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Objectives: The incidence of sexually transmitted infections (STIs) and HIV infection remains high in gay, bisexual, and other men who have sex with men (MSM) in the UK, and sexualized drug use (“chemsex”) and injecting drug use (“slamsex”) may play a part in this. We aimed to characterize HIV‐positive MSM engaging in chemsex/slamsex and to assess the associations with self‐reported STI diagnoses and sexual behaviours. Methods: Data from a 2014 survey of people attending HIV clinics in England and Wales were linked to clinical data from national HIV surveillance records and weighted to be nationally representative. Multivariable logistic regression assessed the associations of chemsex and slamsex with self‐reported unprotected anal intercourse (UAI), serodiscordant UAI (sdUAI) (i.e. UAI with an HIV‐negative or unknown HIV status partner), sdUAI with a detectable viral load (>50 HIV‐1 RNA copies/mL), hepatitis C, and bacterial STIs. Results: In the previous year, 29.5% of 392 sexually active participants engaged in chemsex, and 10.1% in slamsex. Chemsex was significantly associated with increased odds of UAI [adjusted odds ratio (AOR) 5.73; P < 0.001], sdUAI (AOR 2.34; P < 0.05), sdUAI with a detectable viral load (AOR 3.86; P < 0.01), hepatitis C (AOR 6.58; P < 0.01), and bacterial STI diagnosis (AOR 2.65; P < 0.01). Slamsex was associated with increased odds of UAI (AOR 6.11; P < 0.05), hepatitis C (AOR 9.39; P < 0.001), and bacterial STI diagnosis (AOR 6.11; P < 0.001). Conclusions: Three in ten sexually active HIV‐positive MSM engaged in chemsex in the past year, which was positively associated with self‐reported depression/anxiety, smoking, nonsexual drug use, risky sexual behaviours, STIs, and hepatitis C. Chemsex may therefore play a role in the ongoing HIV and STI epidemics in the UK. [ABSTRACT FROM AUTHOR]

Objectives Involvement of people living with HIV ( PLHIV) in the design of HIV cure studies is important, given the potential risks to participants. We present results of an international survey of PLHIV to define these issues and inform cure research. Methods PLHIV were recruited in June−November 2014 through HIV websites, advocacy forums, social media and 12 UK HIV clinics. The survey included questions concerning demographics, HIV disease history, the desirability of types of cure and the patient's willingness to accept potential toxicity and treatment interruption ( TI). We examined factors associated with TI and willingness to accept substantial risks. Results A total of 982 PLHIV completed the survey; 87% were male, 79% white and 81% men who have sex with men ( MSM). Fifty-one per cent were aged 25-44 years and 69% were UK residents. The median time since diagnosis was 7 years [interquartile range ( IQR) 2-17 years]. Eighty-eight per cent were receiving antiretrovirals (91% reported undetectable viral load). Health/wellbeing improvements (96%) and an inability to transmit HIV (90%) were more desirable cure characteristics than testing HIV-negative (69%). Ninety-five per cent were interested in participating in cure studies, and 59% were willing to accept substantial risks. PLHIV with a low CD4 count [201-350 cells/ μL vs. ≥ 350 cells/ μL; odds ratio ( OR) 2.11; 95% confidence interval ( CI) 1.11-4.00] were more likely to accept risks, whereas those with limited knowledge of HIV treatments vs. excellent/good knowledge and those aged ≥ 65 years vs. 45-64 years were less likely to accept risks [ OR 0.58 (95% CI 0.37-0.90) and OR 0.18 (95% CI 0.07-0.45), respectively]. TI was acceptable for 62% of participants, with the main concerns being becoming unwell (82%), becoming infectious (76%) and HIV spreading through the body (76%). Conclusions Cure research was highly acceptable to the PLHIV surveyed. Most individuals would accept risks, including TI, even in the absence of personal benefit. An optimal cure would improve health and minimize onward transmission risk. [ABSTRACT FROM AUTHOR]

