknown. Our aim was to pilot a methodology in the UK to review specialty guidelines and ascertain if HIV was discussed and testing recommended. Methods UK and European HIV testing guidelines were reviewed to produce a list of 25 ADCs and 49 ICs. UK guidelines for these conditions were identified from searches of the websites of specialist societies, the National Institute of Clinical Excellence ( NICE) website, the NICE Clinical Knowledge Summaries ( CKS) website, the Scottish Intercollegiate Guidance Network ( SIGN) website and the British Medical Journal Best Practice database and from Google searches. Results We identified guidelines for 12 of 25 ADCs (48%) and 36 of 49 (73%) ICs. In total, 78 guidelines were reviewed (range 0-13 per condition). HIV testing was recommended in six of 17 ADC guidelines (35%) and 24 of 61 IC guidelines (39%). At least one guideline recommended HIV testing for six of 25 ADCs (24%) and 16 of 49 ICs (33%). There was no association between recommendation to test and publication year ( P = 0.62). Conclusions The majority of guidelines for ICs do not recommend testing. Clinicians managing ICs may be unaware of recommendations produced by HIV societies or the prevalence of undiagnosed HIV infection among these patients. We are piloting methods to engage with guideline development groups to ensure that patients diagnosed with ICs/ ADCs are tested for HIV. We then plan to apply our methodology in other European settings as part of the Optimising Testing and Linkage to Care for HIV across Europe (Opt TEST) project. [ABSTRACT FROM AUTHOR]

Objectives Routine HIV testing in nonspecialist settings has been shown to be acceptable to patients and staff in pilot studies. The question of how to embed routine HIV testing, and make it sustainable, remains to be answered. Methods We established a service of routine HIV testing in an emergency department ( ED) in London, delivered by ED staff as part of routine clinical care. All patients aged 16 to 65 years were offered an HIV test (latterly the upper age limit was removed). Meetings were held weekly and two outcome measures examined: test offer rate (coverage) and test uptake. Sustainability methodology (process mapping; plan-do-study-act ( PDSA) cycles) was applied to maximize these outcome measures. Results Over 30 months, 44 582 eligible patients attended the ED. The mean proportion offered an HIV test was 14%, varying from 6% to 54% per month over the testing period. The mean proportion accepting a test was 63% (range 33-100%). A total of 4327 HIV tests have been performed. Thirteen patients have been diagnosed with HIV infection (0.30%). PDSA cycles having the most positive and sustained effects on the outcome measures include the expansion to offer blood-based HIV tests in addition to the original oral fluid tests, and the engagement of ED nursing staff in the programme. Conclusions HIV testing can be delivered in the ED, but constant innovation and attention have been required to maintain it over 30 months. Patient uptake remains high, suggesting acceptability, but time will be required before true embedding in routine clinical practice is achieved. [ABSTRACT FROM AUTHOR]

Objectives UK guidelines recommend routine HIV testing in general clinical settings when the local HIV prevalence is > 0.2%. During pilot programmes evaluating the guidelines, we used laboratory-based testing of oral fluid from patients accepting tests. Samples ( n = 3721) were tested manually using the Bio- Rad Genscreen Ultra HIV Ag- Ab test ( Bio- Rad Laboratories Ltd, Hemel Hempstead, UK). This was a methodologically robust method, but handling of samples was labour intensive. We performed a validation study to ascertain whether automation of oral fluid HIV testing using the fourth-generation HIV test on the Abbott Architect ( Abbott Diagnostics, Maidenhead, UK) platform was possible. Methods Oral fluid was collected from 143 patients (56 known HIV-positive volunteers and 87 others having contemporaneous HIV serological tests) using the Oracol+ device ( Malvern Medicals, Worcester, UK). Samples were tested concurrently: manually using the Genscreen Ultra test and automatically on the Abbott Architect. Results For oral fluid, the level of agreement of results between the platforms was 100%. All results agreed with HIV serology. The use of the Oracol+ device produced high-quality samples. Subsequent field use of the test has shown a specificity of 99.97% after nearly 3000 tests. Conclusions Laboratory-based HIV testing of oral fluid requires less training of local staff, with fewer demands on clinical time and space than near-patient testing. It is acceptable to patients. The validation exercise and subsequent clinical experience support automation, with test performance preserved. Automation reduces laboratory workload and speeds up the release of results. Automated oral fluid testing is thus a viable option for large-scale HIV screening programmes. [ABSTRACT FROM AUTHOR]

