Behaviour changes following HIV diagnosis among men who have sex with men in the era of treatment as prevention: data from a prospective study.

We described the longitudinal changes in sexual behaviour and associated factors among newly diagnosed with HIV men who have sex with men participating in a prospective observational study from a London HIV clinic (2015-2018). Participants self-completed questionnaires at baseline, months 3 and 12. Information collected included socio-demographic, sexual behaviour, health, lifestyle and social support. Trends in sexual behaviours over one year following diagnosis and associated factors were assessed using generalized estimating equations with logit link. Condomless sex (CLS) dropped from 62.2% at baseline to 47.6% at month-three but increased again to 61.8% at month-12 (p-trend = 0.790). Serodiscordant-CLS increased between month-three and month-12 (from 13.1% to 35.6%, p-trend < 0.001). The prevalence of serodiscordant-CLS with high risk of transmitting to their partners at month-three was 10.7%. CLS was higher among men who reported recreational drug use (adjusted Odds Ratio (aOR) 3.03, 95%CI 1.47-6.24, p = 0.003), those with undetectable viral load (aOR 2.17, 95%CI 1.22-3.84, p = 0.008) and those who agreed with a statement "condoms are not necessary when HIV viral load is undetectable" (aOR 3.41, 95%CI 1.58-7.38, p = 0.002). MSM continued to engage in CLS after HIV diagnosis, which coincided with U = U publications and increased throughout the study.

Evaluating the long-term impact of an antimicrobial stewardship programme in a Central London mixed medical and surgical intensive care unit.

Background: Antimicrobial overuse causes increased antimicrobial resistance in ICUs; antimicrobial stewardship programmes (ASPs) aim to optimize usage. Following an MDR Acinetobacter baumannii (MRAb) outbreak in 2008, an ASP was implemented at a London ICU, and then continued as a long-term programme. This study aimed to determine long-term changes in antimicrobial prescribing 9 years on. Methods: Data were collected from ICU patients in 2008 immediately before ASP implementation, and thereafter for 6 month cohort periods in 2010-2011, 2012 and 2017. Antimicrobial usage in DDD per 1000 occupied bed days (OBD) were compared. Multivariate linear regression models for antimicrobial days were fitted, adjusting for APACHE II score and patient days. Antimicrobial resistance in Pseudomonas aeruginosa (as an indicator organism) was compared across cohort periods. Findings: Across 400 patients over 9 years, antimicrobial use changed significantly (P < 0.011) and remained lower in all post-ASP cohorts compared with pre-ASP [(2008; 1827 DDD/1000 OBD), (2010; 1264 DDD/1000 OBD), (2012; 1270 DDD/1000 OBD) and (2017; 1566 DDD/1000 OBD)]. There was reduction in usage of all antimicrobial classes except ß-lactams (where there was no significant increase nor decrease, P = 0.178) and aminoglycosides (where there was a significant increase in usage, P < 0.0001). The latter was temporally associated with restrictions on specific carbapenems. There was an increase in carbapenem-resistant P. aeruginosa in 2012 only (P = 0.028) but not subsequently. Conclusions: Following ASP implementation after an outbreak of MRAb, reduced antimicrobial prescribing was maintained 9 years on. We identify several factors influencing successful long-term maintenance of ASPs in ICUs.

Efficiency of the EmERGE Pathway of Care in Five European HIV Centres.

OBJECTIVE: We aimed to calculate the efficiency of the EmERGE Pathway of Care in five European HIV clinics, developed and implemented for medically stable people living with HIV. METHODS: Participants were followed up for 1 year before and after implementation of EmERGE, between April 2016 and October 2019. Micro-costing studies were performed in the outpatient services of the clinics. Unit costs for outpatient services were calculated in national currencies and converted to US$ 2018 OECD purchasing parity prices to enable between clinic comparisons in terms of outcomes and costs. Unit costs were linked to the mean use of services for medically stable people living with HIV,  before and after implementation of EmERGE. Primary outcome measures were CD4 count and viral load; secondary outcomes were patient activation (PAM13) and quality of life (PROQOL-HIV). Out-of-pocket expenditure data were collected. RESULTS: There were 2251 participants: 87-93% were male, mean age at entry was 41-47 years. Medically stable people living with HIV had outpatient visits in four sites which decreased by 9-31% and costs by 5-33%; visits and costs increased by 8% in one site, which had to revert back to face-to-face visits. Antiretroviral drugs comprised 83-91% of annual costs: the Portuguese site had the highest antiretroviral drug costs in US$ purchasing parity prices. Primary and secondary outcome measures of participants did not change during the study. CONCLUSIONS: EmERGE is acceptable and provided cost savings in different socio-economic settings. Antiretroviral drug costs remain the main cost drivers in medically stable people living with HIV. While antiretroviral drug prices in local currencies did not differ that much between countries, conversion to US$ purchasing parity prices revealed antiretroviral drugs were more expensive in the least wealthy countries. This needs to be taken into consideration when countries negotiate drug prices with pharmaceutical vendors. Greater efficiencies can be anticipated by extending the use of the EmERGE Pathway to people with complex HIV infection or other chronic diseases. Extending such use should be systematically monitored, implementation should be evaluated and funding should be provided to monitor and evaluate future changes in service provision.