Objectives: We provide the first estimate of HIV prevalence among trans and gender‐diverse people living in England and compare outcomes of people living with HIV according to gender identity. Methods: We analysed a comprehensive national HIV cohort and a nationally representative self‐reported survey of people accessing HIV care in England (Positive Voices). Gender identity was recorded using a two‐step question co‐designed with community members and civil society. Responses were validated by clinic follow‐up and/or self‐report. Population estimates were obtained from national government offices. Results: In 2017, HIV prevalence among trans and gender‐diverse people was estimated at 0.46–4.78 per 1000, compared with 1.7 (95% credible interval: 1.6–1.7) in the general population. Of 94 885 people living with diagnosed HIV in England, 178 (0.19%) identified as trans or gender‐diverse. Compared with cisgender people, trans and gender‐diverse people were more likely to be London residents (57% vs. 43%), younger (median age 42 vs. 46 years), of white ethnicity (61% vs. 52%), under psychiatric care (11% vs. 4%), to report problems with self‐care (37% vs. 13%), and to have been refused or delayed healthcare (23% vs. 11%). Antiretroviral uptake and viral suppression were high in both groups. Conclusions: HIV prevalence among trans and gender‐diverse people living in England is relatively low compared with international estimates. Furthermore, no inequalities were observed with regard to HIV care. Nevertheless, trans and gender‐diverse people with HIV report poorer mental health and higher levels of discrimination compared with cisgender people. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of the study were to describe 10‐year trends in HIV diagnosis setting and to explore predictors of being diagnosed outside a sexual health clinic (SHC). Methods: Analyses of national HIV surveillance data were restricted to adults (aged ≥ 15 years) diagnosed in 2005–2014 in England, Wales and Northern Ireland. Logistic regression identified factors associated with diagnosis outside an SHC (2011–2014). Results: Between 2005 and 2014, 63 599 adults were newly diagnosed with HIV infection; 83% had a diagnosis setting reported. Most people were diagnosed in SHCs (69%) followed by: medical admissions/accident and emergency (A&E; 8.6%), general practice (6.4%), antenatal services (5.5%), out‐patient services (3.6%), infectious disease units (2.7%) and other settings (4.0%). The proportion of people diagnosed outside SHCs increased from 2005 to 2014, overall (from 27% to 32%, respectively) and among men who have sex with men (MSM) (from 14% to 21%) and black African men (from 25% to 37%) and women (from 39% to 52%) (all trend P < 0.001). Median CD4 increased across all settings, but was highest in SHCs (384 cells/μL) and lowest in medical admissions/A&E (94 cells/μL). Predictors of being diagnosed outside SHCs included: acquiring HIV through heterosexual contact [adjusted odds ratio (aOR) 1.99; 95% confidence interval (CI) 1.81–2.18] or injecting drug use (aOR: 3.28; 95% CI: 2.56–4.19; reference: MSM), being diagnosed late (< 350 cells/μL) (aOR: 2.55; 95% CI: 2.36–2.74; reference: diagnosed promptly) and being of older age at diagnosis (35–49 years: aOR: 1.60; 95% CI: 1.39–1.83; ≥ 50 years: aOR: 2.48; 95% CI: 2.13–2.88; reference: 15–24 years). Conclusions: The proportion of HIV diagnoses made outside SHCs has increased over the past decade in line with evolving HIV testing guidelines. However, the rate of late diagnosis remains high, indicating that further expansion of testing is necessary, as many people may have had missed opportunities for earlier diagnosis. [ABSTRACT FROM AUTHOR]

Background: People living with HIV experience burdensome multidimensional symptoms and concerns requiring person-centred care. Routine use of patient reported outcome measures can improve outcomes. There is no brief patient reported outcome measure (PROM) that currently reflects the breadth of concerns for people living with HIV. This study aimed to develop and cognitively test a brief novel patient reported outcome measure for use within routine adult HIV care- the "Positive Outcomes" HIV PROM.Methods: Development followed the COSMIN taxonomy and guidance for relevance and comprehensiveness, and Rothrock guidance on development of valid patient reported outcome measures. The Positive Outcomes HIV PROM was developed by a steering group (people living with HIV, HIV professionals and health services researchers) using findings from a previously reported qualitative study of priority outcomes for people living with HIV. The prototype measure was cognitively tested with a purposive sample of people living with HIV.Results: The Positive Outcomes HIV PROM consists of 23 questions (22 structured, and one open question) informed by the priorities of key stakeholders (n = 28 people living with HIV, n = 21 HIV professionals and n = 8 HIV commissioners) to ensure face and content validity, and refined through cognitive testing (n = 6 people living with HIV). Cognitive testing demonstrated high levels of acceptability and accessibility.Conclusions: The Positive Outcomes HIV PROM is the first brief patient reported outcome measure reflecting the diverse needs of people living with HIV designed specifically for use in the clinical setting to support patient assessment and care, and drive service quality improvement. It is derived from primary data on the priority outcomes for people living with HIV and is comprehensive and acceptable. Further psychometric testing is required to ensure reliability and responsiveness. [ABSTRACT FROM AUTHOR]