Objectives The aim of the paper was to describe the association of religion with HIV outcomes in newly diagnosed Africans living in London. Methods A survey of newly diagnosed HIV-positive Africans attending 15 HIV treatment centres across London was carried out between April 2004 and February 2006. Confidential self-completed questionnaires were used, linked to clinical records. Bivariate analyses were conducted to ascertain whether religious beliefs were associated with late diagnosis, antiretroviral therapy, and immunological and virological outcome 6 months post diagnosis. Results A total of 246 Black Africans were eligible and included in the analysis: 62.6% were women, and the median age was 34 years. The median CD4 count at diagnosis was 194 cells/ μL (range 0-1334 cells/ μL) and 75.6% presented late, as defined as a CD4 count < 350 cells/ μL. Most participants were religious: non- Roman Catholic Christians (55.7%), Roman Catholics (35.2%) and Muslims (6.1%). Only 1.2% stated that they did not have a religion. Participants who attended religious services at least monthly were more likely to believe that 'faith alone can cure HIV' than those who attended less frequently (37.7% vs. 15.0%; P = 0.002). A small proportion (5.2%) believed that taking antiretroviral therapy implied a lack of faith in God. Bivariate analysis found no relationship between religiousness (as measured using frequency of attendance at religious services and religious attitudes or beliefs) and late diagnosis, changes in CD4 count/viral load 6 months post diagnosis, or initiation of antiretroviral therapy. Conclusions Strong religious beliefs about faith and healing are unlikely to act as a barrier to accessing HIV testing or antiretroviral treatment for Black Africans living in London. [ABSTRACT FROM AUTHOR]

Objective: To determine retrospectively whether patients seen by GPs and hospital doctors in South London with symptoms and signs compatible with acute HIV infection remain undiagnosed. Methods: All request cards sent to the virology laboratory at St Thomas's Hospital between 5/1998 and 5/1999 were reviewed. Patients with symptoms and signs compatible with acute HIV infection were entered into the study (314). Trust databases were cross-referenced and those with other diagnoses (28), recent HW tests (two) and insufficient serum for testing (16) were excluded. After anonymization, samples were pooled into batches of 10 and each pool HIV antibody tested (microparticle enzyme immunoassay (MEIA), Abbott Axsym system). Samples in HIV antibody pools were re-tested individually and Western blots performed on those testing antibody positive. HIV antibody negative serum was pooled into batches of 10 and each pool tested for HIV RNA using nucleic acid sequence based amplification (NASBA, Organon-Teknika). Results: 8/268 (3%) of patients were HIV antibody positive; 2/268 (0.8%) had Western blot profiles compatible with acute HIV infection. None of the HIV antibody negative serum samples tested NASBA positive. Conclusion: Patients with acure HIV infection, seen by GPs and hospital doctors, remain undiagnosed. This study emphasizes the need for more risk assessment and HIV testing if patients are to be diagnosed early and potentially benefit from better treatment available now and in the future. [ABSTRACT FROM AUTHOR]

Introduction: PI-associated lipodystrophy and dyslipidaemia have well documented. Some authors suggest a change to an NNRTIbased regimen to ameliorate or even reverse these events. Results: Three patients treated at our centre were switched from a PI-containing regimen to an EFV-containing regimen to manage lipodystrophy/dyslipidaemia but showed a significant worsening of their status. Patient 3 had gross stigmata of lipodystrophy: these reduced only slightly on changing to EFV. Mean change in maximum total cholesterol (chol) on EFV-containing regimen compared to PI-containing regimen was +4.03 mmol/1; mean change in triglycerides (TG) was 29.3 mmol/1. Time from change to EFV to maximum increase in lipids was approximately 12 weeks. Max chol Max IG Max chol Max TG on PI on PI on EFV on EFV Outcome Pt 1 10.2 13.3 19.5 53.00 Treatment with fenofibrate Pt 2 12.0 16.2 14.8 67.6 Switched to NVP+ fenofibrate; lipids return to baseline Pt 3 7.7 8.1 7.7 4.9 Death due to MI Conclusion: As the exact mechanism for ARV-induced lipodystrophy/dyslipidaemia is unknown, close monitoring of lipids and glucose is strongly advised in patients changing from PIs to EFVcontaining regimens. [ABSTRACT FROM AUTHOR]

Objective: To describe the lymphoproliferative responses (LPR) following therapy change from PI- to NNRTI-based HAART. Methods: Patients switching from PI- to NNRTI-based regimens were identitied. CD4 cell counts, viral loads (VL) and LPR to recall antigens, mitogens and HIV-1 recombinant antigens were performed at baseline (BL) and at 12 and 24 weeks (12W, 24W). Results: Six patients were identitied (five drug intolerance, one virological failure). CD4 count (cells/µL) Virai load (copies/mL) Patient BL 12W 24W BL 12W 24W 1 41 205 287 1116 BLD BLD 2 418 622 665 6794 753 394 3 243 214 267 55068 BLD BLD 4 503 449 373 BLD BLD BLD 5 256 190 306 BLD BLD BLD 6 185 269 283 BLD BLD BLD Following therapy switch, a 67% proportional increase in mitogen response (95% confidence interval (CI) 45-88%) and a 52% increase (CI 35-70%) in response to recall antigens was seen. The latter was more likely in patients with a detectable VL at BL. All patients were more likely to respond to low-dose IL-2 stimulation (83%, CI 54-100%). Three patients showed increased HIV-specific responses, two had detectable virus at BL. Condusion: NNRTI substitution for a PI appears to result in an improvement in LPR. [ABSTRACT FROM AUTHOR]