Reflections on a specialist HIV menopause service: Experiences of managing menopause in women living with HIV: Experiences of managing menopause in women living with HIV.

OBJECTIVES: We describe here characteristics and clinical outcomes of women living with HIV attending an HIV menopause service. METHODS: This was a retrospective case note review of women attending the monthly HIV menopause clinic from January 2015 to July 2018. RESULTS: In all, 55 women attended the service. The overall mean age was 49 years; 50% were black and 20% had a previous AIDS-defining condition. All were on antiretroviral therapy (ART); the median CD4 count was 678 cells/µL; 93% had a viral load < 50 copies/mL; 7% had previous hepatitis C infection; 27% had a history of smoking; 45% had risk factors or existing cardiovascular disease; 24% had a mental health condition. The median duration of symptoms before clinic attendance was 18 months. Vasomotor symptoms (84%), menstrual cycle changes (62%), psychological (56%) and urogenital symptoms (29%) were reported. Twenty-two per cent had early menopause or premature ovarian insufficiency. The mean age at attendance of women diagnosed with menopause (n = 24) was 52 years. However, their average duration of symptoms prior to review was 28 months. A total of 61% had osteopenia/osteoporosis, 73% received menopausal hormone therapy (MHT), and 73% had symptomatic improvement, although 58% of these required higher doses of MHT. Median time on MHT was 10 months. Five patients had their ART modified. No serious MHT adverse effects were observed. CONCLUSIONS: Menopausal hormone therapy uptake was high, with most women observing an improvement in symptoms. Comorbidities were common, highlighting the need for integrated care based on a woman's needs. The long delay from initial symptoms to treatment demonstrates the need for better access to specialist advice for women experiencing menopause.

Short Communication: Predictive Value of HIV-Related Versus Traditional Risk Factors for Coronary Atherosclerosis in People Aging with HIV.

Cardiovascular disease (CVD) is an important cause of morbidity in people living with HIV (PLWH). We compared the predictive value of HIV-related and traditional CVD risk factors to assess which factors best predict the presence of subclinical coronary atherosclerosis in PLWH. This is a cross-sectional study in PLWH over 50 years of age who performed computed tomography coronary artery calcium (CAC) scoring between 2009 and 2019 at Chelsea and Westminster Hospital. The following outcomes were analyzed: CAC = 0 (no calcification), CAC >0 (any calcification), CAC >100 (moderate calcification), and CAC >400 (severe calcification). Univariate and multivariate logistic regression analyses were performed to assess predictors of coronary calcification. A total of 744 patients were included (mean age 56 ± 5.7 years, 94.8% male, 84% white). A CAC >0 was found in 392 (52.7%), CAC >100 in 90 (12.1%), and CAC >400 in 42 (5.6%) subjects. CAC >100 was strongly associated with hypertension [odds ratio, OR: 2.91, (95% confidence interval: 1.93-4.36), p < .001], dyslipidemia [2.71 (1.81-4.06), p < .001], and diabetes [2.53 (1.29-4.96), p = .01]. Regarding HIV-specific factors, a significant association was found with exposure (>6 years) to protease inhibitors [1.67 (1.06-2.61), p = .05], whereas exposure to tenofovir (>8 years) was negatively associated with CAC >100 [0.54 (0.30-0.98), p = .05]. Despite the high prevalence of hypertension (45.4%) only 21.5% were on antihypertensives, whereas only 29.2% of eligible candidates were receiving lipid-lowering drugs for primary prevention of CVD. Traditional cardiometabolic risk factors remain the strongest predictors of coronary atherosclerosis in PLWH as in the general population. These results underscore the importance of optimizing treatment of hypertension and promoting primary prevention strategies that may be underused in PLWH.