Background and Purpose Intestinal nutrient transporters may mediate the uptake of drugs. The aim of this study was to investigate whether sertraline interacts with the intestinal proton-coupled amino acid transporter 1 PAT1 ( SLC36A1). Experimental Approach In vitro investigations of interactions between sertraline and human ( h)PAT1, hSGLT1 (sodium-glucose linked transporter 1) and hPepT1 (proton-coupled di-/tri-peptide transporter 1) were conducted in Caco-2 cells using radiolabelled substrates. In vivo pharmacokinetic investigations were conducted in male Sprague- Dawley rats using gaboxadol (10 mg·kg−1, p.o.) as a PAT1 substrate and sertraline (0-30.6 mg·kg−1). Gaboxadol was quantified by hydrophilic interaction chromatography followed by MS/ MS detection. Key Results Sertraline inhibited hPAT1-mediated L-[ 3H]- Pro uptake in Caco-2 cells. This interaction between sertraline and PAT1 appeared to be non-competitive. The uptake of the hSGLT1 substrate [ 14C]-α-methyl-D-glycopyranoside and the hPepT1 substrate [ 14C]- Gly- Sar in Caco-2 cells was also decreased in the presence of 0.3 mM sertraline. In rats, the administration of sertraline (0.1-10 mM, corresponding to 0.3-30.6 mg·kg−1, p.o.) significantly reduced the maximal gaboxadol plasma concentration and AUC after its administration p.o. Conclusions and Implications Sertraline is an apparent non-competitive inhibitor of hPAT1-mediated transport in vitro. This inhibitory effect of sertraline is not specific to hPAT1 as substrate transport via hPepT1 and hSGLT1 was also reduced in the presence of sertraline. In vivo, sertraline reduced the amount of gaboxadol absorbed, suggesting that the inhibitory effect of sertraline on PAT1 occurs both in vitro and in vivo. Hence, sertraline could alter the bioavailability of drugs absorbed via PAT1. [ABSTRACT FROM AUTHOR]

We show that aromatic amino acids on aggregated and immobilized Ag nanocrystals degrade upon laser illumination (λ = 514.5 nm). Surface-enhanced Raman scattering (SERS) data, using tyrosine as the precursor, point to a linear one-photon induced reaction. This interpretation is supported by ab initio calculations of tyrosine-Ag+ complexes. Spectral fluctuations and bleaching-effects suggest that the observed SERS signal is due to a variety of chromophores that continuously form from aromatic precursors and eventually break down at the Ag surface. The final photoproduct is similar to amorphous carbon (AC) but the spectral details are determined by the precursor. We found that precoating the Ag particles with thiophenol inhibits photoinduced degradation of tyrosine in H2O. [ABSTRACT FROM AUTHOR]

Ethylene, a biologically active natural compound, inhibited aflatoxin accumulation by Aspergillus parasiticus on a solid growth medium in a dose-dependent manner at concentrations of 0.1 to 150 ppm. The activity of the nor-1 promoter (an early aflatoxin gene) was reduced to nondetectable levels by similar quantities of ethylene, suggesting that the inhibitory effect on toxin synthesis occurred, at least in part, at the level of transcription. The inhibitory effect of ethylene on aflatoxin accumulation was also observed when A. parasiticus was grown on raw peanuts. Under similar growth conditions and doses, ethylene strongly inhibited development of asci and ascospores in Aspergillus nidulans, with no detectable effect on Hülle cell formation, conidiation, or sterigmatocystin accumulation. During early growth, A. parasiticus and A. nidulans produced ethylene with approximately twofold higher quantities measured in continuous light than in the dark. 1-Methylcyclopropene (an inhibitor of ethylene receptors in plants), light, CO2, temperature, and growth medium composition altered the effect of ethylene on A. nidulans and A. parasiticus. These observations are consistent with the existence of an ethylene sensor molecule that mediates the function of an ethylene-responsive signaling pathway(s) in Aspergillus. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to identify and describe the characteristics of persons born in the UK who acquire HIV infection abroad. Methods Analyses using case reports and follow-up data from the national HIV database held at the Health Protection Agency were performed. Results Fifteen per cent (2066 of 13 891) of UK-born adults diagnosed in England, Wales and Northern Ireland between 2002 and 2010 acquired HIV infection abroad. Thailand (534), the USA (117) and South Africa (108) were the countries most commonly reported. As compared with UK-born adults acquiring HIV infection in the UK, those acquiring HIV infection abroad were significantly ( P < 0.01) more likely to have acquired it heterosexually (70% vs. 22%, respectively), to be of older age at diagnosis (median 42 years vs. 36 years, respectively), and to have reported sex with a commercial sex worker (5.6% vs. 1%, respectively). Among men infected in Thailand, 11% reported sex with a commercial sex worker. Conclusions A substantial number of UK-born adults are acquiring HIV infection in countries with generalized HIV epidemics, and in common holiday destinations. Of particular concern is the high proportion of men infected reporting sex with a commercial sex worker. We recommend HIV prevention and testing efforts be extended to include travellers abroad, and that sexual health advice be provided routinely in travel health consultations and in occupational health travel advice packs, particularly to those travelling to high HIV prevalence areas and destinations for sex tourism. Safer sex messages should include an awareness of the potential detrimental health and social impacts of the sex industry. [ABSTRACT FROM AUTHOR]