Objective: To describe the lymphoproliferative responses (LPR) following therapy change from PI- to NNRTI-based HAART. Methods: Patients switching from PI- to NNRTI-based regimens were identitied. CD4 cell counts, viral loads (VL) and LPR to recall antigens, mitogens and HIV-1 recombinant antigens were performed at baseline (BL) and at 12 and 24 weeks (12W, 24W). Results: Six patients were identitied (five drug intolerance, one virological failure). CD4 count (cells/µL) Virai load (copies/mL) Patient BL 12W 24W BL 12W 24W 1 41 205 287 1116 BLD BLD 2 418 622 665 6794 753 394 3 243 214 267 55068 BLD BLD 4 503 449 373 BLD BLD BLD 5 256 190 306 BLD BLD BLD 6 185 269 283 BLD BLD BLD Following therapy switch, a 67% proportional increase in mitogen response (95% confidence interval (CI) 45-88%) and a 52% increase (CI 35-70%) in response to recall antigens was seen. The latter was more likely in patients with a detectable VL at BL. All patients were more likely to respond to low-dose IL-2 stimulation (83%, CI 54-100%). Three patients showed increased HIV-specific responses, two had detectable virus at BL. Conclusion: NNRTI substitution for a PI appears to result in an improvement in LPR. [ABSTRACT FROM AUTHOR]

Objectives: To characterise the new patient referrals to a combined vulva clinic and to assess the role of genitourinary services within the clinic., Methods: A case note review of all new patients attending a monthly, multidisciplinary vulva clinic over a 12-month period., Results: The mean age of the 135 women was 43 years (range 18-86 years). The majority of patients, 64 (47%), were referred by their general practitioner (GP). Using nurse and physician triage 85 (63%) patients were seen by a dermatologist, 55 (41%) by a genitourinary medicine physician, 38 (28%) by a gynaecologist and six (4%) by a psychosexual physician. Fifty-one (38%) women required a consultation by at least two specialties. Itch was the most frequent presenting symptom (70%) and 59 (44%) women had experienced symptoms for between 6 months and 2 years. A previous STD screen had been performed in only 57 (42%), which was negative in 45 (79%). The most frequent initial clinical diagnoses were lichen sclerosus (35, 26%), vaginal candidiasis (21, 16%), vulvodynia (16, 12%), lichen simplex chronicus (13, 10%) and Bowenoid papulosis (13, 10%). Thirty-eight (28%) women had microbiological investigations revealing 13/135 (10%) had vaginal candidiasis and two (2%) bacterial vaginosis, all symptomatic. A biopsy was performed in 32 (24%) confirming the initial diagnosis in 20 (63%) cases. Treatment was initiated in 101 (75%) women: 62 (46%) were prescribed steroid cream, 46 (34%) emollient cream and 22 (16%) treatment for candida infection. Fifty-three (39%) women received more than one treatment. 94 (70%) patients were followed-up in the vulval clinic, five (4%) in the genitourinary clinic and 12 (9%) by their GP., Conclusions: Despite having genitourinary symptoms less than half the patients had been tested for infection prior to attending the clinic. More than a third of the patients, 46 (34%), were diagnosed with a genitourinary infection. There is a significant role for genitourinary services in the diagnosis, management and ongoing care of patients in a vulva clinic.

An acquired IgG inhibitor to factor XIII was identified in a 30-year-old Vietnamese woman with systemic lupus erythematosus. The IgG fraction was isolated from plasma by chromatography on an agarose gel column and by protein G adsorption. The anti-factor XIII activity, identified within the IgG fraction, inhibited factor XIII from both normal plasma (a2b2) and platelets (a2). A normal level of the b subunit was measured by immunoelectrophoresis of the patient's plasma, but the a subunit was not detected. These results suggested the presence of an IgG immunoglobulin which recognized the a subunit and interfered with its activity.

The majority of cells of the human leukaemic line HL60 appear to be promyelocytes which can be stimulated to mature into functioning neutrophils. We report here the derivation of stable subclones from the parent line which differ. Two forms of variant were obtained: (1) those with a defined lesion, selected by resistance to kill by 6-thioguanine, which matured in the presence of DMSO and retinoic acid but not in hypoxanthine. They also continued to express peroxidase and a major granulocyte antigen, and (2) those obtained by clonal growth in DMSO which did not mature in the presence of any compound tested including hypoxanthine, DMSO, retinoic acid and actinomycin D and lacked granules, peroxidase and the granulocyte antigen. The concurrent loss of the characteristic of maturability and the phenotype of myeloid commitment suggests that the control of the two phenomena may be related. These variant cell lines provide a useful model in which to study how human leukaemic cells may become arrested in less differentiated stages of development.