FRAX assessment in people ageing with HIV.

OBJECTIVES: Current British HIV Association (BHIVA) guidelines recommend the use of FRAX for the routine assessment of bone fracture risk in people living with HIV over 50 years of age every 3 years. Bone mineral density measurement with dual-energy X-ray absorptiometry (DXA) scan is recommended for those with increased fracture risk (FRAX major > 10%). Our objectives were to estimate the prevalence of and risk factors for osteoporosis in a population of PLWH aged > 50 years and assess the utility of FRAX in predicting the presence of DXA-proven osteoporosis in this cohort. METHODS: This was a cross-sectional study of a cohort of PLWH aged > 50 years attending the Chelsea and Westminster Hospital and who had a DXA scan between January 2009 and December 2018. FRAX scores were calculated using the Sheffield algorithm. Multiple regression models and Cohen's kappa values were used to assess risk factors for osteoporosis and agreement between FRAX and DXA scan results, respectively. RESULTS: In all, 744 patients were included (92.9% male, mean age 56 ± 5 years). The prevalence rates of osteoporosis (at DXA scans) and osteopenia were 12.2% and 63.7%, respectively. FRAX major was > 10% in only two patients, while 90/91 (98.9%) patients with osteoporosis had a normal FRAX score. The presence of osteoporosis was significantly associated with low body mass index and estimated glomerular filtration rate (p < 0.05). CONCLUSION: Our results indicate that FRAX scores did not predict the presence of osteoporosis in our population of PLWH over 50 years of age and therefore FRAX scores may not be the appropriate tool to define eligibility to perform DXA scans in PLWH.

Impact of inhalation injury on outcomes in critically ill burns patients: 12-year experience at a regional burns centre.

INTRODUCTION: Burns inhalation injury increases the attributable mortality of burns related trauma. However, diagnostic uncertainties around bronchoscopically graded severity, and its effect on outcomes, remain. This study evaluated the impact of different bronchoscopic burns inhalation injury grades on outcomes. METHODS: A single-centre cohort study of all patients admitted to the London Burns centre intensive care unit (BICU) over 12 years. Demographic data, burn and burns inhalation injury characteristics, and ICU-related parameters were collected retrospectively. The primary outcome was mortality. Secondary outcomes were hospital and ICU lengths of stay. The impact of pneumonia was determined. Univariate and multivariable Cox's proportional hazards regression analyses informed factors predicting mortality. RESULTS: Burns inhalation injury was diagnosed in 84 of 231 (36%) critically ill burns patients; 20 mild (grade 1), 41 severe (grades 2/3) and 23 unclassified bronchoscopically. Median (IQR) total body surface area burned (TBSA) was 20% (10-40). Mortality was significantly higher in patients with burns inhalation injury vs those without burns inhalation injury (38/84 [45%] vs 35/147 [24%], p < 0.001). Patients with pneumonia had a higher mortality than those without (34/125 [27%] vs 8/71 [11%], p = 0.009). In multivariable analysis, severe burns inhalation injury significantly increased mortality (adjusted HR=2.14, 95%CI: 1.12-4.09, p = 0.022), compared with mild injury (adjusted HR=0.58, 95% CI: 0.18-1.86, p = 0.363). Facial burns (adjusted HR=3.13, 95%CI: 1.69-5.79, p < 0.001), higher TBSA (adjusted HR=1.05, 95%CI: 1.04-1.06, p < 0.001) and older age (adjusted HR=1.04, 95%CI: 1.02-1.07, p < 0.001) also independently predicted mortality, though pneumonia did not. CONCLUSIONS: Severe burns inhalation injury is a significant risk factor for mortality in critically ill burns patients. However, pneumonia did not increase mortality from burns inhalation injury. This work confirms prior implications of bronchoscopically graded burns inhalation injury. Further study is suggested, through registries, into the diagnostic accuracy and reliability of bronchoscopy in burns related lung injury.

Demographics and incidence of anal squamous cell carcinoma in people living in high HIV prevalence geographical areas.

OBJECTIVES: Anal squamous cell carcinoma (ASCC) is an uncommon cancer that is rapidly increasing in incidence. HIV is a risk factor in the development of ASCC, and it is thought that the rapidly increasing incidence in men is related to increasing numbers of people living with HIV (PLWH). We undertook a population-based study comparing the demographics and incidence of ASCC in patients residing high HIV prevalence areas in England to patients living in average HIV prevalence areas in England. METHODS: This is a cross-sectional study following the 'Strengthening the Reporting of Observational Studies in Epidemiology' statement. Demographic data and incidence rates of ASCC within Clinical Commissioning Groups (CCGs) between 2013 and 2018 were extracted from the Cancer Outcomes and Services Dataset. CCGs were then stratified by HIV prevalence from data given by Public Health England, and high HIV prevalence geographical areas were compared with average HIV geographical areas. RESULTS: Patients in high HIV areas were more likely to be young and male with higher levels of social deprivation. Incidence rates in men between 2013 and 2017 were higher in high HIV areas than average HIV areas with a rapidly increasing incidence rates in early-stage disease and a 79.1% reduction in incidence of metastatic stage 4 disease.Whereas women in high HIV areas had lower ASCC incidence than the national average and a low incidence of early-stage disease; however, metastatic disease in women had quintupled in incidence in high HIV areas since 2013. CONCLUSIONS: Patients presenting with ASCC in high HIV geographical areas have different demographics to patients presenting in average HIV geographical areas. This may be related to screening programmes for PLWH in high HIV areas.

The efficiency of the EmERGE platform for medically stable people living with HIV in Portugal.

Background: The aim of this study was to calculate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV in the Hospital Capuchos, Centro Hospitalar Universitário de Lisboa Central (HC-CHLC). The app enables individuals to receive HIV treatment information and communicate with caregivers. Methods: This before-and-after study collected the use of services data 1 year before implementation and after implementation of EmERGE from November 1, 2016, to October 30, 2019. Departmental unit costs were calculated and linked to mean use of outpatient services per patient-year (MPPY). Annual costs per patient-year were combined with primary (CD4 count; viral load) and secondary outcomes (PAM-13; PROQOL-HIV). Results: Five hundred eighty-six EmERGE participants used HIV outpatient services. Annual outpatient visits decreased by 35% from 3.1 MPPY (95% confidence interval [CI]: 3.0-3.3) to 2.0 (95% CI: 1.9-2.1) as did annual costs per patient-year from €301 (95% CI: €288-€316) to €193 (95% CI: €182-€204). Laboratory tests and costs increased by 2%, and radiology investigations decreased by 40% as did costs. Overall annual cost for HIV outpatient services decreased by 5% from €2093 (95% CI: €2071-€2112) to €1984 (95% CI: €1968-€2001); annual outpatient costs decreased from €12,069 (95% CI: €12,047-€12,088) to €11,960 (95% CI: €11,944-€11,977), with 83% of annual cost because of antiretroviral therapy (ART). Primary and secondary outcome measures did not differ substantially between periods. Conclusions: The EmERGE Pathway produced cost savings after implementation-extended to all people living with HIV additional savings are likely to be produced, which can be used to address other needs. Antiretroviral drugs (ARVs) were the main cost drivers and more expensive in Portugal compared with ARV costs in the other EmERGE sites.

Lactate dehydrogenase activity staining demonstrates time-dependent immune cell infiltration in human ex-vivo burn-injured skin.

Burn injuries constitute one of the most serious accidental injuries. Increased metabolic rate is a hallmark feature of burn injury. Visualising lactate dehydrogenase (LDH) activity has been previously used to identify metabolic activity differences, hence cell viability and burn depth in burn skin. LDH activity was visualised in injured and uninjured skin from 38 sub-acute burn patients. LDH activity aided the identification of spatially correlating immunocompetent cells in a sub-group of six patients. Desorption Electrospray Ionisation Mass Spectrometry Imaging (DESI MSI) was used to describe relative lactate and pyruvate abundance in burned and uninjured tissue. LDH activity was significantly increased in the middle and deep regions of burnt skin compared with superficial areas in burnt skin and uninjured tissue and positively correlated with post-burn time. Regions of increased LDH activity showed high pyruvate and low lactate abundance when examined with DESI-MSI. Areas of increased LDH activity exhibited cellular infiltration, including CD3 + and CD4 + T-lymphocytes and CD68 + macrophages. Our data demonstrate a steady increase in functional LDH activity in sub-acute burn wounds linked to cellular infiltration. The cell types associated are related to tissue restructuring and inflammation. This region in burn wounds is likely the focus of dysregulated inflammation and hypermetabolism.

The Role of Demographics, Social Deprivation and Ethnicity on Anal Squamous Cell Carcinoma Incidence in England.

Anal Squamous Cell Carcinoma (ASCC) is an HPV-related malignancy with increasing incidence in high-income economies. Although ethnicity and social deprivation are known to be risk factors in other malignancies, little is known about socioeconomic status and risk of ASCC. This is a cross-sectional study following the STROBE Statement. Demographic data from the English Clinical Outcomes and Services Dataset (COSD) were extracted for all patients diagnosed with ASCC in England between 2013 and 2018. Outcomes included ethnicity, social deprivation, staging and treatment. This study included 5457 patients. Incidence increased by 23.4% in 5 years, with female incidence increasing more rapidly than male incidence (28.6% vs. 13.5%). Men were more likely to present with early staging (p < 0.001) and have surgery as their only treatment (p < 0.001). The rate of incidence of Stage 1 tumours in men was 106.9%; however, women had the greatest increase in metastatic tumours (76.1%). Black Caribbean and Black African patients were more likely to present at an earlier age with later staging (p < 0.001) and social deprivation was associated with younger age (p < 0.001). ASCC incidence is rapidly increasing in patterns consistent with two separate populations: one male with early staging, the other female and related to social deprivation and ethnicity factors.

The cost of care for people living with stable HIV in Croatia and the efficiency of EmERGE.

AIM: To estimate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV (PLHIV) at the University Hospital for Infectious Diseases (UHID), Zagreb. The Pathway includes a mobile application enabling individuals to communicate with their caregivers. METHODS: This study involving 293 participants collected data on the use of HIV outpatient services one year before and after EmERGE implementation. In departments supporting HIV outpatients, a micro-costing exercise was performed to calculate unit costs. These were combined with mean use of HIV services per patient year (MPPY) to estimate average annual costs. Primary outcomes were CD4 count, viral load, and secondary outcomes were patient activation, PAM13; and quality of life, PROQOL-HIV. Information on out-of-pocket expenditures was also collected. RESULTS: Outpatient visits decreased by 17%, from 4.0 (95% CI 3.8-4.3) to 3.3 MPPY (95% CI 3.1-3.5). Tests, including CD4 count, decreased, all contributing to a 33% reduction of annual costs: 7139 HRK (95% CI 6766-7528) to 4781 HRK (95% CI 4504-5072). Annual costs including anti-retroviral drugs (ARVs) decreased by 5%: 43101 HRK (95% CI 42728-43,490) to 40 743 HRK (95% CI 40466-41,034). ARVs remain the main cost driver in stable PLHIV. Primary and secondary outcomes did not change substantially between periods. CONCLUSION: EmERGE Pathway was a cost-saving intervention associated with changes in management, and a reduction in outpatient visits, tests, and costs. ARV costs dominated costs. Future efficiencies are possible if EmERGE is introduced to other PLHIV across the UHID and if ARV prices are reduced.

Fetal fractional limb volumes in pregnancies following bariatric surgery.

INTRODUCTION: Obesity rates have reached an epidemic level and bariatric surgery is the most effective method of sustainable weight loss. Pregnancy following bariatric surgery is associated with an increased prevalence of small babies. The objective of the study is to compare the fetal fat distribution, as assessed by fractional arm and thigh volume using three-dimensional ultrasonography, in pregnancies following maternal bariatric surgery with those without such history. MATERIAL AND METHODS: This is a prospective, longitudinal, observational study conducted in a Maternity Unit in the UK. The study included 189 pregnant women; 63 with previous bariatric surgery [27 restrictive (13 with gastric band, 14 with sleeve gastrectomy) and 36 malabsorptive procedures] and 126 with no previous surgery but similar maternal booking body mass index. Fetal arm and thigh volume were obtained at 30-33 and 35-37 weeks' gestation and fractional limb volumes were calculated using a commercially available software. Women underwent a 75 g, 2 h oral glucose tolerance test at 28-31 weeks of gestation. RESULTS: Overall, adjusted fetal arm and thigh volume were smaller in the post-bariatric, compared to the no surgery, group and this was more marked in women who had undergone a previous sleeve gastrectomy (P < .001 and P = .002, respectively) or a malabsorptive procedure (P < .001 for both). There was a strong positive correlation between maternal fasting/post-prandial (2 h) glucose levels, at the time of the oral glucose tolerance test, and arm and thigh volume at both 30-33 and 35-37 weeks (P < .01 for all). CONCLUSIONS: The study has demonstrated that in the third trimester of pregnancy, fetuses of women with previous bariatric surgery have smaller fractional limb volumes, therefore less soft tissue, compared to fetuses of women without such surgery and this may be related to the lower maternal glucose levels seen in the former pregnancies.

Pregnancy Gestation Impacts on HIV-1-Specific Granzyme B Response and Central Memory CD4 T Cells.

Pregnancy induces alterations in peripheral T-cell populations with both changes in subset frequencies and anti-viral responses found to alter with gestation. In HIV-1 positive women anti-HIV-1 responses are associated with transmission risk, however detailed investigation into both HIV-1-specific memory responses associated with HIV-1 control and T-cell subset changes during pregnancy have not been undertaken. In this study we aimed to define pregnancy and gestation related changes to HIV-1-specific responses and T-cell phenotype in ART treated HIV-1 positive pregnant women. Eleven non-pregnant and 24 pregnant HIV-1 positive women were recruited, peripheral blood samples taken, fresh cells isolated, and compared using ELISpot assays and flow cytometry analysis. Clinical data were collected as part of standard care, and non-parametric statistics used. Alterations in induced IFNγ, IL-2, IL-10, and granzyme B secretion by peripheral blood mononuclear cells in response to HIV-1 Gag and Nef peptide pools and changes in T-cell subsets between pregnant and non-pregnant women were assessed, with data correlated with participant clinical parameters and longitudinal analysis performed. Cross-sectional comparison identified decreased IL-10 Nef response in HIV-1 positive pregnant women compared to non-pregnant, while correlations exhibited reversed Gag and Nef cytokine and protease response associations between groups. Longitudinal analysis of pregnant participants demonstrated transient increases in Gag granzyme B response and in the central memory CD4 T-cell subset frequency during their second trimester, with a decrease in CD4 effector memory T cells from their second to third trimester. Gag and Nef HIV-1-specific responses diverge with pregnancy time-point, coinciding with relevant T-cell phenotype, and gestation associated immunological adaptations. Decreased IL-10 Nef and both increased granzyme B Gag response and central memory CD4 T cells implies that amplified antigen production is occurring, which suggests a period of compromised HIV-1 control in pregnancy.

Does the political will exist to bring quality-assured and affordable drugs to low- and middle-income countries?

BACKGROUND: Increased coverage with antiretroviral therapy for people living with HIV in low- and middle-income countries has increased their life expectancy associated with non-HIV comorbidities and the need for quality-assured and affordable non-communicable diseases drugs . Funders are leaving many middle-income countries that will have to pay and provide quality-assured and affordable HIV and non-HIV drugs, including for non-communicable diseases. OBJECTIVE: To estimate costs for originator and generic antiretroviral therapy as the number of people living with HIV are projected to increase between 2016 and 2026, and discuss country, regional and global factors associated with increased access to generic drugs. METHODS: Based on estimates of annual demand and prices, annual cost estimates were produced for generic and originator antiretroviral drug prices in low- and middle-income countries and projected for 2016-2026. RESULTS: Drug costs varied between US$1.5 billion and US$4.8 billion for generic drugs and US$ 8.2 billion and US$16.5 billion for originator drugs between 2016 and 2026. DISCUSSION: The global HIV response increased access to affordable generic drugs in low- and middle-income countries. Cheaper active pharmaceutical ingredients and market competition were responsible for reduced drug costs. The development and implementation of regulatory changes at country, regional and global levels, covering intellectual property rights and public health, and flexibilities in patent laws enabled prices to be reduced. These changes have not yet been applied in many low- and middle-income countries for HIV, nor for other infectious and non-communicable diseases, that lack the profile and political attention of HIV. Licensing backed up with Trade-Related Aspects of Intellectual Property Rights safeguards should become the norm to provide quality-assured and affordable drugs within competitive generic markets. CONCLUSION: Does the political will exist among policymakers and other stakeholders to develop and implement these country, regional and global frameworks for non-HIV drugs as they did for antiretroviral drugs?

Short Communication: Therapeutic Immunization Benefits Mucosal-Associated Invariant T Cell Recovery in Contrast to Interleukin-2, Granulocyte-Macrophage Colony-Stimulating Factor, and Recombinant Human Growth Hormone Addition in HIV-1+ Treated Patients: Individual Case Reports from Phase I Trial.

Mucosal-associated invariant T (MAIT) cell populations are reduced in frequency in HIV-1+ patients, and this disruption is associated with systemic immune activation. Reconstitution of MAIT frequency may benefit HIV-1-infected individuals; however, only recently has in vivo work been endeavored. Treatment with interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), and recombinant human growth hormone (rhGH) immunotherapy combined with an HIV-1 vaccine in the context of antiretroviral therapy (ART) has shown to reconstitute CD4 T cell population numbers and function. In this study cryopreserved peripheral blood mononuclear cells (PBMCs) from 12 HIV-1+ patients who were undergoing a combination of HIV-1 vaccine and/or IL-2, GM-CSF and rhGH immunotherapy in conjunction with ART were analyzed to assess the potential of this treatment to promote MAIT cell proliferation. PBMCs were thawed from study baseline, weeks 2 and 48 time points, fluorescently stained for MAIT cell markers, and assessed by flow cytometric analysis. Matched pairs and intergroup results were statistically compared using appropriate methods. MAIT cell frequency was increased from baseline at 48 weeks in participants who received vaccine only, whereas individuals receiving IL-2, GM-CSF, and rhGH immunotherapy with or without vaccine did not show additional benefit. Although IL-2, GM-CSF, and rhGH treatment promotes CD4 T cell reconstitution and HIV-1-specific T cell function, it does not support MAIT cell recovery in patients on suppressive ART. Therapeutic immunization however has a positive effect, highlighting the importance of aiming for balanced promotion of T cell population reconstitution to impact on HIV-1 transmission and pathogenesis.

Attribution bias underlying burns-induced anxiety symptoms.

INTRODUCTION: Burn injuries are a debilitating cause of morbidity and mortality associated with the long-term impact of psychological factors on quality of life. Accurate assessment of the differential impact of burn sequelae and anxiety is often complicated by the overlap between psychological and somatic symptoms in burns patients. The Beck Anxiety Inventory (BAI) is one validated psychometric tool for anxiety assessment. The primary objective of this study is to investigate whether utilising the BAI as a tool to assess for anxiety in burns patients is biased due to the confounding of symptoms of anxiety with the physical sequelae of a burn injury. METHODS: This is a single-centre, prospective, cross-sectional study. The study was conducted in accordance with the UK Good Clinical Practice guidelines (CAPP reference number 506). Patients were recruited over a three-month period from November 2016 to February 2017 and were offered a modified BAI questionnaire to complete. Patients were asked to indicate to what degree they attributed each symptom to their physical injury or their psychological state on a visual analogue scale (VAS). RESULTS: 50 patients, comprising 33 females (66%) and 17 males (34%), participated in the study with a median age of 33.5 years (range: 20-88). Date of injury spanned May 1991 to January 2017. Percentage of the total body surface area (% TBSA) affected by burn ranged from 1 to 86%. Patients attributed eight of the 21 self-report items within the BAI as being more physical than psychological in origin. The results reveal a statistical significant difference in patient VAS scores between physical (mean: 34.16, 95% CI: 29.04-39.28) and psychological (mean: 61.2, 95% CI: 56.33-66.17) BAI items, with p<0.0001. In addition, patients with a facial burn injury were more likely to report 'face flushed' (Mann-Whitney U Test, Z=-2.11, p<0.05) and patients with a hand burn injury were more likely to report 'hands trembling' (Mann-Whitney U Test, Z=-2.52, p<0.05). CONCLUSIONS: This feasibility study found preliminary evidence suggesting that the BAI may, in part, represent misattributed symptoms of cutaneous injury from burns. However, whilst our findings suggest an attribution bias, there is not enough evidence from this data to comment on whether its use should be restricted in burns patients. Further research is needed to formally quantify convergent and divergent validity through structured interviews. In addition, further research using other self-report tools of anxiety in burns patients would be useful to corroborate the prospect of biased and confounded anxiety scores.